Sample records for potential clinical implications
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Wong, Christopher X; Ganesan, Anand N; Selvanayagam, Joseph B
2017-05-01
Obesity is increasingly recognized as a major modifiable determinant of atrial fibrillation (AF). Although body mass index and other clinical measures are useful indications of general adiposity, much recent interest has focused on epicardial fat, a distinct adipose tissue depot that can be readily assessed using non-invasive imaging techniques. A growing body of data from epidemiological and clinical studies has demonstrated that epicardial fat is consistently associated with the presence, severity, and recurrence of AF across a range of clinical settings. Evidence from basic science and translational studies has also suggested that arrhythmogenic mechanisms may involve adipocyte infiltration, pro-fibrotic, and pro-inflammatory paracrine effects, oxidative stress, and other pathways. Despite these advances, however, significant uncertainty exists and many questions remain unanswered. In this article, we review our present understanding of epicardial fat, including its classification and quantification, existing evidence implicating its role in AF, potential mechanisms, implications for clinicians, and future directions for research. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.
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A review of the clinical implications of bisphosphonates in dentistry.
Borromeo, G L; Tsao, C E; Darby, I B; Ebeling, P R
2011-03-01
Bisphosphonates are drugs that suppress bone turnover and are commonly prescribed to prevent skeletal related events in malignancy and for benign bone diseases such as osteoporosis. Bisphosphonate associated jaw osteonecrosis (ONJ) is a potentially debilitating, yet poorly understood condition. A literature review was undertaken to review the dental clinical implications of bisphosphonates. The present paper briefly describes the postulated pathophysiology of ONJ and conditions with similar clinical presentations. The implications of bisphosphonates for implantology, periodontology, orthodontics and endodontics are reviewed. Whilst bisphosphonates have potential positive applications in some clinical settings, periodontology particularly, further clinical research is limited by the risk of ONJ. Prevention and management are reviewed, including guidelines for reducing cumulative intravenous bisphosphonate dose, cessation of bisphosphonates prior to invasive dental treatment or after ONJ development, and the use of serum beta-CTX-1 in assessing risk. In the context of substantial uncertainty, the implications of bisphosphonate use in the dental clinical setting are still being determined. © 2010 Australian Dental Association.
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Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs
2017-10-01
Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.
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miRNAs in inflammatory skin diseases and their clinical implications
DEFF Research Database (Denmark)
Løvendorf, Marianne B; Skov, Lone
2015-01-01
biological processes. The clinical implications of miRNAs are intriguing, both from a diagnostic and a therapeutic perspective. Accordingly, there is emerging evidence for the clinical potential of miRNAs as both biomarkers and possible therapeutic targets in skin diseases. Future studies will hopefully...... incomplete; however, it is known that miRNAs are implicated in various cellular processes of both normal and diseased skin. Some miRNAs appear to be consistently deregulated in several different inflammatory skin diseases, including psoriasis and atopic dermatitis, indicating a common role in fundamental...
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Wideł, Maria; Przybyszewski, Waldemar; Rzeszowska-Wolny, Joanna
2009-08-18
It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the "bystander effect" or "radiation-induced bystander effect" (RIBE). This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy), but also after conventional irradiation (X-rays, gamma rays) at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not definitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effect may have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation field and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The bystander effect may be a
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Directory of Open Access Journals (Sweden)
Maria Wideł
2009-08-01
Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The
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Multidrug efflux pumps in Staphylococcus aureus and their clinical implications.
Jang, Soojin
2016-01-01
Antibiotic resistance is rapidly spreading among bacteria such as Staphylococcus aureus, an opportunistic bacterial pathogen that causes a variety of diseases in humans. For the last two decades, bacterial multidrug efflux pumps have drawn attention due to their potential association with clinical multidrug resistance. Numerous researchers have demonstrated efflux-mediated resistance in vitro and in vivo and found novel multidrug transporters using advanced genomic information about bacteria. This article aims to provide a concise summary of multidrug efflux pumps and their important clinical implications, focusing on recent findings concerning S. aureus efflux pumps.
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Clinical implications of contemporary gender theory.
Kulish, Nancy
2010-04-01
The current intellectual scene in psychoanalysis is marked by vigorous theoretical controversies about gender. The ideas being debated have important implications for clinical work, which have not been thoroughly explicated or integrated into common practice. These implications include the following: gender can accrue idiosyncratic meanings; gender identity is considered fluid and rigidity of gender identity deemed problematic; gender-related conflicts are typically described as divergent; analysis of superego conflicts related to gender becomes particularly important; and, finally, gender-related biases are seen as inevitable and must be taken into account in the clinical situation. A detailed clinical example illustrates the application of these ideas. While the more dramatic cases related to gender have been more frequent subjects of study, conflicts about gender are everyday occurrences for our patients and deserve further attention.
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Terror management theory applied clinically: implications for existential-integrative psychotherapy.
Lewis, Adam M
2014-01-01
Existential psychotherapy and Terror Management Theory (TMT) offer explanations for the potential psychological effects of death awareness, although their respective literatures bases differ in clarity, research, and implications for treating psychopathology. Existential therapy is often opaque to many therapists, in part due to the lack of consensus on what constitutes its practice, limited published practical examples, and few empirical studies examining its efficacy. By contrast, TMT has an extensive empirical literature base, both within social psychology and spanning multiple disciplines, although previously unexplored within clinical and counseling psychology. This article explores the implications of a proposed TMT integrated existential therapy (TIE), bridging the gap between disciplines in order to meet the needs of the aging population and current challenges facing existential therapists.
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Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.
Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P
2012-08-01
Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.
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Clinical Ethics Consultation After God: Implications for Advocacy and Neutrality.
Parker, J Clint
2018-06-01
In After God: Morality and Bioethics in a Secular Age, H. Tristram Engelhardt, Jr. explores the broad implications for moral reasoning once a culture has lost a God's-eye perspective. In this paper, I focus on the implications of Engelhardt's views for clinical ethics consultation. I begin by examining the question of whether clinical ethics consultants (CECs) should advocate a particular viewpoint and/or process during consultations or adopt a neutral stance. I then examine the implications of Engelhardt's views for this question. Finally, I discuss some of Engelhardt's foundational ontological, metaphysical, meta-ethical, and epistemological commitments and how these commitments connect to his views on clinical ethics consultation.
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Brain microbleeds: Epidemiology and clinical implications.
Boyano, I; Bravo, N; Miranda, J; Gil-Gregorio, P; Olazarán, J
2016-06-22
Brain microbleeds (BMB) are haemosiderin deposits contained within macrophages, which are displayed as hypointense images in some T2-weighted magnetic resonance imaging sequences. There are still many questions to be answered about the pathophysiology and clinical relevance of BMB. We conducted a literature review of the main epidemiological, clinical, and anatomical pathology studies of BMB performed in the general population, in patients at risk of or already suffering from a vascular disease, and in patients with cognitive impairment. We analysed the prevalence of BMB, risk factors, and potential pathophysiological mechanisms and clinical implications. The prevalence of BMB is highly variable (3%-27% in the general population, 6%-80% in patients with vascular risk factors or vascular disease, and 16%-45% in patients with cognitive impairment). BMB are associated with ageing, Alzheimer disease (AD), and in particular haemorrhagic or ischaemic cerebrovascular disease. The pathological substrate of BMB is either lipohyalinosis (subcortical BMB) or cerebral amyloid angiopathy (lobar BMB). BMB exacerbate cognitive impairment, possibly through cortical-subcortical and intracortical disconnection, and increase the risk of death, mostly due to vascular causes. BMB also increase the risk of cerebral haemorrhage, particularly in patients with multiple lobar BMB (probable erebral amyloid angiopathy). Therefore, anticoagulant treatment may be contraindicated in these patients. In patients with lower risk of bleeding, the new oral anticoagulants and the combination of clinical and magnetic resonance imaging follow-up could be helpful in the decision-making process. Copyright © 2016 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.
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Clinical Implications Of Childhood Bilingualism | Southwood ...
African Journals Online (AJOL)
Stellenbosch Papers in Linguistics Plus. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 32 (2003) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Clinical Implications Of Childhood Bilingualism.
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α-Synuclein oligomers and clinical implications for Parkinson disease
Kalia, Lorraine V.; Kalia, Suneil K.; McLean, Pamela J.; Lozano, Andres M.; Lang, Anthony E.
2012-01-01
Protein aggregation within the central nervous system has been recognized as a defining feature of neurodegenerative diseases since the early 20th century. Since that time, there has been a growing list of neurodegenerative disorders, including Parkinson disease, which are characterized by inclusions of specific pathogenic proteins. This has led to the long-held dogma that these characteristic protein inclusions, which are composed of large insoluble fibrillar protein aggregates and visible by light microscopy, are responsible for cell death in these diseases. However, the correlation between protein inclusion formation and cytotoxicity is inconsistent suggesting another form of the pathogenic proteins may be contributing to neurodegeneration. There is emerging evidence implicating soluble oligomers, smaller protein aggregates not detectable by conventional microscopy, as potential culprits in the pathogenesis of neurodegenerative diseases. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites. However, α-synuclein also forms oligomeric species with certain conformations being toxic to cells. The mechanisms by which these α-synuclein oligomers cause cell death are being actively investigated as they may provide new strategies for diagnosis and treatment of Parkinson disease and related disorders. Here we review the possible role of α-synuclein oligomers in cell death in Parkinson disease and discuss the potential clinical implications. PMID:23225525
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An updated concept of coagulation with clinical implications.
Romney, Gregory; Glick, Michael
2009-05-01
Over the past century, a series of models have been put forth to explain the coagulation mechanism. The coagulation cascade/waterfall model has gained the most widespread acceptance. This model, however, has problems when it is used in different clinical scenarios. A more recently proposed cell-based model better describes the coagulation process in vivo and provides oral health care professionals (OHCPs) with a better understanding of the clinical implications of providing dental care to patients with potentially increased bleeding tendencies. The authors conducted a literature search using the PubMed database. They searched for key words including "coagulation," "hemostasis," "bleeding," "coagulation factors," "models," "prothrombin time," "activated partial thromboplastin time," "international normalized ratio," "anticoagulation therapy" and "hemophilia" separately and in combination. The coagulation cascade/waterfall model is insufficient to explain coagulation in vivo, predict a patient's bleeding tendency, or correlate clinical outcomes with specific laboratory screening tests such as prothrombin time, activated partial thromboplastin time and international normalized ratio. However, the cell-based model of coagulation that reflects the in vivo process of coagulation provides insight into the clinical ramifications of treating dental patients with specific coagulation factor deficiencies. Understanding the in vivo coagulation process will help OHCPs better predict a patient's bleeding tendency. In addition, applying the theoretical concept of the cell-based model of coagulation to commonly used laboratory screening tests for coagulation and bleeding will result in safer and more appropriate dental care.
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Dependence on carbonated water: Clinical and policy implications
Directory of Open Access Journals (Sweden)
Sumit Kumar Gupta
2015-01-01
Full Text Available A case of caffeine dependence syndrome with preference for a specific brand of carbonated water (popularly known as soft drinks or colas is discussed to highlight the clinical and policy implications.
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Medicare Part D Roulette, Potential Implications of Random..
U.S. Department of Health & Human Services — Medicare Part D Roulette, Potential Implications of Random Assignment and Plan Restrictions Dual-eligible (Medicare and Medicaid) beneficiaries are randomly assigned...
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Walters, Nathan T; Spengler, Paul M
2016-09-01
Mental health professionals are increasingly aware of the need for competence in the treatment of clients with pornography-related concerns. However, while researchers have recently sought to explore efficacious treatments for pornography-related concerns, few explorations of potential clinical judgment issues have occurred. Due to the sensitive, and at times uncomfortable, nature of client disclosures of sexual concerns within therapy, therapists are required to manage their own discomfort while retaining fidelity to treatment. The present paper explores clinician examples of judgment errors that may result from feelings of discomfort, and specifically from client use of pornography. Issues of potential bias, bias management techniques, and therapeutic implications are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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Santamaría-García, Hernando; Santangelo, Gabriella
2018-01-01
Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM), emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs), most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients' management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD), or may emerge during the disease course as critical aspects, such as for Parkinson's and Alzheimer's diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients' well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits. PMID:29854017
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Directory of Open Access Journals (Sweden)
Foteini Christidi
2018-01-01
Full Text Available Social cognitive function, involved in the perception, processing, and interpretation of social information, has been shown to be crucial for successful communication and interpersonal relationships, thereby significantly impacting mental health, well-being, and quality of life. In this regard, assessment of social cognition, mainly focusing on four key domains, such as theory of mind (ToM, emotional empathy, and social perception and behavior, has been increasingly evaluated in clinical settings, given the potential implications of impairments of these skills for therapeutic decision-making. With regard to neurodegenerative diseases (NDs, most disorders, characterized by variable disease phenotypes and progression, although similar for the unfavorable prognosis, are associated to impairments of social cognitive function, with consequent negative effects on patients’ management. Specifically, in some NDs these deficits may represent core diagnostic criteria, such as for behavioral variant frontotemporal dementia (bvFTD, or may emerge during the disease course as critical aspects, such as for Parkinson’s and Alzheimer’s diseases. On this background, we aimed to revise the most updated evidence on the neurobiological hypotheses derived from network-based approaches, clinical manifestations, and assessment tools of social cognitive dysfunctions in NDs, also prospecting potential benefits on patients’ well-being, quality of life, and outcome derived from potential therapeutic perspectives of these deficits.
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The biology, function and clinical implications of exosomes in lung cancer.
Zhou, Li; Lv, Tangfeng; Zhang, Qun; Zhu, Qingqing; Zhan, Ping; Zhu, Suhua; Zhang, Jianya; Song, Yong
2017-10-28
Exosomes are 30-100 nm small membrane vesicles of endocytic origin that are secreted by all types of cells, and can also be found in various body fluids. Increasing evidence implicates that exosomes confer stability and can deliver their cargos such as proteins and nucleic acids to specific cell types, which subsequently serve as important messengers and carriers in lung carcinogenesis. Here, we describe the biogenesis and components of exosomes mainly in lung cancer, we summarize their function in lung carcinogenesis (epithelial mesenchymal transition, oncogenic cell transformation, angiogenesis, metastasis and immune response in tumor microenvironment), and importantly we focus on the clinical potential of exosomes as biomarkers and therapeutics in lung cancer. In addition, we also discuss current challenges that might impede the clinical use of exosomes. Further studies on the functional roles of exosomes in lung cancer requires thorough research. Copyright © 2017 Elsevier B.V. All rights reserved.
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HBV DNA Integration: Molecular Mechanisms and Clinical Implications
Tu, Thomas; Budzinska, Magdalena A.; Shackel, Nicholas A.; Urban, Stephan
2017-01-01
Chronic infection with the Hepatitis B Virus (HBV) is a major cause of liver-related morbidity and mortality. One peculiar observation in cells infected with HBV (or with closely‑related animal hepadnaviruses) is the presence of viral DNA integration in the host cell genome, despite this form being a replicative dead-end for the virus. The frequent finding of somatic integration of viral DNA suggests an evolutionary benefit for the virus; however, the mechanism of integration, its functions, and the clinical implications remain unknown. Here we review the current body of knowledge of HBV DNA integration, with particular focus on the molecular mechanisms and its clinical implications (including the possible consequences of replication-independent antigen expression and its possible role in hepatocellular carcinoma). HBV DNA integration is likely to influence HBV replication, persistence, and pathogenesis, and so deserves greater attention in future studies. PMID:28394272
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Lifescience Database Archive (English)
Full Text Available 15069387 Innate immunity and toll-like receptors: clinical implications of basic science...te immunity and toll-like receptors: clinical implications of basic scienceresearch. PubmedID 15069387 Title... Innate immunity and toll-like receptors: clinical implications of basic sciencer
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Intra-tumor heterogeneity in head and neck cancer and its clinical implications
Directory of Open Access Journals (Sweden)
Edmund A. Mroz
2016-06-01
Full Text Available The presence of heritable differences among cancer cells within a tumor, called intra-tumor genetic heterogeneity, has long been suspected of playing a role in poor responses to therapy. Research over the past decade has documented the existence of such heterogeneity within tumors of individual patients and documented its potential clinical significance. The research methods for identifying this heterogeneity were not, however, readily adaptable to widespread clinical application. After a brief review of this background, we describe the development of a measure of intra-tumor genetic heterogeneity, based on whole-exome sequencing of individual tumor samples, that could be applied to biopsy specimens in a clinical setting. This measure has now been used in head and neck squamous cell carcinoma (HNSCC to document, for the first time, a relation of high intra-tumor genetic heterogeneity to shorter overall survival in a large, multi-institutional study. The implications of heterogeneity for research and clinical care thus now need to be addressed. Keywords: Head and neck squamous cell carcinoma, Intra-tumor genetic heterogeneity, Next-generation sequencing, Targeted therapy
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Lahiri, Shouri; Boro, Alexis D; Shiloh, Ariel L; Milstein, Mark J; Savel, Richard H
2015-10-01
Periodic epileptiform discharges (PEDs) are frequently encountered during continuous electroencephalography monitoring in the intensive care unit. Their implications and management are variable and highly dependent on the clinical context. This article is intended for the nonneurologist intensivist, reviews basic terminology and clinical implications (including causes, prognosis, and association with seizures), and suggests an approach to management. Several case vignettes are included to illustrate the clinical variability associated with PEDs. © The Author(s) 2013.
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Potential Clinical Implications of the Urotensin II Receptor Antagonists
Directory of Open Access Journals (Sweden)
Emilie Kane
2011-07-01
Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.
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Heat Shock Proteins: Pathogenic Role in Atherosclerosis and Potential Therapeutic Implications
Directory of Open Access Journals (Sweden)
Arman Kilic
2012-01-01
Full Text Available Heat shock proteins (HSPs are a highly conserved group of proteins that are constitutively expressed and function as molecular chaperones, aiding in protein folding and preventing the accumulation of misfolded proteins. In the arterial wall, HSPs have a protective role under normal physiologic conditions. In disease states, however, HSPs expressed on the vascular endothelial cell surface can act as targets for detrimental autoimmunity due to their highly conserved sequences. Developing therapeutic strategies for atherosclerosis based on HSPs is challenged by the need to balance such physiologic and pathologic roles of these proteins. This paper summarizes the role of HSPs in normal vascular wall processes as well as in the development and progression of atherosclerosis. The potential implications of HSPs in clinical therapies for atherosclerosis are also discussed.
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Supernatural impotence: historical review with anthropological and clinical implications.
Margolin, J; Witztum, E
1989-12-01
The historical and cultural background of the belief in supernatural impotence is presented, emphasizing its possible implications for clinical practice. A brief historical survey of the concept in Judaism and Christianity is followed by a short anthropological survey of supernatural impotence in different ethnic subcultures in Israel. A case demonstration exemplifies the connection between understanding the patient's cultural background and beliefs and the clinical competence of the therapist. The relationship between the clinical-therapeutic process in psychiatric practice and knowledge of the patient's cultural background and beliefs is stressed.
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Clinical review: Ethnic differences in bone mass--clinical implications.
Leslie, William D
2012-12-01
Differences in bone mineral density (BMD) as assessed with dual-energy x-ray absorptiometry are observed between geographic and ethnic groups, with important implications in clinical practice. PubMed was employed to identify relevant studies. A review of the literature was conducted, and data were summarized and integrated. The available data highlight the complex ethnic variations in BMD, which only partially account for observed variations in fracture rates. Factors contributing to ethnic differences include genetics, skeletal size, body size and composition, lifestyle, and social determinants. Despite BMD differences, the gradient of risk for fracture from BMD and other clinical risk factors appears to be similar across ethnic groups. Furthermore, BMD variation is greater within an ethnic population than between ethnic populations. New imaging technologies have identified ethnic differences in bone geometry, volumetric density, microarchitecture, and estimated bone strength that may contribute to a better understanding of ethnic differences in fracture risk. Factors associated with ethnicity affect BMD and fracture risk through direct and indirect mechanisms.
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The practice and clinical implications of tablet splitting in international health
Elliott, Ivo; Mayxay, Mayfong; Yeuichaixong, Sengchanh; Lee, Sue J; Newton, Paul N
2014-01-01
Objective Tablet splitting is frequently performed to facilitate correct dosing, but the practice and implications in low-income settings have rarely been discussed. Methods We selected eight drugs, with narrow therapeutic indices or critical dosages, frequently divided in the Lao PDR (Laos). These were split, by common techniques used in Laos, by four nurses and four laypersons. The mean percentage deviation from the theoretical expected weight and weight loss of divided tablets/capsules were recorded. Results Five of eight study drugs failed, on splitting, to meet European Pharmacopoeia recommendations for tablet weight deviation from the expected weight of tablet/capsule halves with 10% deviating by more than 25%. There was a significant difference in splitting accuracy between nurses and laypersons (P = 0.027). Coated and unscored tablets were less accurately split than uncoated (P = 0.03 and 0.0019 for each half) and scored (0.0001 for both halves) tablets. Conclusion These findings have potential clinical implications on treatment outcome and the development of antimicrobial resistance. Investment by drug companies in a wider range of dosage units, particularly for narrow therapeutic index and critical dosage medicines, is strongly recommended. PMID:24702766
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Venous chest anatomy: clinical implications
International Nuclear Information System (INIS)
Chasen, M.H.; Charnsangavej, C.
1998-01-01
This article provides a practical approach to the clinical implications and importance of understanding the collateral venous anatomy of the thorax. Routine radiography, conventional venography, computed tomography (CT), and magnetic resonance (MR) imaging studies provide correlative anatomic models for the demonstration of how interconnecting collateral vascular networks within the thorax maintain venous stability at all times. Five major systems comprise the collateral venous network of the thorax ( Fig. 1 ). These include the paravertebral, azygos-hemiazygos, internal mammary, lateral thoracic, and anterior jugular venous systems (AJVS). The five systems are presented in the following sequence: (a) a brief introduction to the importance of catheter position and malposition in understanding access to the thoracic venous system, (b) the anatomy of the azygos-hemiazygos systems and their relationship with the paravertebral plexus, (c) the importance of the AJVS, (d) 'loop' concepts interconnecting the internal mammary and azygos-hemiazygos systems by means of the lateral thoracic and intercostal veins, and (e) the interconnecting venous networks on the thoracic side of the thoracoabdominal junction. Certain aspects of the venous anatomy of the thorax will not be discussed in this chapter and include (a) the intra-abdominal anastomoses between the superior and inferior vena cavae (IVC) via the internal mammary, lateral thoracic, and azygos-hemiazygos systems (beyond the scope of this article), (b) potential collateral vessels involving vertebral, parascapular, thyroidal, thymic, and other smaller veins that might anastomose with the major systems, and (c) anatomic variants and pitfalls that may mimic pathologic conditions (space limitations). (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)
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Point-of-care testing for chlamydia and gonorrhoea: implications for clinical practice.
Directory of Open Access Journals (Sweden)
Lisa Natoli
Full Text Available Point-of-care (POC testing for chlamydia (CT and gonorrhoea (NG offers a new approach to the diagnosis and management of these sexually transmitted infections (STIs in remote Australian communities and other similar settings. Diagnosis of STIs in remote communities is typically symptom driven, and for those who are asymptomatic, treatment is generally delayed until specimens can be transported to the reference laboratory, results returned and the patient recalled. The objective of this study was to explore the clinical implications of using CT/NG POC tests in routine clinical care in remote settings.In-depth qualitative interviews were conducted with a purposively selected group of 18 key informants with a range of sexual health and laboratory expertise.Participants highlighted the potential impact POC testing would have on different stages of the current STI management pathway in remote Aboriginal communities and how the pathway would change. They identified implications for offering a POC test, specimen collection, conducting the POC test, syndromic management of STIs, pelvic inflammatory disease diagnosis and management, interpretation and delivery of POC results, provision of treatment, contact tracing, management of client flow and wait time, and re-testing at 3 months after infection.The introduction of POC testing to improve STI service delivery requires careful consideration of both its advantages and limitations. The findings of this study will inform protocols for the implementation of CT/NG POC testing, and also STI testing and management guidelines.
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Point-of-Care Testing for Chlamydia and Gonorrhoea: Implications for Clinical Practice
Natoli, Lisa; Maher, Lisa; Shephard, Mark; Hengel, Belinda; Tangey, Annie; Badman, Steven G.; Ward, James; Guy, Rebecca J.
2014-01-01
Objectives Point-of-care (POC) testing for chlamydia (CT) and gonorrhoea (NG) offers a new approach to the diagnosis and management of these sexually transmitted infections (STIs) in remote Australian communities and other similar settings. Diagnosis of STIs in remote communities is typically symptom driven, and for those who are asymptomatic, treatment is generally delayed until specimens can be transported to the reference laboratory, results returned and the patient recalled. The objective of this study was to explore the clinical implications of using CT/NG POC tests in routine clinical care in remote settings. Methods In-depth qualitative interviews were conducted with a purposively selected group of 18 key informants with a range of sexual health and laboratory expertise. Results Participants highlighted the potential impact POC testing would have on different stages of the current STI management pathway in remote Aboriginal communities and how the pathway would change. They identified implications for offering a POC test, specimen collection, conducting the POC test, syndromic management of STIs, pelvic inflammatory disease diagnosis and management, interpretation and delivery of POC results, provision of treatment, contact tracing, management of client flow and wait time, and re-testing at 3 months after infection. Conclusions The introduction of POC testing to improve STI service delivery requires careful consideration of both its advantages and limitations. The findings of this study will inform protocols for the implementation of CT/NG POC testing, and also STI testing and management guidelines. PMID:24956111
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Hypertensive response to exercise: mechanisms and clinical implication
Kim, Darae; Ha, Jong-Won
2016-01-01
A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates tha...
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The potential implication of eosinophil activation in the pathogenesis ...
African Journals Online (AJOL)
Ehab
The potential implication of eosinophil activation in the pathogenesis of childhood asthma. INTRODUCTION. Asthma is recognized as an eosinophil mediated inflammation of the airways1. Eosinophils are major contributors to the damage in the airways of asthmatic patients which when activated, degranulate and release ...
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Obesity Paradox in Lung Cancer Prognosis: Evolving Biological Insights and Clinical Implications.
Zhang, Xueli; Liu, Yamin; Shao, Hua; Zheng, Xiao
2017-10-01
The survival rate of lung cancer remains low despite the progress of surgery and chemotherapy. With the increasing comorbidity of obesity in patients with lung cancer, new challenges are emerging in the management of this patient population. A key issue of interest is the prognostic effect of obesity on surgical and chemotherapeutic outcomes in patients with lung cancer, which is fueled by the growing observation of survival benefits in overweight or obese patients. This unexpected inverse relationship between obesity and lung cancer mortality, called the obesity paradox, remains poorly understood. The evolving insights into the heterogeneity of obesity phenotypes and associated biological connections with lung cancer progression in recent years may help explain some of the seemingly paradoxical relationship, and well-designed clinical studies looking at the causal role of obesity-associated molecules are expected. Here, we examine potential biological mechanisms behind the protective effects of obesity in lung cancer. We highlight the need to clarify the clinical implications of this relationship toward an updated intervention strategy in the clinical care of patients with lung cancer and obesity. Copyright © 2017 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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Statin-associated immune-mediated myopathy: biology and clinical implications.
Christopher-Stine, Lisa; Basharat, Pari
2017-04-01
In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.
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Implications of Nursing Clinical Practice to The Student’s Spiritual Health
Directory of Open Access Journals (Sweden)
Bhandesa Asthadi Mahendra
2018-01-01
Full Text Available This study aimed to clarify the implications of Nursing Clinical Practice (PLKK to the spiritual health of STIKES Bali students. This study employed purposive sampling method to determine the number of respondents. To conduct this study, the fourth grade of nursing students were recruited as the sample with total number 136 respondents. A questionnaire about spirituality from World Health Organization (WHO was used in this study as the instrument. In addition, the data were analysed by using quantitative descriptive technique. The result showed that 50.0% of students had a very good spiritual health, 42.6% had good spiritual health, 6.6% had moderate spiritual health, and 0.7 % had poor spiritual health. It can be interpreted that spiritual health of nursing students of STIKES Bali is good after conducting Nursing Clinical Practice. Thus, this study can be concluded that Nursing Clinical Practice has implication to the ability of students to love themselves and others meaningfully as the evidence of students’ spiritual health.
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Knudsen, Hannah K; Roman, Paul M; Abraham, Amanda J
2013-01-01
Counselor emotional exhaustion has negative implications for treatment organizations as well as the health of counselors. Quality clinical supervision is protective against emotional exhaustion, but research on the mediating mechanisms between supervision and exhaustion is limited. Drawing upon data from 934 counselors affiliated with treatment programs in the National Institute on Drug Abuse's Clinical Trials Network (CTN), this study examined commitment to the treatment organization and commitment to the counseling occupation as potential mediators of the relationship between quality clinical supervision and emotional exhaustion. The final ordinary least squares (OLS) regression model, which accounted for the nesting of counselors within treatment organizations, indicated that these two types of commitment were plausible mediators of the association between clinical supervision and exhaustion. Higher quality clinical supervision was strongly correlated with commitment to the treatment organization as well as commitment to the occupation of SUD counseling. These findings suggest that quality clinical supervision has the potential to yield important benefits for counselor well-being by strengthening ties to both their employing organization as well the larger treatment field, but longitudinal research is needed to establish these causal relationships. Copyright © 2013 Elsevier Inc. All rights reserved.
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Ferro, Suellen; Azevedo-Silva, João; Casal, Margarida; Côrte-Real, Manuela; Baltazar, Fatima; Preto, Ana
2016-01-01
Acetate, together with other short chain fatty acids has been implicated in colorectal cancer (CRC) prevention/therapy. Acetate was shown to induce apoptosis in CRC cells. The precise mechanism underlying acetate transport across CRC cells membrane, that may be implicated in its selectivity towards CRC cells, is not fully understood and was addressed here. We also assessed the effect of acetate in CRC glycolytic metabolism and explored its use in combination with the glycolytic inhibitor 3-bromopyruvate (3BP). We provide evidence that acetate enters CRC cells by the secondary active transporters MCT1 and/or MCT2 and SMCT1 as well as by facilitated diffusion via aquaporins. CRC cell exposure to acetate upregulates the expression of MCT1, MCT4 and CD147, while promoting MCT1 plasma membrane localization. We also observed that acetate increases CRC cell glycolytic phenotype and that acetate-induced apoptosis and anti-proliferative effect was potentiated by 3BP. Our data suggest that acetate selectivity towards CRC cells might be explained by the fact that aquaporins and MCTs are found overexpressed in CRC clinical cases. Our work highlights the importance that acetate transport regulation has in the use of drugs such as 3BP as a new therapeutic strategy for CRC. PMID:28874966
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Gastrointestinal Motility Disorders and Their Clinical Implications in Cirrhosis
Directory of Open Access Journals (Sweden)
Eleni Theocharidou
2017-01-01
Full Text Available Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.
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Jasiak-Zatonska, Michalina; Kalinowska-Lyszczarz, Alicja; Michalak, Slawomir; Kozubski, Wojciech
2016-03-02
Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%-25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients.
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Jasiak-Zatonska, Michalina; Kalinowska-Lyszczarz, Alicja; Michalak, Slawomir; Kozubski, Wojciech
2016-01-01
Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis. Nevertheless, AQP4-IgG seronegativity in 10%–25% of NMO patients suggests that there are several other factors involved in NMO immunopathogenesis, i.e., autoantibodies against aquaporin-1 (AQP1-Abs) and antibodies against myelin oligodendrocyte glycoprotein (MOG-IgGs). This manuscript reviews current knowledge about NMO immunopathogenesis, pointing out the controversial issues and showing potential directions for future research. Further efforts should be made to broaden our knowledge of NMO immunology which could have important implications for clinical practice, including the use of potential novel biomarkers to facilitate an early and accurate diagnosis, and modern treatment strategies improving long-term outcome of NMO patients. PMID:26950113
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Goldsmith, Jonathan C; Bonham, Vence L; Joiner, Clinton H; Kato, Gregory J; Noonan, Allan S; Steinberg, Martin H
2012-03-01
Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.
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Pharmacokinetic drug-drug interaction and their implication in clinical management.
Palleria, Caterina; Di Paolo, Antonello; Giofrè, Chiara; Caglioti, Chiara; Leuzzi, Giacomo; Siniscalchi, Antonio; De Sarro, Giovambattista; Gallelli, Luca
2013-07-01
Drug-drug interactions (DDIs) are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.
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Diet and Sleep Physiology: Public Health and Clinical Implications
Directory of Open Access Journals (Sweden)
Sarah Frank
2017-08-01
Full Text Available This mini-review examines the complex relationship between diet and sleep and explores the clinical and public health implications of the current evidence. Dietary quality and intake of specific nutrients can impact regulatory hormonal pathways to alter sleep quantity and quality. Sleep, in turn, affects the intake of total energy, as well as of specific foods and nutrients, through biological and behavioral mechanisms. Initial research in this field focused primarily on the effects of short sleep duration on nutritional quality. However, more recent studies have explored the dynamic relationship between long sleep duration and diet. Current evidence suggests that extremes of sleep duration alter sleep patterns, hormonal levels, and circadian rhythms, which contribute to weight-related outcomes and obesity, and other risk factors for the development of chronic disease such as type 2 diabetes and cardiovascular disease. These patterns may begin as early as childhood and have impacts throughout the life course. Given that non-communicable diseases are among the leading causes of death globally, deeper understanding of the interactions between sleep and nutrition has implications for both public health and clinical practice.
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Identification and Pathogenic Potential of Clinical Bacillus and Paenibacillus Isolates.
Directory of Open Access Journals (Sweden)
Francesco Celandroni
Full Text Available The soil-related Bacillus and Paenibacillus species have increasingly been implicated in various human diseases. Nevertheless, their identification still poses problems in the clinical microbiology laboratory and, with the exception of Bacillus anthracis and Bacillus cereus, little is known on their pathogenicity for humans. In this study, we evaluated the use of matrix-assisted laser desorption-ionization time of flight mass spectrometry (MALDI-TOF MS in the identification of clinical isolates of these genera and conducted genotypic and phenotypic analyses to highlight specific virulence properties. Seventy-five clinical isolates were subjected to biochemical and MALDI-TOF MS identification. 16S rDNA sequencing and supplemental tests were used to solve any discrepancies or failures in the identification results. MALDI-TOF MS significantly outperformed classical biochemical testing for correct species identification and no misidentification was obtained. One third of the collected strains belonged to the B. cereus species, but also Bacillus pumilus and Bacillus subtilis were isolated at high rate. Antimicrobial susceptibility testing showed that all the B. cereus, B. licheniformis, B. simplex, B. mycoides, Paenibacillus glucanolyticus and Paenibacillus lautus isolates are resistant to penicillin. The evaluation of toxin/enzyme secretion, toxin-encoding genes, motility, and biofilm formation revealed that B. cereus displays the highest virulence potential. However, although generally considered nonpathogenic, most of the other species were shown to swim, swarm, produce biofilms, and secrete proteases that can have a role in bacterial virulence. In conclusion, MALDI-TOF MS appears useful for fast and accurate identification of Bacillus and Paenibacillus strains whose virulence properties make them of increasing clinical relevance.
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A neurophysiological approach to tinnitus: clinical implications.
Jastreboff, P J; Hazell, J W
1993-02-01
This paper presents a neurophysiological approach to tinnitus and discusses its clinical implications. A hypothesis of discordant damage of inner and outer hair cells systems in tinnitus generation is outlined. A recent animal model has facilitated the investigation of the mechanisms of tinnitus and has been further refined to allow for the measurement of tinnitus pitch and loudness. The analysis of the processes involved in tinnitus detection postulates the involvement of an abnormal increase of gain within the auditory system. Moreover, it provides a basis for treating patients with hyperacusis, which we are considering to be a pre-tinnitus state. Analysis of the process of tinnitus perception allows for the possibility of facilitating the process of tinnitus habituation for the purpose of its alleviation. The combining of theoretical analysis with clinical findings has resulted in the creation of a multidisciplinary Tinnitus Centre. The foundation of the Centre focuses on two goals: the clinical goal is to remove tinnitus perception from the patient's consciousness, while directing research toward finding a mechanism-based method for the suppression of tinnitus generators and processes responsible for enhancement of tinnitus-related neuronal activity.
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Stokes, Caroline S; Lammert, Frank; Volmer, Dietrich A
2018-02-01
A plethora of contradictory research surrounds vitamin D and its influence on health and disease. This may, in part, result from analytical difficulties with regard to measuring vitamin D metabolites in serum. Indeed, variation exists between analytical techniques and assays used for the determination of serum 25-hydroxyvitamin D. Research studies into the effects of vitamin D on clinical endpoints rely heavily on the accurate assessment of vitamin D status. This has important implications, as findings from vitamin D-related studies to date may potentially have been hampered by the quantification techniques used. Likewise, healthcare professionals are increasingly incorporating vitamin D testing and supplementation regimens into their practice, and measurement errors may be also confounding the clinical decisions. Importantly, the Vitamin D Standardisation Programme is an initiative that aims to standardise the measurement of vitamin D metabolites. Such a programme is anticipated to eliminate the inaccuracies surrounding vitamin D quantification. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Directory of Open Access Journals (Sweden)
Vincenzo Salpietro
2014-01-01
Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by
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Exploring accountability of clinical ethics consultants: practice and training implications.
Weise, Kathryn L; Daly, Barbara J
2014-01-01
Clinical ethics consultants represent a multidisciplinary group of scholars and practitioners with varied training backgrounds, who are integrated into a medical environment to assist in the provision of ethically supportable care. Little has been written about the degree to which such consultants are accountable for the patient care outcome of the advice given. We propose a model for examining degrees of internally motivated accountability that range from restricted to unbounded accountability, and support balanced accountability as a goal for practice. Finally, we explore implications of this model for training of clinical ethics consultants from diverse academic backgrounds, including those disciplines that do not have a formal code of ethics relating to clinical practice.
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Pharmacokinetic drug-drug interaction and their implication in clinical management
Directory of Open Access Journals (Sweden)
Palleria Caterina
2013-01-01
Full Text Available Drug-drug interactions (DDIs are one of the commonest causes of medication error in developed countries, particularly in the elderly due to poly-therapy, with a prevalence of 20-40%. In particular, poly-therapy increases the complexity of therapeutic management and thereby the risk of clinically important DDIs, which can both induce the development of adverse drug reactions or reduce the clinical efficacy. DDIs can be classify into two main groups: pharmacokinetic and pharmacodynamic. In this review, using Medline, PubMed, Embase, Cochrane library and Reference lists we searched articles published until June 30 2012, and we described the mechanism of pharmacokinetic DDIs focusing the interest on their clinical implications.
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Gee, Rebekah E; Brindis, Claire D; Diaz, Angela; Garcia, Francisco; Gregory, Kimberly; Peck, Magda G; Reece, E Albert
2011-12-01
In July 2011, in response to language in the Affordable Care Act (ACA) the Office of the Assistant Secretary for Planning and Evaluation of the US Department of Health and Human Services (HHS) tasked the Institute of Medicine (IOM) to develop a report on the clinical preventive services necessary for women. The committee proposed eight new clinical preventive service recommendations aimed at closing significant gaps in preventive healthcare. This article reviews the process, findings, and the implications for obstetrician gynecologists and other primary care clinicians. Obstetricians and gynecologists play a major role in delivering primary care to women and many of the services recommended by the Committee are part of the core set of obstetrics and gynecology services. The women's health amendment to the ACA (Federal Register, 2010) requires that new private health plans cover - with no cost-sharing requirements - preventive healthcare services for women. Congress requested that a review be conducted to ascertain whether there were any additional needed preventive services specific to women's health that should be included. The IOM Committee on Preventive Services for Women recommended eight clinical measures specific to women's health that should be considered for coverage without co-payment. The US Department of HHS reviewed and adopted these recommendations, and, as a result, new health plans will need to include these services as part of insurance policies with plan years beginning on or after 1 August 2012. The authors discuss the implications of the IOM recommendations on practicing clinicians and on their potential impact on women's health and well being.
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Emerging roles of innate lymphoid cells in inflammatory diseases: Clinical implications.
Kortekaas Krohn, I; Shikhagaie, M M; Golebski, K; Bernink, J H; Breynaert, C; Creyns, B; Diamant, Z; Fokkens, W J; Gevaert, P; Hellings, P; Hendriks, R W; Klimek, L; Mjösberg, J; Morita, H; Ogg, G S; O'Mahony, L; Schwarze, J; Seys, S F; Shamji, M H; Bal, S M
2018-04-01
Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
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Prostate cancer epigenetics and its clinical implications.
Yegnasubramanian, Srinivasan
2016-01-01
Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.
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Prostate cancer epigenetics and its clinical implications
Directory of Open Access Journals (Sweden)
Srinivasan Yegnasubramanian
2016-01-01
Full Text Available Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.
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Silvoni, S; Konicar, L; Prats-Sedano, M A; Garcia-Cossio, E; Genna, C; Volpato, C; Cavinato, M; Paggiaro, A; Veser, S; De Massari, D; Birbaumer, N
2016-01-01
We investigated neurophysiological brain responses elicited by a tactile event-related potential paradigm in a sample of ALS patients. Underlying cognitive processes and neurophysiological signatures for brain-computer interface (BCI) are addressed. We stimulated the palm of the hand in a group of fourteen ALS patients and a control group of ten healthy participants and recorded electroencephalographic signals in eyes-closed condition. Target and non-target brain responses were analyzed and classified offline. Classification errors served as the basis for neurophysiological brain response sub-grouping. A combined behavioral and quantitative neurophysiological analysis of sub-grouped data showed neither significant between-group differences, nor significant correlations between classification performance and the ALS patients' clinical state. Taking sequential effects of stimuli presentation into account, analyses revealed mean classification errors of 19.4% and 24.3% in healthy participants and ALS patients respectively. Neurophysiological correlates of tactile stimuli presentation are not altered by ALS. Tactile event-related potentials can be used to monitor attention level and task performance in ALS and may constitute a viable basis for future BCIs. Implications for brain-computer interface implementation of the proposed method for patients in critical conditions, such as the late stage of ALS and the (completely) locked-in state, are discussed. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
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Kura, Branislav; Babal, Pavel; Slezak, Jan
2017-10-01
Radiotherapy is the most commonly used methodology to treat oncological disease, one of the most widespread causes of death worldwide. Oncological patients cured by radiotherapy applied to the mediastinal area have been shown to suffer from cardiovascular disease. The increase in the prevalence of radiation-induced heart disease has emphasized the need to seek new therapeutic targets to mitigate the negative impact of radiation on the heart. In this regard, microRNAs (miRNAs) have received considerable interest. miRNAs regulate post-transcriptional gene expression by their ability to target various mRNA sequences because of their imperfect pairing with mRNAs. It has been recognized that miRNAs modulate a diverse spectrum of cardiac functions with developmental, pathophysiological, and clinical implications. This makes them promising potential targets for diagnosis and treatment. This review summarizes the recent findings about the possible involvement of miRNAs in radiation-induced heart disease and their potential use as diagnostic or treatment targets in this respect.
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Ethical, legal, and social implications (ELSI) of microdose clinical trials.
Kurihara, Chieko
2011-06-19
A "microdose clinical trial" (microdosing) is one kind of early phase exploratory clinical trial, administering the compound at doses estimated to have no pharmacological or toxicological effects, aimed at screening candidates for further clinical development. This article's objective is to clarify the ethical, legal, and social implications (ELSI) of such an exploratory minimum-risk human trial. The definition and non-clinical study requirements for microdosing have been harmonized among the European Union (EU), United States (US), and Japan. Being conducted according to these regulations, microdosing seems to be ethically well justified in terms of respect for persons, beneficence, justice, human dignity, and animal welfare. Three big projects have been demonstrating the predictability of therapeutic dose pharmacokinetics from microdosing. The article offers suggestions as how microdosing can become a more useful and socially accepted strategy. Copyright © 2011 Elsevier B.V. All rights reserved.
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The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications
DEFF Research Database (Denmark)
Barloese, Mads C J
2018-01-01
, it is obvious that this brainstem reflex is regulated by higher centers that seemingly play a pivotal role in the attacks and the wide range of other symptoms indicating a homeostatic disturbance. These symptoms, as well as a number of well-validated findings, implicate the hypothalamus in the pathophysiology....... over the course of the past 2-3 decades, novel therapies and technological advances have helped increase our knowledge of these clinical syndromes, and will likely continue to do so in the coming years as we witness the arrival of new drugs and neurostimulation options. In this review, the clinical...
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Portfolio assessment and evaluation: implications and guidelines for clinical nursing education.
Chabeli, M M
2002-08-01
With the advent of Outcomes-Based Education in South Africa, the quality of nursing education is debatable, especially with regard to the assessment and evaluation of clinical nursing education, which is complex and renders the validity and reliability of the methods used questionable. This paper seeks to explore and describe the use of portfolio assessment and evaluation, its implications and guidelines for its effective use in nursing education. Firstly, the concepts of assessment, evaluation, portfolio and alternative methods of evaluation are defined. Secondly, a comparison of the characteristics of the old (traditional) methods and the new alternative methods of evaluation is made. Thirdly, through deductive analysis, synthesis and inference, implications and guidelines for the effective use of portfolio assessment and evaluation are described. In view of the qualitative, descriptive and exploratory nature of the study, a focus group interview with twenty students following a post-basic degree at a university in Gauteng regarding their perceptions on the use of portfolio assessment and evaluation method in clinical nursing education was used. A descriptive method of qualitative data analysis of open coding in accordance with Tesch's protocol (in Creswell 1994:155) was used. Resultant implications and guidelines were conceptualised and described within the existing theoretical framework. Principles of trustworthiness were maintained as described by (Lincoln & Guba 1985:290-327). Ethical considerations were in accordance with DENOSA's standards of research (1998:7).
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Uljarević, Mirko; Katsos, Napoleon; Hudry, Kristelle; Gibson, Jenny L
2016-11-01
Language and communication skills are essential aspects of child development, which are often disrupted in children with neurodevelopmental disorders. Cutting edge research in psycholinguistics suggests that multilingualism has potential to influence social, linguistic and cognitive development. Thus, multilingualism has implications for clinical assessment, diagnostic formulation, intervention and support offered to families. We present a systematic review and synthesis of the effects of multilingualism for children with neurodevelopmental disorders and discuss clinical implications. We conducted systematic searches for studies on multilingualism in neurodevelopmental disorders. Keywords for neurodevelopmental disorders were based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition categories as follows; Intellectual Disabilities, Communication Disorders, Autism Spectrum Disorder (ASD), Attention-Deficit/Hyperactivity Disorder, Specific Learning Disorder, Motor Disorders, Other Neurodevelopmental Disorders. We included only studies based on empirical research and published in peer-reviewed journals. Fifty studies met inclusion criteria. Thirty-eight studies explored multilingualism in Communication Disorders, 10 in ASD and two in Intellectual Disability. No studies on multilingualism in Specific Learning Disorder or Motor Disorders were identified. Studies which found a disadvantage for multilingual children with neurodevelopmental disorders were rare, and there appears little reason to assume that multilingualism has negative effects on various aspects of functioning across a range of conditions. In fact, when considering only those studies which have compared a multilingual group with developmental disorders to a monolingual group with similar disorders, the findings consistently show no adverse effects on language development or other aspects of functioning. In the case of ASD, a positive effect on communication and social functioning has
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Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen
2014-01-01
The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.
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Implications of Derived Rule Following of Roulette Gambling for Clinical Practice.
Wilson, Alyssa N; Grant, Tara
2015-05-01
Problem gambling is a global concern, and behavior analytic attention has increasingly focused on reasons for why problem gambling occurs and conditions under which it is maintained. However, limited knowledge currently exists on the process to which self-generated rules maintain gambling behaviors. Therefore, the current study assessed six recreational gamblers on a roulette game before and after discrimination training to establish a self-rule to wager on red or black. Following discrimination training, all six participants altered their response allocation among red or black and consistently responded according to the newly derived self-rule. Results maintained during 1-week follow-up sessions across all participants. Implications for clinical application of self-awareness and self-generated rule following are discussed. Implications for practice • Demonstration of how stimuli such as color can alter gambling behavior • Procedures to assist clients with changing self-rules about gambling behavior • Using self-generated rule formulation for more contextually appropriate target behaviors • Highlights how self-generated rules can be altered to change clinical target behaviors.
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Roles of Ubiquitination and SUMOylation on Prostate Cancer: Mechanisms and Clinical Implications
Directory of Open Access Journals (Sweden)
Zhenbang Chen
2015-02-01
Full Text Available The initiation and progression of human prostate cancer are highly associated with aberrant dysregulations of tumor suppressors and proto-oncogenes. Despite that deletions and mutations of tumor suppressors and aberrant elevations of oncogenes at the genetic level are reported to cause cancers, emerging evidence has revealed that cancer progression is largely regulated by posttranslational modifications (PTMs and epigenetic alterations. PTMs play critical roles in gene regulation, cellular functions, tissue development, diseases, malignant progression and drug resistance. Recent discoveries demonstrate that ubiquitination and SUMOylation are complicated but highly-regulated PTMs, and make essential contributions to diseases and cancers by regulation of key factors and signaling pathways. Ubiquitination and SUMOylation pathways can be differentially modulated under various stimuli or stresses in order to produce the sustained oncogenic potentials. In this review, we discuss some new insights about molecular mechanisms on ubiquitination and SUMOylation, their associations with diseases, oncogenic impact on prostate cancer (PCa and clinical implications for PCa treatment.
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Implications of caries diagnostic strategies for clinical management decisions
DEFF Research Database (Denmark)
Baelum, Vibeke; Hintze, Hanne; Wenzel, Ann
2012-01-01
-specificity) were calculated for each diagnostic strategy. RESULTS: Visual-tactile examination provided a true-positive rate of 34.2% and a false-positive rate of 1.5% for the detection of a cavity. The combination of a visual-tactile and a radiographic examination using the lesion in dentin threshold......OBJECTIVES: In clinical practice, a visual-tactile caries examination is frequently supplemented by bitewing radiography. This study evaluated strategies for combining visual-tactile and radiographic caries detection methods and determined their implications for clinical management decisions...... and cavitated lesions while the radiographic examination determined lesion depth. Direct inspection of the surfaces following tooth separation for the presence of cavitated or noncavitated lesions was the validation method. The true-positive rate (i.e. the sensitivity) and the false-positive rate (i.e. 1...
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Pathophysiology and clinical implications of peroperative fluid management in elective surgery
DEFF Research Database (Denmark)
Holte, Kathrine
2010-01-01
The purpose of this thesis was to describe pathophysiological aspects of perioperative fluid administration and create a rational background for future, clinical outcome studies. In laparoscopic cholecystectomy, we have found "liberal" crystalloid administration ( approximately 3 liters) to improve....... Based on the current evidence, administration of liters intravenous fluid without specific indication in major surgical procedures should be avoided, while administration of liters in patients with anastomoses may not be recommended, an issue needing clarification in large-scale clinical studies...... perioperative physiology and clinical outcome, which has implication for fluid management in other laparoscopic procedures such as laparoscopic fundoplication, laparoscopic repair of ventral hernia, hysterectomy etc., where 2-3 liters crystalloid should be administered based on the present evidence. That equal...
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Stewart, Jessica K; Smith, Tony P; Kim, Charles Y
To determine the clinical implications of acute pelvicaliceal hematoma formation during percutaneous catheter nephrostomy (PCN) insertion. Collecting system hematoma burden was retrospectively assessed for 694 PCN insertions in 502 patients. Pelvicaliceal hematoma formation occurred in 146 kidneys (21%) in 136 patients. Clinically significant blood loss occurred in 3 patients with hematomas within one week compared to 4 patients without hematomas (p=0.39). Twenty-four patients with hematomas underwent catheter exchange within one week, compared to 55 patients without hematomas (p=0.49). Pelvicaliceal hematoma formation after PCN insertion is not uncommon and is associated with very rare clinical sequelae. Copyright © 2017 Elsevier Inc. All rights reserved.
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Niggemann, Pascal; Kuchta, Johannes; Beyer, Hans-Konrad; Grosskurth, D; Schulze, Thorsten; Delank, Karl-Stefan
2011-10-15
Imaging study with an evaluation of incidences and clinical correlation. To evaluate the incidence of 3 different types of instabilities in patients with spondylolysis or isthmic spondylolisthesis. Clinical findings are correlated with imaging findings, and the imaging findings are analyzed with regard to their clinical implications. Spondylolysis and isthmic spondylolisthesis are common disorders. An unstable slip is the most well-known form of instability, but other forms also exist. However, the incidence of these instabilities and their clinical implications are yet unclear. A total of 140 patients with 141 levels of spondylolysis identified by MRI (magnetic resonance imaging) were included in this study. Using positional MRI, the instability of the slip, an increased angular movement, and movement in the spondylolytic cleft were assessed. On the basis of clinical findings, the patients were classified as presenting with either radicular or nonradicular symptoms. The incidence of the instabilities was recorded and correlated with the incidence of radicular symptoms. Fifteen patients had an unstable slip (anterior instability); 35, an increased angular movement (angular instability); and 34 patients, a movement in the spondylolytic cleft (posterior instability). All forms of instability could be found together. No instability at all was found in 76 patients. Radicular symptoms were found significantly more often in patients with one or more of the described instabilities compared with patients without instability. All 3 described forms of instability are common in spondylolysis or isthmic spondylolisthesis and associated with radicular pain. This finding stresses the value of positional MRI in the evaluation of patients with spondylolysis and isthmic spondylolisthesis, especially if radicular symptoms are present.
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Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer
Directory of Open Access Journals (Sweden)
Daniel L. Suzman
2015-09-01
Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.
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Iyegbe, Conrad; Campbell, Desmond; Butler, Amy; Ajnakina, Olesya; Sham, Pak
2014-02-01
Schizophrenia is a devastating mental disorder. The level of risk in the general population is sustained by the persistence of social, environmental and biological factors, as well as their interactions. Socio-environmental risk factors for schizophrenia are well established and robust. The same can belatedly be said of genetic risk factors for the disorder. Recent progress in schizophrenia genetics is primarily fuelled by genome-wide association, which is able to leverage substantial proportions of additional explained variance previously classified as 'missing'. Here, we provide an outline of the emerging genetic landscape of schizophrenia and demonstrate how this knowledge can be turned into a simple empirical measure of genetic risk, known as a polygenic risk score. We highlight the statistical framework used to assess the clinical potential of the new score and finally, draw relevance to and discuss the clinical implications for the study of gene-environment interaction.
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Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.
Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J
2017-07-01
Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.
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Tunnelling in a time dependent quartic potential: Possible implications for cosmology
International Nuclear Information System (INIS)
Kabir, R; Mukherjee, A
2014-01-01
The theory of a real scalar field with an arbitrary potential plays an important role in cosmology, particularly in the context of inflationary scenarios. However, in most applications, the potential is treated as independent of time, whereas in an evolving universe, for example, before the onset of inflation, the potential is actually likely to be changing with time. As pointed out by Berry in the context of single-particle quantum mechanics, the existence of multiple time scales can lead to results that are qualitatively different from those obtained with a static potential. The present paper reports on numerical investigations in a scalar field theory with a double-well potential that depends explicitly on time. The transition rate per unit volume for the decay of the false vacuum is found to depend strongly on time. Possible implications for old inflation are discussed
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Typology of Internet gaming disorder and its clinical implications.
Lee, Seung-Yup; Lee, Hae Kook; Choo, Hyekyung
2017-07-01
Various perspectives exist regarding Internet gaming disorder. While the concept of behavioral addiction is gaining recognition, some view the phenomenon as merely excessive indulgence in online pastimes. Still, in recent years, complaints from patients or their family members about problems related to Internet use, particularly Internet gaming, have become more common. However, the clinical picture of Internet gaming disorder could be obscured by its heterogeneous manifestations with other intertwined factors, such as psychiatric comorbidities, neurodevelopmental factors, sociocultural factors, and game-related factors, which may influence the pathogenesis as well as the clinical course. To mitigate such problems, clinicians should be able to consider diverse aspects related to Internet gaming disorder. Classifying such a heterogeneous problem into subtypes that share a similar etiology or phenomenology may provide additional clues in the diagnostic process and allow us to designate available clinical resources for particularly vulnerable factors. In this review paper, we suggest a typology of 'impulsive/aggressive,' 'emotionally vulnerable,' 'socially conditioned,' and 'not otherwise specified' as subtypes of the heterogeneous phenomena of pathological Internet gaming. The implications of these subtypes for assessment and treatment planning will also be highlighted. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.
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Suetterlin, Karen Joan; Sayer, Avan Aihie
2014-05-01
Proprioception, the sense of where one is in space, is essential for effective interaction with the environment. A lack of or reduction in proprioceptive acuity has been directly correlated with falls and with reduced functional independence in older people. Proprioceptive losses have also been shown to negatively correlate with functional recovery post stroke and play a significant role in other conditions such as Parkinson's disease. However, despite its central importance to many geriatric syndromes, the clinical assessment of proprioception has remained remarkably static. We look at approaches to the clinical assessment of proprioception, changes in proprioception across the life course, functional implications of proprioception in health and disease and the potential for targeted interventions in the future such as joint taping, and proprioception-specific rehabilitation and footwear.
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Peacock, James; Diaz, Keith M.; Viera, Anthony J.; Schwartz, Joseph E.; Shimbo, Daichi
2014-01-01
‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared to sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustained hypertension (elevated clinic and ambulatory BP). The confluence of increased cardiovascular risk and a failure to be diagnosed by the conventional approach of clinic BP measurement makes masked hypertension a significant public health concern. However, many important questions remain. First, the definition of masked hypertension varies across studies. Further, the best approach in the clinical setting to exclude masked hypertension also remains unknown. It is unclear whether home BP monitoring is an adequate substitute for ambulatory BP monitoring in identifying masked hypertension. Few studies have examined the mechanistic pathways that may explain masked hypertension. Finally, scarce data are available on the best approach to treating individuals with masked hypertension. Herein, we review the current literature on masked hypertension including definition, prevalence, clinical implications, special patient populations, correlates, issues related to diagnosis, treatment, and areas for future research. PMID:24573133
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Berryman, Darlene E; Henry, Brooke; Hjortebjerg, Rikke; List, Edward O; Kopchick, John J
2016-01-01
Adipose tissue (AT) is a well-established target of growth hormone (GH) and is altered in clinical conditions associated with excess, deficiency and absence of GH action. Due to the difficulty in collecting AT from clinical populations, genetically modified mice have been useful in better understanding how GH affects this tissue. Recent findings in mice would suggest that the impact of GH on AT is beyond alterations of lipolysis, lipogenesis or proliferation/ differentiation. AT depot-specific alterations in immune cells, extracellular matrix, adipokines, and senescence indicate an expanded role for GH in AT physiology. This mouse data will guide additional studies necessary to evaluate the therapeutic potential and safety of GH for conditions associated with altering AT, such as obesity. In this review, we introduce several relatively new intricacies of GH's effect on AT, focusing on recent studies in mice. Finally, we summarize the clinical implications of these findings.
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International Nuclear Information System (INIS)
Brooks, R.; Porter, R.A.R.; Kalos, F.; Grosser, A.E.
1975-01-01
A velocity selected molecular beam of D 2 O was crossed with a nozzle beam of Ar and the angular distribution of the scattered D 2 O was measured mass spectrometrically. By varying the velocity of the D 2 O beam, the differential cross section was measured at two collision energies. The experimental results were compared with synthetic differential cross sections calculated from Lennard-Jones and Kihara-Stockmayer trial potentials to determine potential parameters. Implications for the H 2 O pair potential are discussed
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Jiang, Jian; Peng, Wenbo; Gu, Tieguang; King, Catherine; Yin, J Kevin
2016-01-01
The increasing acceptance of traditional Chinese medicine (TCM) worldwide has highlighted the importance of ensuring the provision of high-quality TCM clinical education. This clinical training should be partly guided by a robust assessment of patient data outcomes in TCM teaching clinics. We undertook a comprehensive literature review to examine the data evaluation in TCM teaching clinics outside China and its implications for TCM education. Literature was retrieved via MEDLINE (from 1946 to January 2015), EMBASE (from 1980 to February 2015), and Google Scholar for studies conducted outside China. The search was restricted to English articles reporting empirical findings related to the assessments of patient data in TCM teaching clinics, with implications for TCM education in countries other than China. Only seven articles from six studies met the inclusion criteria. The characteristics and main symptoms of patients who received any TCM treatment in the context of teaching clinics among all included studies were similar. Symptom relief as well as a high level of patient satisfaction with TCM treatment were found in TCM teaching clinics. Conventional healthcare providers and other complementary practitioners were not the main source of referral to TCM practitioners but rather patients׳ friends/relatives. Patients received acupuncture treatment more frequently than treatments utilizing Chinese herbal medicine in teaching clinics. A standardized and consistent framework for patient records within TCM teaching clinics is currently lacking. There was no robust study which "translated" TCM clinic data evaluation findings into implications for TCM education and clinical training. Recognizing that TCM evolves over time and its practice varies in different settings, there is an urgent need to conduct large-scale, rigorous evaluations of TCM clinic data to address the findings of our review, with the purpose of better informing TCM education and clinical training in
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Left ventricular hypertrophy in valvular aortic stenosis: mechanisms and clinical implications.
Rader, Florian; Sachdev, Esha; Arsanjani, Reza; Siegel, Robert J
2015-04-01
Valvular aortic stenosis is the second most prevalent adult valve disease in the United States and causes progressive pressure overload, invariably leading to life-threatening complications. Surgical aortic valve replacement and, more recently, transcatheter aortic valve replacement effectively relieve the hemodynamic burden and improve the symptoms and survival of affected individuals. However, according to current American College of Cardiology/American Heart Association guidelines on the management of valvular heart disease, the indications for aortic valve replacement, including transcatheter aortic valve replacement, are based primarily on the development of clinical symptoms, because their presence indicates a dismal prognosis. Left ventricular hypertrophy develops in a sizeable proportion of patients before the onset of symptoms, and a growing body of literature demonstrates that regression of left ventricular hypertrophy resulting from aortic stenosis is incomplete after aortic valve replacement and associated with adverse early postoperative outcomes and worse long-term outcomes. Thus, reliance on the development of symptoms alone without consideration of structural abnormalities of the myocardium for optimal timing of aortic valve replacement potentially constitutes a missed opportunity to prevent postoperative morbidity and mortality from severe aortic stenosis, especially in the face of the quickly expanding indications of lower-risk transcatheter aortic valve replacement. The purpose of this review is to discuss the mechanisms and clinical implications of left ventricular hypertrophy in severe valvular aortic stenosis, which may eventually move to center stage as an indication for aortic valve replacement in the asymptomatic patient. Copyright © 2015 Elsevier Inc. All rights reserved.
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Mental Imagery in Depression: Phenomenology, Potential Mechanisms, and Treatment Implications.
Holmes, Emily A; Blackwell, Simon E; Burnett Heyes, Stephanie; Renner, Fritz; Raes, Filip
2016-01-01
Mental imagery is an experience like perception in the absence of a percept. It is a ubiquitous feature of human cognition, yet it has been relatively neglected in the etiology, maintenance, and treatment of depression. Imagery abnormalities in depression include an excess of intrusive negative mental imagery; impoverished positive imagery; bias for observer perspective imagery; and overgeneral memory, in which specific imagery is lacking. We consider the contribution of imagery dysfunctions to depressive psychopathology and implications for cognitive behavioral interventions. Treatment advances capitalizing on the representational format of imagery (as opposed to its content) are reviewed, including imagery rescripting, positive imagery generation, and memory specificity training. Consideration of mental imagery can contribute to clinical assessment and imagery-focused psychological therapeutic techniques and promote investigation of underlying mechanisms for treatment innovation. Research into mental imagery in depression is at an early stage. Work that bridges clinical psychology and neuroscience in the investigation of imagery-related mechanisms is recommended.
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Evidenced-based review of clinical studies on periodontics.
2009-08-01
Periodontal diseases have several implications for the practice of endodontics. First, advanced periodontitis often has direct implications for the long-term prognosis of the case and requires careful evaluation and coordinated treatment of both the periodontic and endodontic diseases. Second, the potential for functional interactions between odontogenic pathoses and marginal periodontitis requires careful collection of clinical observations and monitoring the outcome of various treatments. In this section, we provide an analysis of recent clinical studies in this area.
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Militello, Laura G; Arbuckle, Nicole B; Saleem, Jason J; Patterson, Emily; Flanagan, Mindy; Haggstrom, David; Doebbeling, Bradley N
2014-03-01
This article identifies sources of variation in clinical workflow and implications for the design and implementation of electronic clinical decision support. Sources of variation in workflow were identified via rapid ethnographic observation, focus groups, and interviews across a total of eight medical centers in both the Veterans Health Administration and academic medical centers nationally regarded as leaders in developing and using clinical decision support. Data were reviewed for types of variability within the social and technical subsystems and the external environment as described in the sociotechnical systems theory. Two researchers independently identified examples of variation and their sources, and then met with each other to discuss them until consensus was reached. Sources of variation were categorized as environmental (clinic staffing and clinic pace), social (perception of health information technology and real-time use with patients), or technical (computer access and information access). Examples of sources of variation within each of the categories are described and discussed in terms of impact on clinical workflow. As technologies are implemented, barriers to use become visible over time as users struggle to adapt workflow and work practices to accommodate new technologies. Each source of variability identified has implications for the effective design and implementation of useful health information technology. Accommodating moderate variability in workflow is anticipated to avoid brittle and inflexible workflow designs, while also avoiding unnecessary complexity for implementers and users.
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Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer
DEFF Research Database (Denmark)
Espersen, Maiken Lise Marcker; Olsen, Jesper; Linnemann, Dorte
2015-01-01
Colorectal cancer (CRC) still has one of the highest incidence and mortality rate among cancers. Therefore, improved differential diagnostics and personalized treatment are still needed. Several intestinal stem cell markers have been found to be associated with CRC and might have a prognostic...... and predictive significance in CRC patients. This review provides an overview of the intestinal stem cell markers leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), B cell–specific Moloney murine leukemia virus insertion site 1 (BMI1), Musashi1 (MSI1), and sex-determining region y-box 9 (SOX9......) and their implications in human CRC. The exact roles of the intestinal stem cell markers in CRC development and progression remain unclear; however, high expression of these stem cell markers have a potential prognostic significance and might be implicated in chemotherapy resistance...
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Directory of Open Access Journals (Sweden)
Estevez-Garcia Purificacion
2012-11-01
Full Text Available Abstract Background Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC. Methods VEGFR2, PDGFRα and PDGFRβ mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. Results Four SNPs were identified, three in PDGFRα [exon 12 (A12: c.1701A>G; exon 13 (A13: c.1809G>A; and exon 17 (A17: c.2439+58C>A] and one in PDGFRβ [exon 19 (B19: c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205, was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA than for those harboring the G-allele genotype (GA or GG (51% vs 17%; p=0.073. Multivariate analysis confirmed SNP B19 (p=0.029 was a significant prognostic factor for survival, independent of age (p=0.060 or TNM stage (p Conclusions PDGFRβ exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated.
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International Nuclear Information System (INIS)
Estevez-Garcia, Purificacion; Carnero, Amancio; Paz-Ares, Luis; Garcia-Carbonero, Rocio; Castaño, Angel; Martin, Ana C; Lopez-Rios, Fernando; Iglesias, Joaquin; Muñoz-Galván, Sandra; Lopez-Calderero, Iker; Molina-Pinelo, Sonia; Pastor, Maria D
2012-01-01
Angiogenesis plays an essential role in tumor growth and metastasis, and is a major target in cancer therapy. VEGFR and PDGFR are key players involved in this process. The purpose of this study was to assess the incidence of genetic variants in these receptors and its potential clinical implications in colorectal cancer (CRC). VEGFR2, PDGFRα and PDGFRβ mutations were evaluated by sequencing their tyrosine kinase domains in 8 CRC cell lines and in 92 samples of patients with CRC. Correlations with clinicopathological features and survival were analyzed. Four SNPs were identified, three in PDGFRα [exon 12 (A12): c.1701A>G; exon 13 (A13): c.1809G>A; and exon 17 (A17): c.2439+58C>A] and one in PDGFRβ [exon 19 (B19): c.2601A>G]. SNP B19, identified in 58% of tumor samples and in 4 cell lines (LS174T, LS180, SW48, COLO205), was associated with higher PDGFR and pPDGFR protein levels. Consistent with this observation, 5-year survival was greater for patients with PDGFR B19 wild type tumors (AA) than for those harboring the G-allele genotype (GA or GG) (51% vs 17%; p=0.073). Multivariate analysis confirmed SNP B19 (p=0.029) was a significant prognostic factor for survival, independent of age (p=0.060) or TNM stage (p<0.001). PDGFRβ exon 19 c.2601A>G SNP is commonly encountered in CRC patients and is associated with increased pathway activation and poorer survival. Implications regarding its potential influence in response to PDGFR-targeted agents remain to be elucidated
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Ethical implications for clinical practice and future research in "at risk" individuals.
Singh, Fiza; Mirzakhanian, Heline; Fusar-Poli, Paolo; de la Fuente-Sandoval, Camilo; Cadenhead, Kristin S
2012-01-01
The last 15 years have witnessed a shift in schizophrenia research with increasing interest in earlier stages of illness with the hope of early intervention and ultimately prevention of psychotic illness. Large-scale longitudinal studies have identified clinical and biological risk factors associated with increased risk of psychotic conversion, which together with symptomatic and demographic risk factors may improve the power of prediction algorithms for psychotic transition. Despite these advances, 45-70% of at risk subjects in most samples do not convert to frank psychosis, but continue to function well below their age matched counterparts. The issue is of utmost importance in light of the upcoming DSM-V and the possible inclusion of the attenuated psychotic symptoms syndrome (APSS) diagnosis, with clinical and ethical implications. Clinical considerations include feasibility of reliably diagnosing the at risk state in non-academic medical centers, variable psychotic conversion rates, a non-uniform definition of conversion and extensive debate about treatment for individuals with an ill-defined outcome. On the ethical side, diagnosing APSS could lead to unnecessary prescribing of antipsychotics with long-term deleterious consequences, slow research by providing a false sense of comfort in the diagnosis, and have psychosocial implications for those who receive a diagnosis. Thus it may be prudent to engage at risk populations early and to use broad-spectrum treatments with low risk benefit ratios to relieve functional impairments, while simultaneously studying all subsets of the at risk population.
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Glutamate in schizophrenia: clinical and research implications.
Goff, D C; Wine, L
1997-10-30
The excitatory amino acids, glutamate and aspartate, are of interest to schizophrenia research because of their roles in neurodevelopment, neurotoxicity and neurotransmission. Recent evidence suggests that densities of glutamatergic receptors and the ratios of subunits composing these receptors may be altered in schizophrenia, although it is unclear whether these changes are primary or compensatory. Agents acting at the phencyclidine binding site of the NMDA receptor produce symptoms of schizophrenia in normal subjects, and precipitate relapse in patients with schizophrenia. The improvement of negative symptoms with agents acting at the glycine modulatory site of the NMDA receptor, as well as preliminary evidence that clozapine may differ from conventional neuroleptic agents in its effects on glutamatergic systems, suggest that clinical implications may follow from this model. While geriatric patients may be at increased risk for glutamate-mediated neurotoxicity, very little is known about the specific relevance of this model to geriatric patients with schizophrenia.
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[Clinical implications of polycystic ovary syndrome].
Dravecká, Ingrid
Polycystic ovary syndrome (PCOS) is a heterogeneous and complex endocrine disease which among the female population belongs to the most widespread endocrinopathies and it is the most frequent cause of hyperthyroidism, anticoagulation and infertility. Insulin resistance is one of the important diabetology factors impacting hyperglycaemia in a majority of women with PCOS (60-80 %). Clinical expressions of PCOS include reproduction disorders, metabolic characteristics and psychological implications. Reproduction disorders include hyperthyroidism, menstruation cycle disorders, infertility and pregnancy complications as well as early abortions, gestational diabetes and pregnancy induced hypertension. Long-term metabolic risks of PCOS include type 2 diabetes mellitus, dyslipidemia, arterial hypertension and endothelial dysfunction. The available data confirms higher incidence of cardiovascular diseases in women with PCOS. In particular among obese women PCOS is more frequently associated with non-alcoholic hepatic steatosis, sleep apnoea syndrome and endometrial cancer. The literature includes some controversial data about the relationship between PCOS and autoimmunity. Women with PCOS are more prone to suffer from insufficient confidence with higher incidence of anxiety, depression, bipolar disorder and eating disorders. autoimmunity - diabetes mellitus - pregnancy - insulin resistance - metabolic syndrome - menstrual disorders - polycystic ovary syndrome.
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Geller, Gail; Dvoskin, Rachel; Thio, Chloe L; Duggal, Priya; Lewis, Michelle H; Bailey, Theodore C; Sutherland, Andrea; Salmon, Daniel A; Kahn, Jeffrey P
2014-01-01
Advances in genomics are contributing to the development of more effective, personalized approaches to the prevention and treatment of infectious diseases. Genetic sequencing technologies are furthering our understanding of how human and pathogen genomic factors - and their interactions - contribute to individual differences in immunologic responses to vaccines, infections and drug therapies. Such understanding will influence future policies and procedures for infectious disease management. With the potential for tailored interventions for particular individuals, populations or subpopulations, ethical, legal and social implications (ELSIs) may arise for public health and clinical practice. Potential considerations include balancing health-related benefits and harms between individuals and the larger community, minimizing threats to individual privacy and autonomy, and ensuring just distribution of scarce resources. In this Opinion, we consider the potential application of pathogen and host genomic information to particular viral infections that have large-scale public health consequences but differ in ELSI-relevant characteristics such as ease of transmission, chronicity, severity, preventability and treatability. We argue for the importance of anticipating these ELSI issues in advance of new scientific discoveries, and call for the development of strategies for identifying and exploring ethical questions that should be considered as clinical, public health and policy decisions are made.
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Correale, Jorge; Chiquete, Erwin; Boyko, Alexey; Beran, Roy G; Strauch, Jorge Barahona; Milojevic, Snezana; Frider, Nadina
2016-01-01
Both proprietary and nonproprietary medicines are expected to undergo rigorous preapproval testing and both should meet stringent health authority regulatory requirements related to quality to obtain approval. Nonproprietary (also known as copy, or generic) medicines, which base their authorization and use on the proprietary documentation and label, are often viewed as a means to help lower the cost and, thus, increase patient access. If these medicines fail to meet quality standards, such as good manufacturing practice and bioequivalence (in humans), they are then defined as substandard copies and can pose serious risks to patients in terms of safety and efficacy. Potentially noncontrolled or different manufacturing process and excipients in nonproprietary medicines may result in poor batch-to-batch reproducibility (accurate and consistent quantity of each ingredient in each capsule/tablet) and lower quality. Substandard, nonproprietary copies of medicines that are immunomodulatory or immunosuppressive are of concern to patients due to their possible untoward safety and lack of efficacy events. This article reviews the potential risks associated with nonproprietary medicines that do not meet the regulatory requirements of the United States Food and Drug Administration, the European Medicines Agency, or the World Health Organization. The clinical implications for patients are described. This article focuses on nonproprietary medicines for multiple sclerosis, particularly fingolimod, that are not identical to proprietary versions and could thus fail to meet efficacy expectations or have different impact on the safety of patients with multiple sclerosis. PMID:27418809
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Benjaminy, Shelly; Bubela, Tania
2014-07-16
Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of media coverage. We analyzed leading newspaper articles about ocular gene transfer (1990-2012) from United States (n = 55), Canada (n = 26), and United Kingdom (n = 77) from Factiva and Canadian Newsstand databases using pre-defined coding categories. We evaluated the content of newspaper articles about ocular gene transfer for hereditary retinopathies, exploring representations of framing techniques, research design, risks/benefits, and translational timelines. The dominant frame in 61% of stories was a celebration of progress, followed by human-interest in 30% of stories. Missing from the positive frames were explanations of research design; articles conflated clinical research with treatment. Conflicts-of-interest and funding sources were similarly omitted. Attention was directed to the benefits of gene transfer, while risks were only reported in 43% of articles. A range of visual outcomes was described from slowing vision loss to cure, but the latter was the most frequently represented even though it is clinically infeasible. Despite the prominence of visual benefit portrayals, 87% of the articles failed to provide timelines for the commencement of clinical trials or for clinical implementation. Our analysis confirms
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Horowitz, Robert; Aierstuck, Sara; Williams, Elizabeth A.; Melby, Bernette
2010-01-01
Objective: The authors described clinical presentations of oral and genital herpes simplex virus (HSV) infections in a university health population and implications of these findings. Participants and Methods: Using a standardized data collection tool, 215 records of patients with symptomatic culture-positive HSV infections were reviewed. Results:…
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Clinically relevant potential drug-drug interactions among outpatients: A nationwide database study.
Jazbar, Janja; Locatelli, Igor; Horvat, Nejc; Kos, Mitja
2018-06-01
Adverse drug events due to drug-drug interactions (DDIs) represent a considerable public health burden, also in Slovenia. A better understanding of the most frequently occurring potential DDIs may enable safer pharmacotherapy and minimize drug-related problems. The aim of this study was to evaluate the prevalence and predictors of potential DDIs among outpatients in Slovenia. An analysis of potential DDIs was performed using health claims data on prescription drugs from a nationwide database. The Lexi-Interact Module was used as the reference source of interactions. The influence of patient-specific predictors on the risk of potential clinically relevant DDIs was evaluated using logistic regression model. The study population included 1,179,803 outpatients who received 15,811,979 prescriptions. The total number of potential DDI cases identified was 3,974,994, of which 15.6% were potentially clinically relevant. Altogether, 9.3% (N = 191,213) of the total population in Slovenia is exposed to clinically relevant potential DDIs, and the proportion is higher among women and the elderly. After adjustment for cofactors, higher number of medications and older age are associated with higher odds of clinically relevant potential DDIs. The burden of DDIs is highest with drug combinations that increase risk of bleeding, enhance CNS depression or anticholinergic effects or cause cardiovascular complications. The current study revealed that 1 in 10 individuals in the total Slovenian population is exposed to clinically relevant potential DDIs yearly. Taking into account the literature based conservative estimate that approximately 1% of potential DDIs result in negative health outcomes, roughly 1800 individuals in Slovenia experience an adverse health outcome each year as a result of clinically relevant potential interactions alone. Copyright © 2017 Elsevier Inc. All rights reserved.
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Controversies surrounding the clinical potential of cinnamon for the management of diabetes.
Rafehi, H; Ververis, K; Karagiannis, T C
2012-06-01
Obesity levels have increased significantly in the past five decades and are predicted to continue rising, resulting in important health implications. In particular, this has translated to an increase in the occurrence of type II diabetes mellitus (T2D). To alleviate associated problems, certain nutraceuticals have been considered as potential adjuncts or alternatives to conventional prescription drugs. Cinnamon, a commonly consumed spice originating from South East Asia, is currently being investigated as a potential preventative supplement and treatment for insulin resistance, metabolic syndrome and T2D. Extensive in vitro evidence has shown that cinnamon may improve insulin resistance by preventing and reversing impairments in insulin signalling in skeletal muscle. In adipose tissue, it has been shown that cinnamon increases the expression of peroxisome proliferator-activated receptors including, PPARγ. This is comparable to the action of commonly used thiazolinediones, which are PPAR agonists. Studies have also shown that cinnamon has potent anti-inflammatory properties. However, numerous human clinical trials with cinnamon have been conducted with varying findings. While some studies have showed no beneficial effect, others have indicated improvements in cholesterol levels, systolic blood pressure, insulin sensitivity and postprandial glucose levels with cinnamon. However, the only measurement consistently improved by cinnamon consumption is fasting glucose levels. While it is still premature to suggest the use of cinnamon supplementation based on the evidence, further investigation into mechanisms of action is warranted. Apart from further characterization of genetic and epigenetic changes in model systems, systematic large-scale clinical trials are required. In this study, we discuss the mechanisms of action of cinnamon in the context of T2D and we highlight some of the associated controversies. © 2011 Blackwell Publishing Ltd.
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Can we prevent OA? Epidemiology and public health insights and implications.
Runhaar, Jos; Zhang, Yuqing
2018-05-01
This narrative review discusses the potential of prevention of OA in different stages of the disease. The theoretical background for primary prevention (i.e. prevention of occurrence of definite structural or clinical OA in subjects free of the disease) and secondary prevention (i.e. prevention of progression of the disease in subjects with pre-clinical pathological changes to the joint) is provided and evidence for effective strategies is discussed. Since direct evidence for the prevention of OA development and progression is scarce, indirect evidence enhancing our current knowledge on the potential of OA prevention is additionally discussed. Also, implications of preventive strategies for study design and public health are considered. Prevention of OA has great potential, but as deliberated in the current review, there are still large gaps in our current knowledge and the implications of preventive strategies for the development and progression of OA require consideration.
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Vela, Emili; Tényi, Ákos; Cano, Isaac; Monterde, David; Cleries, Montserrat; Garcia-Altes, Anna; Hernandez, Carme; Escarrabill, Joan; Roca, Josep
2018-01-01
Background Clinical management of patients with chronic obstructive pulmonary disease (COPD) shows potential for improvement provided that patients’ heterogeneities are better understood. The study addresses the impact of comorbidities and its role in health risk assessment. Objective To explore the potential of health registry information to enhance clinical risk assessment and stratification. Design Fixed cohort study including all registered patients with COPD in Catalonia (Spain) (7.5 million citizens) at 31 December 2014 with 1-year (2015) follow-up. Methods A total of 264 830 patients with COPD diagnosis, based on the International Classification of Diseases (Ninth Revision) coding, were assessed. Performance of multiple logistic regression models for the six main dependent variables of the study: mortality, hospitalisations (patients with one or more admissions; all cases and COPD-related), multiple hospitalisations (patients with at least two admissions; all causes and COPD-related) and users with high healthcare costs. Neither clinical nor forced spirometry data were available. Results Multimorbidity, assessed with the adjusted morbidity grouper, was the covariate with the highest impact in the predictive models, which in turn showed high performance measured by the C-statistics: (1) mortality (0.83), (2 and 3) hospitalisations (all causes: 0.77; COPD-related: 0.81), (4 and 5) multiple hospitalisations (all causes: 0.80; COPD-related: 0.87) and (6) users with high healthcare costs (0.76). Fifteen per cent of individuals with highest healthcare costs to year ratio represented 59% of the overall costs of patients with COPD. Conclusions The results stress the impact of assessing multimorbidity with the adjusted morbidity grouper on considered health indicators, which has implications for enhanced COPD staging and clinical management. Trial registration number NCT02956395. PMID:29511004
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Clinical Implications of TiGRT Algorithm for External Audit in Radiation Oncology
Daryoush Shahbazi-Gahrouei; Mohsen Saeb; Shahram Monadi; Iraj Jabbari
2017-01-01
Background: Performing audits play an important role in quality assurance program in radiation oncology. Among different algorithms, TiGRT is one of the common application software for dose calculation. This study aimed to clinical implications of TiGRT algorithm to measure dose and compared to calculated dose delivered to the patients for a variety of cases, with and without the presence of inhomogeneities and beam modifiers. Materials and Methods: Nonhomogeneous phantom as quality dose veri...
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Potential facilitators and barriers to adopting standard treatment guidelines in clinical practice.
Sharma, Sangeeta; Pandit, Ajay; Tabassum, Fauzia
2017-04-18
Purpose The purpose of this paper is to assess medicines information sources accessed by clinicians, if sources differed in theory and practice and to find out the barriers and facilitators to effective guideline adoption. Design/methodology/approach In all, 183 doctors were surveyed. Barriers and facilitators were classified as: communication; potential adopters; innovation; organization characteristics and environmental/social/economic context. Findings Most of the clinicians accessed multiple information sources including standard treatment guidelines, but also consulted seniors/colleagues in practice. The top three factors influencing clinical practice guideline adoption were innovation characteristics, environmental context and individual characteristics. The respondents differed in the following areas: concerns about flexibility offered by the guideline; denying patients' individuality; professional autonomy; insights into gaps in current practice and evidence-based practice; changing practices with little or no benefit. Barriers included negative staff attitudes/beliefs, guideline integration into organizational structures/processes, time/resource constraints. Fearing third parties (government and insurance companies) restricting medicines reimbursement and poor liability protection offered by the guidelines emerged as the barriers. Facilitators include aligning organizational structures/processes with the innovation; providing leadership support to guide diffusion; increasing awareness and enabling early innovation during pre/in-service training, with regular feedback on outcomes and use. Practical implications Guideline adoption in clinical practice is partly within doctors' control. There are other key prevailing factors in the local context such as environmental, social context, professional and organizational culture affecting its adoption. Organizational policy and accreditation standards necessitating adherence can serve as a driver. Originality
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Directory of Open Access Journals (Sweden)
Stefan Meyer
2012-01-01
Full Text Available Fanconi anaemia (FA is an inherited disease with congenital and developmental abnormalities, bone marrow failure, and extreme risk of leukemic transformation. Bone marrow surveillance is an important part of the clinical management of FA and often reveals cytogenetic aberrations. Here, we review bone marrow findings in FA and discuss the clinical and biological implications of chromosomal aberrations associated with leukemic transformation.
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A rare variant of the ulnar artery with important clinical implications: a case report
Directory of Open Access Journals (Sweden)
Casal Diogo
2012-11-01
Full Text Available Abstract Background Variations in the major arteries of the upper limb are estimated to be present in up to one fifth of people, and may have significant clinical implications. Case presentation During routine cadaveric dissection of a 69-year-old fresh female cadaver, a superficial brachioulnar artery with an aberrant path was found bilaterally. The superficial brachioulnar artery originated at midarm level from the brachial artery, pierced the brachial fascia immediately proximal to the elbow, crossed superficial to the muscles that originated from the medial epicondyle, and ran over the pronator teres muscle in a doubling of the antebrachial fascia. It then dipped into the forearm fascia, in the gap between the flexor carpi radialis and the palmaris longus. Subsequently, it ran deep to the palmaris longus muscle belly, and superficially to the flexor digitorum superficialis muscle, reaching the gap between the latter and the flexor carpi ulnaris muscle, where it assumed is usual position lateral to the ulnar nerve. Conclusion As far as the authors could determine, this variant of the superficial brachioulnar artery has only been described twice before in the literature. The existence of such a variant is of particular clinical significance, as these arteries are more susceptible to trauma, and can be easily confused with superficial veins during medical and surgical procedures, potentially leading to iatrogenic distal limb ischemia.
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Deeply discounted medications: Implications of generic prescription drug wars.
Czechowski, Jessica L; Tjia, Jennifer; Triller, Darren M
2010-01-01
To describe the history of generic prescription pricing programs at major pharmacy chains and their potential implications on prescribing, quality of care, and patient safety. Publicly available generic prescription discount program drug lists as of May 1, 2009. Fierce competition among major pharmacy chains such as Walgreens, CVS, and Walmart has led to a generic prescription pricing war with unclear public health implications. Introduced in 2006, currently 7 of the 10 largest pharmacy chains advertise a version of a deeply discounted medication (DDM) program, accounting for more than 25,000 locations nationally. By early 2008, almost 70 million Americans had used these programs. Although DDM programs lower drug costs for many patients, DDM formularies include potentially ineffective or harmful medications, have the potential to influence physician prescribing behavior, and may impair pharmacists' ability to review complete drug-dispensing records. DDMs are widespread but have the potential for unintended consequences on patients, providers, and the health care system. A systematic review of DDMs needs to evaluate the clinical, economic, and system-level implications of such programs.
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Clinical implications of vitamin D deficiency
Directory of Open Access Journals (Sweden)
Beata Matyjaszek-Matuszek
2015-06-01
Full Text Available Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.
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A combined third and fourth branchial arch anomaly: clinical and embryological implications.
Mehrzad, H; Georgalas, C; Huins, C; Tolley, N S
2007-08-01
Embryological abnormalities of the branchial apparatus present an interesting diagnostic and surgical challenge. Thymic cysts are a rare form of branchial apparatus anomaly, resulting from abnormal development of the third pharyngeal pouch. We present two cases of a thymic cyst coexisting with a non recurrent inferior laryngeal nerve (NRILN), two anomalies that to our knowledge have not been associated previously. A possible embryological explication for this double abnormality is discussed, while the clinical implications of this association are presented.
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Obolski, Uri; Dellus-Gur, Eynat; Stein, Gideon Y; Hadany, Lilach
2016-06-01
Antibiotic resistance is an important public health issue, and vast resources are invested in researching new ways to fight it. Recent experimental works have shown that resistance to some antibiotics can result in increased susceptibility to others, namely induce cross-sensitivity. This phenomenon could be utilized to increase efficiency of antibiotic treatment strategies that minimize resistance. However, as conditions in experimental settings and in the clinic may differ substantially, the implications of cross-sensitivity for clinical settings are not guaranteed and should be examined. In this work we analyzed data of Escherichia coli isolates from patients' blood, sampled in Rabin Medical Center, Israel, to examine co-occurrence of resistance to antibiotics in the clinic. We compared the co-occurrence patterns with cross-sensitivity patterns observed in the lab. Our data showed only positively associated occurrence of resistance, even with antibiotics that were shown to induce cross-sensitivity in laboratory conditions. We used a mathematical model to examine the potential effects of cross-sensitivity versus co-occurrence on the spread of drug resistance. We conclude that resistance frequencies in the clinic can have a substantial effect on the success of treatment strategies, and should be considered alongside experimental evidence of cross-sensitivity. Copyright © 2016. Published by Elsevier B.V.
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Panizza, Benedict; Warren, Timothy A; Solares, C Arturo; Boyle, Glen M; Lambie, Duncan; Brown, Ian
2014-11-01
Nonmelanoma skin cancer (NMSC) with perineural invasion (PNI) is most commonly seen in cutaneous squamous cell carcinoma of the head and neck (SCCHN). The cranial nerves are a conduit for skin cancer to reach the brainstem. The histopathological features of 51 tissue specimens from 49 patients with cutaneous SCCHN and clinical PNI were assessed with consecutive transverse and longitudinal sections. No skip lesions were identified. Tumor spread was contiguous in all specimens. No tumor spread into the perineural space from surrounding or adjacent tumor was seen. Proximal large cranial nerves showed epineural involvement in 3.9% in areas with large tumor bulk, extensive PNI, and intraneural invasion. Perineural tumor spread in cutaneous SCCHN was contiguous and no skip lesions were evident in nerve specimens assessed in this series. Spread beyond cranial nerve perineurium was uncommon, reflecting its multilayer barrier function at this level. These findings may have treatment implications. © 2013 Wiley Periodicals, Inc.
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International Nuclear Information System (INIS)
Yoshida, Zensho; Yamada, Hiroshi.
1988-07-01
The Bohm equation of electrostatic potential distributions in one-dimensional plasmas has been studied for various Mach numbers and plasma potentials. Solvability and structural stability have been discussed using the Sagdeev potential. Implications of the structural stability for the L/H transitions in tokamak plasmas has been also discussed. (author)
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James M. Vose; Chelcy F. Miniat; Ge Sun; Peter V. Caldwell
2014-01-01
The potential expansion of freeze-tolerant (FT) Eucalyptus plantations in the United States has raised concerns about the implications for water resources. Modeling was used to examine the potential effects of expanding the distribution of FT Eucalyptus plantations in US Department of Agriculture Plant Hardiness Zones 8b and...
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Poole-Wilson, Philip A.; Kirwan, Bridget-Anne; Voko, Zoltan; de Brouwer, Sophie; Dunselman, Peter H. J. M.; van Dalen, Frederik J.; Lubsen, Jacobus
Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine
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A Rare Chromosome 3 Imbalance and Its Clinical Implications
Directory of Open Access Journals (Sweden)
Karen Sims
2012-01-01
Full Text Available The duplication of chromosome 3q is a rare disorder with varying chromosomal breakpoints and consequently symptoms. Even rarer is the unbalanced outcome from a parental inv(3 resulting in duplicated 3q and a deletion of 3p. Molecular karyotyping should aid in precisely determining the length and breakpoints of the 3q+/3p− so as to better understand a child’s future development and needs. We report a case of an infant male with a 57.5 Mb duplication from 3q23-qter. This patient also has an accompanying 1.7 Mb deletion of 3p26.3. The duplicated segment in this patient encompasses the known critical region of 3q26.3-q27, which is implicated in the previously reported 3q dup syndrome; however, the accompanying 3p26.3 deletion is smaller than the previously reported cases. The clinical phenotype of this patient relates to previously reported cases of 3q+ that may suggest that the accompanying 1.7 Mb heterozygous deletion is not clinically relevant. Taken together, our data has refined the location and extent of the chromosome 3 imbalance, which will aid in better understanding the molecular underpinning of the 3q syndrome.
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Clinical Implications of Changing Parameters on an Elliptical Trainer.
Kaplan, Yonatan; Nyska, Meir; Palmanovich, Ezequiel; Shanker, Rebecca
2014-06-01
Specific weightbearing instructions continue to be a part of routine orthopaedic clinical practice on an injured or postoperative extremity. Researchers and clinicians have struggled to define the best weightbearing strategies to maximize clinical outcomes. To investigate the average percentage body weight (APBW) values, weightbearing distribution percentages (WBDP), and cadence values on the entire foot, hindfoot, and forefoot during changing resistance and incline on an elliptical trainer, as well as to suggest clinical implications. Descriptive laboratory study. An original research study was performed consisting of 30 asymptomatic subjects (mean age, 29.54 ± 12.64 years; range, 21-69 years). The protocol included 3 consecutive tests of changing resistance and incline within a speed range of 70 to 95 steps/min. The SmartStep weightbearing gait analysis system was utilized to measure the values. The APBW values for the entire foot ranged between 70% and 81%, the hindfoot values were between 27% and 57%, and the forefoot values between 42% and 70%. With regard to WBDP, the forefoot remained planted on the pedal (stance phase) 2 to 3 times more as compared with the hindfoot raise in the swing phase. The study findings highlight the fact that elliptical training significantly reduces weightbearing in the hindfoot, forefoot, and entire foot even at higher levels of resistance and incline. Weightbearing on the hindfoot consistently displayed the lowest weightbearing values. Orthopaedic surgeons, now equipped with accurate weightbearing data, may recommend using the elliptical trainer as a weightbearing exercise early on following certain bony or soft tissue pathologies and lower limb surgical procedures.
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Nur, Erfan; Biemond, Bart J; Otten, Hans-Martin; Brandjes, Dees P; Schnog, John-John B
2011-06-01
Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management. Copyright © 2011 Wiley-Liss, Inc.
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Directory of Open Access Journals (Sweden)
Correale J
2016-06-01
each ingredient in each capsule/tablet and lower quality. Substandard, nonproprietary copies of medicines that are immunomodulatory or immunosuppressive are of concern to patients due to their possible untoward safety and lack of efficacy events. This article reviews the potential risks associated with nonproprietary medicines that do not meet the regulatory requirements of the United States Food and Drug Administration, the European Medicines Agency, or the World Health Organization. The clinical implications for patients are described. This article focuses on nonproprietary medicines for multiple sclerosis, particularly fingolimod, that are not identical to proprietary versions and could thus fail to meet efficacy expectations or have different impact on the safety of patients with multiple sclerosis.Keywords: bioequivalence, fingolimod, multiple sclerosis, proprietary, substandard copies, toxicity
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Genetic recombination of the hepatitis C virus: clinical implications.
Morel, V; Fournier, C; François, C; Brochot, E; Helle, F; Duverlie, G; Castelain, S
2011-02-01
Genetic recombination is a well-known feature of RNA viruses that plays a significant role in their evolution. Although recombination is well documented for Flaviviridae family viruses, the first natural recombinant strain of hepatitis C virus (HCV) was identified as recently as 2002. Since then, a few other natural inter-genotypic, intra-genotypic and intra-subtype recombinant HCV strains have been described. However, the frequency of recombination may have been underestimated because not all known HCV recombinants are screened for in routine practice. Furthermore, the choice of treatment regimen and its predictive outcome remain problematic as the therapeutic strategy for HCV infection is genotype dependent. HCV recombination also raises many questions concerning its mechanisms and effects on the epidemiological and physiopathological features of the virus. This review provides an update on recombinant HCV strains, the process that gives rise to recombinants and clinical implications of recombination. © 2010 Blackwell Publishing Ltd.
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Hypertensive response to exercise: mechanisms and clinical implication.
Kim, Darae; Ha, Jong-Won
2016-01-01
A hypertensive response to exercise (HRE) is frequently observed in individuals without hypertension or other cardiovascular disease. However, mechanisms and clinical implication of HRE is not fully elucidated. Endothelial dysfunction and increased stiffness of large artery contribute to development of HRE. From neurohormonal aspects, excess stimulation of sympathetic nervous system and augmented rise of angiotensin II seems to be important mechanism in HRE. Increasing evidences indicates that a HRE is associated with functional and structural abnormalities of left ventricle, especially when accompanied by increased central blood pressure. A HRE harbors prognostic significance in future development of hypertension and increased cardiovascular events, particularly if a HRE is documented in moderate intensity of exercise. As supported by previous studies, a HRE is not a benign phenomenon, however, currently, whether to treat a HRE is controversial with uncertain treatment strategy. Considering underlying mechanisms, angiotensin receptor blockers and beta blockers can be suggested in individuals with HRE, however, evidences for efficacy and outcomes of treatment of HRE in individuals without hypertension is scarce and therefore warrants further studies.
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Simulated degradation of biochar and its potential environmental implications
International Nuclear Information System (INIS)
Liu, Zhaoyun; Demisie, Walelign; Zhang, Mingkui
2013-01-01
A simulated oxidation technique was used to examine the impacts of degradation on the surface properties of biochar and the potential implications of the changes in biochar properties were discussed. To simulate the short- and long-term environmental degradation, mild and harsh degradation were employed. Results showed that after mild degradation, the biochar samples showed significant reductions in surface area and pore volumes. After harsh degradation, the biochar samples revealed dramatic variations in their surface chemistry, surface area, pore volumes, morphology and adsorption properties. The results clearly indicate that changes of biochar surface properties were affected by biochar types and oxidative conditions. It is suggested that biochar surface properties are likely to be gradually altered during environmental exposure. This implies that these changes have potential effects for altering the physicochemical properties of biochar amended soils. -- Highlights: •Mild and harsh degradation were employed to simulate natural degradation of biochar. •Mild degradation could reduce the surface area and micropore volumes of biochar. •Harsh degradation caused severe changes of all of the biochar surface properties. •Biochar types and oxidative conditions may dominate the changes of its properties. -- The simulated degradation of biochar in this study could provide a mechanism for forecasting short- or long-term environmental degradation of biochar
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Directory of Open Access Journals (Sweden)
Yin-Kai Chen
Full Text Available Robo4 is involved in hematopoietic stem/progenitor cell homeostasis and essential for tumor angiogenesis. Expression of Robo4 was recently found in solid tumors and leukemia stem cells. However, the clinical implications of Robo4 expression in patients with acute myeloid leukemia (AML remain unclear.We investigated the clinical and prognostic relevance of mRNA expression of Robo4 in bone marrow (BM mononuclear cells from 218 adult patients with de novo AML. We also performed immunohistochemical staining to assess the Robo4 protein expression in the BM biopsy specimens from 30 selected AML patients in the cohort.Higher Robo4 expression was closely associated with lower white blood cell counts, expression of HLA-DR, CD13, CD34 and CD56 on leukemia cells, t(8;21 and ASXL1 mutation, but negatively correlated with t(15;17 and CEBPA mutation. Compared to patients with lower Robo4 expression, those with higher expression had significantly shorter disease-free survival (DFS and overall survival (OS. This result was confirmed in an independent validation cohort. Furthermore, multivariate analyses showed that higher Robo4 expression was an independent poor prognostic factor for DFS and OS in total cohort and patients with intermediate-risk cytogenetics, irrespective of age, WBC count, karyotype, and mutation status of NPM1/FLT3-ITD, and CEBPA.BM Robo4 expression can serve as a new biomarker to predict clinical outcomes in AML patients and Robo4 may serve as a potential therapeutic target in patients with higher Robo4 expression.
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Prehospital Ultrasound in Trauma: A Review of Current and Potential Future Clinical Applications
Directory of Open Access Journals (Sweden)
Tharwat El Zahran
2018-01-01
Full Text Available Ultrasound (US is an essential tool for evaluating trauma patients in the hospital setting. Many previous in-hospital studies have been extrapolated to out of hospital setting to improve diagnostic accuracy in prehospital and austere environments. This review article presents the role of prehospital US in blunt and penetrating trauma management with emphasis on its current clinical applications, challenges, and future implications of such use.
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Neurophysiology and Clinical Implications of the Laryngeal Adductor Reflex.
Domer, Amanda S; Kuhn, Maggie A; Belafsky, Peter C
2013-09-01
The laryngeal adductor reflex (LAR) is an involuntary protective response to stimuli in the larynx. The superior laryngeal nerve (SLN) acts as the afferent limb and the recurrent laryngeal nerve (RLN) as the efferent limb of this reflex, which is modulated by the central nervous system. Perhaps the most clinically significant application of the LAR is its use in laryngopharyngeal (LP) sensory discrimination testing. Importantly, aberrations in the LAR may predict dysphagia or portend clinical phenotypes of chronic cough, vocal cord dysfunction or pediatric apneas. LP sensation is a potential target for interventions addressing the aforementioned conditions though currently remains an area of active investigation.
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Paradigm Shift or Annoying Distraction: Emerging Implications of Web 2.0 for Clinical Practice
Spallek, H.; O’Donnell, J.; Clayton, M.; Anderson, P.; Krueger, A.
2010-01-01
Web 2.0 technologies, known as social media, social technologies or Web 2.0, have emerged into the mainstream. As they grow, these new technologies have the opportunity to influence the methods and procedures of many fields. This paper focuses on the clinical implications of the growing Web 2.0 technologies. Five developing trends are explored: information channels, augmented reality, location-based mobile social computing, virtual worlds and serious gaming, and collaborative research network...
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Stewart, Sherry M; Dowers, Kristy L; Cerda, Jacey R; Schoenfeld-Tacher, Regina M; Kogan, Lori R
2014-01-01
Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.
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Accessory muscle of the flexor digitorum superficialis and its clinical implications
Directory of Open Access Journals (Sweden)
Edie Benedito Caetano
Full Text Available ABSTRACT Anatomical variations of the flexor digitorum superficialis (FDS muscle and tendon unit are frequently reported by anatomists and clinicians. Anatomical muscle variations of the FDS and its tendons may include variations of muscle belly, presence of accessory or duplicate tendons, abnormal tendon connections, and absence of muscle or tendon components. Such variations may or may not have clinical implications. This report presents a case not described previously: a unilateral accessory muscle of the flexor digitorum superficialis which was connected by a thick tendon to the flexor digitorum superficialis muscle; it was directed proximally to the insertion of the medial epicondyle of the humerus, next to the superficialis head of the pronator teres muscle. The belly of the accessory muscle was positioned anterior to the median and anterior interosseous nerve. This anatomical variation is known as type V in the classification of Elliot et al. The knowledge of these anatomical variations helps hand surgeons interpret the clinical examination, particularly in the evaluation of patients who have suffered tendon injuries or show sign s of possible peripheral nerve entrapment.
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Circulating mesenchymal stem cells and their clinical implications
Directory of Open Access Journals (Sweden)
Liangliang Xu
2014-01-01
Full Text Available Circulating mesenchymal stem cells (MSCs is a new cell source for tissue regeneration and tissue engineering. The characteristics of circulating MSCs are similar to those of bone marrow-derived MSCs (BM-MSCs, but they exist at a very low level in healthy individuals. It has been demonstrated that MSCs are able to migrate to the sites of injury and that they have some distinct genetic profiles compared to BM-MSCs. The current review summaries the basic knowledge of circulating MSCs and their potential clinical applications, such as mobilizing the BM-MSCs into circulation for therapy. The application of MSCs to cure a broad spectrum of diseases is promising, such as spinal cord injury, cardiovascular repair, bone and cartilage repair. The current review also discusses the issues of using of allogeneic MSCs for clinical therapy.
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Consitt, L A; Clark, B C
2018-01-01
The age-related loss of skeletal muscle (sarcopenia) is a major health concern as it is associated with physical disability, metabolic impairments, and increased mortality. The coexistence of sarcopenia with obesity, termed 'sarcopenic obesity', contributes to skeletal muscle insulin resistance and the development of type 2 diabetes, a disease prevalent with advancing age. Despite this knowledge, the mechanisms contributing to sarcopenic obesity remain poorly understood, preventing the development of targeted therapeutics. This article will discuss the clinical and physiological consequences of sarcopenic obesity and propose myostatin as a potential candidate contributing to this condition. A special emphasis will be placed on examining the role of myostatin signaling in impairing both skeletal muscle growth and insulin signaling. In addition, the role of myostatin in regulating muscle-to fat cross talk, further exacerbating metabolic dysfunction in the elderly, will be highlighted. Lastly, we discuss how this knowledge has implications for the design of myostatin-inhibitor clinical trials.
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Shea, Shawn Christopher
2009-01-01
Over the past several decades, exciting advances have been made in the art and science of teaching clinical interviewing, which are supported by an ever-growing evidence base documenting their effectiveness. In this second article in a 2-part series, the training and research implications of an innovative approach to improving medication adherence based on these educational advances--the medication interest model (MIM)--are described. The objective is to provide an "insider's view" of how to creatively teach the MIM to case managers, as well as design state-of-the-art courses and research platforms dedicated to improving medication adherence through improved clinical interviewing skills in both nursing and medical student education. The teaching and research design concepts are applicable to all primary care settings as well as specialty areas from endocrinology and cardiology to psychiatry. Evidence-based advances in the teaching of clinical interviewing skills such as response-mode research, facilic supervision, microtraining, and macrotraining lend a distinctive quality and integrative power to the MIM. The model delineates several new platforms for training and research regarding the enhancement of medication adherence including an approach for collecting individual interviewing techniques into manageable "learning modules" amenable to competency evaluation and potential certification.
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Non-specific effects of vaccines: plausible and potentially important, but implications uncertain.
Pollard, Andrew J; Finn, Adam; Curtis, Nigel
2017-11-01
Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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Paradigm shift or annoying distraction: emerging implications of web 2.0 for clinical practice.
Spallek, H; O'Donnell, J; Clayton, M; Anderson, P; Krueger, A
2010-01-01
Web 2.0 technologies, known as social media, social technologies or Web 2.0, have emerged into the mainstream. As they grow, these new technologies have the opportunity to influence the methods and procedures of many fields. This paper focuses on the clinical implications of the growing Web 2.0 technologies. Five developing trends are explored: information channels, augmented reality, location-based mobile social computing, virtual worlds and serious gaming, and collaborative research networks. Each trend is discussed based on their utilization and pattern of use by healthcare providers or healthcare organizations. In addition to explorative research for each trend, a vignette is presented which provides a future example of adoption. Lastly each trend lists several research challenge questions for applied clinical informatics.
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Isolated persistent left superior vena cava: A case report and its clinical implications
Directory of Open Access Journals (Sweden)
Samarjit Bisoyi
2017-01-01
Full Text Available The venous anomaly of a persistent left superior vena cava (PLSVC affects 0.3%-0.5% of the general population. PLSVC with absent right superior vena cava, also termed as "isolated PLSVC," is an extremely rare venous anomaly. Almost half of the patients with isolated PLSVC have cardiac anomalies in the form of atrial septal defect, endocardial cushion defects, or tetralogy of Fallot. Isolated PLSVC is usually innocuous. Its discovery, however, has important clinical implications. It can pose clinical difficulties with central venous access, cardiothoracic surgeries, and pacemaker implantation. When it drains to the left atrium, it may create a right to left shunt. In this case report, we present the incidental finding of isolated PLSVC in a patient who underwent aortic valve replacement. Awareness about this condition and its variations is important to avoid complications.
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Nolan, Danielle; Carlson, Martha
2016-06-01
Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations. © The Author(s) 2016.
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Climate change: potential implications for Ireland's biodiversity
Donnelly, Alison
2018-03-01
A national biodiversity and climate change adaptation plan is being developed for Ireland by the Department of Communications, Climate Action, and Environment. In order to inform such a plan, it was necessary to review and synthesize some of the recent literature pertaining to the impact of climate change on biodiversity in Ireland. Published research on this topic fell within three broad categories: (i) changes in the timing of life-cycle events (phenology) of plants, birds, and insects; (ii) changes in the geographic range of some bird species; and (iii) changes in the suitable climatic zones of key habitats and species. The synthesis revealed evidence of (i) a trend towards earlier spring activity of plants, birds, and insects which may result in a change in ecosystem function; (ii) an increase in the number of bird species; and (iii) both increases and decreases in the suitable climatic area of key habitats and species, all of which are expected to impact Ireland's future biodiversity. This process identified data gaps and limitations in available information both of which could be used to inform a focused research strategy. In addition, it raises awareness of the potential implications of climate change for biodiversity in Ireland and elsewhere and demonstrates the need for biodiversity conservation plans to factor climate change into future designs.
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7T: Physics, safety, and potential clinical applications.
Kraff, Oliver; Quick, Harald H
2017-12-01
With more than 60 installed magnetic resonance imaging (MRI) systems worldwide operating at a magnetic field strength of 7T or higher, ultrahigh-field (UHF) MRI has been established as a platform for clinically oriented research in recent years. Profound technical and methodological developments have helped overcome the inherent physical challenges of UHF radiofrequency (RF) signal homogenization in the human body. The ongoing development of dedicated RF coil arrays was pivotal in realizing UHF body MRI, beyond mere brain imaging applications. Another precondition to clinical application of 7T MRI is the safety testing of implants and the establishment of safety concepts. Against this backdrop, 7T MRI and MR spectroscopy (MRS) recently have demonstrated capabilities and potentials for clinical diagnostics in a variety of studies. This article provides an overview of the immanent physical challenges of 7T UHF MRI and discusses recent technical solutions and safety concepts. Furthermore, recent clinically oriented studies are highlighted that span a broad application spectrum from 7T UHF brain to body MRI. 4 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1573-1589. © 2017 International Society for Magnetic Resonance in Medicine.
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[Anaesthetic-induced myocardial preconditioning: fundamental basis and clinical implications].
Chiari, P; Bouvet, F; Piriou, V
2005-04-01
Volatile halogenated anaesthetics offer a myocardial protection when they are administrated before a myocardial ischaemia. Cellular mechanisms involved in anaesthetic preconditioning are now better understood. The objectives of this review are to understand the anaesthetic-induced preconditioning underlying mechanisms and to know the clinical implications. References were obtained from PubMed data bank (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) using the following keywords: volatile anaesthetic, isoflurane, halothane, sevoflurane, desflurane, preconditioning, protection, myocardium. Ischaemic preconditioning (PC) is a myocardial endogenous protection against ischaemia. It has been described as one or several short ischaemia before a sustained ischemia. These short ischaemia trigger a protective signal against this longer ischaemia. An ischemic organ is able to precondition a remote organ. It is possible to replace the short ischaemia by a preadministration of halogenated volatile anaesthetic with the same protective effect, this is called anaesthetic PC (APC). APC and ischaemic PC share similar underlying biochemical mechanisms including protein kinase C, tyrosine kinase activation and mitochondrial and sarcolemnal K(ATP) channels opening. All halogenated anaesthetics can produce an anaesthetic PC effect. Myocardial protection during reperfusion, after the long ischaemia, has been shown by successive short ischaemia or volatile anaesthetic administration, this is called postconditioning. Ischaemic PC has been described in humans in 1993. Clinical studies in human cardiac surgery have shown the possibility of anaesthetic PC with volatile anaesthetics. These studies have shown a decrease of postoperative troponin in patient receiving halogenated anaesthetics.
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Nothing New (Ethically Under the Sun: Policy & Clinical Implications of Nanomedicine
Directory of Open Access Journals (Sweden)
MacDonald, Chris
2012-06-01
Full Text Available Nanotechnology research is beginning to see widespread coverage in the media and popular science literatures, but discussions of hopes and fears about nanotechnology have already become polarised into utopian and dystopian visions. More moderate discussions focus on the near-term applications of nanotechnologies, and on potential benefits and harms. However, in exploring the social and ethical implications of nanotechnology (or nanomedicine, the focus of this paper, important lessons should be learned from experiences in other fields. In particular, studies of the ethical, legal, and social issues (ELSI of genetics research have successfully mapped out many of the issues (and social and political responses that arise when new technologies are deployed. It is our contention that, for the most part, the ethical and social issues arising in nanomedicine are not altogether new, and thus do not require novel ethical principles or frameworks, nor a massive investment in ‘NELSI’ research. Instead, what is needed is support for the development of a culture of ethics amongst scientists and clinicians, basic scientific and medical knowledge for bioethicists, and a social competency for citizens to participate actively in debates about the implications of new technologies in general.
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Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications
Yoon, Sarah; Jo, Yuna; Kwon, So Mee; Kim, Kyoung Min; Kwon, Keun Sang; Kim, Chan Young; Woo, Hyun Goo
2015-01-01
Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient's clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10−9, RFS: P = 2.2 × 10−8). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic. PMID:26540566
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Tyler, Patrick M; White, Stuart F; Thompson, Ronald W; Blair, R J R
2018-02-12
A cognitive neuroscience perspective seeks to understand behavior, in this case disruptive behavior disorders (DBD), in terms of dysfunction in cognitive processes underpinned by neural processes. While this type of approach has clear implications for clinical mental health practice, it also has implications for school-based assessment and intervention with children and adolescents who have disruptive behavior and aggression. This review articulates a cognitive neuroscience account of DBD by discussing the neurocognitive dysfunction related to emotional empathy, threat sensitivity, reinforcement-based decision-making, and response inhibition. The potential implications for current and future classroom-based assessments and interventions for students with these deficits are discussed.
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Capital planning for clinical integration.
Grauman, Daniel M; Neff, Gerald; Johnson, Molly Martha
2011-04-01
When assessing the financial implications of a physician alignment and clinical integration initiative, a hospital should measure the initiative's potential ROI, perhaps best using a combination of net present value and payback period. The hospital should compare its own historical and projected performance with rating agency median benchmarks for key financial indicators of profitability, debt service, capital and cash flow, and liquidity. The hospital should also consider potential indirect benefits, such as retained outpatient/ancillary revenue, increased inpatient revenue, improved cost control, and improved quality and reporting transparency.
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Chemistry, metabolism, and toxicology of cannabis: clinical implications.
Sharma, Priyamvada; Murthy, Pratima; Bharath, M M Srinivas
2012-01-01
Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (▵(9_)THC), produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.
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Chemistry, Metabolism, and Toxicology of Cannabis: Clinical Implications
Directory of Open Access Journals (Sweden)
M.M. Srinivas Bharath
2012-12-01
Full Text Available Cannabis is one of the most widely abused substances throughout the world. The primary psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (Δ9_THC, produces a myriad of pharmacological effects in animals and humans. Although it is used as a recreational drug, it can potentially lead to dependence and behavioral disturbances and its heavy use may increase the risk for psychotic disorders.Many studies that endeavor to understand the mechanism of action of cannabis concentrate on pharmacokinetics and pharmacodynamics of cannabinoids in humans. However, there is limited research on the chronic adverse effects and retention of cannabinoids in human subjects.Cannabis can be detected in body fluids following exposure through active/passive inhalation and exposure through breastfeeding. Cannabis detection is directly dependent on accurate analytical procedures for detection of metabolites and verification of recent use.In this review, an attempt has been made to summarize the properties of cannabis and its derivatives, and to discuss the implications of its use with emphasis on bioavailability, limit of detection, carry over period and passive inhalation, important factors for detection and diagnosis.
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Clinical Relevance of Brain Volume Measures in Multiple Sclerosis
DEFF Research Database (Denmark)
De Stefano, Nicola; Airas, Laura; Grigoriadis, Nikolaos
2014-01-01
Multiple sclerosis (MS) is a chronic disease with an inflammatory and neurodegenerative pathology. Axonal loss and neurodegeneration occurs early in the disease course and may lead to irreversible neurological impairment. Changes in brain volume, observed from the earliest stage of MS...... therefore have important clinical implications affecting treatment decisions, with several clinical trials now demonstrating an effect of disease-modifying treatments (DMTs) on reducing brain volume loss. In clinical practice, it may therefore be important to consider the potential impact of a therapy...
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Impulse control disorders in Parkinson's disease: clinical characteristics and implications.
Leeman, Robert F; Potenza, Marc N
2011-04-01
Impulse control disorders (ICDs), specifically those related to excessive gambling, eating, sex and shopping, have been observed in a subset of people with Parkinson's disease (PD). Although some initial case reports claimed that dopamine replacement therapies, particularly dopamine agonists, cause ICDs, more recent, larger and better controlled studies indicate a more complicated picture. While dopamine replacement therapy use is related to ICDs, other vulnerabilities, some related to PD and/or its treatment directly and others seemingly unrelated to PD, have also been associated with ICDs in PD. This suggests a complex etiology with multiple contributing factors. As ICDs occur in a sizable minority of PD patients and can be associated with significant distress and impairment, further investigation is needed to identify factors that can predict who may be more likely to develop ICDs. Clinical implications are discussed and topics for future research are offered.
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Stenne, R; Hurlimann, T; Godard, Béatrice
2012-01-01
Nutrigenetics is a promising field, but the achievability of expected benefits is challenged by the methodological limitations that are associated with clinical research in that field. The mere existence of these limitations suggests that promises about potential outcomes may be premature. Thus, benefits claimed in scientific journal articles in which these limitations are not acknowledged might stimulate biohype. This article aims to examine whether nutrigenetics clinical research articles are a potential source of biohype. Of the 173 articles identified, 16 contained claims in which clinical applications were extrapolated from study results. The methodological limitations being incompletely acknowledged, these articles could potentially be a source of biohype.
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Mechanisms of radiation interaction with DNA: Potential implications for radiation protection
International Nuclear Information System (INIS)
Sinclair, W.K.; Fry, R.J.M.
1987-01-01
An overview of presentations and discussions which took place at the US Department of Energy/Commission of European Communities (DOE/CEC) workshop on ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection,'' held at San Diego, California, January 21-22, 1987, is provided. The Department has traditionally supported fundamental research on interactions of ionizing radiation with different biological systems and at all levels of biological organization. The aim of this workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection
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Clinical efficacy of bromocriptine and the influence of serum ...
African Journals Online (AJOL)
Background: Psoriasis is a T-cell mediated hyperproliferative cutaneous disease of multifactorial etiology. Prolactin (PRL) has been implicated in the pathogenesis of psoriasis and several studies have pointed to a potential therapeutic role of bromocriptine in psoriasis. Aim: To assess the clinical efficacy of bromocriptine ...
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Energy Drinks: Implications for the Breastfeeding Mother.
Thorlton, Janet; Ahmed, Azza; Colby, David A
2016-01-01
Breastfeeding women may experience disrupted sleep schedules and be tempted to turn to popular energy drinks to reduce fatigue and enhance alertness, prompting the question: What are the maternal and child health implications for breastfeeding mothers consuming energy drinks? Caffeine and vitamin-rich energy drinks contain a variety of herbal ingredients and vitamins; however, ingredient amounts may not be clearly disclosed on product labels. Interactions between herbal ingredients and caffeine are understudied and not well defined in the literature. Some infants can be sensitive to caffeine and display increased irritability and sleep disturbances when exposed to caffeine from breastmilk. Breastfeeding women who consume energy drinks may be ingesting herbal ingredients that have not undergone scientific evaluation, and if taking prenatal vitamins, may unknowingly exceed the recommended daily intake. Caffeinated products are marketed in newer ways, fueling concerns about health consequences of caffeine exposure. We present implications associated with consumption of caffeine and vitamin-rich energy drinks among breastfeeding women. Product safety, labeling, common ingredients, potential interactions, and clinical implications are discussed. Healthcare providers should encourage breastfeeding women to read product labels for ingredients, carbohydrate content, serving size, and to discourage consumption of energy drinks when breastfeeding and/or taking prenatal vitamins, to avoid potential vitamin toxicity.
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Hyperferritinemia and iron metabolism in Gaucher disease: Potential pathophysiological implications.
Regenboog, Martine; van Kuilenburg, André B P; Verheij, Joanne; Swinkels, Dorine W; Hollak, Carla E M
2016-11-01
Gaucher disease (GD) is characterized by large amounts of lipid-storing macrophages and is associated with accumulation of iron. High levels of ferritin are a hallmark of the disease. The precise mechanism underlying the changes in iron metabolism has not been elucidated. A systematic search was conducted to summarize available evidence from the literature on iron metabolism in GD and its potential pathophysiological implications. We conclude that in GD, a chronic low grade inflammation state can lead to high ferritin levels and increased hepcidin transcription with subsequent trapping of ferritin in macrophages. Extensive GD manifestations with severe anemia or extreme splenomegaly can lead to a situation of iron-overload resembling hemochromatosis. We hypothesize that specifically this latter situation carries a risk for the occurrence of associated conditions such as the increased cancer risk, metabolic syndrome and neurodegeneration. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Personal Narratives: Cultural Differences and Clinical Implications
Bliss, Lynn S.; McCabe, Allyssa
2008-01-01
A study was conducted to examine the misdiagnosis of cultural difference deficits and how mistaking deficits in narrative production for cultural differences can be avoided. Findings reveal the implications for intervention.
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Does the concept of borderline personality features have clinical utility in childhood?
Hawes, David J
2014-01-01
Phenotypic features of borderline personality disorder may first emerge during childhood, alongside symptoms of common externalizing and internalizing disorders. Children with these borderline personality features (BPF) are, therefore, likely to come into contact with clinical services prior to adolescence. This raises the question of whether BPF may be clinically informative with respect to the formulation and treatment of childhood psychopathology. BPF in late childhood appear to be highly heritable, while also predicted by environmental risk factors that overlap with those related to both externalizing and internalizing disorders. These risk factors include hostile parenting, maternal insensitivity to infant attachment cues, and early peer victimization, thereby implicating both family and peer processes that play out across early development. Children with BPF appear to be further characterized by social-cognitive factors including social perspective coordination deficits, a shame-prone self-concept, and hypermentalizing, which may represent potential therapeutic targets. Clinical research into the implications of BPF for the treatment of childhood psychopathology is a current priority. It is proposed that the research designs that have contributed to recent evidence for the clinical utility of childhood psychopathic traits may likewise aid in understanding the potential clinical utility of BPF in children.
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CSIR Research Space (South Africa)
Musee, N
2011-11-01
Full Text Available and Nanotechnology Summer School Pretoria, South Africa, 22nd NOV? 2nd DEC 2009 Potential risks of nanotechnology to humans and the environment: implications and response mechanisms in Africa Ndeke Musee, Lucky Sikhwivhilu, Nomakhwezi Nota, Lisa Schaefer... COVISET Conference, Johannesburg, South Africa, 22-25 Nov 2011? CSIR 2006 www.csir.co.za Effect of SWCNT on Eschericia coli (a) SEM image of E. Coli incubated without SWCNTs for 60 min. [Source: Kang et al. / Langmuir 2007, 23...
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Directory of Open Access Journals (Sweden)
Jude Igumbor
2016-03-01
Full Text Available Background: The shortage of nurses in public healthcare facilities in South Africa is well documented; finding creative solutions to this problem remains a priority. Objective: This study sought to establish the amount of time that clinical nurse practitioners (CNPs in one district of the Western Cape spend on clinical services and the implications for staffing and skills mix in order to deliver quality patient care. Methods: A descriptive cross-sectional study was conducted across 15 purposively selected clinics providing primary health services in 5 sub-districts. The frequency of activities and time CNPs spent on each activity in fixed and mobile clinics were recorded. Time spent on activities and health facility staff profiles were correlated and predictors of the total time spent by CNPs with patients were identified. Results: The time spent on clinical activities was associated with the number of CNPs in the facilities. CNPs in fixed clinics spent a median time of about 13 minutes with each patient whereas CNPs in mobile clinics spent 3 minutes. Fixed-clinic CNPs also spent more time on their non-core functions than their core functions, more time with patients, and saw fewer patients compared to mobile-clinic CNPs. Conclusions: The findings give insight into the time CNPs in rural fixed and mobile clinics spend with their patients, and how patient caseload may affect consultation times. Two promising strategies were identified – task shifting and adjustments in health workerd eployment – as ways to address staffing and skills mix, which skills mix creates the potential for using healthcare workers fully whilst enhancing the long-term health of these rural communities.
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The clinical implications of immunogenomics in colorectal cancer: A path for precision medicine.
Riley, Jenny M; Cross, Ashley W; Paulos, Chrystal M; Rubinstein, Mark P; Wrangle, John; Camp, E Ramsay
2018-04-15
Colorectal cancer (CRC) remains the third most common malignancy and the second-leading cause of cancer-related deaths in the United States. Large multi-omic databases, such as The Cancer Genome Atlas and the International Colorectal Cancer Subtyping Consortium, have identified distinct molecular subtypes related to anatomy. The identification of genomic alterations in CRC is now critical because of the recent success and US Food and Drug Administration approval of pembrolizumab and nivolumab for microsatellite-instable tumors. In parallel, landmark studies have established the prognostic significance of the CRC tumor-infiltrating lymphocyte and the clinical impact of the tumor immune microenvironment. As a result, there is a growing appreciation for immunogenomics, the interconnected relation between tumor genomics and the immune microenvironment. The clinical implications of CRC immunogenomics continue to expand, and it will likely serve as a guide for next-generation immunotherapy strategies for improving outcomes for this disease. Cancer 2018;124:1650-9. © 2018 American Cancer Society. © 2018 American Cancer Society.
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Directory of Open Access Journals (Sweden)
Jan Lidbeck
2002-01-01
Full Text Available Recent investigations of dysfunctional pain processing in the central nervous system have contributed much knowledge about the development of chronic musculoskeletal pain. Many common chronic musculoskeletal pain syndromes - including regional myofascial pain syndromes, whiplash pain syndromes, refractory work-related neck-shoulder pain, certain types of chronic low back pain, fibromyalgia and others - may essentially be explained by abnormalities in central pain modulation. The growing awareness of dysfunctional central pain modulation may be a conceptual breakthrough leading to a better understanding of common chronic pain disorders. A new paradigm will have multiple clinical implications, including re-evaluation of clinical practice routines and rehabilitation methods, and will focus on controversial issues of medicolegal concern. The concept of dysfunctional central pain processing will also necessitate a mechanism-based classification of pain for the selection of individual treatment and rehabilitation programs for subgroups of patients with chronic musculoskeletal pain due to different pathophysiological mechanisms.
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Mass Spectrometry for Translational Proteomics: Progress and Clinical Implications
Energy Technology Data Exchange (ETDEWEB)
Baker, Erin Shammel; Liu, Tao; Petyuk, Vladislav A.; Burnum-Johnson, Kristin E.; Ibrahim, Yehia M.; Anderson, Gordon A.; Smith, Richard D.
2012-08-31
Mass spectrometry (MS)-based proteomics measurements have become increasingly utilized in a wide range of biological and biomedical applications, and have significantly enhanced the understanding of the complex and dynamic nature of the proteome and its connections to biology and diseases. While some MS techniques such as those for targeted analysis are increasingly applied with great success, others such as global quantitative analysis (for e.g. biomarker discovery) are more challenging and continue to be developed and refined to provide the desired throughput, sensitivity and/ or specificity. New MS capabilities and proteomics-based pipelines/strategies also keep enhancing for the advancement of clinical proteomics applications such as protein biomarker discovery and validation. Herein, we provide a brief review to summarize the current state of MS-based proteomics with respect to its advantages and present limitations, while highlighting its potential in future clinical applications.
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Sanchez, CL; Biskup, CS; Herpertz, S; Gaber, TJ; Kuhn, CM; Hood, SH
2015-01-01
The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research. PMID:25991656
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Baladi, J F; Bailey, P A; Black, S; Bouchard, R W; Farcnik, K D; Gauthier, S; Kertesz, A; Mohr, E; Robillard, A
2000-12-01
Clinical studies have shown that patients with Alzheimer's disease (AD) who are treated with rivastigmine have statistically significantly better scores on 5 scales used to assess AD than control patients receiving placebo. However, the clinical meaning and cost implications of these differences are not clear. The purpose of this study was to assess the clinical meaning and cost implications of statistically significant results obtained in clinical trials of rivastigmine for the treatment of AD. Potential cost implications for the health care system, caregivers, and society are considered. Data on clinical effects of rivastigmine were obtained from published North American and European clinical studies of patients with mild to moderately severe AD receiving rivastigmine 6 to 12 mg/d (n = 828) or placebo (n = 647). Differences in scores on the Alzheimer's Disease Assessment Scale-Cognitive Function, Clinician's Interview-Based Impression of Change with both clinical and caregiver information considered, Progressive Deterioration Scale, Mini-Mental State Examination (MMSE), and Global Deterioration Scale were assessed. A convenience panel of 9 Canadian specialists experienced in the treatment of AD provided their opinions on the clinical importance of the trial results. Chart review was performed to identify specific behaviors that improved, and cost implications of improvements were assessed. The panel determined that statistically significant differences in scores on all scales except the MMSE were likely associated with functional or cognitive differences that were clinically relevant for patients, reflecting stabilization that would have beneficial consequences for caregivers and health care resource use. Subsequent chart review showed that improvement on specific scale items confirmed the physician panel's opinion. Analysis of possible cost implications to society indicated that medication expenditures would be offset largely by delays in the need for paid home
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International Nuclear Information System (INIS)
Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M.
2016-01-01
Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE
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Energy Technology Data Exchange (ETDEWEB)
Sun, Fei, E-mail: feisun@ccmijesususon.com; Crisóstomo, Verónica, E-mail: crisosto@ccmijesususon.com; Báez-Díaz, Claudia, E-mail: cbaez@ccmijesususon.com; Sánchez, Francisco M., E-mail: msanchez@ccmijesususon.com [Jesús Usón Minimally Invasive Surgery Centre (Spain)
2016-01-15
Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.
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Sun, Fei; Crisóstomo, Verónica; Báez-Díaz, Claudia; Sánchez, Francisco M
2016-01-01
Pathological features of benign prostatic hyperplasia (BPH) dictate various responses to prostatic artery embolization (PAE). Typically, BPH originates in the transition zone and periurethral region, where should be considered the primary target area in PAE procedures. Given that histological heterogeneity of components in hyperplasia nodules, epithelial or stromal, identifying the more responsive nodules to PAE will have clinical implications. Since some lower urinary tract symptoms (LUTS) in patients with BPH are usually related to bladder outlet obstruction-induced changes in bladder function rather than to outflow obstruction directly, proper selection of candidate patients prior to PAE is of great clinical importance. BPH is a typical chronic progressive condition, suggesting PAE could aim not only to relieve LUTS but also to delay or prevent the clinical progression. Awareness of the pathological background of BPH is essential for interventional radiologists to improve clinical outcomes and develop new treatment strategies in clinical practice of PAE.
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Johnson, Dwight R; Kurlan, Roger; Leckman, James; Kaplan, Edward L
2010-02-15
Determination of an immune response to group A Streptococcus (GAS) antigens, frequently anti-streptolysin O and anti-DNase B, is crucial for documentation of bona fide GAS infection. Although the importance of immunologic confirmation of infection is widely accepted, the immediate and long-term immunokinetics of the human antibody response are incompletely documented and poorly understood. Pediatric study participants (n = 160) were followed during a 2-year study with monthly throat cultures (n = 3491) and blood samples (n = 1679) obtained every 13 weeks. Recovered GAS were characterized; serum anti-streptolysin O and anti-DNase B antibody titers were determined. Antibody titers and GAS culture results were temporally correlated and analyzed. The analyses clearly document, in some instances for the first time, that an increase in antibody titer more accurately defines infection than does an absolute titer (eg, "upper limit of normal"), that antibody titers can remain elevated for many months even without GAS, and that some individuals may harbor GAS continuously for months or years without symptoms of infection and without an associated immune response. Measuring 2 different antibodies is more accurate in defining infection. Single time-point cultures and single antibody titers are often misleading. Sequential samples more accurately define infection, allowing correlation of titer increases with temporal confirmation of GAS acquisition. Understanding kinetics of the immune response(s) to GAS infection is necessary in formulating accurate clinical diagnostic conclusions, to appropriate design of clinical and epidemiological studies examining the association of GAS with subsequent sequelae, and to providing insight into pathogenetic mechanisms associated with this important human pathogen.
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Tacit knowledge in dental clinical teaching.
Fugill, M
2012-02-01
The term 'tacit' is used to describe knowledge that is not necessarily understood in words. We frequently make use of such knowledge without conscious awareness that we are doing so. This article explores two different conceptions of tacit knowledge and considers their implications for the clinical teaching of dentistry. It recognises the communication barrier that clinical dependence on tacit knowledge creates between teacher and student. It identifies the ability to surface tacit clinical knowledge for the student as one of the most significant skills of the clinical teacher. Finally, the article examines the potential for conflict between the evidence-based practice paradigm, with its dependence on codified, explicit knowledge and the notion of clinical practice, which is at least partly experiential and tacit. © 2011 John Wiley & Sons A/S.
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Ajjan, Ramzi A; Cummings, Michael H; Jennings, Peter; Leelarathna, Lalantha; Rayman, Gerry; Wilmot, Emma G
2018-02-01
Continuous glucose monitoring and flash glucose monitoring technologies measure glucose in the interstitial fluid and are increasingly used in diabetes care. Their accuracy, key to effective glycaemic management, is usually measured using the mean absolute relative difference of the interstitial fluid sensor compared to reference blood glucose readings. However, mean absolute relative difference is not standardised and has limitations. This review aims to provide a consensus opinion on assessing accuracy of interstitial fluid glucose sensing technologies. Mean absolute relative difference is influenced by glucose distribution and rate of change; hence, we express caution on the reliability of comparing mean absolute relative difference data from different study systems and conditions. We also review the pitfalls associated with mean absolute relative difference at different glucose levels and explore additional ways of assessing accuracy of interstitial fluid devices. Importantly, much data indicate that current practice of assessing accuracy of different systems based on individualised mean absolute relative difference results has limitations, which have potential clinical implications. Healthcare professionals must understand the factors that influence mean absolute relative difference as a metric for accuracy and look at additional assessments, such as consensus error grid analysis, when evaluating continuous glucose monitoring and flash glucose monitoring systems in diabetes care. This in turn will ensure that management decisions based on interstitial fluid sensor data are both effective and safe.
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Directory of Open Access Journals (Sweden)
Erik Z Woody
2013-09-01
Full Text Available Research indicates that there is a specially adapted, hard-wired brain circuit, the security motivation system, which evolved to manage potential threats, such as the possibility of contamination or predation. The existence of this system may have important implications for policy-making related to security. The system is sensitive to partial, uncertain cues of potential danger, detection of which activates a persistent, potent motivational state of wariness or anxiety. This state motivates behaviours to probe the potential danger, such as checking, and to correct for it, such as washing. Engagement in these behaviours serves as the terminating feedback for the activation of the system. Because security motivation theory makes predictions about what kinds of stimuli activate security motivation and what conditions terminate it, the theory may have applications both in understanding how policy-makers can best influence others, such as the public, and also in understanding the behavior of policy-makers themselves.
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Legarda, Stella B; McMahon, Doreen; Othmer, Siegfried; Othmer, Sue
2011-08-01
Trends in alternative medicine use by American health care consumers are rising substantially. Extensive literature exists reporting on the effectiveness of neurofeedback in the treatment of autism, closed head injury, insomnia, migraine, depression, attention deficit hyperactivity disorder, epilepsy, and posttraumatic stress disorder. We speculated that neurofeedback might serve as a therapeutic modality for patients with medically refractory neurological disorders and have begun referring patients to train with clinical neurofeedback practitioners. The modality is not always covered by insurance. Confident their child's medical and neurological needs would continue to be met, the parents of 3 children with epilepsy spectrum disorder decided to have their child train in the modality. The children's individual progress following neurofeedback are each presented here. A proposed mechanism and practice implications are discussed.
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Rutstein, Sarah E; Ananworanich, Jintanat; Fidler, Sarah; Johnson, Cheryl; Sanders, Eduard J; Sued, Omar; Saez-Cirion, Asier; Pilcher, Christopher D; Fraser, Christophe; Cohen, Myron S; Vitoria, Marco; Doherty, Meg; Tucker, Joseph D
2017-06-28
The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective
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Bai, Mei; Yang, Jiefu; Li, Yingying
2009-12-01
Brain natriuretic peptide (BNP) is increasingly being used for screening and monitoring of congestive heart failure. However, the role of BNP in patients with atrial fibrillation (AF) and normal left ventricular function has not been determined. This study investigates serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level and its clinical implications in patients with AF. Serum NT-proBNP levels were measured by enzyme-linked immunosorbent assay (ELISA) and transthoracic echocardiography was performed in 136 subjects (90 cases with AF and 46 cases with sinus rhythm [SR]). Subjects were excluded if they had a history of myocardial infarction, cardiomyopathy, rheumatic heart disease, or hyperthyroidism that preceded the onset of AF. Controls (n = 30) were from a healthy outpatient primary care population. Potential determinants of serum NT-proBNP levels were identified by univariate and multivariate analyses. Individuals with AF had higher serum NT-proBNP levels (689.56 +/- 251.87 fmol/ml) than those with SR (456.11 +/- 148.14 fmol/ml, P NT-proBNP levels (P > 0.05). The regression model of serum NT-proBNP levels and clinical predictors showed that presence of AF, older age, and larger right atrial diameter were independently predictive of higher serum NT-proBNP values. Patients with AF were associated with increased serum NT-proBNP levels. Examining the change of serum NT-proBNP levels is helpful to evaluate the cardiac function in patients with AF. Copyright 2009 Wiley Periodicals, Inc.
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Directory of Open Access Journals (Sweden)
Hicks Madelyn
2006-06-01
Full Text Available Abstract Background A bill to legalize physician-assisted suicide in the UK recently made significant progress in the British House of Lords and will be reintroduced in the future. Until now there has been little discussion of the clinical implications of physician-assisted suicide for the UK. This paper describes problematical issues that became apparent from a review of the medical and psychiatric literature as to the potential effects of legalized physician-assisted suicide. Discussion Most deaths by physician-assisted suicide are likely to occur for the illness of cancer and in the elderly. GPs will deal with most requests for assisted suicide. The UK is likely to have proportionately more PAS deaths than Oregon due to the bill's wider application to individuals with more severe physical disabilities. Evidence from other countries has shown that coercion and unconscious motivations on the part of patients and doctors in the form of transference and countertransference contribute to the misapplication of physician-assisted suicide. Depression influences requests for hastened death in terminally ill patients, but is often under-recognized or dismissed by doctors, some of whom proceed with assisted death anyway. Psychiatric evaluations, though helpful, do not solve these problems. Safeguards that are incorporated into physician-assisted suicide criteria probably decrease but do not prevent its misapplication. Summary The UK is likely to face significant clinical problems arising from physician-assisted suicide if it is legalized. Terminally ill patients with mental illness, especially depression, are particularly vulnerable to the misapplication of physician-assisted suicide despite guidelines and safeguards.
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[Recommendations for the clinical use of motor evoked potentials in multiple sclerosis].
Fernández, V; Valls-Sole, J; Relova, J L; Raguer, N; Miralles, F; Dinca, L; Taramundi, S; Costa-Frossard, L; Ferrandiz, M; Ramió-Torrentà, Ll; Villoslada, P; Saiz, A; Calles, C; Antigüedad, A; Alvarez-Cermeño, J C; Prieto, J M; Izquierdo, G; Montalbán, X; Fernández, O
2013-09-01
To establish clinical guidelines for the clinical use and interpretation of motor evoked potentials (MEP) in diagnosing and monitoring patients with multiple sclerosis (MS). Recommendations for MEP use and interpretation will help us rationalise and optimise resources used in MS patient diagnosis and follow up. We completed an extensive literature review and pooled our own data to produce a consensus statement with recommendations for the clinical use of MEPs in the study of MS. MEPs, in addition to spinal and cranial magnetic resonance imaging (MRI), help us diagnose and assess MS patients whose disease initially presents as spinal cord syndrome and those with non-specific brain MRI findings, or a normal brain MRI and clinical signs of MS. Whenever possible, a multimodal evoked potential study should be performed on patients with suspected MS in order to demonstrate involvement of the motor pathway which supports a diagnosis of dissemination in space. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.
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Clarifying assumptions to enhance our understanding and assessment of clinical reasoning.
Durning, Steven J; Artino, Anthony R; Schuwirth, Lambert; van der Vleuten, Cees
2013-04-01
Deciding on a diagnosis and treatment is essential to the practice of medicine. Developing competence in these clinical reasoning processes, commonly referred to as diagnostic and therapeutic reasoning, respectively, is required for physician success. Clinical reasoning has been a topic of research for several decades, and much has been learned. However, there still exists no clear consensus regarding what clinical reasoning entails, let alone how it might best be taught, how it should be assessed, and the research and practice implications therein.In this article, the authors first discuss two contrasting epistemological views of clinical reasoning and related conceptual frameworks. They then outline four different theoretical frameworks held by medical educators that the authors believe guide educators' views on the topic, knowingly or not. Within each theoretical framework, the authors begin with a definition of clinical reasoning (from that viewpoint) and then discuss learning, assessment, and research implications. The authors believe these epistemologies and four theoretical frameworks also apply to other concepts (or "competencies") in medical education.The authors also maintain that clinical reasoning encompasses the mental processes and behaviors that are shared (or evolve) between the patient, physician, and the environment (i.e., practice setting). Clinical reasoning thus incorporates components of all three factors (patient, physician, environment). The authors conclude by outlining practical implications and potential future areas for research.
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Neurobiology and clinical implications of lucid dreaming.
Mota-Rolim, Sérgio A; Araujo, John F
2013-11-01
Several lines of evidence converge to the idea that rapid eye movement sleep (REMS) is a good model to foster our understanding of psychosis. Both REMS and psychosis course with internally generated perceptions and lack of rational judgment, which is attributed to a hyperlimbic activity along with hypofrontality. Interestingly, some individuals can become aware of dreaming during REMS, a particular experience known as lucid dreaming (LD), whose neurobiological basis is still controversial. Since the frontal lobe plays a role in self-consciousness, working memory and attention, here we hypothesize that LD is associated with increased frontal activity during REMS. A possible way to test this hypothesis is to check whether transcranial magnetic or electric stimulation of the frontal region during REMS triggers LD. We further suggest that psychosis and LD are opposite phenomena: LD as a physiological awakening while dreaming due to frontal activity, and psychosis as a pathological intrusion of dream features during wake state due to hypofrontality. We further suggest that LD research may have three main clinical implications. First, LD could be important to the study of consciousness, including its pathologies and other altered states. Second, LD could be used as a therapy for recurrent nightmares, a common symptom of depression and post-traumatic stress disorder. Finally, LD may allow for motor imagery during dreaming with possible improvement of physical rehabilitation. In all, we believe that LD research may clarify multiple aspects of brain functioning in its physiological, altered and pathological states. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Mattheos, Nikos; Li, Xiaona; Zampelis, Antonios; Ma, Li; Janda, Martin
2016-11-01
The aim of this pilot study was to investigate the morphological micro-features of three commercially available implant-abutment joints, using compatible and original prosthetic components. Furthermore, possible correlations between the micromorphology and potential functional complications were investigated with the use of finite element analysis. Three abutments (one original and two compatibles) were torqued on original Straumann RN implants, as according to each of the manufacturer's instructions. The implant-abutment units were sliced in the microtome and photographed under different magnifications (10×-500×) through a scanning electron microscope. Finite element analysis models were reconstructed for each of the implant-abutment units using the precise measurements from the SEM. Differences in stress, strain and deformation for the three different abutments were then calculated using ANSYS Workbench v13. Major dimensional differences were identified between all studied contact areas of the three units. The tight contact in the implant shoulder was similar in all three units, but engagement of the internal connection and, in particular, the anti-rotation elements was seriously compromised in the compatible abutments. One compatible abutment demonstrated compromised engagement of the abutment screw as well. Equivalent stress and strain in the FEA were much higher for the compatible abutments. An evaluation of the sequence of preload application revealed differences in the pattern of deformation between the original and compatible abutments, which can have serious clinical implications. Compatible abutments can present critical morphological differences from the original ones. The differences in the cross-sectional geometry result in large differences in the overall contact areas, both in terms of quality and quantity which could have serious implications for the long-term stability of the prosthesis. © 2015 John Wiley & Sons A/S. Published by John Wiley
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Goekoop, R; Goekoop, J G
2016-01-01
In a recent publication we reported the existence of around 11 (to 15) 'elementary syndromes' that may combine in various ways, rather like 'building blocks', to explain the wide range of psychiatric symptoms. 'Bridge symptoms' seem to be responsible both for combining large sets of symptoms into elementary syndromes and for combining the various elementary syndromes to form one globally connected network structure. To discuss the implication of these findings for clinical practice. We performed a network analysis of symptom scores. Elementary syndromes provide a massive simplification of the description of psychiatric disease. Instead of the more than 300 categories in DSM-5, we now need to consider only a handful of elementary syndromes and personality domains. This modular representation of psychiatric illnesses allows us to make a complete, systematic and efficient assessment of patients and a systematic review of treatment options. Clinicians, patients, managerial staff and insurance companies can verify whether symptom reduction is taking place in the most important domains of psychopathology. Unlike classic multidimensional methods of disease description, network models of psychopathology can be used to explain comorbidity patterns, predict the clinical course of psychopathology and to designate primary targets for therapeutic interventions. A network view on psychopathology could significantly improve everyday clinical practice.
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The Clinical Nurse Leader--new nursing role with global implications.
Baernholdt, M; Cottingham, S
2011-03-01
This paper describes the development of the Clinical Nurse Leader (CNL ©) role and education, the CNL's impact and potential to improve quality globally. The need for clinical nurse leadership to improve the quality of health care systems while controlling costs is recognized in reports internationally. In the USA, a new nursing role, the CNL, was developed in response to such reports. CNLs are master's level nurse graduates (although not necessarily recruited from a nursing background) with the skills and knowledge to create change within complex systems and improve outcomes while they remain direct care providers. This innovative role can be adapted worldwide to improve the quality of health care systems. © 2010 The Authors. International Nursing Review © 2010 International Council of Nurses.
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Clinical implications of microRNAs in human glioblastoma
Directory of Open Access Journals (Sweden)
Masahiro eMizoguchi
2013-02-01
Full Text Available Glioblastoma (GBM is one of the most common and dismal brain tumors in adults. Further elucidation of the molecular pathogenesis of GBM is mandatory to improve the overall survival of patients. A novel small non-coding RNA molecule, microRNA (miRNA, appears to represent one of the most attractive target molecules contributing to the pathogenesis of various types of tumors. Recent global analyses have revealed that several miRNAs are clinically implicated in GBM, with some reports indicating the association of miRNA dysregulation with acquired temozolomide (TMZ resistance. More recent studies have revealed that miRNAs could play a role in cancer stem cell (CSC properties, contributing to treatment resistance. In addition, greater impact might be expected from miRNA-targeted therapies based on tumor-derived exosomes that contain numerous functional miRNAs, which could be transferred between tumor cells and surrounding structures. Tumor-derived miRNAs are now considered to be a novel molecular mechanism promoting the progression of GBM. Establishment of miRNA-targeted therapies based on miRNA dysregulation of CSCs could provide effective therapeutic strategies for TMZ-resistant GBM. Recent progress has revealed that miRNAs are not only putative biological markers for diagnosis, but also one of the most promising targets for GBM treatment. Herein, we summarize the translational aspects of miRNAs in the diagnosis and treatment of GBM.
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Prescription opioid abuse, pain and addiction: clinical issues and implications.
Ling, Walter; Mooney, Larissa; Hillhouse, Maureen
2011-05-01
Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial µ agonist buprenorphine in the management of concurrent pain and opioid addiction. Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy. © 2011 Australasian Professional Society on Alcohol and other Drugs.
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Bonilauri Ferreira, Ana Paula Ribeiro; Ferreira, Rodrigo Fernando; Rajgor, Dimple; Shah, Jatin; Menezes, Andrea; Pietrobon, Ricardo
2010-04-20
Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.
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Time course of clinical change following neurofeedback.
Rance, Mariela; Walsh, Christopher; Sukhodolsky, Denis G; Pittman, Brian; Qiu, Maolin; Kichuk, Stephen A; Wasylink, Suzanne; Koller, William N; Bloch, Michael; Gruner, Patricia; Scheinost, Dustin; Pittenger, Christopher; Hampson, Michelle
2018-05-02
Neurofeedback - learning to modulate brain function through real-time monitoring of current brain state - is both a powerful method to perturb and probe brain function and an exciting potential clinical tool. For neurofeedback effects to be useful clinically, they must persist. Here we examine the time course of symptom change following neurofeedback in two clinical populations, combining data from two ongoing neurofeedback studies. This analysis reveals a shared pattern of symptom change, in which symptoms continue to improve for weeks after neurofeedback. This time course has several implications for future neurofeedback studies. Most neurofeedback studies are not designed to test an intervention with this temporal pattern of response. We recommend that new studies incorporate regular follow-up of subjects for weeks or months after the intervention to ensure that the time point of greatest effect is sampled. Furthermore, this time course of continuing clinical change has implications for crossover designs, which may attribute long-term, ongoing effects of real neurofeedback to the control intervention that follows. Finally, interleaving neurofeedback sessions with assessments and examining when clinical improvement peaks may not be an appropriate approach to determine the optimal number of sessions for an application. Copyright © 2018 Elsevier Inc. All rights reserved.
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International Nuclear Information System (INIS)
Paschoa, A.S.
1998-01-01
The immense volume of naturally occurring radioactive materials (NORM) wastes produced annually by extracting industries throughout the world deserves to come to the attention of international and national environmental protection agencies and regulatory bodies. Although a great deal of work has been done in the fields of radiation protection and remedial actions concerning uranium and other mines, the need to dispose of diffuse NORM wastes will have environmental and regulatory implications that thus far are not fully appreciated. NORM wastes constitute, by and large, unwanted byproducts of industrial activities as diverse as thorium and uranium milling, niobium, tin and gold mining extraction, water treatment, and the production of oil, gas, phosphate fertilizer, coal fire and aluminium. The volumes of NORM wastes produced annually could reach levels so high that the existing low level radioactive waste (LLRW) facilities would be readily occupied by NORM if controlled disposal procedures were not adopted. On the other hand, NORM cannot just be ignored as being below radiological concern (BRC) or lower than exempt concentration levels (ECLs), because sometimes NORM concentrations reach levels as high as 1 x 10 3 kBq/kg for 226 Ra, and not much less for 228 Ra. Unfortunately, thus far, there is not enough information available concerning NORM wastes in key industries, though the international scientific community has been concerned, for a long time now, with technologically enhanced natural radiation exposures (TENRE). This article is written with the intention of examining, to the extent possible, the potential environmental and regulatory implications of NORM wastes being produced in selected industries. (Author)
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Octogenarians' post-acute care use after cardiac valve surgery and recovery: clinical implications.
Edmiston, Elizabeth; Dolansky, Mary A; Zullo, Melissa; Forman, Daniel E
2017-12-21
Octogenarians receiving cardiac valve surgery is increasing and recovery is challenging. Post-acute care (PAC) services assist with recovery, yet services provided in facilities do not provide adequate cardiac-focused care or long-term self-management support. The purpose of the paper was to report post-acute care discharge rates in octogenarians and propose clinical implications to improve PAC services. Using a 2003 Medicare Part A database, we studied post-acute care service use in octogenarians after cardiac valve surgery. We propose expansion of the Geriatric Cardiac Care model to include broader clinical therapy dynamics. The sample (n = 10,062) included patients over 80 years discharged from acute care following valve surgery. Post-acute care services were used by 68% of octagarians following cardiac valve surgery (1% intermediate rehabilitation, 35% skilled nursing facility, 32% home health). The large percentage of octagarians using PAC point to the importance of integrating geriatric cardiac care into post-acute services to optimize recovery outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.
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Clinical implications of in silico mathematical modeling for glioblastoma: a critical review.
Protopapa, Maria; Zygogianni, Anna; Stamatakos, Georgios S; Antypas, Christos; Armpilia, Christina; Uzunoglu, Nikolaos K; Kouloulias, Vassilis
2018-01-01
Glioblastoma remains a clinical challenge in spite of years of extensive research. Novel approaches are needed in order to integrate the existing knowledge. This is the potential role of mathematical oncology. This paper reviews mathematical models on glioblastoma from the clinical doctor's point of view, with focus on 3D modeling approaches of radiation response of in vivo glioblastomas based on contemporary imaging techniques. As these models aim to provide a clinically useful tool in the era of personalized medicine, the integration of the latest advances in molecular and imaging science and in clinical practice by the in silico models is crucial for their clinical relevance. Our aim is to indicate areas of GBM research that have not yet been addressed by in silico models and to point out evidence that has come up from in silico experiments, which may be worth considering in the clinic. This review examines how close these models have come in predicting the outcome of treatment protocols and in shaping the future of radiotherapy treatments.
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Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla
2008-12-01
This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.
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Directory of Open Access Journals (Sweden)
Kimberly A. Redic, PharmD
2017-06-01
Conclusions: This pilot study showed potential roles for pharmacy personnel involvement in medication reconciliation in the clinical research setting. Pharmacists have the opportunity to ensure that IDs are accurately included in patient medication lists and to identify the use of potential protocol prohibited concomitant medications.
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Best clinical trials reported in 2010.
Garner, John B; Grayburn, Paul A; Yancy, Clyde W
2011-07-01
Each year, a number of clinical trials emerge with data sufficient to change clinical practice. Determining which findings will result in practice change and which will provide only incremental benefit can be a dilemma for clinicians. The authors review selected clinical trials reported in 2010 in journals, at society meetings, and at conferences, focusing on those studies that have the potential to change clinical practice. This review offers 3 separate means of analysis: an abbreviated text summary, organized by subject area; a comprehensive table of relevant clinical trials that provides a schematic review of the hypotheses, interventions, methods, primary end points, results, and implications; and a complete bibliography for further reading as warranted. It is hoped that this compilation of relevant clinical trials and their important findings released in 2010 will be of benefit in the everyday practice of cardiovascular medicine. Copyright © 2011 Elsevier Inc. All rights reserved.
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Hannam, A G
2011-03-01
Computational models of interactions in the craniomandibular apparatus are used with increasing frequency to study biomechanics in normal and abnormal masticatory systems. Methods and assumptions in these models can be difficult to assess by those unfamiliar with current practices in this field; health professionals are often faced with evaluating the appropriateness, validity and significance of models which are perhaps more familiar to the engineering community. This selective review offers a foundation for assessing the strength and implications of a craniomandibular modelling study. It explores different models used in general science and engineering and focuses on current best practices in biomechanics. The problem of validation is considered at some length, because this is not always fully realisable in living subjects. Rigid-body, finite element and combined approaches are discussed, with examples of their application to basic and clinically relevant problems. Some advanced software platforms currently available for modelling craniomandibular systems are mentioned. Recent studies of the face, masticatory muscles, tongue, craniomandibular skeleton, temporomandibular joint, dentition and dental implants are reviewed, and the significance of non-linear and non-isotropic material properties is emphasised. The unique challenges in clinical application are discussed, and the review concludes by posing some questions which one might reasonably expect to find answered in plausible modelling studies of the masticatory apparatus. © 2010 Blackwell Publishing Ltd.
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Directory of Open Access Journals (Sweden)
David Filgueiras-Rama
2013-01-01
Full Text Available Obstructive sleep apnea (OSA is a common disorder characterized by repetitive interruption of ventilation during sleep caused by recurrent upper airway collapse, which leads to intermittent hypoxia. The disorder is commonly undiagnosed despite its relationship with substantial cardiovascular morbidity and mortality. Moreover, the effects of the disorder appear to be particularly dangerous in young subjects. In the last decade, substantial clinical evidence has identified OSA as independent risk factor for both bradyarrhythmias and tachyarrhythmias. To date the mechanisms leading to such arrhythmias have not been completely understood. However, recent data from animal models and new molecular analyses have increased our knowledge of the field, which might lead to future improvement in current therapeutic strategies mainly based on continuous positive airway pressure. This paper aims at providing readers a brief and specific revision of current knowledge about the mechanisms underlying atrial arrhythmias in OSA and their clinical and therapeutic implications.
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The potential of telehealth for 'business as usual' in outpatient clinics.
Day, Karen; Kerr, Patricia
2012-04-01
A six-month pilot study was conducted to ascertain the value of using high-definition videoconferencing equipment in an outpatients' setting. The videoconferencing equipment, which included digital biometric equipment, was installed in the outpatient clinics of a remote health service in New Zealand. Use of the equipment was evaluated using action research techniques. Clinicians were interviewed about their assessment of the equipment's usefulness. Patients and their carers completed questionnaires about their clinic experience. During the pilot trial, 109 patients were seen in 25 clinics of six different specialities. Questionnaire results showed that patients and their companions had a good user experience, similar to a face-to-face appointment. Clinicians found that the large screen, sense of proximity, video clarity and definition, and lack of sound/picture lag worked well for certain types of outpatients' clinics, e.g. methadone maintenance clinics. The need for process changes made it difficult to turn telehealth into business as usual in an environment built for face-to-face appointments. We conclude that videoconference equipment has potential to become integral to outpatients' clinics.
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Clinical leadership in contemporary clinical practice: implications for nursing in Australia.
Davidson, P M; Elliott, D; Daly, J
2006-04-01
Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.
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CT Image Contrast of High-Z Elements: Phantom Imaging Studies and Clinical Implications.
FitzGerald, Paul F; Colborn, Robert E; Edic, Peter M; Lambert, Jack W; Torres, Andrew S; Bonitatibus, Peter J; Yeh, Benjamin M
2016-03-01
To quantify the computed tomographic (CT) image contrast produced by potentially useful contrast material elements in clinically relevant imaging conditions. Equal mass concentrations (grams of active element per milliliter of solution) of seven radiodense elements, including iodine, barium, gadolinium, tantalum, ytterbium, gold, and bismuth, were formulated as compounds in aqueous solutions. The compounds were chosen such that the active element dominated the x-ray attenuation of the solution. The solutions were imaged within a modified 32-cm CT dose index phantom at 80, 100, 120, and 140 kVp at CT. To simulate larger body sizes, 0.2-, 0.5-, and 1.0-mm-thick copper filters were applied. CT image contrast was measured and corrected for measured concentrations and presence of chlorine in some compounds. Each element tested provided higher image contrast than iodine at some tube potential levels. Over the range of tube potentials that are clinically practical for average-sized and larger adults-that is, 100 kVp and higher-barium, gadolinium, ytterbium, and tantalum provided consistently increased image contrast compared with iodine, respectively demonstrating 39%, 56%, 34%, and 24% increases at 100 kVp; 39%, 66%, 53%, and 46% increases at 120 kVp; and 40%, 72%, 65%, and 60% increases at 140 kVp, with no added x-ray filter. The consistently high image contrast produced with 100-140 kVp by tantalum compared with bismuth and iodine at equal mass concentration suggests that tantalum could potentially be favorable for use as a clinical CT contrast agent.
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Engineered BDNF producing cells as a potential treatment for neurologic disease
Deng, Peter; Anderson, Johnathon D.; Yu, Abigail S.; Annett, Geralyn; Fink, Kyle D.; Nolta, Jan A.
2018-01-01
Introduction Brain-derived neurotrophic factor (BDNF) has been implicated in wide range of neurological diseases and injury. This neurotrophic factor is vital for neuronal health, survival, and synaptic connectivity. Many therapies focus on the restoration or enhancement of BDNF following injury or disease progression. Areas covered The present review will focus on the mechanisms in which BDNF exerts its beneficial functioning, current BDNF therapies, issues and potential solutions for delivery of neurotrophic factors to the central nervous system, and other disease indications that may benefit from overexpression or restoration of BDNF. Expert opinion Due to the role of BDNF in neuronal development, maturation, and health, BDNF is implicated in numerous neurological diseases making it a prime therapeutic agent. Numerous studies have shown the therapeutic potential of BDNF in a number of neurodegenerative disease models and in acute CNS injury, however clinical translation has fallen short due to issues in delivering this molecule. The use of MSC as a delivery platform for BDNF holds great promise for clinical advancement of neurotrophic factor restoration. The ease with which MSC can be engineered opens the door to the possibility of using this cell-based delivery system to advance a BDNF therapy to the clinic. PMID:27159050
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Pickersgill, M D
2009-11-01
The British National Institute for Health and Clinical Excellence (NICE) has recently (28 January 2009) released new guidelines for the diagnosis, treatment and prevention of the psychiatric category antisocial personality disorder (ASPD). Evident in these recommendations is a broader ambiguity regarding the ontology of ASPD. Although, perhaps, a mundane feature of much of medicine, in this case, ontological uncertainty has significant ethical implications as a product of the profound consequences for an individual categorised with this disorder. This paper argues that in refraining from emphasising uncertainty, NICE risks reifying a controversial category. This is particularly problematical given that the guidelines recommend the identification of individuals "at risk" of raising antisocial children. Although this paper does not argue that NICE is "wrong" in any of its recommendations, more emphasis should have been placed on discussions of the ethical implications of diagnosis and treatment, especially given the multiple uncertainties associated with ASPD. It is proposed that these important issues be examined in more detail in revisions of existing NICE recommendations, and be included in upcoming guidance. This paper thus raises key questions regarding the place and role of ethics within the current and future remit of NICE.
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What are the clinical implications of nodular gastritis? Clues from histopathology.
Sokmensuer, Cenk; Onal, Ibrahim Koral; Yeniova, Ozgur; Ersoy, Osman; Aydinli, Musa; Yonem, Ozlem; Harmanci, Ozgur; Onal, Eda Demir; Altinok, Gulcin; Batman, Figen; Bayraktar, Yusuf
2009-10-01
There is no widely accepted histopathological definition for nodular gastritis. In this study we aim to uncover the pathologic entity responsible for the nodular appearance and to find clues about the clinical implications of nodular gastritis. Antral biopsy specimens of 160 patients with nodular gastritis and 133 patients without nodular gastritis were examined by an experienced pathologist for dysplasia, foveolar hyperplasia, inflammatory activity, intraepithelial lymphocytosis, intestinal metaplasia, and lymphoid follicle/aggregate formation, and comparative analysis was performed between the two groups of patients. The presence of intraepithelial lymphocytosis was more frequent in patients with nodular gastritis (P < 0.05). There was no difference between the two groups regarding the other pathological features such as presence of dysplasia, inflammatory activity, intestinal metaplasia, lymphoid hyperplasia, and Helicobacter pylori (H. pylori) infection. Increase of intraepithelial lymphocytes may contribute to formation of macroscopical nodules in this peculiar type of gastritis. Nodular gastritis would not indicate a new therapeutic approach in addition to the current measures for Helicobacter pylori infection.
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Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications
DEFF Research Database (Denmark)
Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter
2009-01-01
PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...
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Directory of Open Access Journals (Sweden)
Ana Paula Ribeiro Bonilauri Ferreira
Full Text Available BACKGROUND: Little is known about the reasoning mechanisms used by physicians in decision-making and how this compares to diagnostic clinical practice guidelines. We explored the clinical reasoning process in a real life environment. METHOD: This is a qualitative study evaluating transcriptions of sixteen physicians' reasoning during appointments with patients, clinical discussions between specialists, and personal interviews with physicians affiliated to a hospital in Brazil. RESULTS: FOUR MAIN THEMES WERE IDENTIFIED: simple and robust heuristics, extensive use of social environment rationality, attempts to prove diagnostic and therapeutic hypothesis while refuting potential contradictions using positive test strategy, and reaching the saturation point. Physicians constantly attempted to prove their initial hypothesis while trying to refute any contradictions. While social environment rationality was the main factor in the determination of all steps of the clinical reasoning process, factors such as referral letters and number of contradictions associated with the initial hypothesis had influence on physicians' confidence and determination of the threshold to reach a final decision. DISCUSSION: Physicians rely on simple heuristics associated with environmental factors. This model allows for robustness, simplicity, and cognitive energy saving. Since this model does not fit into current diagnostic clinical practice guidelines, we make some propositions to help its integration.
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Passik, Steven D; Lowery, Amy
2011-06-01
Opioid-related deaths in the United States have become a public health problem, with accidental and unintended overdoses being especially troubling. Screening for psychological risk factors is an important first step in safeguarding against nonadherence practices and identifying patients who may be vulnerable to the risks associated with opioid therapy. Validated screening instruments can aid in this attempt as a complementary tool to clinicians' assessments. A structured screening is imperative as part of an assessment, as clinician judgment is not the most reliable method of identifying nonadherence. As a complement to formal screening, we present for discussion and possible future study certain psychological variables observed during years of clinical practice that may be linked to medication nonadherence and accidental overdose. These variables include catastrophizing, fear, impulsivity, attention deficit disorders, existential distress, and certain personality disorders. In our experience, chronic pain patients with dual diagnoses may become "chemical copers" as a way of coping with their negative emotion. For these patients, times of stress could lead to accidental overdose. Behavioral, cognitive-behavioral (acceptance and commitment, dialectical behavior), existential (meaning-centered, dignity), and psychotropic therapies have been effective in treating these high-risk comorbidities, while managing expectations of pain relief appears key to preventing accidental overdose. Wiley Periodicals, Inc.
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Potential benefits and risks of clinical xenotransplantation
Directory of Open Access Journals (Sweden)
Cooper DKC
2012-07-01
Full Text Available David KC Cooper,1 David Ayares21Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 2Revivicor, Blacksburg, VA, USAAbstract: The transplantation of organs and cells from pigs into humans could overcome the critical and continuing problem of the lack of availability of deceased human organs and cells for clinical transplantation. Developments in the genetic engineering of pigs have enabled considerable progress to be made in the experimental laboratory in overcoming the immune barriers to successful xenotransplantation. With regard to pig organ xenotransplantation, antibody- and cell-mediated rejection have largely been overcome, and the current major barrier is the development of coagulation dysregulation. This is believed to be due to a combination of immune activation of the vascular endothelial cells of the graft and molecular incompatibilities between the pig and primate coagulation–anticoagulation systems. Pigs with new genetic modifications specifically directed to this problem are now becoming available. With regard to less complex tissues, such as islets (for the treatment of diabetes, neuronal cells (for the treatment of Parkinson's disease, and corneas, the remaining barriers are less problematic, and graft survival in nonhuman primate models extends for >1 year in all three cases. In planning the initial clinical trials, consideration will be concentrated on the risk–benefit ratio, based to a large extent on the results of preclinical studies in nonhuman primates. If the benefit to the patient is anticipated to be high, eg, insulin-independent control of glycemia, and the potential risks low, eg, minimal risk of transfer of a porcine infectious agent, then a clinical trial would be justified.Keywords: infection, pigs, genetically-engineered, xenotransplantation, islets, xenotransplantation, organs
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Albumin-drug interaction and its clinical implication.
Yamasaki, Keishi; Chuang, Victor Tuan Giam; Maruyama, Toru; Otagiri, Masaki
2013-12-01
Human serum albumin acts as a reservoir and transport protein for endogenous (e.g. fatty acids or bilirubin) and exogenous compounds (e.g. drugs or nutrients) in the blood. The binding of a drug to albumin is a major determinant of its pharmacokinetic and pharmacodynamic profile. The present review discusses recent findings regarding the nature of drug binding sites, drug-albumin binding in certain diseased states or in the presence of coadministered drugs, and the potential of utilizing albumin-drug interactions in clinical applications. Drug-albumin interactions appear to predominantly occur at one or two specific binding sites. The nature of these drug binding sites has been fundamentally investigated as to location, size, charge, hydrophobicity or changes that can occur under conditions such as the content of the endogenous substances in question. Such findings can be useful tools for the analysis of drug-drug interactions or protein binding in diseased states. A change in protein binding is not always a problem in terms of drug therapy, but it can be used to enhance the efficacy of therapeutic agents or to enhance the accumulation of radiopharmaceuticals to targets for diagnostic purposes. Furthermore, several extracorporeal dialysis procedures using albumin-containing dialysates have proven to be an effective tool for removing endogenous toxins or overdosed drugs from patients. Recent findings related to albumin-drug interactions as described in this review are useful for providing safer and efficient therapies and diagnoses in clinical settings. This article is part of a Special Issue entitled Serum Albumin. Copyright © 2013 Elsevier B.V. All rights reserved.
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The mandible and its foramen: anatomy, anthropology, embryology and resulting clinical implications.
Lipski, M; Tomaszewska, I M; Lipska, W; Lis, G J; Tomaszewski, K A
2013-11-01
The aim of this paper is to summarise the knowledge about the anatomy, embryology and anthropology of the mandible and the mandibular foramen and also to highlight the most important clinical implications of the current studies regarding anaesthesia performed in the region of the mandible. An electronic journal search was undertaken to identify all the relevant studies published in English. The search included MEDLINE and EMBASE databases and years from 1950 to 2012. The subject search used a combination of controlled vocabulary and free text based on the search strategy for MEDLINE using key words: 'mandible', 'mandibular', 'foramen', 'anatomy', 'embryology', 'anthropology', and 'mental'. The reference lists of all the relevant studies and existing reviews were screened for additional relevant publications. Basing on relevant manuscripts, this short review about the anatomy, embryology and anthropology of the mandible and the mandibular foramen was written.
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Gestational Diabetes Mellitus: a review of the diagnosis, clinical implications and management
Directory of Open Access Journals (Sweden)
Vincent Wing-Ming Wong
2013-04-01
Full Text Available Gestational diabetes mellitus (GDM is a condition that affects the wellbeing of mother and fetus. Women with GDM are at risk of type 2 diabetes mellitus in the future, while fetal exposure to hyperglycaemia in-utero may affect their glycometabolic profile later in life. Appropriate screening and management of this problem is important in ensuring good pregnancy outcomes. In this review, the clinical implications, the various ways to screen and diagnose GDM, and management strategies during pregnancy will be discussed. For years, insulin is the mainstay of treatment if medical nutrition therapy fails to maintain adequate glycaemic control, but use of other oral pharmacotherapy may gain greater acceptance in the future. Following delivery, ongoing follow-up of these women is worthwhile as early intervention through lifestyle or pharmacotherapy may prevent the development of diabetes.
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Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.
Sdrulla, Andrei D; Guan, Yun; Raja, Srinivasa N
2018-03-11
Spinal cord stimulation (SCS) is a minimally invasive therapy used for the treatment of chronic neuropathic pain. SCS is a safe and effective alternative to medications such as opioids, and multiple randomized controlled studies have demonstrated efficacy for difficult-to-treat neuropathic conditions such as failed back surgery syndrome. Conventional SCS is believed mediate pain relief via activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing. Although potentiation of inhibition, as suggested by Wall and Melzack's gate control theory, continues to be the leading explanatory model, other segmental and supraspinal mechanisms have been described. Novel, non-standard, stimulation waveforms such as high-frequency and burst have been shown in some studies to be clinically superior to conventional SCS, however their mechanisms of action remain to be determined. Additional studies are needed, both mechanistic and clinical, to better understand optimal stimulation strategies for different neuropathic conditions, improve patient selection and optimize efficacy. © 2018 World Institute of Pain.
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Directory of Open Access Journals (Sweden)
Min-Hee Jang
2014-12-01
Full Text Available Objectives Nanoscale zero-valent iron (nZVI particles are widely used in the field of various environmental contaminant remediation. Although the potential benefits of nZVI are considerable, there is a distinct need to identify any potential risks after environmental exposure. In this respect, we review recent studies on the environmental applications and implications of nZVI, highlighting research gaps and suggesting future research directions. Methods Environmental application of nZVI is briefly summarized, focusing on its unique properties. Ecotoxicity of nZVI is reviewed according to type of organism, including bacteria, terrestrial organisms, and aquatic organisms. The environmental fate and transport of nZVI are also summarized with regards to exposure scenarios. Finally, the current limitations of risk determination are thoroughly provided. Results The ecotoxicity of nZVI depends on the composition, concentration, size and surface properties of the nanoparticles and the experimental method used, including the species investigated. In addition, the environmental fate and transport of nZVI appear to be complex and depend on the exposure duration and the exposure conditions. To date, field-scale data are limited and only short-term studies using simple exposure methods have been conducted. Conclusions In this regard, the primary focus of future study should be on 1 the development of an appropriate and valid testing method of the environmental fate and ecotoxicity of reactive nanoparticles used in environmental applications and 2 assessing their potential environmental risks using in situ field scale applications.
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Variability of CSF Alzheimer's disease biomarkers: implications for clinical practice.
Directory of Open Access Journals (Sweden)
Stephanie J B Vos
Full Text Available BACKGROUND: Cerebrospinal fluid (CSF biomarkers are increasingly being used for diagnosis of Alzheimer's disease (AD. OBJECTIVE: We investigated the influence of CSF intralaboratory and interlaboratory variability on diagnostic CSF-based AD classification of subjects and identified causes of this variation. METHODS: We measured CSF amyloid-β (Aβ 1-42, total tau (t-tau, and phosphorylated tau (p-tau by INNOTEST enzyme-linked-immunosorbent assays (ELISA in a memory clinic population (n = 126. Samples were measured twice in a single or two laboratories that served as reference labs for CSF analyses in the Netherlands. Predefined cut-offs were used to classify CSF biomarkers as normal or abnormal/AD pattern. RESULTS: CSF intralaboratory variability was higher for Aβ1-42 than for t-tau and p-tau. Reanalysis led to a change in biomarker classification (normal vs. abnormal of 26% of the subjects based on Aβ1-42, 10% based on t-tau, and 29% based on p-tau. The changes in absolute biomarker concentrations were paralleled by a similar change in levels of internal control samples between different assay lots. CSF interlaboratory variability was higher for p-tau than for Aβ1-42 and t-tau, and reanalysis led to a change in biomarker classification of 12% of the subjects based on Aβ1-42, 1% based on t-tau, and 22% based on p-tau. CONCLUSIONS: Intralaboratory and interlaboratory CSF variability frequently led to change in diagnostic CSF-based AD classification for Aβ1-42 and p-tau. Lot-to-lot variation was a major cause of intralaboratory variability. This will have implications for the use of these biomarkers in clinical practice.
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Clinical perspectives of cancer stem cell research in radiation oncology
International Nuclear Information System (INIS)
Bütof, Rebecca; Baumann, Michael; Dubrovska, Anna
2013-01-01
Radiotherapy has a proven potential to eradicate cancer stem cells which is reflected by its curative potential in many cancer types. Considerable progress has been made in identification and biological characterisation of cancer stem cells during the past years. Recent biological findings indicate significant inter- and intratumoural and functional heterogeneity of cancer stem cells and lead to more complex models which have potential implications for radiobiology and radiotherapy. Clinical evidence is emerging that biomarkers of cancer stem cells may be prognostic for the outcome of radiotherapy in some tumour entities. Perspectives of cancer stem cell based research for radiotherapy reviewed here include their radioresistance compared to the mass of non-cancer stem cells which form the bulk of all tumour cells, implications for image- and non-image based predictive bio-assays of the outcome of radiotherapy and a combination of novel systemic treatments with radiotherapy
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Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P
2013-07-01
Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.
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Lee, Sang-Hwa; Lee, Jae-June; Kwon, Youngsuk; Kim, Jong-Ho; Sohn, Jong-Hee
2017-01-01
higher in patients with TTH compared with controls ( p < 0.001). However, no differences were observed in the prevalence of HP infection between the groups. The observed association in this study may suggest that primary headache sufferers who experience migraines or TTH are more prone to GI disorders, which may have various clinical implications. Further research concerning the etiology of the association between headaches and GI disorders is warranted.
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Rethinking dry eye disease: a perspective on clinical implications.
Bron, Anthony J; Tomlinson, Alan; Foulks, Gary N; Pepose, Jay S; Baudouin, Christophe; Geerling, Gerd; Nichols, Kelly K; Lemp, Michael A
2014-04-01
Publication of the DEWS report in 2007 established the state of the science of dry eye disease (DED). Since that time, new evidence suggests that a rethinking of traditional concepts of dry eye disease is in order. Specifically, new evidence on the epidemiology of the disease, as well as strategies for diagnosis, have changed the understanding of DED, which is a heterogeneous disease associated with considerable variability in presentation. These advances, along with implications for clinical care, are summarized herein. The most widely used signs of DED are poorly correlated with each other and with symptoms. While symptoms are thought to be characteristic of DED, recent studies have shown that less than 60% of subjects with other objective evidence of DED are symptomatic. Thus the use of symptoms alone in diagnosis will likely result in missing a significant percentage of DED patients, particularly with early/mild disease. This could have considerable impact in patients undergoing cataract or refractive surgery as patients with DED have less than optimal visual results. The most widely used objective signs for diagnosing DED all show greater variability between eyes and in the same eye over time compared with normal subjects. This variability is thought to be a manifestation of tear film instability which results in rapid breakup of the tearfilm between blinks and is an identifier of patients with DED. This feature emphasizes the bilateral nature of the disease in most subjects not suffering from unilateral lid or other unilateral destabilizing surface disorders. Instability of the composition of the tears also occurs in dry eye disease and shows the same variance between eyes. Finally, elevated tear osmolarity has been reported to be a global marker (present in both subtypes of the disease- aqueous-deficient dry eye and evaporative dry eye). Clinically, osmolarity has been shown to be the best single metric for diagnosis of DED and is directly related to
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The development of human visual cortex and clinical implications
Directory of Open Access Journals (Sweden)
Siu CR
2018-04-01
Full Text Available Caitlin R Siu,1 Kathryn M Murphy1,2 1McMaster Integrative Neuroscience Discovery and Study (MiNDS Program, McMaster University, Hamilton, ON, Canada; 2Department of Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada Abstract: The primary visual cortex (V1 is the first cortical area that processes visual information. Normal development of V1 depends on binocular vision during the critical period, and age-related losses of vision are linked with neurobiological changes in V1. Animal studies have provided important details about the neurobiological mechanisms in V1 that support normal vision or are changed by visual diseases. There is very little information, however, about those neurobiological mechanisms in human V1. That lack of information has hampered the translation of biologically inspired treatments from preclinical models to effective clinical treatments. We have studied human V1 to characterize the expression of neurobiological mechanisms that regulate visual perception and neuroplasticity. We have identified five stages of development for human V1 that start in infancy and continue across the life span. Here, we describe these stages, compare them with visual and anatomical milestones, and discuss implications for translating treatments for visual disorders that depend on neuroplasticity of V1 function. Keywords: development, human visual cortex, amblyopia, synaptic plasticity, glutamatergic, GABAergic, receptors
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Toxicology and clinical potential of nanoparticles
Yildirimer, Lara; Thanh, Nguyen T.K.; Loizidou, Marilena; Seifalian, Alexander M.
2011-01-01
Summary In recent years, nanoparticles (NPs) have increasingly found practical applications in technology, research and medicine. The small particle size coupled to their unique chemical and physical properties is thought to underlie their exploitable biomedical activities. Here, we review current toxicity studies of NPs with clinical potential. Mechanisms of cytotoxicity are discussed and the problem of extrapolating knowledge gained from cell-based studies into a human scenario is highlighted. The so-called ‘proof-of-principle’ approach, whereby ultra-high NP concentrations are used to ensure cytotoxicity, is evaluated on the basis of two considerations; firstly, from a scientific perspective, the concentrations used are in no way related to the actual doses required which, in many instances, discourages further vital investigations. Secondly, these inaccurate results cast doubt on the science of nanomedicine and thus, quite dangerously, encourage unnecessary alarm in the public. In this context, the discrepancies between in vitro and in vivo results are described along with the need for a unifying protocol for reliable and realistic toxicity reports. PMID:23293661
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Clinical Implication of Aortic Wall Biopsy in Aortic Valve Disease with Bicuspid Valve Pathology
Directory of Open Access Journals (Sweden)
Yong Han Kim
2016-12-01
Full Text Available Background: Although unique aortic pathology related to bicuspid aortic valve (BAV has been previously reported, clinical implications of BAV to aortopathy risk have yet to be investigated. We looked for potential differences in matrix protein expressions in the aortic wall in BAV patients. Methods: Aorta specimens were obtained from 31 patients: BAV group (n=27, tricuspid aortic valve (TAV group (n=4. The BAV group was categorized into three subgroups: left coronary sinus-right coronary sinus (R＋L group; n=13, 42%, right coronary sinus-non-coronary sinus (R＋N group; n=8, 26%, and anteroposterior (AP group; n=6, 19%. We analyzed the expression of endothelial nitric oxide synthase (eNOS, matrix metalloproteinase (MMP-9, and tissue inhibitor of matrix metalloproteinase (TIMP-2. Results: Based on the mean value of the control group, BAV group showed decreased expression of eNOS in 72.7% of patients, increased MMP-9 in 82.3%, and decreased TIMP in 79.2%. There was a higher tendency for aortopathy in the BAV group: eNOS (BAV:TAV= 53%±7%:57%±11%, MMP-9 (BAV:TAV=48%±10%:38%±1%. The AP group showed lower expression of eNOS than the fusion (R＋L, R＋N group did; 48%±5% vs. 55%±7% (p=0.081. Conclusion: Not all patients with BAV had expression of aortopathy; however, for patients who had a suspicious form of bicuspid valve, aortic wall biopsy could be valuable to signify the presence of aortopathy.
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The potential role for a pharmacist in a multidisciplinary general practitioner super clinic.
Bajorek, Beata; LeMay, Kate; Gunn, Kate; Armour, Carol
2015-01-01
The Australian government's General Practitioner (GP) super clinics programme aims to provide well-integrated, multidisciplinary, patient-centred care for people with chronic disease. However, there is no research into the current role of pharmacists in this setting. To explore the perspectives of GP super clinic staff on current and potential (future) pharmacist-led services provided in this setting. Individual interviews (facilitated using a semi-structured interview guide and thematically analysed) were conducted with purposively sampled staff of a GP super clinic in a semirural location in the state of New South Wales, until theme saturation. Participating staff included (n=9): three GPs, one pharmacist, one nurse, one business manager, and three reception staff. Three themes emerged conveying perspectives on: working relationships between staff; a pharmacist's current role; and potential future roles for a pharmacist. All clinic staff actively engaged the pharmacist in their "team approach". Currently established roles for home medicines reviews (HMRs) and drug information were well supported, but needed to be expanded, for example, with formalised case conferences between GPs, pharmacists, and other staff. New roles needed be explored in auditing medication use, optimising medication records, specialised drug information, dispensing, and prescribing. Although GPs had differing views about opportunities for pharmacists' prescribing in this setting, they saw several benefits to this service, such as reducing the time pressure on GPs to enable more effective consultations. Results suggest a pharmacist's services can potentially be better used within the multidisciplinary super clinic model of care to address current gaps within the semi-rural practice setting. Any future role for the pharmacist could be addressed as part of a formalised, strategic approach to creating an integrated healthcare team, with attention to funding and government legislation.
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LENUS (Irish Health Repository)
Abdul-Jalil, Khairun I
2014-08-01
Locally advanced rectal cancer (LARC: T3\\/4 and\\/or node-positive) is treated with preoperative\\/neoadjuvant chemoradiotherapy (CRT), but responses are not uniform. The phosphatidylinositol 3-kinase (PI3K), MAP kinase (MAPK), and related pathways are implicated in rectal cancer tumorigenesis. Here, we investigated the association between genetic mutations in these pathways and LARC clinical outcomes.
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The pathophysiology of migraine: implications for clinical management.
Charles, Andrew
2018-02-01
The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Roelants, Fabienne; Pospiech, Audrey; Momeni, Mona; Watremez, Christine
2016-01-01
The aim of this review is to summarize data published on the use of perioperative hypnosis in patients undergoing breast cancer surgery (BCS). Indeed, the majority of BCS patients experience stress, anxiety, nausea, vomiting, and pain. Correct management of the perioperative period and surgical removal of the primary tumor are clearly essential but can affect patients on different levels and hence have a negative impact on oncological outcomes. This review examines the effect of clinical hypnosis performed during the perioperative period. Thanks to its specific properties and techniques allowing it to be used as complementary treatment preoperatively, hypnosis has an impact most notably on distress and postoperative pain. During surgery, hypnosis may be applied to limit immunosuppression, while, in the postoperative period, it can reduce pain, anxiety, and fatigue and improve wound healing. Moreover, hypnosis is inexpensive, an important consideration given current financial concerns in healthcare. Of course, large randomized prospective studies are now needed to confirm the observed advantages of hypnosis in the field of oncology. PMID:27635132
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Potentially preventable infant and child deaths identified at autopsy; findings and implications.
Bamber, Andrew R; Mifsud, William; Wolfe, Ingrid; Cass, Hilary; Pryce, Jeremy; Malone, Marian; Sebire, Neil J
2015-09-01
The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.
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Stem Cell Research and Clinical Translation: A Roadmap about Good Clinical Practice and Patient Care
Directory of Open Access Journals (Sweden)
Paola Frati
2017-01-01
Full Text Available The latest research achievements in the field of stem cells led in 2016 to the publication of “Guidelines for Stem Cell Research and Clinical Translation” by the International Society for Stem Cell Research (ISSCR. Updating the topics covered in previous publications, the new recommendations offer interesting ethical and scientific insights. Under the common principles of research integrity, protection of patient’s welfare, respect for the research subjects, transparency and social justice, the centrality of good clinical practice, and informed consent in research and translational medicine is supported. The guidelines implement the abovementioned publications, requiring rigor in all areas of research, promoting the validity of the scientific activity results and emphasizing the need for an accurate and efficient public communication. This paper aims to analyze the aforementioned guidelines in order to provide a valid interpretive tool for experts. In particular, a research activity focused on the bioethical, scientific, and social implications of the new recommendations is carried out in order to provide food for thought. Finally, as an emerging issue of potential impact of current guidelines, an overview on implications of compensation for egg donation is offered.
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On the Science of Consciousness: Epistemological Reflections and Clinical Implications.
Facco, Enrico; Lucangeli, Daniela; Tressoldi, Patrizio
Consciousness has been one of the most important and tantalizing issues ever since the origin of philosophy and medicine. The concept of consciousness and the so-called "hard problem" (i.e., the mind-brain relationship) are highly complex topics that have yet to be elucidated, involving the realms of both science and philosophy with profound epistemological implications. In the lively debate on the foundations of the science of consciousness there are several potential biases of an essentially philosophical nature, such as those related to the paradigm and axioms adopted, and the ostensible logical contradiction between monism and dualism. Their origin dates back largely to Descartes' thinking and the birth of the new sciences as a compromise with the Inquisition, but they have been handed down through the Enlightenment and Positivism. A proper investigation of consciousness and the world of subjectivity demands a careful reflection on the paradigm of scientific medicine to identify possible flaws and overcome the limits of the mechanistic-reductionist approach. Copyright © 2017 Elsevier Inc. All rights reserved.
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Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.
Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy
2014-07-01
The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.
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Connolly, Angela
2015-04-01
When Jung introduced the concepts of synchronicity and the psychoid unconscious, he expanded analytical psychology into decidedly uncanny territory. Despite the early interest shown by Freud, anomalous phenomena such as telepathy have become a taboo subject in psychoanalysis. Today, however, there is an increasing interest in thought transference and synchronicity, thus opening the way for a fruitful exchange between different psychoanalytical schools on their clinical implications. I propose to examine some of the ambiguities of Jung's thinking, to clarify how we define synchronicity, the relationship between synchronicities and parapsychological events, and their clinical significance. At the present moment, we are still unsure if such events should be considered as normal and a way of facilitating individuation, or as an indication of psychopathology in the patient or in the analyst, just as we are uncertain about the particular characteristics of the intersubjective field that can lead to synchronicities. Making use of the typology of mind-matter correlations presented by Atmanspacher and Fach, and the distinction they draw between acategorial and non-categorial states of mind, I will use two clinical vignettes to illustrate the different states of mind in analyst and analysand that can lead to synchronicities. In particular I will focus on the relationship between analytical reverie and synchronicity. © 2015, The Society of Analytical Psychology.
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Immunosuppression by hypoxic cell radiosensitizers: a phenomenon of potential clinical importance
International Nuclear Information System (INIS)
Rockwell, S.; Kapp, D.S.
1982-01-01
The nitroimidazoles metronidazole, misonidazol, and desmethyl misonidazole are currently undergoing clinical trials as possible adjuncts to radiotherapy. Ongoing clinical trials are evaluating the effectiveness of these agents and also documenting the pharmacokinetics and toxicities of radiosensitizing doses of these drugs in man. A variety of toxic effects have been noted in man, including anorexia, nausea and vomiting, peripheral neuropathy, central nervous system symptoms, ototoxicity, allergy, and fear. Laboratory studies have also suggested that these agents have potential to be mutagenic, carcinogenic, and teratogenic. In the editorial presented, the author attempts to draw attention to an additional toxic effect of nitroimidazoles - the inhibition of cell-mediated immune responses
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Derendorf, H; Meltzer, E O
2008-10-01
Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.
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Dependence and caring in clinical communication: The relevance of attachment and other theories
Salmon, Peter; Young, Bridget
2009-01-01
Objective Clinical relationships are usually asymmetric, being defined by patients’ dependence and practitioners’ care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Methods Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Results Attachment theory helps to understand patients’ need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners’ caring. Different theories that formulate practitioners’ care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners’ emotions, values and sense of role in understanding their clinical communication. Conclusion Extending the theoretical grounding of clinical communication can accommodate patients’ dependence and practitioners’ caring without return to medical paternalism. Practice implications A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be. PMID:19157761
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Mammary Stem Cells and Breast Cancer Stem Cells: Molecular Connections and Clinical Implications.
Celià-Terrassa, Toni
2018-05-04
Cancer arises from subpopulations of transformed cells with high tumor initiation and repopulation ability, known as cancer stem cells (CSCs), which share many similarities with their normal counterparts. In the mammary gland, several studies have shown common molecular regulators between adult mammary stem cells (MaSCs) and breast cancer stem cells (bCSCs). Cell plasticity and self-renewal are essential abilities for MaSCs to maintain tissue homeostasis and regenerate the gland after pregnancy. Intriguingly, these properties are similarly executed in breast cancer stem cells to drive tumor initiation, tumor heterogeneity and recurrence after chemotherapy. In addition, both stem cell phenotypes are strongly influenced by external signals from the microenvironment, immune cells and supportive specific niches. This review focuses on the intrinsic and extrinsic connections of MaSC and bCSCs with clinical implications for breast cancer progression and their possible therapeutic applications.
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HIV-1 Genetic Variability in Cuba and Implications for Transmission and Clinical Progression.
Blanco, Madeline; Machado, Liuber Y; Díaz, Héctor; Ruiz, Nancy; Romay, Dania; Silva, Eladio
2015-10-01
INTRODUCTION Serological and molecular HIV-1 studies in Cuba have shown very low prevalence of seropositivity, but an increasing genetic diversity attributable to introduction of many HIV-1 variants from different areas, exchange of such variants among HIV-positive people with several coinciding routes of infection and other epidemiologic risk factors in the seropositive population. The high HIV-1 genetic variability observed in Cuba has possible implications for transmission and clinical progression. OBJECTIVE Study genetic variability for the HIV-1 env, gag and pol structural genes in Cuba; determine the prevalence of B and non-B subtypes according to epidemiologic and behavioral variables and determine whether a relationship exists between genetic variability and transmissibility, and between genetic variability and clinical disease progression in people living with HIV/AIDS. METHODS Using two molecular assays (heteroduplex mobility assay and nucleic acid sequencing), structural genes were characterized in 590 people with HIV-1 (480 men and 110 women), accounting for 3.4% of seropositive individuals in Cuba as of December 31, 2013. Nonrandom sampling, proportional to HIV prevalence by province, was conducted. Relationships between molecular results and viral factors, host characteristics, and patients' clinical, epidemiologic and behavioral variables were studied for molecular epidemiology, transmission, and progression analyses. RESULTS Molecular analysis of the three HIV-1 structural genes classified 297 samples as subtype B (50.3%), 269 as non-B subtypes (45.6%) and 24 were not typeable. Subtype B prevailed overall and in men, mainly in those who have sex with men. Non-B subtypes were prevalent in women and heterosexual men, showing multiple circulating variants and recombinant forms. Sexual transmission was the predominant form of infection for all. B and non-B subtypes were encountered throughout Cuba. No association was found between subtypes and
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The image schema and innate archetypes: theoretical and clinical implications.
Merchant, John
2016-02-01
Based in contemporary neuroscience, Jean Knox's 2004 JAP paper 'From archetypes to reflective function' honed her position on image schemas, thereby introducing a model for archetypes which sees them as 'reliably repeated early developmental achievements' and not as genetically inherited, innate psychic structures. The image schema model is used to illustrate how the analyst worked with a patient who began life as an unwanted pregnancy, was adopted at birth and as an adult experienced profound synchronicities, paranormal/telepathic phenomena and visions. The classical approach to such phenomena would see the intense affectivity arising out of a ruptured symbiotic mother-infant relationship constellating certain archetypes which set up the patient's visions. This view is contrasted with Knox's model which sees the archetype an sich as a developmentally produced image schema underpinning the emergence of later imagery. The patient's visions can then be understood to arise from his psychoid body memory related to his traumatic conception and birth. The contemporary neuroscience which supports this view is outlined and a subsequent image schema explanation is presented. Clinically, the case material suggests that a pre-birth perspective needs to be explored in all analytic work. Other implications of Knox's image schema model are summarized. © 2016, The Society of Analytical Psychology.
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Triñanes, Yolanda; González-Villar, Alberto; Gómez-Perretta, Claudio; Carrillo-de-la-Peña, María T
2014-11-01
The heterogeneity found in fibromyalgia (FM) patients has led to the investigation of disease subgroups, mainly based on clinical features. The aim of this study was to test the hypothesis that clinical FM subgroups are associated with different underlying pathophysiological mechanisms. Sixty-three FM patients were classified in type I or type II, according to the Fibromyalgia Impact Questionnaire (FIQ), and in mild/moderate versus severe FM, according to the severity of three cardinal symptoms considered in the American College of Rheumatology (ACR) 2010 criteria (unrefreshed sleep, cognitive problems and fatigue). To validate the subgroups obtained by these two classifications, we calculated the area under the receiver operating characteristic curves for various clinical variables and for two potential biomarkers of FM: Response to experimental pressure pain (algometry) and the amplitude/intensity slopes of the auditory evoked potentials (AEPs) obtained to stimuli of increasing intensity. The variables that best discriminated type I versus type II were those related to depression, while the indices of clinical or experimental pain (threshold or tolerance) did not significantly differ between them. The variables that best discriminated the mild/moderate versus severe subgroups were those related to the algometry. The AEPs did not allow discrimination among the generated subsets. The FIQ-based classification allows the identification of subgroups that differ in psychological distress, while the index based on the ACR 2010 criteria seems to be useful to characterize the severity of FM mainly based on hyperalgesia. The incorporation of potential biomarkers to generate or validate classification criteria is crucial to advance in the knowledge of FM and in the understanding of pathophysiological pathways.
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DEFF Research Database (Denmark)
Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg
2008-01-01
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease...... after resection of the primary tumour. Availability of validated biological markers for early detection, selection for adjuvant therapy, prediction of treatment efficacy and monitoring of treatment efficacy would most probably increase survival. Tissue inhibitor of metalloproteinases-1 (TIMP-1) may...... patients, suggesting that TIMP-1 could have a tumour-promoting function. Furthermore, measurement of plasma TIMP-1 has been shown to be useful for disease detection, with a high sensitivity and high specificity for early-stage colon cancer. This review describes some basic information on the current...
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Morphological and clinical aspects of the occurrence of accessory (multiple) renal arteries
Gulas, Ewelina; Wysiadecki, Grzegorz; Szymański, Jacek; Majos, Agata; Stefańczyk, Ludomir; Topol, Mirosław
2016-01-01
Renal vascularization variants vastly differ between individuals due to the very complex embryogenesis of the kidneys. Moreover, each variant may have implications for clinical and surgical interventions. The number of operating procedures continues to grow, and includes renal transplants, aneurysmorrhaphy and other vascular reconstructions. In any surgical technique, unawareness of the presence of multiple renal arteries may result in a fatal outcome, especially if laparoscopic methods are used. The aim of this review is to comprehensively identify the variation within multiple renal arteries and to highlight the connections between the presence of accessory renal arteries and the coexistence of other variants of vascularization. Another aim is to determine the potential clinical implications of the presence of accessory renal arteries. This study is of particular importance for surgeons, intervention radiologists, nephrologists and vascular surgeons. PMID:29593819
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Associated factors and clinical implications of serum aminotransferase elevation in scrub typhus.
Su, Tung-Hung; Liu, Chun-Jen; Shu, Pei-Yun; Fu, Yang-Hsien; Chang, Chi-Hsien; Jao, Ping; Kao, Jia-Horng
2016-12-01
Timely diagnosis and prompt treatment can reduce the complications of scrub typhus. It is thus important to find easy laboratory tests to help in the diagnosis, especially in patients without eschar at initial presentation. Because serum aminotransferase elevation is common in scrub typhus, its associated factors and clinical implications need further investigations. We conducted a retrospective study in Kinmen, Taiwan, to collect clinically suspected scrub typhus patients notified to Taiwan Centers for Disease Control for confirmation during 2005-2010. Scrub typhus was diagnosed and Orientia tsutsugamushi was genotyped by serological or molecular assays. The laboratory data and clinical information were recorded for analysis. Overall, 344 suspected scrub typhus patients were reported to Taiwan Centers for Disease Control and 288 of them were certified scrub typhus. Scrub typhus patients had significantly more thrombocytopenia, serum aminotransferase elevation (76% vs. 54%, p = 0.001), higher frequency of fever, eschar, and lymphadenopathy, compared with nontyphus patients. Hepatic dysfunction in scrub typhus was associated with older age, longer fever duration, and absence of lymphadenopathy, but seemed to be unrelated to the rickettsial genotypes. Multivariate analysis showed that serum aminotransferase elevation (odds ratio: 3.75; p = 0.003; 95% confidence interval: 1.56-9.01) independently predicted scrub typhus. Furthermore, in suspected scrub typhus patients without eschar, 92% of true typhus patients had serum aminotransferase elevation compared with the nontyphus ones (odds ratio: 6.47; p = 0.028, 95% confidence interval: 1.23-34.11). Hepatic dysfunction in scrub typhus patients is associated with older age, longer fever duration, and absence of lymphadenopathy. Serum aminotransferase elevation can aid in the diagnosis of scrub typhus, especially in suspected patients without eschar. Copyright © 2014. Published by Elsevier B.V.
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Clinical Implications of Human Population Differences in Genome-wide Rates of Functional Genotypes
Directory of Open Access Journals (Sweden)
Ali eTorkamani
2012-11-01
Full Text Available There have been a number of recent successes in the use of whole genome sequencing and sophisticated bioinformatics techniques to identify pathogenic DNA sequence variants responsible for individual idiopathic congenital conditions. However, the success of this identification process is heavily influenced by the ancestry or genetic background of a patient with an idiopathic condition. This is so because potential pathogenic variants in a patient’s genome must be contrasted with variants in a reference set of genomes made up of other individuals’ genomes of the same ancestry as the patient. We explored the effect of ignoring the ancestries of both an individual patient and the individuals used to construct reference genomes. We pursued this exploration in two major steps. We first considered variation in the per-genome number and rates likely functional derived (i.e., non-ancestral, based on the chimp genome single nucleotide variants and small indels in 52 individual whole human genomes sampled from 10 different global populations. We took advantage of a suite of computational and bioinformatics techniques to predict the functional effect of over 24 million genomic variants, both coding and non-coding, across these genomes. We found that the typical human genome harbors ~5.5-6.1 million total derived variants, of which ~12,000 are likely to have a functional effect (~5000 coding and ~7000 non-coding. We also found that the rates of functional genotypes per the total number of genotypes in individual whole genomes differ dramatically between human populations. We then created tables showing how the use of comparator or reference genome panels comprised of genomes from individuals that do not have the same ancestral background as a patient can negatively impact pathogenic variant identification. Our results have important implications for clinical sequencing initiatives.
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International Nuclear Information System (INIS)
Liu Chuanping; Luo Chunling; Gao Yun; Li Fangbai; Lin Lanwen; Wu Changan; Li Xiangdong
2010-01-01
In an extensive environmental study, field samples, including soil, water, rice, vegetable, fish, human hair and urine, were collected at an abandoned tungsten mine in Shantou City, southern China. Results showed that arsenic (As) concentration in agricultural soils ranged from 3.5 to 935 mg kg -1 with the mean value of 129 mg kg -1 . In addition, As concentration reached up to 325 μg L -1 in the groundwater, and the maximum As concentration in local food were 1.09, 2.38 and 0.60 mg kg -1 for brown rice, vegetable and fish samples, respectively, suggesting the local water resource and food have been severely contaminated with As. Health impact monitoring data revealed that As concentrations in hair and urine samples were up to 2.92 mg kg -1 and 164 μg L -1 , respectively, indicating a potential health risk among the local residents. Effective measurements should be implemented to protect the local community from the As contamination in the environment. - It is the first report on arsenic contamination and potential health risk implications at abandoned Lianhuashan tungsten mine.
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Dieng, Hamady; Saifur, Rahman G M; Hassan, Ahmad Abu; Salmah, M R Che; Boots, Michael; Satho, Tomomitsu; Jaal, Zairi; AbuBakar, Sazaly
2010-07-27
The mosquito Ae. albopictus is usually adapted to the peri-domestic environment and typically breeds outdoors. However, we observed its larvae in most containers within homes in northern peninsular Malaysia. To anticipate the epidemiological implications of this indoor-breeding, we assessed some fitness traits affecting vectorial capacity during colonization process. Specifically, we examined whether Ae. albopictus exhibits increased survival, gonotrophic activity and fecundity due to the potential increase in blood feeding opportunities. In a series of experiments involving outdoors and indoors breeding populations, we found that Ae. albopictus lives longer in the indoor environment. We also observed increased nighttime biting activity and lifetime fecundity in indoor/domestic adapted females, although they were similar to recently colonized females in body size. Taken together these data suggest that accommodation of Ae. albopictus to indoor/domestic environment may increase its lifespan, blood feeding success, nuisance and thus vectorial capacity (both in terms of increased vector-host contacts and vector population density). These changes in the breeding behavior of Ae. albopictus, a potential vector of several human pathogens including dengue viruses, require special attention.
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Gillespie, Mary
2010-11-01
Nurses' clinical decision-making is a complex process that holds potential to influence the quality of care provided and patient outcomes. The evolution of nurses' decision-making that occurs with experience has been well documented. In addition, literature includes numerous strategies and approaches purported to support development of nurses' clinical decision-making. There has been, however, significantly less attention given to the process of assessing nurses' clinical decision-making and novice clinical educators are often challenged with knowing how to best support nurses and nursing students in developing their clinical decision-making capacity. The Situated Clinical Decision-Making framework is presented for use by clinical educators: it provides a structured approach to analyzing nursing students' and novice nurses' decision-making in clinical nursing practice, assists educators in identifying specific issues within nurses' clinical decision-making, and guides selection of relevant strategies to support development of clinical decision-making. A series of questions is offered as a guide for clinical educators when assessing nurses' clinical decision-making. The discussion presents key considerations related to analysis of various decision-making components, including common sources of challenge and errors that may occur within nurses' clinical decision-making. An exemplar illustrates use of the framework and guiding questions. Implications of this approach for selection of strategies that support development of clinical decision-making are highlighted. Copyright © 2010 Elsevier Ltd. All rights reserved.
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Human iPS Cell-Derived Germ Cells: Current Status and Clinical Potential
Directory of Open Access Journals (Sweden)
Tetsuya Ishii
2014-10-01
Full Text Available Recently, fertile spermatozoa and oocytes were generated from mouse induced pluripotent (iPS cells using a combined in vitro and in vivo induction system. With regard to germ cell induction from human iPS cells, progress has been made particularly in the male germline, demonstrating in vitro generation of haploid, round spermatids. Although iPS-derived germ cells are expected to be developed to yield a form of assisted reproductive technology (ART that can address unmet reproductive needs, genetic and/or epigenetic instabilities abound in iPS cell generation and germ cell induction. In addition, there is still room to improve the induction protocol in the female germline. However, rapid advances in stem cell research are likely to make such obstacles surmountable, potentially translating induced germ cells into the clinical setting in the immediate future. This review examines the current status of the induction of germ cells from human iPS cells and discusses the clinical potential, as well as future directions.
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Hendriks, Saskia; Dondorp, Wybo; de Wert, Guido; Hamer, Geert; Repping, Sjoerd; Dancet, Eline A F
2015-01-01
Recent progress in the formation of artificial gametes, i.e. gametes generated from progenitors or somatic cells, has led to scientific and societal discussion about their use in medically assisted reproduction. In animals, live births have already been achieved using artificial gametes of varying (cell type) sources and biological research seems to be progressing steadily toward clinical application in humans. Artificial gametes could potentially help not only infertile heterosexual couples of reproductive age of which one or both partners lacks functional gametes, but also post-menopausal women and same-sex couples, to conceive a child who will be genetically related to them. But as clinical application of these new technologies may have wider societal consequences, a proactive consideration of the possible impact seems timely and important. This review aims to contribute to this by providing a systematic overview of the potential consequences of clinical application of artificial gametes anticipated by different stakeholders. The electronic database 'Medline/Pubmed' was systematically searched with medical subject heading terms (MesH) for articles published in English between January 1970 and December 2013. Articles were selected based on eligibility and reference lists of eligible studies were hand searched. The reported potential consequences of clinical application of artificial gametes were extracted from the articles and were grouped into categories by content analysis. Per category, we noted which stakeholders referred to which potential consequences, based on author affiliations and, if applicable, study participants. The systematic search yielded 2424 articles, and 84 studies were included after screening. Nine positive consequences, 21 specific consequences requiring consideration and 22 recommendations referring to clinical application of artificial gametes were documented. All positive consequences, consequences requiring consideration and
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Non-Invasive Prenatal Testing: Review of Ethical, Legal and Social Implications
Directory of Open Access Journals (Sweden)
Haidar, Hazar
2016-02-01
Full Text Available Non-invasive prenatal testing (NIPT using cell-free fetal DNA (cffDNA from maternal blood has recently entered clinical practice in many countries, including Canada. This test can be performed early during pregnancy to detect Down syndrome and other conditions. While NIPT promises numerous benefits, it also has challenging ethical, legal and social implications (ELSI. This paper reviews concerns currently found in the literature on the ELSI of NIPT. We make four observations. First, NIPT seems to exacerbate some of the already existing concerns raised by other prenatal tests (amniocentesis and maternal serum screening such as threats to women’s reproductive autonomy and the potential for discrimination and stigmatization of disabled individuals and their families. This may be due to the likely upcoming large scale implementation and routinization of NIPT. Second, the distinction between NIPT as a screening test (as it is currently recommended and as a diagnostic test (potentially in the future, has certain implications for the ELSI discussion. Third, we observed a progressive shift in the literature from initially including mostly conceptual analysis to an increasing number of empirical studies. This demonstrates the contribution of empirical bioethics approaches as the technology is being implemented into clinical use. Finally, we noted an increasing interest in equity and justice concerns regarding access to NIPT as it becomes more widely implemented.
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Hudson, Peter; Hudson, Rosalie; Philip, Jennifer; Boughey, Mark; Kelly, Brian; Hertogh, Cees
2015-10-01
Despite the availability of palliative care in many countries, legalization of euthanasia and physician-assisted suicide (EAS) continues to be debated-particularly around ethical and legal issues--and the surrounding controversy shows no signs of abating. Responding to EAS requests is considered one of the most difficult healthcare responsibilities. In the present paper, we highlight some of the less frequently discussed practical implications for palliative care provision if EAS were to be legalized. Our aim was not to take an explicit anti-EAS stance or expand on findings from systematic reviews or philosophical and ethico-legal treatises, but rather to offer clinical perspectives and the potential pragmatic implications of legalized EAS for palliative care provision, patients and families, healthcare professionals, and the broader community. We provide insights from our multidisciplinary clinical experience, coupled with those from various jurisdictions where EAS is, or has been, legalized. We believe that these issues, many of which are encountered at the bedside, must be considered in detail so that the pragmatic implications of EAS can be comprehensively considered. Increased resources and effort must be directed toward training, research, community engagement, and ensuring adequate resourcing for palliative care before further consideration is given to allocating resources for legalizing euthanasia and physician-assisted suicide.
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The clinical experiences of dyslexic healthcare students
Energy Technology Data Exchange (ETDEWEB)
Murphy, Fred [Directorate of Radiography, School of Health Care Professions, University of Salford, Allerton Building, Salford, Greater Manchester M6 6PU (United Kingdom)], E-mail: f.j.murphy@salford.ac.uk
2009-11-15
This paper reflects on the experiences of healthcare students with dyslexia in order to raise awareness of the potential challenges for dyslexic student radiographers and their clinical educators. With widening participation policies it is likely that the number of student radiographers with specific learning difficulties such as dyslexia will continue to increase. A review of the literature associated with dyslexia in healthcare education was performed in order to provide an overview of the current position. Although Higher Education Institutions (HEIs) have embraced the support and learning opportunities for dyslexic students at university, evidence would suggest that this is not reflected in the clinical departments. The current literature strongly suggests that since the risk of errors with clinical information is far more significant within the clinical placement, there is an immediate requirement for greater understanding, robust support and risk assessment systems. This review considers the problems experienced by dyslexic students, coping strategies they employ and the possible implications for clinical radiography education.
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The clinical experiences of dyslexic healthcare students
International Nuclear Information System (INIS)
Murphy, Fred
2009-01-01
This paper reflects on the experiences of healthcare students with dyslexia in order to raise awareness of the potential challenges for dyslexic student radiographers and their clinical educators. With widening participation policies it is likely that the number of student radiographers with specific learning difficulties such as dyslexia will continue to increase. A review of the literature associated with dyslexia in healthcare education was performed in order to provide an overview of the current position. Although Higher Education Institutions (HEIs) have embraced the support and learning opportunities for dyslexic students at university, evidence would suggest that this is not reflected in the clinical departments. The current literature strongly suggests that since the risk of errors with clinical information is far more significant within the clinical placement, there is an immediate requirement for greater understanding, robust support and risk assessment systems. This review considers the problems experienced by dyslexic students, coping strategies they employ and the possible implications for clinical radiography education.
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TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors
Energy Technology Data Exchange (ETDEWEB)
Das, I. [NYU Langone Medical Center, New York, NY (United States)
2016-06-15
Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803.
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TH-B-BRC-01: How to Identify and Resolve Potential Clinical Errors
International Nuclear Information System (INIS)
Das, I.
2016-01-01
Radiation treatment consists of a chain of events influenced by the quality of machine operation, beam data commissioning, machine calibration, patient specific data, simulation, treatment planning, imaging and treatment delivery. There is always a chance that the clinical medical physicist may make or fail to detect an error in one of the events that may impact on the patient’s treatment. In the clinical scenario, errors may be systematic and, without peer review, may have a low detectability because they are not part of routine QA procedures. During treatment, there might be errors on machine that needs attention. External reviews of some of the treatment delivery components by independent reviewers, like IROC, can detect errors, but may not be timely. The goal of this session is to help junior clinical physicists identify potential errors as well as the approach of quality assurance to perform a root cause analysis to find and eliminate an error and to continually monitor for errors. A compilation of potential errors will be presented by examples of the thought process required to spot the error and determine the root cause. Examples may include unusual machine operation, erratic electrometer reading, consistent lower electron output, variation in photon output, body parts inadvertently left in beam, unusual treatment plan, poor normalization, hot spots etc. Awareness of the possibility and detection of error in any link of the treatment process chain will help improve the safe and accurate delivery of radiation to patients. Four experts will discuss how to identify errors in four areas of clinical treatment. D. Followill, NIH grant CA 180803
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Marshall, Lynette C
2010-01-01
In discussing the potential implications of the attitudes of the registered nurse towards the work of caring for older people, it was helpful to highlight why this work is important, gain some understanding of quality care and how it can be facilitated or hindered. Patient centred care is essential as there is great diversity found amongst older people. It was found that attitudes held by registered nurses and students towards older people have a direct impact on the quality of care provided. Negative attitudes and stereotyping get in the way of quality care while positive attitudes enabled quality care. In identifying the factors that influence these attitudes, registered nurses can take on a leadership role in promoting positive attitudes and challenging negative attitudes towards the care of older people with the goal of providing patient centre care.
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Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela
2015-10-01
A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.
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Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine.
Kim, Nathaniel J; Harris, Alon; Gerber, Austin; Tobe, Leslie Abrams; Amireskandari, Annahita; Huck, Andrew; Siesky, Brent
2014-04-01
The purpose of this review is to discuss the evolution of nanotechnology and its potential diagnostic and therapeutic applications in the field of ophthalmology, particularly as it pertains to glaucoma. We reviewed literature using MEDLINE and PubMed databases with the following search terms: glaucoma, nanotechnology, nanomedicine, nanoparticles, ophthalmology and liposomes. We also reviewed pertinent references from articles found in this search. A brief history of nanotechnology and nanomedicine will be covered, followed by a discussion of the advantages and concerns of using this technology in the field of glaucoma. We will look at various studies concerning the development of nanomedicine, its potential applications in ocular drug delivery, diagnostic and imaging modalities and, surgical techniques. In particular, the challenges of assuring safety and efficacy of nanomedicine will be examined. We conclude that nanotechnology offers a novel approach to expanding diagnostic, imaging and surgical modalities in glaucoma and may contribute to the knowledge of disease pathogenesis at a molecular level. However, more research is needed to better elucidate the mechanism of cellular entry, the potential for nanoparticle cytotoxicity and the assurance of clinical efficacy.
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Overgeneral autobiographical memory bias in clinical and non-clinical voice hearers.
Jacobsen, Pamela; Peters, Emmanuelle; Ward, Thomas; Garety, Philippa A; Jackson, Mike; Chadwick, Paul
2018-03-14
Hearing voices can be a distressing and disabling experience for some, whilst it is a valued experience for others, so-called 'healthy voice-hearers'. Cognitive models of psychosis highlight the role of memory, appraisal and cognitive biases in determining emotional and behavioural responses to voices. A memory bias potentially associated with distressing voices is the overgeneral memory bias (OGM), namely the tendency to recall a summary of events rather than specific occasions. It may limit access to autobiographical information that could be helpful in re-appraising distressing experiences, including voices. We investigated the possible links between OGM and distressing voices in psychosis by comparing three groups: (1) clinical voice-hearers (N = 39), (2) non-clinical voice-hearers (N = 35) and (3) controls without voices (N = 77) on a standard version of the autobiographical memory test (AMT). Clinical and non-clinical voice-hearers also completed a newly adapted version of the task, designed to assess voices-related memories (vAMT). As hypothesised, the clinical group displayed an OGM bias by retrieving fewer specific autobiographical memories on the AMT compared with both the non-clinical and control groups, who did not differ from each other. The clinical group also showed an OGM bias in recall of voice-related memories on the vAMT, compared with the non-clinical group. Clinical voice-hearers display an OGM bias when compared with non-clinical voice-hearers on both general and voices-specific recall tasks. These findings have implications for the refinement and targeting of psychological interventions for psychosis.
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Potential Clinical and Economic Impact of Switching Branded Medications to Generics
Straka, Robert J.; Keohane, Denis J.; Liu, Larry Z.
2017-01-01
Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003–2013 using key words of “generic switching” or “substitution” was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases. PMID:26099048
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Clinical implications for Vascular Endothelial Growth Factor in the lung: friend or foe?
Directory of Open Access Journals (Sweden)
Gourgoulianis Konstantinos I
2006-10-01
Full Text Available Abstract Vascular endothelial growth factor (VEGF is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.
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Clinical Implications of Glucose Variability: Chronic Complications of Diabetes
Directory of Open Access Journals (Sweden)
Hye Seung Jung
2015-06-01
Full Text Available Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE. MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.
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The human gut microbiota and virome: Potential therapeutic implications.
Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio
2015-12-01
Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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Clinical implications of The Red Book.
Culliford, Penny
2012-09-01
This presentation stresses the uniqueness of both the therapist's and patient's personal experience in clinical work and relates this to the significance of The Red Book as Jung's personal odyssey and for me personally as an analyst. I consider The Red Book's enduring relevance alongside recent psychological theories, neuroscience and early mystical writings, and conclude with a clinical vignette of a patient's response to a piece of choral music and subsequent use of active imagination. © 2012, The Society of Analytical Psychology.
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Mechanisms of radiation interaction with DNA: Potential implications for radiation protection
International Nuclear Information System (INIS)
1988-01-01
The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base
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Mechanisms of radiation interaction with DNA: Potential implications for radiation protection
Energy Technology Data Exchange (ETDEWEB)
1988-01-01
The Office of Health and Environmental Research (OHER) of the US Department of Energy conducts a broad multidisciplinary research program which includes basic biophysics, biophysical chemistry, molecular and cellular biology as well as experimental animal studies and opportunistic human studies. This research is directed at understanding how low levels of radiation of various qualities produce the spectrum of biological effects that are seen for such exposures. This workshop was entitled ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection.'' It ws jointly sponsored by the Department of Energy and the Commission of European Communities. The aim of the workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection. The overview of research provided by this multidisciplinary group will be helpful to the Office in program planning. This report includes a summary of the presentations, extended abstracts, the meeting agenda, research recommendations, and a list of participants. Individual papers are processed separately for the data base.
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de Pablo, Oliver Valencia; Estevez, Roberto; Heilborn, Carlos; Cohenca, Nestor
2012-01-01
Root canal anatomy may present clinicians with a complex clinical challenge that requires diagnostic approaches, access modification, and clinical skills to successfully localize, negotiate, disinfect, and seal the root canal system. This article discusses the clinical implications of endodontic therapy on permanent mandibular first molars. The number of roots on the mandibular first molar is directly related to ethnicity. Canal morphology has a significant effect on treatment protocol: Mesial roots present two canals on a regular basis, adopting 2-2 and 2-1 as the most common configurations. A third canal is present in 2.6% of the population. The most common configuration in the distal root is type I (62.7%), followed by type II (14.5%) and type IV (12.4%). Diagnosis and treatment of complex root canal systems often require specialized training that may be beyond the scope of the average general practitioner. Access modifications are required to find extra roots and/or canals. The instrumentation of the third root requires a different access and small, flexible instruments, given the curvature that is usually present buccally in the apical third. The incidence of isthmuses is 55% in the mesial root and 20% in the distal root. This anatomical configuration should be taken into consideration during endodontic treatment as well as during periapical surgery.
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Can resistive breathing injure the lung? Implications for COPD exacerbations
Directory of Open Access Journals (Sweden)
Vassilakopoulos T
2016-09-01
Full Text Available Theodoros Vassilakopoulos, Dimitrios Toumpanakis Pulmonary and Critical Care Medicine, Medical School, National and Kapodistrian University of Athens, Greece Abstract: In obstructive lung diseases, airway inflammation leads to bronchospasm and thus resistive breathing, especially during exacerbations. This commentary discusses experimental evidence that resistive breathing per se (the mechanical stimulus in the absence of underlying airway inflammation leads to lung injury and inflammation (mechanotransduction. The potential implications of resistive breathing-induced mechanotrasduction in COPD exacerbations are presented along with the available clinical evidence. Keywords: resistive breathing, COPD, mechanotransduction, bronchoconstriction, inflammation
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Peselow, Eric D; Karamians, Reneh; Lord, Marie; Tobia, Gabriel; IsHak, Waguih William
2014-03-01
Clinician-rated measures are used in clinical trials and measurement-based clinical care settings to assess baseline symptoms and treatment outcomes of major depressive disorder (MDD), with a widely held dictum that they are sufficient in assessing the patient's clinical status. In this study, we examined clinician-rated measures of depressive and global symptom severity, obtained by interviewing patients as well as informants in an attempt to examine the potential difference or similarity between these two sources of information. The sample consisted of 89 treatment seeking, DSM-IV diagnosed MDD outpatients treated between 1995 and 2004. The clinician-rated measures used included the Montgomery Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI) for Severity. The scores of the clinician-rated measures collected from patients' interviews were compared with those collected from informants' interviews. Clinician-rated scores, collected by interviewing patients, were significantly higher and indicative of greater symptom severity when compared with those collected by interviewing informants. This was true for both the MADRS before (Ppractical in MDD clinical trials or everyday clinical care. The discrepancies observed between the clinician-rated scores obtained from patients and informants emphasize the importance of incorporating collateral information during the assessment and rating of depressive symptom severity in both clinical trials as well as in clinical practice.
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Beck, Olof; Olin, Anna-Carin; Mirgorodskaya, Ekaterina
2016-01-01
Exhaled breath contains nonvolatile substances that are part of aerosol particles of submicrometer size. These particles are formed and exhaled as a result of normal breathing and contain material from distal airways of the respiratory system. Exhaled breath can be used to monitor biomarkers of both endogenous and exogenous origin and constitutes an attractive specimen for medical investigations. This review summarizes the present status regarding potential biomarkers of nonvolatile compounds in exhaled breath. The field of exhaled breath condensate is briefly reviewed, together with more recent work on more selective collection procedures for exhaled particles. The relation of these particles to the surfactant in the terminal parts of the respiratory system is described. The literature on potential endogenous low molecular weight compounds as well as protein biomarkers is reviewed. The possibility to measure exposure to therapeutic and abused drugs is demonstrated. Finally, the potential future role and importance of mass spectrometry is discussed. Nonvolatile compounds exit the lung as aerosol particles that can be sampled easily and selectively. The clinical applications of potential biomarkers in exhaled breath comprise diagnosis of disease, monitoring of disease progress, monitoring of drug therapy, and toxicological investigations. © 2015 American Association for Clinical Chemistry.
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Courtney, Colleen M; Goodman, Samuel M; Nagy, Toni A; Levy, Max; Bhusal, Pallavi; Madinger, Nancy E; Detweiler, Corrella S; Nagpal, Prashant; Chatterjee, Anushree
2017-10-01
The rise of multidrug-resistant (MDR) bacteria is a growing concern to global health and is exacerbated by the lack of new antibiotics. To treat already pervasive MDR infections, new classes of antibiotics or antibiotic adjuvants are needed. Reactive oxygen species (ROS) have been shown to play a role during antibacterial action; however, it is not yet understood whether ROS contribute directly to or are an outcome of bacterial lethality caused by antibiotics. We show that a light-activated nanoparticle, designed to produce tunable flux of specific ROS, superoxide, potentiates the activity of antibiotics in clinical MDR isolates of Escherichia coli , Salmonella enterica , and Klebsiella pneumoniae . Despite the high degree of antibiotic resistance in these isolates, we observed a synergistic interaction between both bactericidal and bacteriostatic antibiotics with varied mechanisms of action and our superoxide-producing nanoparticles in more than 75% of combinations. As a result of this potentiation, the effective antibiotic concentration of the clinical isolates was reduced up to 1000-fold below their respective sensitive/resistant breakpoint. Further, superoxide-generating nanoparticles in combination with ciprofloxacin reduced bacterial load in epithelial cells infected with S. enterica serovar Typhimurium and increased Caenorhabditis elegans survival upon infection with S. enterica serovar Enteriditis, compared to antibiotic alone. This demonstration highlights the ability to engineer superoxide generation to potentiate antibiotic activity and combat highly drug-resistant bacterial pathogens.
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Directory of Open Access Journals (Sweden)
Hamady Dieng
Full Text Available BACKGROUND: The mosquito Ae. albopictus is usually adapted to the peri-domestic environment and typically breeds outdoors. However, we observed its larvae in most containers within homes in northern peninsular Malaysia. To anticipate the epidemiological implications of this indoor-breeding, we assessed some fitness traits affecting vectorial capacity during colonization process. Specifically, we examined whether Ae. albopictus exhibits increased survival, gonotrophic activity and fecundity due to the potential increase in blood feeding opportunities. METHODOLOGY/PRINCIPAL FINDINGS: In a series of experiments involving outdoors and indoors breeding populations, we found that Ae. albopictus lives longer in the indoor environment. We also observed increased nighttime biting activity and lifetime fecundity in indoor/domestic adapted females, although they were similar to recently colonized females in body size. CONCLUSION/SIGNIFICANCE: Taken together these data suggest that accommodation of Ae. albopictus to indoor/domestic environment may increase its lifespan, blood feeding success, nuisance and thus vectorial capacity (both in terms of increased vector-host contacts and vector population density. These changes in the breeding behavior of Ae. albopictus, a potential vector of several human pathogens including dengue viruses, require special attention.
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Application of the MALDI Biotyper to clinical microbiology: progress and potential.
Kostrzewa, Markus
2018-03-01
The introduction of the MALDI Biotyper in laboratories substantially changed microbiology practice, this has been called a revolution. The system accelerated diagnostic while costs were reduced and accuracy was increased. In just a few years MALDI-TOF MS became the first-line identification tool for microorganisms. Ten years after its introduction, more than 2000 MALDI Biotyper systems are installed in laboratories which are performing routine diagnostic, and the number is still increasing. Areas covered: This article summarises changes in clinical microbiology introduced by the MALDI Biotyper and its effects, as it has been published in peer reviewed articles found in PubMed. Further, the potential of novel developments to increase the value of the system is described. Expert commentary: The MALDI Biotyper has significantly improved clinical microbiology in the area of microorganism identification. Now new developments and applications, e.g. for typing and resistance testing, might further increase its value in clinical microbiology. The systems might get the central diagnostic analyser which is getting integrated into the widely automated microbiology laboratories of the future.
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Potential Impact on Clinical Decision Making via a Genome-Wide Expression Profiling: A Case Report
Directory of Open Access Journals (Sweden)
Hyun Kim
2016-11-01
Full Text Available Management of men with prostate cancer is fraught with uncertainty as physicians and patients balance efficacy with potential toxicity and diminished quality of life. Utilization of genomics as a prognostic biomarker has improved the informed decision-making process by enabling more rationale treatment choices. Recently investigations have begun to determine whether genomic information from tumor transcriptome data can be used to impact clinical decision-making beyond prognosis. Here we discuss the potential of genomics to alter management of a patient who presented with high-risk prostate adenocarcinoma. We suggest that this information help selecting patients for advanced imaging, chemotherapies, or clinical trial.
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Potential Immune Biomarkers in Diagnosis and Clinical Management for Systemic Lupus Erythematosus
Directory of Open Access Journals (Sweden)
Zecevic Lamija
2018-04-01
Full Text Available Background: There is still no reliable, specific biomarker for precision diagnosis and clinical monitoring of systemic lupus erythematosus. The aim of this study was to investigate the importance of the determination of immunofenotypic profiles (T, B lymphocytes and NK cells and serum cytokine concentrations (IL-17 and IFN-alpha as potential biomarkers for this disease.
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Bozzaro, Claudia; Schildmann, Jan
2018-04-21
Palliative sedation is an increasingly used and, simultaneously, challenging practice at the end of life. Many controversies associated with this therapy are rooted in implicit differences regarding the understanding of "suffering" as prerequisite for palliative sedation. The aim of this paper is to inform the current debates by a conceptual analysis of two different philosophical accounts of suffering, (1) the subjective and holistic concept and (2) the objective and gradual concept and by a clinical-ethical analysis of the implications of each account for decisions about palliative sedation. We will show that while the subjective and holistic account of suffering fits well with the holistic approach of palliative care, there are considerable challenges to justify limits to requests for palliative sedation. By contrast, the objective and gradual account fits well with the need for an objective basis for clinical decisions in the context of palliative sedation, but runs the risk of falling short when considering the individual and subjective experience of suffering at the end of life. We will conclude with a plea for the necessity of further combined conceptual and empirical research to develop a sound and feasible understanding of suffering which can contribute to consistent decision-making about palliative sedation. Copyright © 2018. Published by Elsevier Inc.
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Prions: Potential Threat to Mankind and Dental Implications
Directory of Open Access Journals (Sweden)
Ajay R Bhoosreddy
2010-01-01
Full Text Available Prion diseases are fatal, infectious, neurodegenerative disorders with special implications for infection control in the health care system. The causative agent is highly resistant to routine disinfection and sterilization processes and has been transmitted during health care interactions. Thus, it is important to use evidence gained through research and case reports to minimize risk of infection. There is no data suggesting that prions are transmitted easily during dental sittings but there remains a rare risk of such transmission if appropriate infection measures are not adhered to.
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Clinical and functional implications of a history of childhood ADHD in first-episode psychosis.
Rho, Aldanie; Traicu, Alexandru; Lepage, Martin; Iyer, Srividya N; Malla, Ashok; Joober, Ridha
2015-07-01
There is mounting evidence indicating that a childhood history of attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for psychotic disorders, including schizophrenia. However, the implications of such a history on the symptomatic and functional outcomes of patients with psychotic disorders are still not well documented. This study examined the prevalence of childhood ADHD in patients with first episode psychosis (FEP) consecutively admitted to a specialized early intervention clinic covering a well-defined catchment area, and compared patients with and without a history of childhood ADHD on socio-demographic, clinical, and functional outcomes over a six to twelve months period. Out of 179 patients with FEP, 27 (15%) were treated for ADHD during childhood, consistent with previous literature indicating an association between childhood ADHD and psychosis. FEP patients with childhood history of ADHD had lower academic achievement, earlier onset of psychosis, and higher rates of childhood conduct and learning disorder. While the two groups had similar scores on psychopathology and functioning at baseline, patients with childhood ADHD showed significantly less improvement in positive and negative symptoms, as well as social and occupational functioning. These results strongly indicate that a history of childhood ADHD in FEP is more frequent than that reported in the general population and predictive of poorer clinical response to treatment. This emphasizes the need for actively screening for a history of ADHD in FEP patients and for treatments that are tailored for these patients. Copyright © 2015 Elsevier B.V. All rights reserved.
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Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.
2013-01-01
Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223
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Electronic health record tools' support of nurses' clinical judgment and team communication.
Kossman, Susan P; Bonney, Leigh Ann; Kim, Myoung Jin
2013-11-01
Nurses need to quickly process information to form clinical judgments, communicate with the healthcare team, and guide optimal patient care. Electronic health records not only offer potential for enhanced care but also introduce unintended consequences through changes in workflow, clinical judgment, and communication. We investigated nurses' use of improvised (self-made) and electronic health record-generated cognitive artifacts on clinical judgment and team communication. Tanner's Clinical Judgment Model provided a framework and basis for questions in an online survey and focus group interviews. Findings indicated that (1) nurses rated self-made work lists and medication administration records highest for both clinical judgment and communication, (2) tools aided different dimensions of clinical judgment, and (3) interdisciplinary tools enhance team communication. Implications are that electronic health record tool redesign could better support nursing work.
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Kim, Dana; Kim, Young Sam; Shin, Dong Wun; Park, Chang Shin; Kang, Ju Hee
2016-10-01
No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.
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Leptin deficiency: clinical implications and opportunities for therapeutic interventions.
Blüher, Susan; Shah, Sunali; Mantzoros, Christos S
2009-10-01
The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.
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Epigenetic developmental programs and adipogenesis: implications for psychotropic induced obesity.
Chase, Kayla; Sharma, Rajiv P
2013-11-01
Psychotropic agents are notorious for their ability to increase fat mass in psychiatric patients. The two determinants of fat mass are the production of newly differentiated adipocytes (adipogenesis), and the volume of lipid accumulation. Epigenetic programs have a prominent role in cell fate commitments and differentiation required for adipogenesis. In parallel, epigenetic effects on energy metabolism are well supported by several genetic models. Consequently, a variety of psychotropics, often prescribed in combinations and for long periods, may utilize a common epigenetic effector path causing an increase in adipogenesis or reduction in energy metabolism. In particular, the recent discovery that G protein coupled signaling cascades can directly modify epigenetic regulatory enzymes implicates surface receptor activity by psychotropic medications. The potential therapeutic implications are also suggested by the effects of the clinically approved antidepressant tranylcypromine, also a histone demethylase inhibitor, which has impressive therapeutic effects on metabolism in the obese phenotype.
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Male Contraception: Research, New Methods, and Implications for Marginalized Populations.
Plana, Olivia
2017-07-01
The majority of research on contraception has focused on manipulating the female reproductive system. Recent studies have identified novel contraceptives for males, including hormonal- and nonhormonal-based therapeutics. Although these new contraceptives are still undergoing clinical trials, their development and potential future use in society necessitate serious consideration of their implications for reproductive health. Through my analysis of the research conducted on male contraception over time and the current therapeutics available, it is clear that male contraception has the potential to shift societal gender dynamics and provide males with greater control over their own reproduction. This article also identifies the implications of these novel contraceptives for marginalized populations, especially men of color and men of lower socioeconomic positions. To overcome barriers to contraception among these populations, public policy efforts are needed in order to motivate the development of programs that facilitate coverage of these new male contraceptives by health plans and to increase their availability to underserved communities. Health care providers will be responsible for educating patients about these novel male contraception options and the need to continue using existing methods (e.g., condoms) in order to prevent sexually transmitted infections. This article analyzes the research conducted on male contraception and identifies the implications of these novel therapeutics for marginalized groups of men in the United States to identify the interventions that will be necessary to help ensure that all men have access to these promising scientific innovations.
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Shneerson, Catherine; Windle, Richard; Cox, Karen
2013-01-01
To discover whether the provision of clinical trials information via a multi-media platform could better meet the needs, preferences and practices of potential cancer trial participants. A mixed qualitative and quantitative questionnaire was delivered to 72 participants from cancer support groups to elicit views on the provision and design features of multimedia resources in delivering clinical trials information. Perceived lack of information is an expressed barrier to clinical trials participation. Multimedia resources were viewed positively as a way to address this barrier by most potential clinical trials participants; in particular by helping to align information to individual needs, promote active engagement with information, and by allowing more control of the learning experience. Whilst text remained the most valued attribute of any resource, other highly rated attributes included the resource being simple to use, easily accessible, having a clear focus, incorporating examples and visual aids, and being interactive. Provision of support for the learning resource was also rated highly. As in other areas, such as education, multimedia resources may enhance the delivery and acceptance of information regarding clinical trials. Better alignment of information may have a positive impact on recruitment and retention into clinical trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Directory of Open Access Journals (Sweden)
Joshua D. Rosenblat
2017-10-01
Full Text Available Bipolar disorder (BD is strongly associated with immune dysfunction. Replicated epidemiological studies have demonstrated that BD has high rates of inflammatory medical comorbidities, including autoimmune disorders, chronic infections, cardiovascular disease and metabolic disorders. Cytokine studies have demonstrated that BD is associated with chronic low-grade inflammation with further increases in pro-inflammatory cytokine levels during mood episodes. Several mechanisms have been identified to explain the bidirectional relationship between BD and immune dysfunction. Key mechanisms include cytokine-induced monoamine changes, increased oxidative stress, pathological microglial over-activation, hypothalamic-pituitary-adrenal (HPA axis over-activation, alterations of the microbiome-gut-brain axis and sleep-related immune changes. The inflammatory-mood pathway presents several potential novel targets in the treatment of BD. Several proof-of-concept clinical trials have shown a positive effect of anti-inflammatory agents in the treatment of BD; however, further research is needed to determine the clinical utility of these treatments. Immune dysfunction is likely to only play a role in a subset of BD patients and as such, future clinical trials should also strive to identify which specific group(s of BD patients may benefit from anti-inflammatory treatments.
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Schimmack, Simon; Lawrence, Ben; Svejda, Bernhard; Alaimo, Daniele; Schmitz-Winnenthal, Hubertus; Fischer, Lars; Büchler, Markus W; Kidd, Mark; Modlin, Irvin
2012-05-15
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) exhibit widely divergent behavior, limited biologic information (apart from Ki-67) is available to characterize malignancy. Therefore, the identification of alternative biomarkers is a key unmet need. Given the role of internexin alpha (INA) in neuronal development, the authors assessed its function in neuroendocrine cell systems and the clinical implications of its expression as a GEP-NEN biomarker. Functional assays were undertaken to investigate the mechanistic role of INA in the pancreatic BON cell line. Expression levels of INA were investigated in 50 pancreatic NENs (43 primaries, 7 metastases), 43 small intestinal NENs (25 primaries, 18 metastases), normal pancreas (n = 10), small intestinal mucosa (n = 16), normal enterochromaffin (EC) cells (n = 9), mouse xenografts (n = 4) and NEN cell lines (n = 6) using quantitative polymerase chain reaction, Western blot, and immunostaining analyses. In BON cells, decreased levels of INA messenger RNA and protein were associated with the inhibition of both proliferation and mitogen-activated protein kinase (MAPK) signaling. INA was not expressed in normal neuroendocrine cells but was overexpressed (from 2-fold to 42-fold) in NEN cell lines and murine xenografts. In pancreatic NENs, INA was overexpressed compared with pancreatic adenocarcinomas and normal pancreas (27-fold [P = .0001], and 9-fold [P = .02], respectively). INA transcripts were correlated positively with Ki-67 (correlation coefficient [r] = 0.5; P biologic information relevant to delineation of both pancreatic NEN tumor phenotypes and clinical behavior. Copyright © 2011 American Cancer Society.
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Hager, Heather A; Sinasac, Sarah E; Gedalof, Ze'ev; Newman, Jonathan A
2014-01-01
In many regions, large proportions of the naturalized and invasive non-native floras were originally introduced deliberately by humans. Pest risk assessments are now used in many jurisdictions to regulate the importation of species and usually include an estimation of the potential distribution in the import area. Two species of Asian grass (Miscanthus sacchariflorus and M. sinensis) that were originally introduced to North America as ornamental plants have since escaped cultivation. These species and their hybrid offspring are now receiving attention for large-scale production as biofuel crops in North America and elsewhere. We evaluated their potential global climate suitability for cultivation and potential invasion using the niche model CLIMEX and evaluated the models' sensitivity to the parameter values. We then compared the sensitivity of projections of future climatically suitable area under two climate models and two emissions scenarios. The models indicate that the species have been introduced to most of the potential global climatically suitable areas in the northern but not the southern hemisphere. The more narrowly distributed species (M. sacchariflorus) is more sensitive to changes in model parameters, which could have implications for modelling species of conservation concern. Climate projections indicate likely contractions in potential range in the south, but expansions in the north, particularly in introduced areas where biomass production trials are under way. Climate sensitivity analysis shows that projections differ more between the selected climate change models than between the selected emissions scenarios. Local-scale assessments are required to overlay suitable habitat with climate projections to estimate areas of cultivation potential and invasion risk.
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Sexual Objectification of Women: Clinical Implications and Training Considerations
Szymanski, Dawn M.; Carr, Erika R.; Moffitt, Lauren B.
2011-01-01
This article focuses on the implications of theory and empirical research on the sexual objectification of women. Drawing largely from the American Psychological Association's 2007 "Guidelines for Psychological Practice With Girls and Women," the 2007 "Report of the American Psychological Association's Task Force on the Sexualization of Girls,"…
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Intraoperative radiotherapy in early stage breast cancer: potential indications and evidence to date
Kirby, A M
2015-01-01
Following early results of recent studies of intraoperative radiotherapy (IORT) in the adjuvant treatment of patients with early breast cancer, the clinical utility of IORT is a subject of much recent debate within the breast oncology community. This review describes the intraoperative techniques available, the potential indications and the evidence to date pertaining to local control and toxicity. We also discuss any implications for current practice and future research. PMID:25734489
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Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare
2010-01-01
Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.
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Top-down control of arousal and sleep: Fundamentals and clinical implications.
Krone, Lukas; Frase, Lukas; Piosczyk, Hannah; Selhausen, Peter; Zittel, Sulamith; Jahn, Friederike; Kuhn, Marion; Feige, Bernd; Mainberger, Florian; Klöppel, Stefan; Riemann, Dieter; Spiegelhalder, Kai; Baglioni, Chiara; Sterr, Annette; Nissen, Christoph
2017-02-01
Mammalian sleep emerges from attenuated activity in the ascending reticular arousal system (ARAS), the main arousal network of the brain. This system originates in the brainstem and activates the thalamus and cortex during wakefulness via a well-characterized 'bottom-up' pathway. Recent studies propose that a less investigated cortico-thalamic 'top-down' pathway also regulates sleep. The present work integrates the current evidence on sleep regulation with a focus on the 'top-down' pathway and explores the potential to translate this information into clinically relevant interventions. Specifically, we elaborate the concept that arousal and sleep continuity in humans can be modulated by non-invasive brain stimulation (NIBS) techniques that increase or decrease cortical excitability. Based on preclinical studies, the modulatory effects of the stimulation are thought to extend to subcortical arousal networks. Further exploration of the 'top-down' regulation of sleep and its modulation through non-invasive brain stimulation techniques may contribute to the development of novel treatments for clinical conditions of disrupted arousal and sleep, which are among the major health problems worldwide. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Patterson, Fiona; Zibarras, Lara Dawn
2017-05-01
The ability to innovate is an important requirement in many organisations. Despite this pressing need, few selection systems in healthcare focus on identifying the potential for creativity and innovation and so this area has been vastly under-researched. As a first step towards understanding how we might select for creativity and innovation, this paper explores the use of a trait-based measure of creativity and innovation potential, and evaluates its efficacy for use in selection for healthcare education. This study uses a sample of 188 postgraduate physicians applying for education and training in UK General Practice. Participants completed two questionnaires (a trait-based measure of creativity and innovation, and a measure of the Big Five personality dimensions) and were also rated by assessors on creative problem solving measured during a selection centre. In exploring the construct validity of the trait-based measure of creativity and innovation, our research clarifies the associations between personality, and creativity and innovation. In particular, our study highlights the importance of motivation in the creativity and innovation process. Results also suggest that Openness to Experience is positively related to creativity and innovation whereas some aspects of Conscientiousness are negatively associated with creativity and innovation. Results broadly support the utility of using a trait-based measure of creativity and innovation in healthcare selection processes, although practically this may be best delivered as part of an interview process, rather than as a screening tool. Findings are discussed in relation to broader implications for placing more priority on creativity and innovation as selection criteria within healthcare education and training in future.
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Clinical potential of meningioma genomic insights: a practical review for neurosurgeons.
Karsy, Michael; Azab, Mohammed A; Abou-Al-Shaar, Hussam; Guan, Jian; Eli, Ilyas; Jensen, Randy L; Ormond, D Ryan
2018-06-01
Meningiomas are among the most common intracranial pathological conditions, accounting for 36% of intracranial lesions treated by neurosurgeons. Although the majority of these lesions are benign, the classical categorization of tumors by histological type or World Health Organization (WHO) grade has not fully captured the potential for meningioma progression and recurrence. Many targeted treatments have failed to generate a long-lasting effect on these tumors. Recently, several seminal studies evaluating the genomics of intracranial meningiomas have rapidly changed the understanding of the disease. The importance of NF2 (neurofibromin 2), TRAF7 (tumor necrosis factor [TNF] receptor-associated factor 7), KLF4 (Kruppel-like factor 4), AKT1, SMO (smoothened), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), and POLR2 (RNA polymerase II subunit A) demonstrates that there are at least 6 distinct mutational classes of meningiomas. In addition, 6 methylation classes of meningioma have been appreciated, enabling improved prediction of prognosis compared with traditional WHO grades. Genomic studies have shed light on the nature of recurrent meningioma, distinct intracranial locations and mutational patterns, and a potential embryonic cancer stem cell-like origin. However, despite these exciting findings, the clinical relevance of these findings remains elusive. The authors review the key findings from recent genomic studies in meningiomas, specifically focusing on how these findings relate to clinical insights for the practicing neurosurgeon.
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ESWT for tendinopathy: technology and clinical implications.
van der Worp, Henk; van den Akker-Scheek, Inge; van Schie, Hans; Zwerver, Johannes
2013-06-01
The general consensus that tendinopathy, at least in the chronic stage, is mainly a degenerative condition and inflammation plays a minor role has led to a shift from treatments that target inflammation towards treatment options that promote regeneration. One of these treatments is extracorporeal shockwave therapy (ESWT), a physical therapy modality that uses pressure waves to treat tendinopathy. This review was undertaken to give an overview of the literature concerning this treatment, and special attention is given to the differences between focused and radial ESWT. A narrative description of wave characteristics, generation methods and in vitro effects of ESWT is given. The literature on ESWT as a treatment for one common tendinopathy, patellar tendinopathy, was systematically reviewed. Waves that are generated for focused and radial ESWT have very different physical characteristics. It is unclear how these characteristics are related to clinical effectiveness. Studies into the biological effects of ESWT have mainly used focused shockwave therapy, showing a number of effects of shockwaves on biological tissue. The systematic review of studies into the clinical effects of ESWT for patellar tendinopathy showed conflicting evidence for its effectiveness. Physical characteristics of focused and radial waves differ substantially, but effect on clinical effectiveness is unclear. Whereas in vitro studies often show the effects of ESWT on tendon tissue, results of clinical studies are inconsistent. Based on the review of the literature, suggestions are given for the use of ESWT in clinical practice regarding timing and treatment parameters.
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Mulvaney, Eamon P; Shilling, Christine; Eivers, Sarah B; Perry, Antoinette S; Bjartell, Anders; Kay, Elaine W; Watson, R William; Kinsella, B Therese
2016-11-08
The prostanoid thromboxane (TX)A2 plays a central role in haemostasis and is increasingly implicated in cancer progression. TXA2 signals through two T Prostanoid receptor (TP) isoforms termed TPα and TPβ, with both encoded by the TBXA2R gene. Despite exhibiting several functional and regulatory differences, the role of the individual TP isoforms in neoplastic diseases is largely unknown.This study evaluated expression of the TPα and TPβ isoforms in tumour microarrays of the benign prostate and different pathological (Gleason) grades of prostate cancer (PCa). Expression of TPβ was significantly increased in PCa relative to benign tissue and strongly correlated with increasing Gleason grade. Furthermore, higher TPβ expression was associated with increased risk of biochemical recurrence (BCR) and significantly shorter disease-free survival time in patients post-surgery. While TPα was more variably expressed than TPβ in PCa, increased/high TPα expression within the tumour also trended toward increased BCR and shorter disease-free survival time. Comparative genomic CpG DNA methylation analysis revealed substantial differences in the extent of methylation of the promoter regions of the TBXA2R that specifically regulate expression of TPα and TPβ, respectively, both in benign prostate and in clinically-derived tissue representative of precursor lesions and progressive stages of PCa. Collectively, TPα and TPβ expression is differentially regulated both in the benign and tumourigenic prostate, and coincides with clinical pathology and altered CpG methylation of the TBXA2R gene. Analysis of TPβ, or a combination of TPα/TPβ, expression levels may have significant clinical potential as a diagnostic biomarker and predictor of PCa disease recurrence.
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The implications and applications of nanotechnology in dentistry: A review.
AlKahtani, Rawan N
2018-04-01
The emerging science of nanotechnology, especially within the dental and medical fields, sparked a research interest in their potential applications and benefits in comparison to conventional materials used. Therefore, a better understanding of the science behind nanotechnology is essential to appreciate how these materials can be utilised in our daily practice. The present paper will help the reader understand nanoscience, and the benefits and limitations of nanotechnology by addressing its ethical, social, and health implications. Additionally, nano-applications in dental diagnostics, dental prevention, and in dental materials will be addressed, with examples of commercially available products and evidence on their clinical performance.
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Long-term potentiation and long-term depression: a clinical perspective
Directory of Open Access Journals (Sweden)
Timothy V.P. Bliss
2011-01-01
Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.
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Directory of Open Access Journals (Sweden)
Douglas W McMillin
Full Text Available Polo-like kinases (PLKs play an important role in cell cycle progression, checkpoint control and mitosis. The high mitotic index and chromosomal instability of advanced cancers suggest that PLK inhibitors may be an attractive therapeutic option for presently incurable advanced neoplasias with systemic involvement, such as multiple myeloma (MM. We studied the PLK 1, 2, 3 inhibitor BI 2536 and observed potent (IC50<40 nM and rapid (commitment to cell death <24 hrs in vitro activity against MM cells in isolation, as well as in vivo activity against a traditional subcutaneous xenograft mouse model. Tumor cells in MM patients, however, don't exist in isolation, but reside in and interact with the bone microenvironment. Therefore conventional in vitro and in vivo preclinical assays don't take into account how interactions between MM cells and the bone microenvironment can potentially confer drug resistance. To probe this question, we performed tumor cell compartment-specific bioluminescence imaging assays to compare the preclinical anti-MM activity of BI 2536 in vitro in the presence vs. absence of stromal cells or osteoclasts. We observed that the presence of these bone marrow non-malignant cells led to decreased anti-MM activity of BI 2536. We further validated these results in an orthotopic in vivo mouse model of diffuse MM bone lesions where tumor cells interact with non-malignant cells of the bone microenvironment. We again observed that BI 2536 had decreased activity in this in vivo model of tumor-bone microenvironment interactions highlighting that, despite BI 2536's promising activity in conventional assays, its lack of activity in microenvironmental models raises concerns for its clinical development for MM. More broadly, preclinical drug testing in the absence of relevant tumor microenvironment interactions may overestimate potential clinical activity, thus explaining at least in part the gap between preclinical vs. clinical efficacy in MM
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Miyake, Saori; Bargiel, Damian
2017-04-01
A growing bioeconomy and increased demand for biomass products on food, health, fibre, industrial products and energy require land resources for feedstock production. It has resulted in significant environmental and socio-economic challenges on a global scale. As a result, consideration of such effects of land use change (LUC) from biomass production (particularly for biofuel feedstock) has emerged as an important area of policy and research, and several potential solutions have been proposed to minimise such adverse LUC effects. One of these solutions is the use of lands that are not in production or not suitable for food crop production, such as 'marginal', 'degraded', 'abandoned' and 'surplus' agricultural lands for future biomass production. The terms referring to these lands are usually associated with the potential production of 'marginal crops', which can grow in marginal conditions (e.g. poor soil fertility, low rainfall, drought) without much water and agrochemical inputs. In our research, we referred to these lands as 'underutilised' agricultural land and attempted to define them for our case study areas located in Australia and Central and Eastern Europe (CEE). Our goal is to identify lands that can be used for future biomass production and to evaluate their environmental implications, particularly impacts related to biodiversity, water and soil at a landscape scale. The identification of these lands incorporates remote sensing and spatially explicit approaches. Our findings confirmed that there was no universal or single definition of the term 'underutilised' agricultural land as the definitions significantly vary by country and region depending not only on the biophysical environment but also political, institutional and socio-economic conditions. Moreover, our results highlighted that the environmental implications of production of biomass on 'underutilised' agricultural land for biomass production are highly controversial. Thus land use change
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Clinical implications of studies with MnDPDP in animal models of hepatic abnormalities
International Nuclear Information System (INIS)
Ni, Y.; Marchal, G.
1997-01-01
Mangafodipir trisodium (manganese dipyridoxal diphosphate or MnDPDP) has been introduced as a hepatobiliary MR contrast agent (Teslascan). It is potential to assist in the characterisation of focal liver lesions, the diagnosis of local and global obstructive cholestasis and the evaluation of hepatic function in diffuse liver diseases has been explored in multiple pre-clinical experiments with appropriate animal models. The prompt negative contrast enhancement and delayed pertumoural rim-enhancement seen after i.v. injection of MnDPDP are 2 typical features of primary and secondary liver tumours with high malignancy, while the persistent positive enhancement is a sign of liver tumours of well preserved hepatocitic nature. Liver with local and total biliary obstruction can be visualized in MnDPDP-enhanced MR images as a region with prolonged signal enhancement. This agent could also be used to non-invasively evaluate diffuse liver diseases of different causes. In the present paper, we review the experimental data in the literature, provide some unpublished results and discuss the potential impact on the clinical use of MnDPDP in the liver. We conclude that MnDPDP is a promising MR liver contrast agent for the detection and characterisation of focal and diffuse liver diseases. (orig.)
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Potential clinical and economic effects of homocyst(e)ine lowering.
Nallamothu, B K; Fendrick, A M; Rubenfire, M; Saint, S; Bandekar, R R; Omenn, G S
Elevated total homocyst(e)ine levels (>/=11 micromol/L) have been identified as a potential risk factor for coronary heart disease. However, the benefits expected from lowering homocyst(e)ine levels with folic acid and vitamin B(12) supplementation have yet to be demonstrated in clinical trials. We constructed a decision analytic model to estimate the clinical benefits and economic costs of 2 homocyst(e)ine-lowering strategies: (1) "treat all"-no screening, daily supplementation with folic acid (400 microg) and vitamin B(12) (cyanocobalamin; 500 microg) for all; (2) "screen and treat"-screening, followed by daily supplementation with folic acid and vitamin B(12) for individuals with elevated homocyst(e)ine levels. Simulated cohorts of 40-year-old men and 50-year-old women in the general population were evaluated. In the base-case analysis, we assumed that lowering elevated levels would reduce excess coronary heart disease risk by 40%; however, this assumption and others were evaluated across a broad range of potential values using sensitivity analysis. Primary outcomes were discounted costs per life-year saved. Although the treat-all strategy was slightly more effective overall, the screen and treat strategy resulted in a much lower cost per life-year saved ($13,600 in men and $27,500 in women) when compared with no intervention. Incremental cost-effectiveness ratios for the treat-all strategy compared with the screen and treat strategy were more than $500,000 per life-year saved in both cohorts. Sensitivity analysis showed that cost-effectiveness ratios for the screen and treat strategy remained less than $50,000 per life-year saved under several unfavorable scenarios, such as when effective homocyst(e)ine lowering was assumed to reduce the relative risk of coronary heart disease-related death by only 11% in men or 23% in women. Homocyst(e)ine lowering with folic acid and vitamin B(12) supplementation could result in substantial clinical benefits at reasonable
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Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya
2012-06-01
The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.
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International Nuclear Information System (INIS)
Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng
2011-01-01
There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity
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Energy Technology Data Exchange (ETDEWEB)
Mendenhall, Nancy P.; Malyapa, Robert S.; Su, Zhong; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng (Univ. of Florida Proton Therapy Inst., Jacksonville, Florida (United States)), e-mail: menden@shands.ufl.edu
2011-08-15
There is a strong rationale for potential benefits from proton therapy (PT) for selected cancers of the head and neck because of the opportunity to improve the therapeutic ratio by improving radiation dose distributions and because of the significant differences in radiation dose distribution achievable with x-ray-based radiation therapy (RT) and PT. Comparisons of dose distributions between x-ray-based and PT plans in selected cases show specific benefits in dose distribution likely to translate into improved clinical outcomes. However, the use of PT in head and neck cancers requires special considerations in the simulation and treatment planning process, and currently available PT technology may not permit realization of the maximum potential benefits of PT. To date, few clinical data are available, but early clinical experiences in sinonasal tumors in particular suggest significant improvements in both disease control and radiation-related toxicity
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Bhaskar, Vaishnavi; Chan, Hsun-Liang; MacEachern, Mark; Kripfgans, Oliver D
2018-05-23
Ultrasonography has shown promising diagnostic value in dental implant imaging research; however, exactly how ultrasound was used and at what stage of implant therapy it can be applied has not been systematically evaluated. Therefore, the aim of this review is to investigate potential indications of ultrasound use in the three implant treatment phases, namely planning, intraoperative and postoperative phase. Eligible manuscripts were searched in major databases with a combination of key words related to the use of ultrasound imaging in implant therapy. An initial search yielded 414 articles, after further review, 28 articles were finally included for this systematic review. Ultrasound was found valuable, though at various development stages, for evaluating (1) soft tissues, (2) hard tissues (3) vital structures and (4) implant stability. B-mode, the main function to image anatomical structures of interest, has been evaluated in pre-clinical and clinical studies. Quantitative ultrasound parameters, e.g. sound speed and amplitude, are being developed to evaluate implant-bone stability, mainly in simulation and pre-clinical studies. Ultrasound could be potentially useful in all 3 treatment phases. In the planning phase, ultrasound could evaluate vital structures, tissue biotype, ridge width/density, and cortical bone thickness. During surgery, it can provide feedback by identifying vital structures and bone boundary. At follow-up visits, it could evaluate marginal bone level and implant stability. Understanding the current status of ultrasound imaging research for implant therapy would be extremely beneficial for accelerating translational research and its use in dental clinics.
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Nuclear energy: potentiality and implications
International Nuclear Information System (INIS)
Bahgat, Gawdat
2008-01-01
After a discussion about a broad definition of energy security and about the main challenges facing a potential nuclear renaissance, the article analyses how the European Union and the United States have addressed these challenges. There is no doubt that nuclear power will remain an important component of global energy mix, but it should not be seen as a panacea to the flows in the global energy markets [it
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Directory of Open Access Journals (Sweden)
José Humberto Tavares Guerreiro Fregnani
Full Text Available CONTEXT: The musculocutaneous nerve is one of the terminal branches of the lateral fasciculus of the brachial plexus, and is responsible for innervation of the flexor musculature of the elbow and for skin sensitivity on the lateral surface of the forearm. Its absence has been described previously, but its real prevalence is unknown. CASE REPORT: A case of absence of the musculocutaneous nerve that was observed during the dissection of the right arm of a male cadaver is described. The area of innervation was supplied by the median nerve. From this, three branches emerged: one to the coracobrachialis muscle, another to the biceps brachii muscle and the third to the brachialis muscle. This last branch continued as a lateral antebrachial cutaneous nerve. This is an anatomical variation that has clinical-surgical implications, considering that injury to the median nerve in this case would have caused unexpected paralysis of the flexor musculature of the elbow and hypoesthesia of the lateral surface of the forearm.
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Mesenchymal stem cells: biological characteristics and potential clinical applications
DEFF Research Database (Denmark)
Kassem, Moustapha
2004-01-01
are among the first stem cell types to be introduced in the clinic. Several studies have demonstrated the possible use of MSC in systemic transplantation for systemic diseases, local implantation for local tissue defects, as a vehicle for genes in gene therapy protocols or to generate transplantable tissues...... and organs in tissue engineering protocols. Before their widespread use in therapy, methods allowing the generation of large number of cells without affecting their differentiation potential as well as technologies that overcome immunological rejection (in case allogenic transplantation) must be developed.......Mesenchymal stem cells (MSC) are clonogenic, non-hematpoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages, for example, osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages, for example, neuronal...
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A clinically feasible method for the detection of potential collision in proton therapy
Energy Technology Data Exchange (ETDEWEB)
Zou Wei; Lin Haibo; Plastaras, John P.; Wang Huanshu; Bui, Viet; Vapiwala, Neha; McDonough, James; Tochner, Zelig; Both, Stefan [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States) and Department of Mechanical Engineering, Drexel University, Philadelphia, Pennsylvania 19104 (United States); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104 (United States)
2012-11-15
Purpose: Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient-machine collisions using patient treatment plan data. Methods: The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patient's CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces. Results: Twenty-four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors' clinic to detect patient-gantry or gantry-couch collisions in the treatment planning
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Clinical implications of the recent homeopathic medicine and its application to oriental medicine
Directory of Open Access Journals (Sweden)
Ok-Byung,Choi
2007-02-01
Full Text Available Objectives : The purpose of this study is to analyze the practical implications of homeopathic medicines, their status, their preparation systems and registration rules, recognized by the European Union and other countries. Contents : This paper covers the background of homeopathic medical principle, homeopathy throughout the world, the medicine status and clinical research, increases of the drug potency, the practical regulation of treatment, preparation techniques of homeopathic drugs and registration rules and the clinical practice. Homeopathy has been currently practised in over eighty countries throughout the world, especially in Europe. It had attracted considerable attentions in South and North America (notably in USA, Brazil, and Argentina, India and Pakistan. Although it is not dominantly popular in North America, constant growth has been nevertheless noted. Over the last thirty years, homeopathy has also developed or appeared in South Africa, Tunisia, Morocco, Venezuela, Israel, and Australia, etc. Result & suggestion : As over 300 million patients have put their trust in homeopathy, the study of the integration of homeopathy to oriental medicine, its development and feasibility in Korea are urgently needed. The products, substances, compositions of Homeopathic drugs are very similar to those of oriental medicine theory. Therefore their preparations and applications should prescribed and practised exclusively by oriental doctors. Applying the homeopathic theory and its preparation techniques to oriental medicine, the herbal acupuncture preparation should be modernized and various oriental products are to be developed. To this end, government and herbal acupuncture society need to interact each other for the development of oriental medicine.
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Sacroiliac Pain: A Clinical Approach for the Neurosurgeon
Moscote-Salazar, Luis Rafael; Alvis-Miranda, Hernando Raphael; Joaquim, Andrei Fernandes; Amaya-Quintero, Jessica; Padilla-Zambrano, Huber S.; Agrawal, Amit
2017-01-01
Pain originating from sacroiliac joint may also cause pain in the lumbar and gluteal region in 15% of the population. The clinical manifestation represents a public health problem due to the great implications on the quality of life and health-related costs. However, this is a diagnosis that is usually ignored in the general clinical practice; probably because of the unknown etiology, making harder to rule out the potential etiologies of this pathology, or maybe because the clinical criteria that support this pathology are unknown. By describing several diagnostic techniques, many authors have studied the prevalence of this pathology, finding more positive data than expected; coming to the conclusion that even though there is no diagnostic gold standard yet, an important amount of cases might be detected by properly applying several tests at the physical examination. Thus, it is necessary to have knowledge of the physiopathology and clinical presentation so that diagnosis can be made to those patients that manifest this problem. We present a clinical approach for the neurosurgeon. PMID:29204025
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Sacroiliac pain: A clinical approach for the neurosurgeon
Directory of Open Access Journals (Sweden)
Luis Rafael Moscote-Salazar
2017-01-01
Full Text Available Pain originating from sacroiliac joint may also cause pain in the lumbar and gluteal region in 15% of the population. The clinical manifestation represents a public health problem due to the great implications on the quality of life and health-related costs. However, this is a diagnosis that is usually ignored in the general clinical practice; probably because of the unknown etiology, making harder to rule out the potential etiologies of this pathology, or maybe because the clinical criteria that support this pathology are unknown. By describing several diagnostic techniques, many authors have studied the prevalence of this pathology, finding more positive data than expected; coming to the conclusion that even though there is no diagnostic gold standard yet, an important amount of cases might be detected by properly applying several tests at the physical examination. Thus, it is necessary to have knowledge of the physiopathology and clinical presentation so that diagnosis can be made to those patients that manifest this problem. We present a clinical approach for the neurosurgeon.
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Differential expression of CD10 in prostate cancer and its clinical implication
Dall'Era, Marc A; True, Lawrence D; Siegel, Andrew F; Porter, Michael P; Sherertz, Tracy M; Liu, Alvin Y
2007-01-01
Background CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis. Methods Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP), were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions. Results CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08–10.75, P = 0.019). Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters. Conclusion These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10 offers potential clinical
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Differential expression of CD10 in prostate cancer and its clinical implication
Directory of Open Access Journals (Sweden)
Porter Michael P
2007-03-01
Full Text Available Abstract Background CD10 is a transmembrane metallo-endopeptidase that cleaves and inactivates a variety of peptide growth factors. Loss of CD10 expression is a common, early event in human prostate cancer; however, CD10 positive cancer cells frequently appear in lymph node metastasis. We hypothesize that prostate tumors expressing high levels of CD10 have a more aggressive biology with an early propensity towards lymph node metastasis. Methods Eighty-seven patients, 53 with and 34 without pathologically organ confined prostate cancer at the time of radical prostatectomy (RP, were used for the study. Fourteen patients with lymph node metastasis found at the time of surgery were identified and included in this study. Serial sections from available frozen tumor specimens in OCT were processed for CD10 immunohistochemistry. Cancer glands were graded for the presence and intensity of CD10 staining, and overall percentage of glands staining positive was estimated. Clinical characteristics including pre- and post-operative PSA and Gleason score were obtained. A similar study as a control for the statistical analysis was performed with CD13 staining. For statistical analysis, strong staining was defined as > 20% positivity based on the observed maximum separation of the cumulative distributions. Results CD10 expression significantly correlated with Gleason grade, tumor stage, and with pre-operative serum PSA. Seventy percent of RP specimens from patients with node metastasis showed strong staining for CD10, compared to 30% in the entire cohort (OR = 3.4, 95% CI: 1.08–10.75, P = 0.019. Increased staining for CD10 was associated with PSA recurrence after RP. CD13 staining did not correlate significantly with any of these same clinical parameters. Conclusion These results suggest that the expression of CD10 by prostate cancer corresponds to a more aggressive phenotype with a higher malignant potential, described histologically by the Gleason score. CD10
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Metabolic fuel and clinical implications for female reproduction.
Mircea, Carmen N; Lujan, Marla E; Pierson, Roger A
2007-11-01
Reproduction is a physiologically costly process that consumes significant amounts of energy. The physiological mechanisms controlling energy balance are closely linked to fertility. This close relationship ensures that pregnancy and lactation occur only in favourable conditions with respect to energy. The primary metabolic cue that modulates reproduction is the availability of oxidizable fuel. An organism's metabolic status is transmitted to the brain through metabolic fuel detectors. There are many of these detectors at both the peripheral (e.g., leptin, insulin, ghrelin) and central (e.g., neuropeptide Y, melanocortin, orexins) levels. When oxidizable fuel is scarce, the detectors function to inhibit the release of gonadotropin-releasing hormone and luteinizing hormone, thereby altering steroidogenesis, reproductive cyclicity, and sexual behaviour. Infertility can also result when resources are abundant but food intake fails to compensate for increased energy demands. Examples of these conditions in women include anorexia nervosa and exercise-induced amenorrhea. Infertility associated with obesity appears to be less related to an effect of oxidizable fuel on the hypothalamic-pituitary-ovarian axis. Impaired insulin sensitivity may play a role in the etiology of these conditions, but their specific etiology remains unresolved. Research into the metabolic regulation of reproductive function has implications for elucidating mechanisms of impaired pubertal development, nutritional amenorrhea, and obesity-related infertility. A better understanding of these etiologies has far-reaching implications for the prevention and management of reproductive dysfunction and its associated comorbidities.
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Knowledge and Awareness Implication on E-Waste Management ...
African Journals Online (AJOL)
Knowledge and Awareness Implication on E-Waste Management among ... and Awareness Implication on E-Waste Management among Nigerian Collegiate ... with e-waste may pose potential threat to human health and the environment.
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Dietzel, Matthias; Hopp, Torsten; Ruiter, Nicole V; Kaiser, Clemens G; Kaiser, Werner A; Baltzer, Pascal A
2015-01-01
4D co-registration of X-ray- and MR-mammograms (XM and MM) is a new method of image fusion. The present study aims to evaluate its clinical feasibility, radiological accuracy, and potential clinical value. XM and MM of 25 patients were co-registered. Results were evaluated by a blinded reader. Precision of the 4D co-registration was "very good" (mean-score [ms]=7), and lesions were "easier to delineate" (ms=5). In 88.8%, "relevant additional diagnostic information" was present, accounting for a more "confident diagnosis" in 76% (ms=5). 4D co-registration is feasible, accurate, and of potential clinical value. Copyright © 2015 Elsevier Inc. All rights reserved.
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Balderson, Michael J; Kirkby, Charles
2015-01-01
In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. In terms of
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The changing face of Usher syndrome: clinical implications.
Cohen, Mazal; Bitner-Glindzicz, Maria; Luxon, Linda
2007-02-01
Usher syndrome is both genetically and phenotypically heterogeneous. Traditionally, the condition has been classified into three clinical types, differentiated by the severity and progression of the hearing impairment and by the presence or absence of vestibular symptoms. Recent advances in molecular genetics have enabled researchers to study the phenotypic expression in confirmed molecular groups of Usher. In response to the expansion of clinical and genetic information on Usher, we report an up to date review of the different clinical forms of Usher in known molecular groups and use the emerging evidence to appraise the diagnostic utility of the traditional classification of Usher. Our findings undermine the traditional view that the clinical types of Usher have distinct genetic causes. The pleiotropic effects of some of the major causes of Usher lead to considerable overlap between the different clinical types, with very little evidence for phenotypic-genotypic correlations. The novel synthesis emerging from this review suggests more productive approaches to the diagnosis of Usher in hearing-impaired children which would provide more accurate prognostic information to families.
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Genital piercings: diagnostic and therapeutic implications for urologists.
Nelius, Thomas; Armstrong, Myrna L; Rinard, Katherine; Young, Cathy; Hogan, LaMicha; Angel, Elayne
2011-11-01
To provide quantitative and qualitative data that will assist evidence-based decision making for men and women with genital piercings (GP) when they present to urologists in ambulatory clinics or office settings. Currently many persons with GP seek nonmedical advice. A comprehensive 35-year (1975-2010) longitudinal electronic literature search (MEDLINE, EMBASE, CINAHL, OVID) was conducted for all relevant articles discussing GP. Authors of general body art literature tended to project many GP complications with potential statements of concern, drawing in overall piercings problems; then the information was further replicated. Few studies regarding GP clinical implications were located and more GP assumptions were noted. Only 17 cases, over 17 years, describe specific complications in the peer-reviewed literature, mainly from international sources (75%), and mostly with "Prince Albert" piercings (65%). Three cross-sectional studies provided further self-reported data. Persons with GP still remain a hidden variable so no baseline figures assess the overall GP picture, but this review did gather more evidence about GP wearers and should stimulate further research, rather than collectively projecting general body piercing information onto those with GP. With an increase in GP, urologists need to know the specific differences, medical implications, significant short- and long-term health risks, and patients concerns to treat and counsel patients in a culturally sensitive manner. Targeted educational strategies should be developed. Considering the amount of body modification, including GP, better legislation for public safety is overdue. Copyright © 2011 Elsevier Inc. All rights reserved.
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Clinical diagnostic potentials of thyroid ultrasonography and scintigraphy; An evaluation
Energy Technology Data Exchange (ETDEWEB)
Torizuka, Tatsuo; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Konishi, Junji (Kyoto Univ. (Japan). Hospital); Endo, Keigo
1993-06-01
This prospective study was designed to evaluate the potential contributions of high resolution ultrasonography (US) and Tc-99m scintigraphy in the routine diagnosis of thyroid disease. The diagnostic impacts of US and Tc-99m scintigraphy results in 177 patients visiting our thyroid clinic were assessed and scored according to the following criteria: when the information provided by either test supported, confirmed or changed the initial clinical diagnosis, they received scores of 2, 3 and 4 respectively, while score 1 was given when the test itself was useless for the differential diagnosis. US identified focal lesions that both palpation and scintigraphy had failed to detect in 14 (12.1%) of 116 patients with diffuse thyroid diseases, suggesting the necessity of Hashimoto's thyroiditis, adenoma, adenocarcinoma and adenomatous goiter, and vice versa in the diagnosis of hyperthyroid and euthyroid Graves's diseases. Thus, the advantages of US over scintigraphy for morphological evaluation were confirmed. US was particularly useful for the differential diagnosis of adenomatous goiter from Hashimoto's thyroiditis or a single nodular disease. In contrast, scintigraphy gave functional images, being especially helpful for the differential diagnosis of thyrotoxicosis. (author).
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Martínez-Múgica, Cristina
2015-12-01
Polypharmacy is a growing problem nowadays, which can increase the risk of potential drug interactions, and result in a loss of effectiveness. This is particularly relevant to the anti-infective therapy, especially when infection is produced by resistant bacteria, because therapeutic options are limited and interactions can cause treatment failure. All antimicrobial prescriptions were retrospectively reviewed during a week in the Pharmacy Department, in order to detect potential drug-interactions and analysing their clinical significance. A total of 314 antimicrobial prescriptions from 151 patients were checked. There was at least one potential interaction detected in 40% of patients, being more frequent and severe in those infected with multidrug-resistant microorganisms. Drugs most commonly involved were quinolones, azoles, linezolid and vancomycin. Potential drug interactions with antimicrobial agents are a frequent problem that can result in a loss of effectiveness. This is why they should be detected and avoided when possible, in order to optimize antimicrobial therapy, especially in case of multidrug resistant infections.
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Diagnostic accuracy of clinical and blood examination for sepsis in potentially infected neonates
Directory of Open Access Journals (Sweden)
Ari Mulyani
2006-10-01
Full Text Available Background Neonatal sepsis remains a diagnostic challenge due to its nonspesific symptoms and signs. Blood culture as the gold standard is still a problem because it takes time, is expensive, and not every health facility is able to perionn. Objective To evaluate the diagnostic accuracy of clinical symptoms, hematologic findings, and C-reactive protein (CRP in neonatal sepsis. Methods Samples were taken from potentially infected neonates admitted to the Matemal-Perinatal Unit of Sardjito Hospital, between December 1st, 2000 and March 31st, 2001 using at least one of the criteria: prematurity, very low birth weight infants, matemal pyrexia during delivery, premature membrane rupture, or thick, cloudy amniotic fluid. Clinical symptoms, total leukocyte, neutrophil, platelet count, CRP, and blood culture as the gold standard were examined. Results Among 99 neonates enrolled, the sensitivity, specificity, positive and negative predictive value of clinical symptoms were 79.3%, 75.7%, 57.5%, and 89.9%, respectively; leukopenia/leukocytosis were 27.6%, 85.7%, 44.4%, and 74.1%; neutropenia! neutrophilia were 41.4%, 71.4%, 37.5%, and 74.6%; thrombocytopenia were 79.3%, 51.8%, 40.4%, and 85.7%; positive CRP were 58.6%,78.6%,53.1%, and 82.1%. Parallel tests increased the sensitivity up to 89.7%. Specificity, positive and negative predictive value, and likelihood ratio were 44.3%, 40%, 91.2%, and 1.6, respectively. Serial tests increased the specificity up to 88.6%. Sensitivity, positive and negative predictive value, and likelihood ratio were 58.6%, 68%, 83.8%, and 5.1, respectively. Conclusion Clinical sepsis, thrombocytopenia, and CRP are sufficiently accurate as diagnostic tests for sepsis in potentially infected neonates. Parallel tests will increase the sensitivity, while serial tests increase the specificity.
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Richesson, Rachel L
2012-01-01
This book provides foundational coverage of key areas, concepts, constructs, and approaches of medical informatics as it applies to clinical research activities, in both current settings and in light of emerging policies. The field of clinical research is fully characterized (in terms of study design and overarching business processes), and there is emphasis on information management aspects and informatics implications (including needed activities) within various clinical research environments. The purpose of the book is to provide an overview of clinical research (types), activities, and are
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Ethical, legal and social implications of incorporating personalized medicine into healthcare.
Brothers, Kyle B; Rothstein, Mark A
As research focused on personalized medicine has developed over the past decade, bioethics scholars have contemplated the ethical, legal and social implications of this type of research. In the next decade, there will be a need to broaden the focus of this work as personalized medicine moves into clinical settings. We consider two broad issues that will grow in importance and urgency. First, we analyze the consequences of the significant increase in health information that will be brought about by personalized medicine. Second, we raise concerns about the potential of personalized medicine to exacerbate existing disparities in healthcare.
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Teaching clinical reasoning to medical students.
Gay, Simon; Bartlett, Maggie; McKinley, Robert
2013-10-01
Keele Medical School's new curriculum includes a 5-week course to extend medical students' consultation skills beyond those historically required for competent inductive diagnosis. Clinical reasoning is a core skill for the practice of medicine, and is known to have implications for patient safety, yet historically it has not been explicitly taught. Rather, it has been assumed that these skills will be learned by accumulating a body of knowledge and by observing expert clinicians. This course aims to assist students to develop their own clinical reasoning skills and promote their greater understanding of, and potential to benefit from, the clinical reasoning skills of others. The course takes place in the fourth or penultimate year, and is integrated with students' clinical placements, giving them opportunities to practise and quickly embed their learning. This course emphasises that clinical reasoning extends beyond initial diagnosis into all other aspects of clinical practice, particularly clinical management. It offers students a variety of challenging and interesting opportunities to engage with clinical reasoning across a wide range of clinical practice. It addresses bias through metacognition and increased self-awareness, considers some of the complexities of prescribing and non-pharmacological interventions, and promotes pragmatic evidence-based practice, information management within the consultation and the maximising of patient adherence. This article describes clinical reasoning-based classroom and community teaching. Early evaluation suggests that students value the course and benefit from it. © 2013 John Wiley & Sons Ltd.
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Hill, Anne E; Davidson, Bronwyn J; Theodoros, Deborah G
2010-06-01
The use of standardized patients has been reported as a viable addition to traditional models of professional practice education in medicine, nursing and allied health programs. Educational programs rely on the inclusion of work-integrated learning components in order to graduate competent practitioners. Allied health programs world-wide have reported increasing difficulty in attaining sufficient traditional placements for students within the workplace. In response to this, allied health professionals are challenged to be innovative and problem-solving in the development and maintenance of clinical education placements and to consider potential alternative learning opportunities for students. Whilst there is a bank of literature describing the use of standardized patients in medicine and nursing, reports of its use in speech-language pathology clinical education are limited. Therefore, this paper aims to (1) provide a review of literature reporting on the use of standardized patients within medical and allied health professions with particular reference to use in speech-language pathology, (2) discuss methodological and practical issues involved in establishing and maintaining a standardized patient program and (3) identify future directions for research and clinical programs using standardized patients to build foundation clinical skills such as communication, interpersonal interaction and interviewing.
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Saltzman, Bryan M; Riboh, Jonathan C
2018-06-01
Articular cartilage injuries and early osteoarthritis are among the most common conditions seen by sports medicine physicians. Nonetheless, treatment options for articular degeneration are limited once the osteoarthritic cascade has started. Intense research is focused on the use of biologics, cartilage regeneration, and transplantation to help maintain and improve cartilage health. An underappreciated component of joint health is the subchondral bone. A comprehensive, nonsystematic review of the published literature was completed via a PubMed/MEDLINE search of the keywords "subchondral" AND "bone" from database inception through December 1, 2016. Clinical review. Level 4. Articles collected via the database search were assessed for the association of bone marrow lesions and osteoarthritis, cartilage regeneration, and ligamentous and meniscal injury; the clinical disorder known as painful bone marrow edema syndrome; and the subchondral bone as a target for medical and surgical intervention. A complex interplay exists between the articular cartilage of the knee and its underlying subchondral bone. The role of subchondral bone in the knee is intimately related to the outcomes from cartilage restoration procedures, ligamentous injury, meniscal pathology, and osteoarthritis. However, subchondral bone is often neglected when it should be viewed as a critical element of the osteochondral unit and a key player in joint health. Continued explorations into the intricacies of subchondral bone marrow abnormalities and implications for the advent of procedures such as subchondroplasty will inform further research efforts on how interventions aimed at the subchondral bone may provide durable options for knee joint preservation.
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Salman, Ali; Nguyen, Claire; Lee, Yi-Hui; Cooksey-James, Tawna
2016-04-01
To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.
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Grill, Joshua D; Hoang, Dan; Gillen, Daniel L; Cox, Chelsea G; Gombosev, Adrijana; Klein, Kirsten; O'Leary, Steve; Witbracht, Megan; Pierce, Aimee
2018-01-01
Potential participant registries are tools to address the challenge of slow recruitment to clinical research. In particular, registries may aid recruitment to secondary prevention clinical trials for Alzheimer's disease (AD), which enroll cognitively normal older individuals meeting specific genetic or biomarker criteria. Evidence of registry effectiveness is sparse, as is guidance on optimal designs or methods of conduct. We report our experiences of developing a novel local potential participant registry that implemented online enrollment and data collection. In the first year of operation, 957 individuals submitted email addresses to the registry, of whom 592 self-reported demographic, family history, and medical data. In addition, registrants provided information related to their interest and willingness to be contacted about studies. Local earned media and community education were the most effective methods of recruitment into the registry. Seventy-six (26%) of 298 registrants contacted about studies in the first year enrolled in those studies. One hundred twenty-nine registrants were invited to enroll in a preclinical AD trial, of whom 25 (18%) screened and 6 were randomized. These results indicate that registries can aid recruitment and provide needed guidance for investigators initiating new local registries.
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Osteoarthritis subpopulations and implications for clinical trial design
S.M. Bierma-Zeinstra (Sita); A.P. Verhagen (Arianne)
2011-01-01
textabstractTreatment guidelines for osteoarthritis have stressed the need for research on clinical predictors of response to different treatments. However, identifying such clinical predictors of response is less easy than it seems, and there is not a given classification of osteoarthritis
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Medicinal Chemistry, Pharmacology, and Clinical Implications of TRPV1 Receptor Antagonists.
Aghazadeh Tabrizi, Mojgan; Baraldi, Pier Giovanni; Baraldi, Stefania; Gessi, Stefania; Merighi, Stefania; Borea, Pier Andrea
2017-07-01
Transient receptor potential vanilloid 1 (TRPV1) is an ion channel expressed on sensory neurons triggering an influx of cations. TRPV1 receptors function as homotetramers responsive to heat, proinflammatory substances, lipoxygenase products, resiniferatoxin, endocannabinoids, protons, and peptide toxins. Its phosphorylation increases sensitivity to both chemical and thermal stimuli, while desensitization involves a calcium-dependent mechanism resulting in receptor dephosphorylation. TRPV1 functions as a sensor of noxious stimuli and may represent a target to avoid pain and injury. TRPV1 activation has been associated to chronic inflammatory pain and peripheral neuropathy. Its expression is also detected in nonneuronal areas such as bladder, lungs, and cochlea where TRPV1 activation is responsible for pathology development of cystitis, asthma, and hearing loss. This review offers a comprehensive overview about TRPV1 receptor in the pathophysiology of chronic pain, epilepsy, cough, bladder disorders, diabetes, obesity, and hearing loss, highlighting how drug development targeting this channel could have a clinical therapeutic potential. Furthermore, it summarizes the advances of medicinal chemistry research leading to the identification of highly selective TRPV1 antagonists and their analysis of structure-activity relationships (SARs) focusing on new strategies to target this channel. © 2016 Wiley Periodicals, Inc.
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Single-cell proteomics: potential implications for cancer diagnostics.
Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T
2016-01-01
Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.
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Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz
2018-04-17
translational and clinical implications of the new approach and its future perspectives. © 2018 John Wiley & Sons, Ltd.
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Haliasos, N; Rezajooi, K; O'neill, K S; Van Dellen, J; Hudovsky, Anita; Nouraei, Sar
2010-04-01
Clinical coding is the translation of documented clinical activities during an admission to a codified language. Healthcare Resource Groupings (HRGs) are derived from coding data and are used to calculate payment to hospitals in England, Wales and Scotland and to conduct national audit and benchmarking exercises. Coding is an error-prone process and an understanding of its accuracy within neurosurgery is critical for financial, organizational and clinical governance purposes. We undertook a multidisciplinary audit of neurosurgical clinical coding accuracy. Neurosurgeons trained in coding assessed the accuracy of 386 patient episodes. Where clinicians felt a coding error was present, the case was discussed with an experienced clinical coder. Concordance between the initial coder-only clinical coding and the final clinician-coder multidisciplinary coding was assessed. At least one coding error occurred in 71/386 patients (18.4%). There were 36 diagnosis and 93 procedure errors and in 40 cases, the initial HRG changed (10.4%). Financially, this translated to pound111 revenue-loss per patient episode and projected to pound171,452 of annual loss to the department. 85% of all coding errors were due to accumulation of coding changes that occurred only once in the whole data set. Neurosurgical clinical coding is error-prone. This is financially disadvantageous and with the coding data being the source of comparisons within and between departments, coding inaccuracies paint a distorted picture of departmental activity and subspecialism in audit and benchmarking. Clinical engagement improves accuracy and is encouraged within a clinical governance framework.
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www.mydrugdealer.com: Ethics and legal implications of Internet-based access to substances of abuse.
Klein, Carolina A; Kandel, Surendra
2011-01-01
The Internet has increasingly become an intrinsic part of everyday life, offering countless possibilities for education, services, recreation, and more. In fact, an entire virtual life within the digitalized World Wide Web is possible and common among many Internet users. Today's psychiatrists must therefore incorporate this dimension of human life into clinical practice, to achieve an adequate assessment of the tools and risks available to the patient. We focus on the Internet as a portal for the trade of and access to substances of abuse. We review the legal regulations that may inform care and standards of practice and analyze the difficulties that arise in assessment and monitoring of the current situation. We consider the potential impact of Internet-based narcotics trade on addiction morbidities and the practice of clinical psychiatry, as well as on the potential legal implications that the forensic expert may face.
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Hartmann, William E; St Arnault, Denise M; Gone, Joseph P
2018-03-01
Community psychology (CP) abandoned the clinic and disengaged from movements for community mental health (CMH) to escape clinical convention and pursue growing aspirations as an independent field of context-oriented, community-engaged, and values-driven research and action. In doing so, however, CP positioned itself on the sidelines of influential contemporary movements that promote potentially harmful, reductionist biomedical narratives in mental health. We advocate for a return to the clinic-the seat of institutional power in mental health-using critical clinic-based inquiry to open sites for clinical-community dialogue that can instigate transformative change locally and nationally. To inform such works within the collaborative and emancipatory traditions of CP, we detail a recently completed clinical ethnography and offer "lessons learned" regarding challenges likely to re-emerge in similar efforts. Conducted with an urban American Indian community behavioral health clinic, this ethnography examined how culture and culture concepts (e.g., cultural competence) shaped clinical practice with socio-political implications for American Indian peoples and the pursuit of transformative change in CMH. Lessons learned identify exceptional clinicians versed in ecological thinking and contextualist discourses of human suffering as ideal partners for this work; encourage intense contextualization and constraining critique to areas of mutual interest; and support relational approaches to clinic collaborations. © Society for Community Research and Action 2017.
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A gene expression signature for RSV: clinical implications and limitations.
Directory of Open Access Journals (Sweden)
Peter J M Openshaw
2013-11-01
Full Text Available Peter Openshaw discusses the challenges in advancing respiratory syncytial virus (RSV treatments and the implications of a study by Mejias and colleagues using a newly identified gene signature for diagnosis and prediction of RSV severity. Please see later in the article for the Editors' Summary.
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Bystander effects and their implications for clinical radiotherapy
International Nuclear Information System (INIS)
Munro, Alastair J
2009-01-01
Radiation-induced bystander effects are defined as those biological effects expressed, after irradiation, by cells whose nuclei have not been directly irradiated. Radiation oncologists are only gradually beginning to appreciate the clinical relevance of radiation-induced bystander effects and associated phenomena: adaptive responses, genomic instability and abscopal effects. Incorporating bystander effects into the science underpinning clinical radiotherapy will involve moving beyond simple mechanistic models and towards a more systems-based approach. It is, given the protean nature of bystander effects, difficult to devise a coherent research strategy to investigate the clinical impact and relevance of bystander phenomena. Epidemiological approaches will be required, the traditional research models based on randomised controlled trials are unlikely to be adequate for the task. Any consideration of bystander effects challenges not only clinicians' preconceptions concerning the effects of radiation on tumours and normal tissues but also their ingenuity. This review covers, from a clinical perspective, the issues and problems associated with radiation-induced bystander effects.
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Cue-induced craving in pathological buying: empirical evidence and clinical implications.
Trotzke, Patrick; Starcke, Katrin; Pedersen, Anya; Brand, Matthias
2014-01-01
Pathological buying is associated with marked distress and impaired functioning in important life domains. It is currently under debate whether pathological buying can be considered a behavioral addiction. In analogy to results reported in addicted individuals, craving reactions elicited by addiction-related cues might be an underlying mechanism for the etiology and pathogenesis of pathological buying. In the present study, 30 pathological buyers and 30 matched control participants were examined with a cue-reactivity paradigm consisting of shopping and control cues. Skin conductance responses, as well as subjective ratings for arousal, valence, and urge to buy, were assessed. Subjective craving reactions were measured before and after the cue-reactivity paradigm. On a physiological level, skin conductance responses toward shopping cues were higher in pathological buyers (mean [M; standard deviation {SD}] = 0.26 [0.13]) compared with control participants (M [SD] = 0.19 [0.09]; t(58) = 2.29, p = .025, d = 0.60). On a behavioral level, the individuals with pathological buying rated the shopping cues as more arousing and more positive, and reported a greater urge to buy compared with control participants and with control cues. An increase in subjective craving after completing the cue-reactivity paradigm was observed only in the pathological buyers (Mpre [SD] = 1.95 [1.47], Mpost [SD] = 2.87 [1.79]; t(29) = 5.07, p buying. The results demonstrate similarities between pathological buying and substance or behavioral addictions and provide implications for clinical treatment.
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Personality traits in patients with Parkinson's disease: assessment and clinical implications.
Poletti, Michele; Bonuccelli, Ubaldo
2012-06-01
This study reviews empirical evidence on the association between personality traits and Parkinson's disease (PD), with a twofold aim. First, to better identify non-motor symptoms, such as affective symptoms and personality changes, that could help to define the pre-motor phase of PD; second, to better understand the neurobiological bases of personality traits, a goal that is not fully accomplished by a purely anatomical approach. A literature review was performed on studies of personality traits in PD patients, in electronic databases ISI Web of Knowledge, Medline and PsychInfo, conducted in July 2011. We found evidence that the existence of a characteristic premorbid personality profile of PD patients is not actually sustained by robust empirical evidence, mainly due to the methodological bias of the retrospective assessment of personality; PD patients present a personality profile of low novelty seeking and high harm avoidance. We concluded that the definition of a pre-motor phase of PD, based on non-motor symptoms, should search for the presence of concomitant affective disorders and for a positive psychiatric history for affective disorders rather than for a typical personality profile or personality changes. The low novelty seeking profile is probably related to the dopaminergic deficit, while the high harm avoidance profile is probably associated with the presence of affective disorders. Clinical implications of these findings, in regard to personality assessment and pharmacological treatments in PD, are also discussed.
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A study of pathogenesis of Acanthosis nigricans and its clinical implications
Directory of Open Access Journals (Sweden)
Neerja Puri
2011-01-01
Full Text Available Background: Acanthosis nigricans (AN is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management. Materials and Methods: We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI, hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH progesterone, dehydroepiandrosterone sulfate (DHEAS, cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels. Results and Discussion: In our study, the flexural involvement (flexures of groins, knees and elbows was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients.
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Anatomical Variations of Brachial Artery - Its Morphology, Embryogenesis and Clinical Implications
KS, Siddaraju; Venumadhav, Nelluri; Sharma, Ashish; Kumar, Neeraj
2014-01-01
Background: Accurate knowledge of variation pattern of the major arteries of upper limb is of considerable practical importance in the conduct of reparative surgery in the arm, forearm and hand however brachial artery and its terminal branches variations are less common. Aim: Accordingly the present study was designed to evaluate the anatomical variations of the brachial artery and its morphology, embryogenesis and clinical implications. Materials and Methods: In an anatomical study 140 upper limb specimens of 70 cadavers (35 males and 35 females) were used and anatomical variations of the brachial artery have been documented. Results: Accessory brachial artery was noted in eight female cadavers (11.43%). Out of eight cadavers in three cadavers (4.29%) an unusual bilateral accessory brachial artery arising from the axillary artery and it is continuing in the forearm as superficial accessory ulnar artery was noted. Rare unusual variant unilateral accessory brachial artery and its reunion with the main brachial artery in the cubital fossa and its variable course in relation to the musculocutaneous nerve and median nerve were also noted in five cadavers (7.14%). Conclusion: As per our knowledge such anatomical variations of brachial artery and its terminal branches with their relation to the surrounding structures are not reported in the modern medical literature. An awareness of such a presence is valuable for the surgeons and radiologists in evaluation of angiographic images, vascular and re-constructive surgery or appropriate treatment for compressive neuropathies. PMID:25653931
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Bohl, Daniel D; Saltzman, Bryan M; Sershon, Robert A; Darrith, Brian; Okroj, Kamil T; Della Valle, Craig J
2017-06-01
The purpose of this study is to determine the incidence, risk factors, and clinical implications of pneumonia following total joint arthroplasty (TJA). The American College of Surgeons National Surgical Quality Improvement Program was used to conduct a retrospective cohort study of patients undergoing TJA. Independent risk factors for the development of pneumonia within 30 days of TJA were identified using multivariate regression. Mortality and readmission rates were compared between patients who did and did not develop pneumonia. Multivariate regression was used to adjust for all demographic, comorbidity, and procedural characteristics. In total, 171,200 patients met inclusion criteria, of whom 66,493 (38.8%) underwent THA and 104,707 (61.2%) underwent TKA. Of the 171,200 patients, 590 developed pneumonia, yielding a rate of 0.34% (95% confidence interval = 0.32%-0.37%). Independent risk factors for pneumonia were chronic obstructive pulmonary disease, diabetes mellitus, greater age (most notably ≥80 years), dyspnea on exertion, dependent functional status, lower body mass index, hypertension, current smoker status, and male sex. The subset of patients who developed pneumonia following discharge had a higher readmission rate (82.1% vs 3.4%, adjusted relative risk [RR] = 16.6, P pneumonia. Pneumonia is a serious complication following TJA that occurs in approximately 1 in 300 patients. Approximately 4 in 5 patients who develop pneumonia are subsequently readmitted, and approximately 1 in 25 die. Given the serious implications of this complication, evidence-based pneumonia prevention programs including oral hygiene with chlorhexidine, sitting upright for meals, elevation of the head of the bed to at least 30°, aggressive incentive spirometry, and early ambulation should be considered for patients at greatest risk. Copyright © 2017 Elsevier Inc. All rights reserved.
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Reassessing carbamazepine in the treatment of bipolar disorder: clinical implications of new data.
Akiskal, Hagop S; Fuller, Matthew A; Hirschfeld, Robert M A; Keck, Paul E; Ketter, Terence A; Weisler, Richard H
2005-06-01
This monograph summarizes the proceedings of a roundtable meeting convened to discuss the role of carbamazepine in the treatment of bipolar disorder, in light of new data and the recent indication of carbamazepine extended-release capsules (CBZ ERC) for use in the treatment of acute manic and mixed episodes. Two lectures were presented, followed by a panel discussion among all 6 participants. A summary of the two pivotal trials of CBZ ERC and their pooled data along with other relevant data is presented first. Next, historical trends of carbamazepine and the agent's use in acute mania, bipolar depression, and maintenance are reviewed, emphasizing clinical implications of efficacy, safety, tolerability, and drug interactions. Finally, the panel discussion provides recommendations for the use of carbamazepine in different phases of the illness, taking into account adverse effects and drug-drug interactions. Panel discussants agree that current data confirm the utility of CBZ ERC as an effective treatment for acute manic and mixed episodes in bipolar disorder. Carbamazepine may also prove to be an option for maintenance treatment. Tolerability of the drug is related to dose and titration, and overall safety limitations regarding carbamazepine usage are comparable to other medications. For some patients, the main challenges to use of carbamazepine may be common drug-drug interactions and increased side effects related to aggressive introduction during treatment of acute manic and mixed episodes. Thus, carbamazepine may be a lower priority option for patients who are taking multiple medications, such as elderly individuals with medical comorbidity, due to the potential for drug interactions. Important benefits of carbamazepine include the low propensity toward weight gain and evidence of good tolerability with long-term treatment. (At present there are no available data from long-term, placebo-controlled studies evaluating the effects of carbamazepine or CBZ ERC on
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Implications of SNOMED CT versioning
Lee, Dennis; Cornet, Ronald; Lau, Francis
2011-01-01
To determine the changes each Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) release undergoes and the implications of those changes. (1) We reviewed the SNOMED CT Component History documentation and analyzed the Component History table in detail. (2) We outlined a list of semantic
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The implication of transcultural psychiatry for clinical practice.
Moldavsky, Daniel
2003-01-01
This article deals with the main concepts of Transcultural Psychiatry and their applications to everyday psychiatric practice. Transcultural psychiatry has undergone a conceptual reformulation in the last two decades. Having started with a comparative approach, which focused on the diverse manifestations of mental disorders among different societies, it broadened its scope, aiming at present to incorporate social and cultural aspects of illness into the clinical framework. Therefore, transcultural psychiatry now focuses more on what is called the illness experience than on the disease process, the latter understood as illness as it is viewed by health practitioners. Western medicine, of which psychiatry is a part, is grounded in positivist epistemological principles that stress the biological processes of disease. The intention of the paper is to develop an interest in alternative but also complementary ways of thinking. Modern transcultural psychiatry interprets some epidemiological and clinical aspects of major mental disorders (such as schizophrenia and depression) in a different light. However, it also distances itself from the absolute relativism of antipsychiatry, centering on clinical facts and helping clinicians in their primary task of alleviating suffering. An important contribution in addressing this task is the formulation of a cultural axis within the DSM model of multiaxial evaluation. A clinical vignette of a cultural formulation applied to a clinical discussion of a case is described.
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Brown, Benjamin; Balatsoukas, Panos; Williams, Richard; Sperrin, Matthew; Buchan, Iain
2018-01-01
Electronic audit and feedback (e-A&F) systems are used worldwide for care quality improvement. They measure health professionals' performance against clinical guidelines, and some systems suggest improvement actions. However, little is known about optimal interface designs for e-A&F, in particular how to present suggested actions for improvement. We developed a novel theory-informed system for primary care (the Performance Improvement plaN GeneratoR; PINGR) that covers the four principal interface components: clinical performance summaries; patient lists; detailed patient-level information; and suggested actions. As far as we are aware, this is the first report of an e-A&F system with all four interface components. (1) Use a combination of quantitative and qualitative methods to evaluate the usability of PINGR with target end-users; (2) refine existing design recommendations for e-A&F systems; (3) determine the implications of these recommendations for patient safety. We recruited seven primary care physicians to perform seven tasks with PINGR, during which we measured on-screen behaviour and eye movements. Participants subsequently completed usability questionnaires, and were interviewed in-depth. Data were integrated to: gain a more complete understanding of usability issues; enhance and explain each other's findings; and triangulate results to increase validity. Participants committed a median of 10 errors (range 8-21) when using PINGR's interface, and completed a median of five out of seven tasks (range 4-7). Errors violated six usability heuristics: clear response options; perceptual grouping and data relationships; representational formats; unambiguous description; visually distinct screens for confusable items; and workflow integration. Eye movement analysis revealed the integration of components largely supported effective user workflow, although the modular design of clinical performance summaries unnecessarily increased cognitive load. Interviews and
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Bhatnagar, D
1997-01-01
Clinical biochemistry departments can be a valuable source of clinical advice for further investigations and the need for referral to specialist clinics. This paper outlines the pattern of clinical advice sought by general practitioners in a district hospital setting, and addresses some of the issues regarding seeking such advice and the implications for continuing medical education and training. PMID:9196966
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Kiyatkin, Eugene A; Ren, Suelynn; Wakabayashi, Ken T; Baumann, Michael H; Shaham, Yavin
2016-01-01
MDMA-induced hyperthermia is highly variable, unpredictable, and greatly potentiated by the social and environmental conditions of recreational drug use. Current strategies to treat pathological MDMA-induced hyperthermia in humans are palliative and marginally effective, and there are no specific pharmacological treatments to counteract this potentially life-threatening condition. Here, we tested the efficacy of mixed adrenoceptor blockers carvedilol and labetalol, and the atypical antipsychotic clozapine, in reversing MDMA-induced brain and body hyperthermia. We injected rats with a moderate non-toxic dose of MDMA (9 mg/kg) during social interaction, and we administered potential treatment drugs after the development of robust hyperthermia (>2.5 °C), thus mimicking the clinical situation of acute MDMA intoxication. Brain temperature was our primary focus, but we also simultaneously recorded temperatures from the deep temporal muscle and skin, allowing us to determine the basic physiological mechanisms of the treatment drug action. Carvedilol was modestly effective in attenuating MDMA-induced hyperthermia by moderately inhibiting skin vasoconstriction, and labetalol was ineffective. In contrast, clozapine induced a marked and immediate reversal of MDMA-induced hyperthermia via inhibition of brain metabolic activation and blockade of skin vasoconstriction. Our findings suggest that clozapine, and related centrally acting drugs, might be highly effective for reversing MDMA-induced brain and body hyperthermia in emergency clinical situations, with possible life-saving results.
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Copper and Anesthesia: Clinical Relevance and Management of Copper Related Disorders
Langley, Adrian; Dameron, Charles T.
2013-01-01
Recent research has implicated abnormal copper homeostasis in the underlying pathophysiology of several clinically important disorders, some of which may be encountered by the anesthetist in daily clinical practice. The purpose of this narrative review is to summarize the physiology and pharmacology of copper, the clinical implications of abnormal copper metabolism, and the subsequent influence of altered copper homeostasis on anesthetic management.
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Clinical potential of lixisenatide once daily treatment for type 2 diabetes mellitus
DEFF Research Database (Denmark)
Petersen, Andreas Brønden; Christensen, Mikkel
2013-01-01
The glucagon-like peptide (GLP)-1 receptor agonist lixisenatide (Lyxumia(®)) was approved for marketing by the European Medicines Agency in February 2013 and has been evaluated in a clinical study program called GetGoal. Lixisenatide activates the GLP-1 receptor and thereby exercises the range of...... of lixisenatide seems to be in combination with basal insulin. A large multicenter study will determine the future potential of lixisenatide in preventing cardiovascular events and mortality, in patients with type 2 diabetes and recent acute coronary syndrome....
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Genetic Manipulation of NK Cells for Cancer Immunotherapy: Techniques and Clinical Implications.
Carlsten, Mattias; Childs, Richard W
2015-01-01
Given their rapid and efficient capacity to recognize and kill tumor cells, natural killer (NK) cells represent a unique immune cell to genetically reprogram in an effort to improve the outcome of cell-based cancer immunotherapy. However, technical and biological challenges associated with gene delivery into NK cells have significantly tempered this approach. Recent advances in viral transduction and electroporation have now allowed detailed characterization of genetically modified NK cells and provided a better understanding for how these cells can be utilized in the clinic to optimize their capacity to induce tumor regression in vivo. Improving NK cell persistence in vivo via autocrine IL-2 and IL-15 stimulation, enhancing tumor targeting by silencing inhibitory NK cell receptors such as NKG2A, and redirecting tumor killing via chimeric antigen receptors, all represent approaches that hold promise in preclinical studies. This review focuses on available methods for genetic reprograming of NK cells and the advantages and challenges associated with each method. It also gives an overview of strategies for genetic reprograming of NK cells that have been evaluated to date and an outlook on how these strategies may be best utilized in clinical protocols. With the recent advances in our understanding of the complex biological networks that regulate the ability of NK cells to target and kill tumors in vivo, we foresee genetic engineering as an obligatory pathway required to exploit the full potential of NK-cell based immunotherapy in the clinic.
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Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew
2016-10-01
Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.
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Said-Mohamed, Rihlat; Pettifor, John M; Norris, Shane A
2018-01-01
Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health. © 2017 Wiley Periodicals, Inc.
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Targeting dormant micrometastases: rationale, evidence to date and clinical implications.
Hurst, Robert E; Bastian, Anja; Bailey-Downs, Lora; Ihnat, Michael A
2016-03-01
In spite of decades of research, cancer survival has increased only modestly. This is because most research is based on models of primary tumors. Slow recognition has begun that disseminated, dormant cancer cells (micrometastatic cells) that are generally resistant to chemotherapy are the culprits in recurrence, and until these are targeted effectively we can expect only slow progress in increasing overall survival from cancer. This paper reviews efforts to understand the mechanisms by which cancer cells can become dormant, and thereby identify potential targets and drugs either on the market or in clinical trials that purport to prevent metastasis. This review targets the most recent literature because several excellent reviews have covered the literature from more than two years ago. The paper also describes recent work in the authors' laboratories to develop a screening-based approach that does not require understanding of mechanisms of action or the molecular target. Success of this approach shows that targeting micrometastatic cells is definitely feasible.
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DEFF Research Database (Denmark)
Glintborg, Bente; Andersen, Stig Ejdrup; Dalhoff, Kim
2005-01-01
OBJECTIVE: Patients use and store considerable amounts of drugs. The aim of the present study was to identify potential drug-drug interactions between drugs used by patients recently discharged from the hospital and, subsequently, to estimate the clinical implications of these interactions. METHODS......: Patients were visited within 1 week following their discharge from hospital and interviewed about their drug use. Stored products were inspected. We used a bibliography (Hansten and Horn; Wolters Kluwer Health, St. Louis, Mo., 2004) to identify and classify potential drug-drug interactions. RESULTS......: eight per patient; range: 1-24). With respect to those drugs used daily or on demand, 476 potential interactions were identified (126 patients); none were class 1 (always avoid drug combination) and 25 were class 2 (usually avoid combination; 24 patients). Eleven of the potential class 2 interactions...
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Viral asthma: implications for clinical practice
Directory of Open Access Journals (Sweden)
Roger Menendez
2010-07-01
Full Text Available Roger Menendez1, Michael D Goldman21Allergy and Asthma Center of El Paso, El Paso, TX, USA; 2Pulmonary Division, UCLA Gaffen School of Medicine, Los Angeles, CA, USAAbstract: The natural history of asthma appears to be driven primarily by the timing and duration of viral respiratory infections. From the very high rate of infections in childhood, to the more sporadic pattern seen in adults, the cycle of acute injury followed by an inefficient repair process helps explain the clinical patterns of asthma severity currently recognized by asthma guidelines. Why the asthmatic host responds to viral injury in a particular way is largely a mystery and the subject of intense investigation. The role of viruses in asthma extends not just to intermittent but to persistent disease, and to both the atopic as well as nonatopic phenotypes. Future therapeutic strategies should include primary prevention via the development of antiviral innate immunity-enhancing vaccines, as well as secondary prevention via the use of antiviral agents, or immunomodulators designed to boost the antiviral response or interrupt the proinflammatory cascade.Keywords: asthma, rhinoviruses, exacerbations, epidemiology, phenotypes, clinical trials
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Jesel, Laurence; Berthon, Charlotte; Messas, Nathan; Lim, Han S; Girardey, Mélanie; Marzak, Halim; Marchandot, Benjamin; Trinh, Annie; Ohlmann, Patrick; Morel, Olivier
2018-04-06
Takotsubo cardiomyopathy (TTC) is a stress-related transient cardiomyopathy. Life-threatening arrhythmias (LTA) can occur and worsen prognosis. The purpose of this study was to assess the incidence and outcome of LTA in TTC, as well as its predictive factors and clinical implications. We studied 214 consecutive cases of TTC over 8 years. The study cohort was divided into 2 groups: those with LTA (LTA group) and those without (non-LTA group). LTA was defined as ventricular tachycardia, ventricular fibrillation, or cardiac arrest. LTA occurred in 10.7% of patients mainly in the first 24 hours of hospitalization: ventricular tachycardia (n = 2), ventricular fibrillation (n = 11), cardiac arrest (n = 10: 5 asystole, 3 complete heart block, and 2 sinoatrial block). LTA were associated with lower left ventricular ejection fraction (LVEF) and a high rate of conduction disturbances. In-hospital (39.1% vs 8.9%; P 105 ms were independent predictors of LTA. In cases where a device was implanted, conduction disturbances persisted after the index event despite complete recovery of LVEF. There was no ventricular arrhythmia recurrence during follow-up. LTA occur early in patients presenting with TTC and is associated with significantly worse short- and long-term prognosis. Left ventricular impairment and QRS duration >105 ms are independent predictors of LTA. Ventricular arrhythmias occurred in the acute phase without further recurrence recorded in hospital survivors, whereas severe conduction disorders persisted during long-term follow-up. These findings may have implications on the choice of device therapy for this specific patient subgroup. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.
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Basedow, Martin; Runciman, William B; Lipworth, Wendy; Esterman, Adrian
2016-11-01
Clinical practice guidelines (CPGs) have been shown to improve processes of care and health outcomes, but there is often a discrepancy between recommendations for care and clinical practice. This study sought to explore general practitioner (GP) attitudes towards CPGs, in general and specifically for osteoarthritis (OA), with the implications for translating OA care into practice. A self-administered questionnaire was conducted in January 2013 with a sample of 228 GPs in New South Wales and South Australia. Seventy-nine GPs returned questionnaires (response rate 35%). Nearly all GPs considered that CPGs support decision-making in practice (94%) and medical education (92%). Very few respondents regarded CPGs as a threat to clinical autonomy, and most recognised that individual patient circumstances must be taken into account. Shorter CPG formats were preferred over longer and more comprehensive formats, with preferences being evenly divided among respondents for short, 2-3-page summaries, flowcharts or algorithms and single page checklists. GPs considered accessibility to CPGs to be important, and electronic formats were popular. Familiarity and use of The Royal Australian College of General Practitioners OA Guideline was poor, with most respondents either not aware of it (30%; 95% confidence interval (CI) 27 - 41%), had never used it (19%; 95% CI 12 - 29%) or rarely used it (34%; 95% CI 25-45%). If CPGs are to assist with the translation of evidence into practice, they must be easily accessible and in a format that encourages use.
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Anastasia, Annalisa; Colletti, Chiara; Cuoco, Valentina; Quartini, Adele; Urso, Stefania; Rinaldi, Raffaella; Bersani, Giuseppe
2016-01-01
Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry "A. Fiorini" Hospital, Terracina (Latina, Italy), was performed. The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium-high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications.
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Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer.
Directory of Open Access Journals (Sweden)
Yoojoo Lim
Full Text Available Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear.Tumor attenuation as measured by Hounsfield units (HU in contrast-enhanced computed tomography (CT and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80 treated with regorafenib in a prospective study.141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%-20.7%. Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson's r = 0.37, p = 0.002. Among 53 patients with lung metastases, 17 (32.1% developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50 and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13.Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies.
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Clinical Implication of Anti-Angiogenic Effect of Regorafenib in Metastatic Colorectal Cancer
Yoon, Jeong Hee; Lee, Jeong Min; Lee, Jung Min; Paeng, Jin Chul; Won, Jae-Kyung; Kang, Gyeong Hoon; Jeong, Seung-Yong; Park, Kyu Joo; Lee, Kyung-Hun; Kim, Jee Hyun; Kim, Tae-You
2015-01-01
Background Regorafenib induces distinct radiological changes that represent its anti-angiogenic effect. However, clinical implication of the changes is unclear. Methods Tumor attenuation as measured by Hounsfield units (HU) in contrast-enhanced computed tomography (CT) and cavitary changes of lung metastases were analyzed in association with treatment outcome of metastatic colorectal cancer patients (N = 80) treated with regorafenib in a prospective study. Results 141 lesions in 72 patients were analyzed with HU. After 2 cycles of regorafenib, 87.5% of patients showed decrease of HU (Median change -23.9%, range -61.5%–20.7%). Lesional attenuation change was modestly associated with metabolic changes of 18-fluoro-deoxyglucose positron emission tomography-CT (Pearson’s r = 0.37, p = 0.002). Among 53 patients with lung metastases, 17 (32.1%) developed cavitary changes. There were no differences in disease control rate, progression-free survival, or overall survival according to the radiological changes. At the time of progressive disease (PD) according to RECIST 1.1, HU was lower than baseline in 86.0% (43/50) and cavitary change of lung metastasis persisted without refilling in 84.6% (11/13). Conclusion Regorafenib showed prominent anti-angiogenic effect in colorectal cancer, but the changes were not associated with treatment outcome. However, the anti-angiogenic effects persisted at the time of PD, which suggests that we may need to develop new treatment strategies. PMID:26671465
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Bajpai, V K; Park, Y-H; Kang, S C
2015-03-01
The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal
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Directory of Open Access Journals (Sweden)
S Vikram
2014-01-01
Full Text Available Metopic suture is a dense fibrous joint extending from the nasion to the bregma. Normally, closure of this suture takes place between 1-8 years of age. Failure of this closure beyond 8 years leads to persistent metopic suture. A rare case of persistent metopic suture in a 60-year-old male is documented, who committed suicide by alleged consumption of organophosphorous compound at District Govt. Wenlock Hospital, Mangalore, Karnataka, India. Metopic suture may mimic skull fracture and may mislead an inexperienced forensic expert. Neurosurgeon should also be aware of this anatomical variation while performing frontal craniotomy, as the persistent metopic suture may mimic vertical fracture of the skull. Hence, in this case report, the clinical and medico-legal implications of the persistent metopic sutures have been discussed.
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Construction and Potential Applications of Biosensors for Proteins in Clinical Laboratory Diagnosis.
Liu, Xuan; Jiang, Hui
2017-12-04
Biosensors for proteins have shown attractive advantages compared to traditional techniques in clinical laboratory diagnosis. In virtue of modern fabrication modes and detection techniques, various immunosensing platforms have been reported on basis of the specific recognition between antigen-antibody pairs. In addition to profit from the development of nanotechnology and molecular biology, diverse fabrication and signal amplification strategies have been designed for detection of protein antigens, which has led to great achievements in fast quantitative and simultaneous testing with extremely high sensitivity and specificity. Besides antigens, determination of antibodies also possesses great significance for clinical laboratory diagnosis. In this review, we will categorize recent immunosensors for proteins by different detection techniques. The basic conception of detection techniques, sensing mechanisms, and the relevant signal amplification strategies are introduced. Since antibodies and antigens have an equal position to each other in immunosensing, all biosensing strategies for antigens can be extended to antibodies under appropriate optimizations. Biosensors for antibodies are summarized, focusing on potential applications in clinical laboratory diagnosis, such as a series of biomarkers for infectious diseases and autoimmune diseases, and an evaluation of vaccine immunity. The excellent performances of these biosensors provide a prospective space for future antibody-detection-based disease serodiagnosis.
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Gould, Dinah; Berridge, Emma-Jane; Kelly, Daniel
2007-01-01
The National Health Service Knowledge and Skills Framework has been introduced as part of the Agenda for Change Reforms in the United Kingdom to link pay and career progression to competency. The purpose of this paper is to consider the implications for nurses, their managers and the impact on university departments delivering continuing professional development for nurses. The new system has the potential to increase the human resources management aspect of the clinical nurse managers' role and could have legal implications, for example if practitioners perceive that their needs for continuing professional development have been overlooked to the detriment of their pay and career aspirations. The new system also has implications for providers of continuing professional development in the universities and is likely to demand closer liaison between education providers and trust staff who commission education and training. The Knowledge and Skills Framework is of interest to nurses and nurse educators internationally because the system, if effective, could be introduced elsewhere.
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Bioenergy costs and potentials with special attention to implications for the land system
Popp, A.; Lotze-Campen, H.; Dietrich, J.; Klein, D.; Bauer, N.; Krause, M.; Beringer, T.; Gerten, D.
2011-12-01
In the coming decades, an increasing competition for global land and water resources can be expected, due to rising demand for agricultural products, goals of nature conservation, and changing production conditions due to climate change. Especially biomass from cellulosic bioenergy crops, such as Miscanthus or poplar, is being proposed to play a substantial role in future energy systems if climate policy aims at stabilizing greenhouse gas (GHG) concentration at low levels. However, the potential of bioenergy for climate change mitigation remains unclear due to large uncertainties about future agricultural yield improvements, land availability for biomass plantations, and implications for the land system. In order to explore the cost-effective contribution of bioenergy to a low carbon transition with special attention to implications for the land system, we present a modeling framework with detailed biophysical and economic representation of the land and energy sector: We have linked the global dynamic vegetation and water balance model LPJmL (Bondeau et al. 2007, Rost et al. 2008), the global land and water use model MAgPIE (Lotze-Campen et al. 2008, Popp et al. 2010), and the global energy-economy-climate model ReMIND (Leimbach et al. 2009). In this modeling framework LPJmL supplies spatially explicit (0.5° resolution) agricultural yields as well as carbon and water stocks and fluxes. Based on this biophysical input MAgPIE delivers cost-optimized land use patterns (0.5° resolution), associated GHG emissions and rates of future yield increases in agricultural production. Moreover, shadow prices are calculated for irrigation water (as an indicator for water scarcity), food commodities, and bioenergy (as an indicator for changes in production costs) under different land use constraints such as forest conservation for climate change mitigation and as a contribution to biodiversity conservation. The energy-economy-climate model ReMIND generates the demand for
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Curcumin and treatment of melanoma: The potential role of microRNAs.
Lelli, Diana; Pedone, Claudio; Sahebkar, Amirhosssein
2017-04-01
Melanoma is the most aggressive type of skin cancer and is characterized by poor prognosis in its advanced stages because treatments are poorly effective and burdened with severe adverse effects. MicroRNAs (miRNAs) are small non-coding RNAs that are implicated in several cellular processes; they are categorized as oncogenic and tumor suppressor miRNAs. Several miRNAs are implicated in the pathogenesis and progression of melanoma, such as the tumor suppressor miR-let7b that targets cyclin D and regulates cell cycle. Curcumin is a natural compound derived from Curcuma longa L. (turmeric) with anti-cancer properties, documented also in melanoma, and is well tolerated in humans. Pharmacological activity of curcumin is mediated by modulation of several pathways, such as JAK-2/STAT3, thus inhibiting melanoma cell migration and invasion and enhancing apoptosis of these cells. The low oral bioavailability of curcumin has led to the development of curcumin analogues, such as EF24, with greater anti-tumor efficacy and metabolic stability. Potential anti-cancer activity of curcumin and its analogues is also mediated by modulation of miRNAs such as miR21, that is implicated in cell cycle regulation and apoptosis through down-regulation of PTEN and PDCD4 proteins. Curcumin has a potential role in the treatment of melanoma, though further studies are necessary to explore its clinical efficacy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
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Maximising the potential of part-time clinical teachers.
Patston, Philip; Holmes, David; Maalhagh-Fard, Ahmad; Ting, Kang; Ziccardi, Vincent B
2010-12-01
A problem faced by health professions education throughout the world is a lack of full-time clinical teachers. This is particularly serious in dentistry and nursing, but is increasingly also true in medicine. To make up for this shortfall there is a growing reliance on part-time clinical teachers. Part-time clinical teachers are essential for the education of students. However, compared with their full-time counterparts, the part-time teachers are often not adequately prepared for their roles as educators within the context of the clinical curriculum. They might not be trained in the latest educational practices, and may be unprepared for the time needed to excel as teachers and mentors. As part-time teachers take on more responsibility, it is important that they take part in orientation and training sessions to assist them in developing the skills they need to succeed. This will require a significant commitment from the institution as well as the part-time teacher, but is critical for maintaining the academic quality of the clinical training programmes. This also represents an untapped area for research into how to ensure the success of part-time clinical teachers. © Blackwell Publishing Ltd 2010.
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Have the Findings from Clinical Risk Prediction and Trials Any Key Messages for Safety Pharmacology?
Directory of Open Access Journals (Sweden)
Jem D. Lane
2017-11-01
Full Text Available Anti-arrhythmic drugs are a mainstay in the management of symptoms related to arrhythmias, and are adjuncts in prevention and treatment of life-threatening ventricular arrhythmias. However, they also have the potential for pro-arrhythmia and thus the prediction of arrhythmia predisposition and drug response are critical issues. Clinical trials are the latter stages in the safety testing and efficacy process prior to market release, and as such serve as a critical safeguard. In this review, we look at some of the lessons to be learned from approaches to arrhythmia prediction in patients, clinical trials of drugs used in the treatment of arrhythmias, and the implications for the design of pre-clinical safety pharmacology testing.
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Biological behaviour and clinical implications of micrometastases.
LENUS (Irish Health Repository)
Kell, M R
2012-02-03
BACKGROUND: The most important prognostic determinant in cancer is the identification of disseminated tumour burden (metastases). Micrometastases are microscopic (smaller than 2 mm) deposits of malignant cells that are segregated spatially from the primary tumour and depend on neovascular formation (angiogenesis) to propagate. METHODS: The electronic literature (1966 to present) on micrometastases and their implications in malignant melanoma and epithelial cancers was reviewed. RESULTS: Immunohistochemical techniques combined with serial sectioning offer the best accuracy for detection of nodal micrometastases. Molecular techniques should be reserved for blood samples or bone marrow aspirates. Detection of micrometastases in regional lymph nodes and\\/or bone marrow confers a poor prognosis in epithelial cancers. The concept of sentinel node biopsy combined with serial sectioning and dedicated screening for micrometastases may improve staging procedures. Strategies against angiogenesis may provide novel therapies to induce and maintain micrometastatic dormancy. CONCLUSION: The concept of micrometastases has resulted in a paradigm shift in the staging of epithelial tumours and our overall understanding of malignant processes.
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Energy Technology Data Exchange (ETDEWEB)
Giantsoudi, Drosoula, E-mail: dgiantsoudi@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States); Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts (United States)
2013-09-01
Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in
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International Nuclear Information System (INIS)
Giantsoudi, Drosoula; Grassberger, Clemens; Craft, David; Niemierko, Andrzej; Trofimov, Alexei; Paganetti, Harald
2013-01-01
Purpose: To investigate the feasibility and potential clinical benefit of linear energy transfer (LET) guided plan optimization in intensity modulated proton therapy (IMPT). Methods and Materials: A multicriteria optimization (MCO) module was used to generate a series of Pareto-optimal IMPT base plans (BPs), corresponding to defined objectives, for 5 patients with head-and-neck cancer and 2 with pancreatic cancer. A Monte Carlo platform was used to calculate dose and LET distributions for each BP. A custom-designed MCO navigation module allowed the user to interpolate between BPs to produce deliverable Pareto-optimal solutions. Differences among the BPs were evaluated for each patient, based on dose–volume and LET–volume histograms and 3-dimensional distributions. An LET-based relative biological effectiveness (RBE) model was used to evaluate the potential clinical benefit when navigating the space of Pareto-optimal BPs. Results: The mean LET values for the target varied up to 30% among the BPs for the head-and-neck patients and up to 14% for the pancreatic cancer patients. Variations were more prominent in organs at risk (OARs), where mean LET values differed by a factor of up to 2 among the BPs for the same patient. An inverse relation between dose and LET distributions for the OARs was typically observed. Accounting for LET-dependent variable RBE values, a potential improvement on RBE-weighted dose of up to 40%, averaged over several structures under study, was noticed during MCO navigation. Conclusions: We present a novel strategy for optimizing proton therapy to maximize dose-averaged LET in tumor targets while simultaneously minimizing dose-averaged LET in normal tissue structures. MCO BPs show substantial LET variations, leading to potentially significant differences in RBE-weighted doses. Pareto-surface navigation, using both dose and LET distributions for guidance, provides the means for evaluating a large variety of deliverable plans and aids in
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Myasthenia gravis and pregnancy: clinical implications and neonatal outcome
Directory of Open Access Journals (Sweden)
Estanol Bruno
2004-11-01
Full Text Available Abstract Background The myasthenia gravis is twice as common in women as in men and frequently affects young women in the second and third decades of life, overlapping with the childbearing years. Generally, during pregnancy in one third of patients the disease exacerbates, whereas in two thirds it remains clinically unchanged. Complete remission can occur in some patients. Methods To describe the clinical course, delivery and neonatal outcome of 18 pregnant women with the diagnosis of myasthenia gravis. Retrospective chart review of pregnant patients with myasthenia gravis, followed at the National Institute of Perinatology in Mexico City over an 8-year period. Data was abstracted from the medical records on the clinical course during pregnancy, delivery and neonatal outcome. Results From January 1, 1996 to December 31, 2003 18 patients with myasthenia gravis were identified and included in the study. The mean ± SD maternal age was 27.4 ± 4.0 years. During pregnancy 2 women (11% had an improvement in the clinical symptoms of myasthenia gravis, 7 women (39% had clinical worsening of the condition of 9 other patients (50% remained clinically unchanged. Nine patients delivered vaginally, 8 delivered by cesarean section and 1 pregnancy ended in fetal loss. Seventeen infants were born at mean ± SD gestational age of 37.5 ± 3.0 weeks and a mean birth weight of 2710 ± 73 g. Only one infant presented with transient neonatal myasthenia gravis. No congenital anomalies were identified in any of the newborns. Conclusions The clinical course of myasthenia gravis during pregnancy is variable, with a significant proportion of patients experiencing worsening of the clinical symptoms. However, neonatal transient myasthenia was uncommon in our patient population.
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Urodilatin, a natriuretic peptide with clinical implications.
Meyer, M; Richter, R; Forssmann, W G
1998-02-21
Natriuretic peptides (NP) constitute hormonal systems of great clinical impact. This report deals with Urodilatin (URO), a renal natriuretic peptide type A. From the gene of NP type A, a message for the preprohormone is transcribed in heart and kidney. The cardiac prohormone CDD/ANP-1-126 is synthesized in the heart atrium and processed during exocytosis forming the circulating hormone CDD/ANP-99-126. URO (CDD/ANP 95-126) is a product from the same gene, but differentially processed in the kidney and detected only in urine. Physiologically, URO acts in a paracrine fashion. After release from distal tubular kidney cells into the tubular lumen, URO binds to luminal receptors (NPR-A) in the collecting duct resulting in a cGMP-dependent signal transduction. cGMP generation is followed by an interaction with the amiloriode-sensitive sodium channel which induces diuresis and natriuresis. In this way, URO physiologically regulates fluid balance and sodium homeostasis. Moreover, URO excretion and natriuresis are in turn dependent on several physiological states, such as directly by sodium homeostasis. Pharmacologically, URO at low dose administered intravenously shows a strong diuretic and natriuretic effect and a low hypotensive effect. Renal, pulmonary, and cardiovascular effects evoked by pharmacological doses indicate that URO is a putative drug for several related diseases. Clinical trials show promising results for various clinical indications. However, the reduction in hemodialysis/hemofiltration in patients suffering from ARF following heart and liver transplantation, derived from preliminary trials recruiting a small number of patients, was not confirmed by a multicenter phase II study. In contrast, data for the prophylactic use of URO in this clinical setting suggest a better outcome for the patients. Furthermore, treatment of asthmatic patients showed a convincingly beneficial effect of URO on pulmonary function. Patients with congestive heart failure may also
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Integrating research, clinical care, and education in academic health science centers.
King, Gillian; Thomson, Nicole; Rothstein, Mitchell; Kingsnorth, Shauna; Parker, Kathryn
2016-10-10
Purpose One of the major issues faced by academic health science centers (AHSCs) is the need for mechanisms to foster the integration of research, clinical, and educational activities to achieve the vision of evidence-informed decision making (EIDM) and optimal client care. The paper aims to discuss this issue. Design/methodology/approach This paper synthesizes literature on organizational learning and collaboration, evidence-informed organizational decision making, and learning-based organizations to derive insights concerning the nature of effective workplace learning in AHSCs. Findings An evidence-informed model of collaborative workplace learning is proposed to aid the alignment of research, clinical, and educational functions in AHSCs. The model articulates relationships among AHSC academic functions and sub-functions, cross-functional activities, and collaborative learning processes, emphasizing the importance of cross-functional activities in enhancing collaborative learning processes and optimizing EIDM and client care. Cross-functional activities involving clinicians, researchers, and educators are hypothesized to be a primary vehicle for integration, supported by a learning-oriented workplace culture. These activities are distinct from interprofessional teams, which are clinical in nature. Four collaborative learning processes are specified that are enhanced in cross-functional activities or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co-using knowledge. Practical implications The model provides an aspirational vision and insight into the importance of cross-functional activities in enhancing workplace learning. The paper discusses the conceptual and empirical basis to the model, its contributions and limitations, and implications for AHSCs. Originality/value The model's potential utility for health care is discussed, with implications for organizational culture and the promotion of cross-functional activities.
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Huart, C; Rombaux, Ph; Hummel, T; Mouraux, A
2013-09-01
The clinical usefulness of olfactory event-related brain potentials (OERPs) to assess olfactory function is limited by the relatively low signal-to-noise ratio of the responses identified using conventional time-domain averaging. Recently, it was shown that time-frequency analysis of the obtained EEG signals can markedly improve the signal-to-noise ratio of OERPs in healthy controls, because it enhances both phase-locked and non phase-locked EEG responses. The aim of the present study was to investigate the clinical usefulness of this approach and evaluate its feasibility in a clinical setting. We retrospectively analysed EEG recordings obtained from 45 patients (15 anosmic, 15 hyposmic and 15 normos- mic). The responses to olfactory stimulation were analysed using conventional time-domain analysis and joint time-frequency analysis. The ability of the two methods to discriminate between anosmic, hyposmic and normosmic patients was assessed using a Receiver Operating Characteristic analysis. The discrimination performance of OERPs identified using conventional time-domain averaging was poor. In contrast, the discrimination performance of the EEG response identified in the time-frequency domain was relatively high. Furthermore, we found a significant correlation between the magnitude of this response and the psychophysical olfactory score. Time-frequency analysis of the EEG responses to olfactory stimulation could be used as an effective and reliable diagnostic tool for the objective clinical evaluation of olfactory function in patients.
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Directory of Open Access Journals (Sweden)
Melisa I. Barliana
2013-09-01
Full Text Available The potential of Drug-Drug Interactions (DDI in prescription have high incidence around the world, including Indonesia. However, scientific evidence regarding DDI in Indonesia is not available. Therefore, in this study we have conducted survey in 2 pharmacies in Bandung against pediatric prescription given by pediatrician. These prescriptions then analyzed the potential for DDI contained in the prescription and clinical manifestation. The analysis showed that in pharmacy A, there are 33 prescriptions (from a total of 155 prescriptions that have potential DDI, or approximately 21.19% (2 prescriptions have the potential DDI major categories, 23 prescriptions categorized as moderate, and 8 prescriptions as minor. In Pharmacy B, there are 6 prescriptions (from a total of 40 prescriptions or 15% of potential DDI (4 prescriptions categorized as moderate and 2 prescriptions as minor. This result showed that potential DDI happened less than 50% in pediatric prescription from both pharmacies. However, this should get attention because DDI should not happen in a prescription considering its clinical manifestations caused by DDI. Moreover, current pharmaceutical care refers to patient oriented than product oriented. In addition, further study for the pediatric prescription on DDI incidence in large scale need to be investigated.
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Salih, Karimeldin Mohamed Ali; El-Samani, El-Fatih; Bilal, Jalal Ali; Eldouch, Widad; Ibrahim, Salah Ahmed
2015-08-01
Blood culture is necessary for appropriate management of clinically severe pneumonia in children under five years of age. However, in limited resource countries it might be unduly costly and waste of valuable time because of the high negative culture rate. This study aims to identify clinical and laboratory parameters that potentially predict a positive blood culture in cases of severe pneumonia. A hospital based study, enrolled 189 cases satisfying the WHO definition of severe pneumonia. Age, gender, clinical history, physical examination, temperature, complete blood count, C-reactive protein, blood culture and Chest X Ray for all the patients were recorded. Forty one patients had positive blood culture giving a prevalence of 21.7%. All variables were used in a dichotomous manner. White Blood Count (WBC) more than 20 000, very high C-reactive protein (C-RP ≥8mg/L) and Temperature more than 40(o)C, had a positive predictive value of 46.1%, 44.3% and 40.0% respectively for a positive culture as well as a Negative Predictive Value of 91.1%, 91.6% and 91.7% respectively. The WBC more than 20 000 and temperature above 40(o)C had a significant association with a positive blood culture. Their adjusted Odds Ratios were 3.9 (95% CI: 1.4-10.90) and 3.1 (95% CI: 1.2-8.4) respectively. This was not the case for C-RP (Odds Ratio=2.2, 95% CI: 0.7-2.2) or positive Chest X Ray (Odds Ratio=1.5, 95% CI: 0.6-3.6). Temperature of more than 40(o)C, Very high C-RP and WBC of more than 20 000 are good indicators of a potential positive blood culture. It is therefore recommended that further research be undertaken to refine these predictors as screening tools before resorting to blood culture. It is also recommended that antibiotic treatment may be initiated on the basis of the high temperature and WBC, while waiting for the culture results.
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'False-positive' and 'false-negative' test results in clinical urine drug testing.
Reisfield, Gary M; Goldberger, Bruce A; Bertholf, Roger L
2009-08-01
The terms 'false-positive' and 'false-negative' are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results. This larger universe, while not solely comprised of technically 'true' or 'false' positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms 'potentially inappropriate' positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation. Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error. Clinical UDT interpretation is a complicated task requiring knowledge of recent prescription, over-the-counter and herbal drug administration, drug metabolism and analytical sensitivities and specificities.
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Colwell, Katie; Lujan, Marla E; Lawson, Karen L; Pierson, Roger A; Chizen, Donna R
2010-05-01
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects 6% to 10% of reproductive aged women. It is a poorly understood and often undiagnosed condition that has implications for the health of affected women. We assessed changes in knowledge, feelings, and daily health practices related to PCOS in clinical research study participants. Sixty-eight women who had received counselling and education about PCOS while participating in a clinical research study were invited to complete an online survey that assessed levels of concern, knowledge, healthy dieting, active living, and health care satisfaction before and after the study. Differences and associations between scores were analyzed by paired t tests and Pearson correlation. Forty-three women (63%) completed the survey. After taking part in a clinical research study, participants believed they had increased knowledge of (P better lifestyle practices (P women felt empowered to participate in the management of their condition and communicate with their primary care providers. Women with PCOS felt that they had more knowledge and motivation to implement preventive health strategies after participating in a clinical research study. Education about how PCOS affects their immediate and long-term health enabled women with PCOS to feel physical and psychological benefits and to engage more with their health care providers.
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MERRF Classification: Implications for Diagnosis and Clinical Trials.
Finsterer, Josef; Zarrouk-Mahjoub, Sinda; Shoffner, John M
2018-03-01
Given the etiologic heterogeneity of disease classification using clinical phenomenology, we employed contemporary criteria to classify variants associated with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and to assess the strength of evidence of gene-disease associations. Standardized approaches are used to clarify the definition of MERRF, which is essential for patient diagnosis, patient classification, and clinical trial design. Systematic literature and database search with application of standardized assessment of gene-disease relationships using modified Smith criteria and of variants reported to be associated with MERRF using modified Yarham criteria. Review of available evidence supports a gene-disease association for two MT-tRNAs and for POLG. Using modified Smith criteria, definitive evidence of a MERRF gene-disease association is identified for MT-TK. Strong gene-disease evidence is present for MT-TL1 and POLG. Functional assays that directly associate variants with oxidative phosphorylation impairment were critical to mtDNA variant classification. In silico analysis was of limited utility to the assessment of individual MT-tRNA variants. With the use of contemporary classification criteria, several mtDNA variants previously reported as pathogenic or possibly pathogenic are reclassified as neutral variants. MERRF is primarily an MT-TK disease, with pathogenic variants in this gene accounting for ~90% of MERRF patients. Although MERRF is phenotypically and genotypically heterogeneous, myoclonic epilepsy is the clinical feature that distinguishes MERRF from other categories of mitochondrial disorders. Given its low frequency in mitochondrial disorders, myoclonic epilepsy is not explained simply by an impairment of cellular energetics. Although MERRF phenocopies can occur in other genes, additional data are needed to establish a MERRF disease-gene association. This approach to MERRF emphasizes standardized classification rather than clinical
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Charmandari, Evangelia; Weise, Martina; Bornstein, Stefan R; Eisenhofer, Graeme; Keil, Margaret F; Chrousos, George P; Merke, Deborah P
2002-05-01
Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients
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Khot, Vinita V; Chavan-Gautam, Preeti; Mehendale, Savita; Joshi, Sadhana R
2017-06-01
Children born preterm are reported to be at increased risk of developing noncommunicable diseases in later life. Altered placental DNA methylation patterns are implicated in fetal programming of adult diseases. Our earlier animal studies focus on micronutrients (folic acid, vitamin B 12 ) and long-chain polyunsaturated fatty acids (LCPUFAs) that interact in the 1 carbon cycle, thereby influencing methylation reactions. Our previous studies in women delivering preterm show altered plasma levels of micronutrients and lower plasma LCPUFA levels. We postulate that alterations in the micronutrient metabolism may affect the regulation of enzymes, methionine adenosyltransferase ( MAT2A), and SAH-hydrolase ( AHCY), involved in the production of methyl donor S-adenosylmethionine (SAM), thereby influencing the methylation potential (MP) in the placenta of women delivering preterm. The present study, therefore, examines the mRNA, protein levels of enzymes ( MAT2A and AHCY), SAM, S-adenosylhomocysteine (SAH) levels, and global DNA methylation levels from preterm (n = 73) and term (n = 73) placentae. The enzyme messenger RNA (mRNA) levels were analyzed by real-time quantitative polymerase chain reaction, protein levels by enzyme-linked immunosorbent assay, and SAM-SAH levels by high-performance liquid chromatography. The mRNA levels for MAT2A and AHCY are higher ( P programming of the developing fetus.
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Directory of Open Access Journals (Sweden)
P. Thomas
2014-01-01
Full Text Available The focus of this review are allergic complications following insertion of metallic orthopedic implants. Such potential allergic reactions encompass eczema, impaired wound and fracture healing, infection-mimicking reactions, effusions, pain and loosening. Nickel, cobalt and chromium seem to be the predominant eliciting allergens. Allergy might be considered prior to planned orthopaedic surgery or in patients with complications following arthroplasty We recommend, that differential diagnoses - in particular infection -should always be excluded in cooperation with surgery collegues. The clinical work up of a patient suspected of suffering from metal implant allergy should include a combined evaluation of medical history, clinical findings, patch testing and histology In vitro testing, namely the lymphocyte transformation test (LTT, can indicate metal sensitization, but needs careful interpretation.
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Recent Progress in Lab-on-a-Chip Technology and Its Potential Application to Clinical Diagnoses
Directory of Open Access Journals (Sweden)
Nae Yoon Lee
2013-03-01
Full Text Available We present the construction of the lab-on-a-chip (LOC system, a state-of-the-art technology that uses polymer materials (i.e., poly[dimethylsiloxane] for the miniaturization of conventional laboratory apparatuses, and show the potential use of these microfluidic devices in clinical applications. In particular, we introduce the independent unit components of the LOC system and demonstrate how each component can be functionally integrated into one monolithic system for the realization of a LOC system. In specific, we demonstrate microscale polymerase chain reaction with the use of a single heater, a microscale sample injection device with a disposable plastic syringe and a strategy for device assembly under environmentally mild conditions assisted by surface modification techniques. In this way, we endeavor to construct a totally integrated, disposable microfluidic system operated by a single mode, the pressure, which can be applied on-site with enhanced device portability and disposability and with simple and rapid operation for medical and clinical diagnoses, potentially extending its application to urodynamic studies in molecular level.
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Sellers, Edward M
2018-02-01
This article brings to the attention of drug developers the Food and Drug Administration's (FDA's) recent final Guidance to Industry on Assessment of Abuse Potential and provides practical suggestions about compliance with the Guidance. The Guidance areas are reviewed, analyzed, and placed in the context of current scientific knowledge and best practices to mitigate regulatory risk. The Guidance provides substantial new detail on what needs to be done at all stages of drug development for central nervous system-active drugs. However, because many psychopharmacologic agents have unique preclinical and clinical features, the plan for each agent needs to be not only carefully prepared but also reviewed and approved by the FDA. Examples are provided where assumptions about interpretation of the Guidance can delay development. If the expertise and experience needed for assessing abuse potential during drug development do not exist within a company, external preclinical and clinical expert should be involved. Consultation with the FDA is encouraged and important because the specific requirements for each drug will vary.
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Clinical Potential of Hyperbaric Pressure-Treated Whey Protein
Piccolomini, André F.; Kubow, Stan; Lands, Larry C.
2015-01-01
Whey protein (WP) from cow’s milk is a rich source of essential and branched chain amino acids. Whey protein isolates (WPI) has been demonstrated to support muscle accretion, antioxidant activity, and immune modulation. However, whey is not readily digestible due to its tight conformational structure. Treatment of WPI with hyperbaric pressure results in protein unfolding. This enhances protein digestion, and results in an altered spectrum of released peptides, and greater release of essential and branched chain amino acids. Pressurized whey protein isolates (pWPI), through a series of cell culture, animal models and clinical studies, have been demonstrated to enhance muscle accretion, reduce inflammation, improve immunity, and decrease fatigue. It is also conceivable that pWPI would be more accessible to digestive enzymes, which would allow for a more rapid proteolysis of the proteins and an increased or altered release of small bioactive peptides. The altered profile of peptides released from WP digestion could thus play a role in the modulation of the immune response and tissue glutathione (GSH) concentrations. The research to date presents potentially interesting applications for the development of new functional foods based on hyperbaric treatment of WPI to produce products with more potent nutritional and nutraceutical properties. PMID:27417773
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Newcombe, J P; Kerridge, I H
2007-01-01
Conflicts of interest arising from pharmaceutical industry sponsorship of clinical research have the potential to bias research outcomes and ultimately prejudice patient care. It is unknown how Australian Human Research Ethics Committees (HREC) assess and manage such conflicts of interest. We aimed to gain an understanding of how HREC approach the problem of potential conflicts of interest arising from pharmaceutical sponsorship of clinical research. We conducted a survey of HREC chairpersons in New South Wales. HREC vary widely in their approaches to conflicts of interest, including in their use of National Health and Medical Research Council guidelines, which were often misinterpreted or overlooked. Many committees rely primarily on researchers disclosing potential conflicts of interest, whereas a majority of HREC use disclosure to research participants as the primary tool for preventing and managing conflicts of interest. Almost no HREC place limitations on researcher relationships with pharmaceutical companies. These findings suggest reluctance on the part of HREC to regulate many potential conflicts of interest between researchers and pharmaceutical sponsors, which may arise from uncertainty regarding the meaning or significance of conflicts of interest in research, from ambiguity surrounding the role of HREC in assessing and managing conflicts of interest in research or from misinterpretation or ignorance of current National Health and Medical Research Council guidelines. Further review of policies and practices in this important area may prove beneficial in safeguarding clinical research and patient care while promoting continuing constructive engagement with the pharmaceutical industry.
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Is a clinical sociolinguistics possible?
Ball, M J
1992-01-01
This paper considers the idea of developing a clinical sociolinguistics. Various areas of the field are examined, and the importance of the 'core' area of the correlation of non-linguistic variables with linguistic variables stressed. Issues concerning language and class, region, sex, age and context of utterance are investigated, together with the implications for clinical linguistics. Finally, the difficulty of integrating such issues into clinical assessment is explored, and a tentative step forward suggested along the lines of a 'clinical sociolinguistic checklist'.
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Schrijver, Iris; Aziz, Nazneen; Farkas, Daniel H; Furtado, Manohar; Gonzalez, Andrea Ferreira; Greiner, Timothy C; Grody, Wayne W; Hambuch, Tina; Kalman, Lisa; Kant, Jeffrey A; Klein, Roger D; Leonard, Debra G B; Lubin, Ira M; Mao, Rong; Nagan, Narasimhan; Pratt, Victoria M; Sobel, Mark E; Voelkerding, Karl V; Gibson, Jane S
2012-11-01
This report of the Whole Genome Analysis group of the Association for Molecular Pathology illuminates the opportunities and challenges associated with clinical diagnostic genome sequencing. With the reality of clinical application of next-generation sequencing, technical aspects of molecular testing can be accomplished at greater speed and with higher volume, while much information is obtained. Although this testing is a next logical step for molecular pathology laboratories, the potential impact on the diagnostic process and clinical correlations is extraordinary and clinical interpretation will be challenging. We review the rapidly evolving technologies; provide application examples; discuss aspects of clinical utility, ethics, and consent; and address the analytic, postanalytic, and professional implications. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
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Instructional Storytelling: Application of the Clinical Judgment Model in Nursing.
Timbrell, Jessica
2017-05-01
Little is known about the teaching and learning implications of instructional storytelling (IST) in nursing education or its potential connection to nursing theory. The literature establishes storytelling as a powerful teaching-learning method in the educational, business, humanities, and health sectors, but little exploration exists that is specific to nursing. An example of a story demonstrating application of the domains of Tanner's clinical judgment model links storytelling with learning outcomes appropriate for the novice nursing student. Application of Tanner's clinical judgment model offers consistency of learning experience while preserving the creativity inherent in IST. Further research into student learning outcomes achievement using IST is warranted as a step toward establishing best practices with IST in nursing education. [J Nurs Educ. 2017;56(5):305-308.]. Copyright 2017, SLACK Incorporated.
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International Nuclear Information System (INIS)
Bohonowych, Jessica ES; Peng, Shuping; Gopal, Udhayakumar; Hance, Michael W; Wing, Shane B; Argraves, Kelley M; Lundgren, Karen; Isaacs, Jennifer S
2011-01-01
Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF) function in a von Hippel-Lindau (VHL) independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC) progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589. The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC) inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression
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Directory of Open Access Journals (Sweden)
Bohonowych Jessica ES
2011-12-01
Full Text Available Abstract Background Perturbing Hsp90 chaperone function targets hypoxia inducible factor (HIF function in a von Hippel-Lindau (VHL independent manner, and represents an approach to combat the contribution of HIF to cell renal carcinoma (CCRCC progression. However, clinical trials with the prototypic Hsp90 inhibitor 17-AAG have been unsuccessful in halting the progression of advanced CCRCC. Methods Here we evaluated a novel next generation small molecule Hsp90 inhibitor, EC154, against HIF isoforms and HIF-driven molecular and functional endpoints. The effects of EC154 were compared to those of the prototypic Hsp90 inhibitor 17-AAG and the histone deacetylase (HDAC inhibitor LBH589. Results The findings indicate that EC154 is a potent inhibitor of HIF, effective at doses 10-fold lower than 17-AAG. While EC154, 17-AAG and the histone deacetylase (HDAC inhibitor LBH589 impaired HIF transcriptional activity, CCRCC cell motility, and angiogenesis; these effects did not correlate with their ability to diminish HIF protein expression. Further, our results illustrate the complexity of HIF targeting, in that although these agents suppressed HIF transcripts with differential dynamics, these effects were not predictive of drug efficacy in other relevant assays. Conclusions We provide evidence for EC154 targeting of HIF in CCRCC and for LBH589 acting as a suppressor of both HIF-1 and HIF-2 activity. We also demonstrate that 17-AAG and EC154, but not LBH589, can restore endothelial barrier function, highlighting a potentially new clinical application for Hsp90 inhibitors. Finally, given the discordance between HIF activity and protein expression, we conclude that HIF expression is not a reliable surrogate for HIF activity. Taken together, our findings emphasize the need to incorporate an integrated approach in evaluating Hsp90 inhibitors within the context of HIF suppression.
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Scott, Stephen H; Dukelow, Sean P
2011-01-01
Robotic technologies have profoundly affected the identification of fundamental properties of brain function. This success is attributable to robots being able to control the position of or forces applied to limbs, and their inherent ability to easily, objectively, and reliably quantify sensorimotor behavior. Our general hypothesis is that these same attributes make robotic technologies ideal for clinically assessing sensory, motor, and cognitive impairments in stroke and other neurological disorders. Further, they provide opportunities for novel therapeutic strategies. The present opinionated review describes how robotic technologies combined with virtual/augmented reality systems can support a broad range of behavioral tasks to objectively quantify brain function. This information could potentially be used to provide more accurate diagnostic and prognostic information than is available from current clinical assessment techniques. The review also highlights the potential benefits of robots to provide upper-limb therapy. Although the capital cost of these technologies is substantial, it pales in comparison with the potential cost reductions to the overall healthcare system that improved assessment and therapeutic interventions offer.
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Stern, Judy E; Hickman, Timothy N; Kinzer, Donna; Penzias, Alan S; Ball, G David; Gibbons, William E
2012-04-01
To assess whether total reproductive potential (TRP), the chance of a live birth from each fresh cycle (fresh cycle plus frozen transfers), could be calculated from the national Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database and whether information not available in SART CORS resulted in significant changes to the TRP calculation. Retrospective study using SART CORS and clinic data. Three assisted reproductive technology clinics. Women undergoing ART. None. Two- and three-year TRPs for 2005 and 2006 were calculated according to patient age at cycle start by linking fresh to frozen cycles up to first live birth. Clinic records were used to adjust for (remove) frozen cycles that used more than one fresh cycle as a source of embryos and for any embryos donated to other patients or research or shipped to another facility before a live birth. TRP was higher than fresh per-cycle rates for most ages at all clinics, although accuracy was compromised when there were fewer than 20 cycles per category. Two- and 3-year TRPs differed in only 2 of 24 calculations. Adjusted TRPs differed less than three percentage points from unadjusted TRPs when volume was sufficient. Clinic TRP can be calculated from SART CORS. Data suggest that calculations of clinic TRP from the national dataset would be meaningful. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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Building a learning health system using clinical registers: a non-technical introduction.
Ovretveit, John; Nelson, Eugene; James, Brent
2016-10-10
Purpose The purpose of this paper is to describe how clinical registers were designed and used to serve multiple purposes in three health systems, in order to contribute practical experience for building learning healthcare systems. Design/methodology/approach Case description and comparison of the development and use of clinical registries, drawing on participants' experience and published and unpublished research. Findings Clinical registers and new software systems enable fact-based decisions by patients, clinicians, and managers about better care, as well as new and more economical research. Designing systems to present the data for users' daily work appears to be the key to effective use of the potential afforded by digital data. Research limitations/implications The case descriptions draw on the experience of the authors who were involved in the development of the registers, as well as on published and unpublished research. There is limited data about outcomes for patients or cost-effectiveness. Practical implications The cases show the significant investments which are needed to make effective use of clinical register data. There are limited skills to design and apply the digital systems to make the best use of the systems and to reduce their disadvantages. More use can be made of digital data for quality improvement, patient empowerment and support, and for research. Social implications Patients can use their data combined with other data to self-manage their chronic conditions. There are challenges in designing and using systems so that those with lower health and computer literacy and incomes also benefit from these systems, otherwise the digital revolution may increase health inequalities. Originality/value The paper shows three real examples of clinical registers which have been developed as part of their host health systems' strategies to develop learning healthcare systems. The paper gives a simple non-technical introduction and overview for
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A scoping review of the potential for chart stimulated recall as a clinical research method.
Sinnott, Carol; Kelly, Martina A; Bradley, Colin P
2017-08-22
Chart-stimulated recall (CSR) is a case-based interviewing technique, which is used in the assessment of clinical decision-making in medical education and professional certification. Increasingly, clinical decision-making is a concern for clinical research in primary care. In this study, we review the prior application and utility of CSR as a technique for research interviews in primary care. Following Arksey & O'Malley's method for scoping reviews, we searched seven databases, grey literature, reference lists, and contacted experts in the field. We excluded studies on medical education or competence assessment. Retrieved citations were screened by one reviewer and full texts were ordered for all potentially relevant abstracts. Two researchers independently reviewed full texts and performed data extraction and quality appraisal if inclusion criteria were met. Data were collated and summarised using a published framework on the reporting of qualitative interview techniques, which was chosen a priori. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines informed the review report. From an initial list of 789 citations, eight studies using CSR in research interviews were included in the review: six from North America, one from the Netherlands, and one from Ireland. The most common purpose of included studies was to examine the influence of guidelines on physicians' decisions. The number of interviewees ranged from seven to twenty nine, while the number of charts discussed per interview ranged from one to twelve. CSR gave insights into physicians' reasoning for actions taken or not taken; the unrecorded social and clinical influences on decisions; and discrepancies between physicians' real and perceived practice. Ethical concerns and the training and influence of the researcher were poorly discussed in most of the studies. Potential pitfalls included the risk of recall, selection and observation biases. Despite the proven validity
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Stem cell therapy clinical research: A regulatory conundrum for academia.
Nagpal, Anjali; Juttner, Chris; Hamilton-Bruce, Monica Anne; Rolan, Paul; Koblar, Simon A
2017-12-01
The encouraging pace of discovery and development in the field of regenerative medicine holds tremendous potential for bringing therapies to the clinic that may offer meaningful benefit to patients, particularly in diseases with no or suboptimal therapeutic options. Academic researchers will continue to play a critical role in developing concepts and therapies, thus determining whether regenerative medicine will be able to live up to this potential that clearly excites clinicians, researchers and patients alike. This review summarises recent developments in regulatory frameworks across different countries that aim to ensure adequate oversight of the development of regenerative medicine products, which are unique in structural and functional complexity when compared to traditional chemical drugs and fully characterised biological drugs. It discusses the implications of these developments for researchers aiming to make the challenging transition from laboratory to clinical development of these therapies and considers possible pragmatic solutions that could accelerate this process that is essential to maintain research credibility and ensure patient safety. Copyright © 2016 Elsevier B.V. All rights reserved.
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Clinical implications of microbial biofilms in chronic rhinosinusitis and orbital cellulitis.
Nayak, Niranjan; Satpathy, Gita; Prasad, Sujata; Thakar, Alok; Chandra, Mahesh; Nag, T C
2016-09-21
Discovery of sessile mode of microbial existence (Biofilm state) focussed much interest, during the recent years, on the study of biofilms in many recurring and chronic infections. However, the exact role of microbial biofilms in chronic rhinosinusitis and orbital cellulitis were not elucidated earlier. The purpose of the present study was to look for the adherent property and biofilm producing ability of the clinical isolates in chronic rhinosinusitis and orbital cellulitis, and to look for the effects of antimicrobial agents on these biofilms by colorimetric assay and ultrastructural analysis. Organisms were isolated and identified from various clinical samples in patients with chronic sinusitis and orbital cellulitis. Antimicrobial sensitivity testing was carried out by the standard protocol. Biofilms were developed; quantified and antimicrobial drug perfusion through the biofilm model was evaluated by the earlier devised procedure. Electronmicroscopic study of the biofilm was performed by the recommended technique. Of the total of 70 clinical samples processed, 48 i.e. 68.5 % grew bacteria and 13 i.e.(18.6 %) fungi. Staphylococcus aureus (20), S epidermidis (16) and Pseudomonas aeruginosa (6) accounted for the majority of the bacterial isolates. Aspergillus flavus (8), however was the commonest amongst the fungi. A total of 40 bacteria and 8 fungi could be tested for biofilm production. Eighteen (45 %) of the 40 bacterial isolates and 4(50 %) out of the 8 A flavus isolates were found to be biofilm producers. In vitro adherence testing revealed that majority i.e. 16 (88.8 %) of the 18 biofilm positive bacteria were adherent to artificial surfaces. Antimicrobial drug perfusion through the biofilm model was poor. Antimicrobial treatment was totally ineffective against strong biofilm producers, whose electron microscopic picture was quite similar to that observed for biofilm producers without any antimicrobial pre-treatment. Filamentous fungi, like bacteria
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Almeida, Maria Cristina Mendes de; Canini, Silvia Rita Marin da Silva; Reis, Renata Karina; Toffano, Silmara Elaine Malaguti; Pereira, Fernanda Maria Vieira; Gir, Elucir
2015-04-01
To assess adherence to clinical appointments by health care workers (HCW) and students who suffered accidents with potentially infectious biological material. A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. A total of 461 individuals exposed to biological material were treated, of which 389 (84.4%) were HCWs and 72 (15.6%) students. Of the 461 exposed individuals, 307 (66.6%) attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83). The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.
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Directory of Open Access Journals (Sweden)
Teresa de Souza Fernandez
2013-01-01
Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.
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Clinical and nutritional implications of radiation enteritis
Energy Technology Data Exchange (ETDEWEB)
Beer, W.H.; Fan, A.; Halsted, C.H.
1985-01-01
The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value.
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Clinical and nutritional implications of radiation enteritis
International Nuclear Information System (INIS)
Beer, W.H.; Fan, A.; Halsted, C.H.
1985-01-01
The clinical and nutritional significance of radiation enteritis was assessed in eight patients with chronic diarrhea which followed curative doses of radiotherapy for pelvic malignancies. Steatorrhea, found in seven malnourished patients, was ascribed to ileal disease or previous surgery, or to bacterial contamination of the small intestine. Lactose intolerance, assessed by breath hydrogen excretion after oral lactose and by jejunal lactase levels, was found in six patients. In a subgroup of five patients, the administration of two different defined formula liquid diets by nasoduodenal infusion decreased fecal fluid and energy losses by about one-half. Compared to Vivonex-HN, the infusion of Criticare-HN was associated with greater likelihood of intestinal gas production but a three-fold greater utilization of protein. Intestinal malabsorption and malnutrition in radiation enteritis has diverse etiologies. Whereas nutritional support by liquid diet limits fecal fluid and energy losses, these diets differ significantly in clinical tolerance and biologic value
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New Potential Pharmacological Functions of Chinese Herbal Medicines via Regulation of Autophagy
Directory of Open Access Journals (Sweden)
Betty Yuen Kwan Law
2016-03-01
Full Text Available Autophagy is a universal catabolic cellular process for quality control of cytoplasm and maintenance of cellular homeostasis upon nutrient deprivation and environmental stimulus. It involves the lysosomal degradation of cellular components such as misfolded proteins or damaged organelles. Defects in autophagy are implicated in the pathogenesis of diseases including cancers, myopathy, neurodegenerations, infections and cardiovascular diseases. In the recent decade, traditional drugs with new clinical applications are not only commonly found in Western medicines, but also highlighted in Chinese herbal medicines (CHM. For instance, pharmacological studies have revealed that active components or fractions from Chaihu (Radix bupleuri, Hu Zhang (Rhizoma polygoni cuspidati, Donglingcao (Rabdosia rubesens, Hou po (Cortex magnoliae officinalis and Chuan xiong (Rhizoma chuanxiong modulate cancers, neurodegeneration and cardiovascular disease via autophagy. These findings shed light on the potential new applications and formulation of CHM decoctions via regulation of autophagy. This article reviews the roles of autophagy in the pharmacological actions of CHM and discusses their new potential clinical applications in various human diseases.
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Comparison of student learning in the out-patient clinic and ward round.
Davis, M H; Dent, J A
1994-05-01
In undergraduate medical education there is a trend away from ward-based teaching towards out-patient and community-based teaching. To study the potential effects of this altered emphasis on student learning, a pilot group of final-year medical students at the University of Dundee was asked to keep individual structured log-books. These contained details of patients seen during their 3-week orthopaedic attachment in both a ward and out-patient setting. A comparison of perceived learning in the two settings showed that students learned more from attending an out-patient clinic than a ward round, but did not make full use of the learning potential of either. The setting did not particularly influence the balance of learning as categorized here but only the ward round supplied experience of surgical complications. The amount of learning taking place in an out-patient clinic was influenced by student ability, measured by examination performance, but not by clinic work-load. The implications of increased use of out-patient clinics and the advantages and disadvantages of the approach employed are discussed. It is concluded that in the situation studied student learning in the outpatient setting is as good as or superior to the ward setting but should not totally replace it.
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High Altitude Emissions of Black Carbon Aerosols: Potential Climate Implications
Satheesh, S. K.
2017-12-01
these, it is hypothesized that such intrusions of black carbon to lower stratosphere and its consequent longer residence time in the stratosphere, would have significant implications for stratospheric chemistry, considering the known ozone depleting potential of black carbon aerosols.
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Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke
Directory of Open Access Journals (Sweden)
Wentao Li
2016-08-01
Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke
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International Nuclear Information System (INIS)
Angelino, Giulia; De Pasquale, Maria Debora; De Sio, Luigi; Serra, Annalisa; Massimi, Luca; De Vito, Rita; Marrazzo, Antonio; Lancella, Laura; Carai, Andrea; Antonelli, Manila; Giangaspero, Felice; Gessi, Marco; Menchini, Laura; Scarciolla, Laura; Longo, Daniela; Mastronuzzi, Angela
2016-01-01
Primary melanocytic neoplasms are rare in the pediatric age. Among them, the pattern of neoplastic meningitis represents a peculiar diagnostic challenge since neuroradiological features may be subtle and cerebrospinal fluid analysis may not be informative. Clinical misdiagnosis of neoplastic meningitis with tuberculous meningitis has been described in few pediatric cases, leading to a significant delay in appropriate management of patients. We describe the case of a child with primary leptomeningeal melanoma (LMM) that was initially misdiagnosed with tuberculous meningitis. We review the clinical and molecular aspects of LMM and discuss on clinical and diagnostic implications. A 27-month-old girl with a 1-week history of vomiting with mild intermittent strabismus underwent Magnetic Resonance Imaging, showing diffuse brainstem and spinal leptomeningeal enhancement. Cerebrospinal fluid analysis was unremarkable. Antitubercular treatment was started without any improvement. A spinal intradural biopsy was suggestive for primary leptomeningeal melanomatosis. Chemotherapy was started, but general clinical conditions progressively worsened and patient died 11 months after diagnosis. Molecular investigations were performed post-mortem on tumor tissue and revealed absence of BRAF V600E , GNAQ Q209 and GNA11 Q209 mutations but the presence of a NRAS Q61K mutation. Our case adds some information to the limited experience of the literature, confirming the presence of the NRAS Q61K mutation in children with melanomatosis. To our knowledge, this is the first case of leptomeningeal melanocytic neoplasms (LMN) without associated skin lesions to harbor this mutation. Isolated LMN presentation might be insidious, mimicking tuberculous meningitis, and should be suspected if no definite diagnosis is possible or if antitubercular treatment does not result in dramatic clinical improvement. Leptomeningeal biopsy should be considered, not only to confirm diagnosis of LMN but also to study
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Selectively starving cancer cells through dietary manipulation: methods and clinical implications.
Simone, Brittany A; Champ, Colin E; Rosenberg, Anne L; Berger, Adam C; Monti, Daniel A; Dicker, Adam P; Simone, Nicole L
2013-07-01
As the link between obesity and metabolic syndrome and cancer becomes clearer, the need to determine the optimal way to incorporate dietary manipulation in the treatment of cancer patients becomes increasingly important. Metabolic-based therapies, such as caloric restriction, intermittent fasting and a ketogenic diet, have the ability to decrease the incidence of spontaneous tumors and slow the growth of primary tumors, and may have an effect on distant metastases in animal models. Despite the abundance of preclinical data demonstrating the benefit of dietary modification for cancer, to date there are few clinical trials targeting diet as an intervention for cancer patients. We hypothesize that this may be due, in part, to the fact that several different types of diet modification exist with no clear recommendations regarding the optimal method. This article will delineate three commonly used methods of dietary manipulation to assess the potential of each as a regimen for cancer therapy.
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Clinical implications of patient-provider agreements in opioid prescribing.
Kraus, Carl N; Baldwin, Alan T; Curro, Frederick A; McAllister, R G
2015-01-01
In June, 2012 the United States Food and Drug Administration (FDA) developed a "blueprint" for prescriber education as a means of directing Certified Medical Education (CME) activities that included content which would meet the regulatory requirements of the class-wide, longacting/ extended-release (LA-ER) opioid Risk Evaluation Mitigation Strategies (REMS). Within the blueprint is the suggested adoption of Patient-Provider Agreements (PPAs) to be used in association with opioid prescribing, but, to our knowledge, there have been no reported evaluations of the role played by opioid-agent PPAs in clinical practice, or of the perceptions of this regulatory mandate by clinicians. Therefore, we conducted a survey regarding PPA perceptions by opioid prescribers that was posted for five weeks on a well-trafficked online CME service provider (Medscape). Of the 1,232 respondents (reflecting a 99.5% completion rate), 52.4% treat acute or chronic pain with opioids. The survey identified an improvement of opioid safe-use education (21% of respondents) as the most frequently selected beneficial element of PPAs. Conversely, the challenges to adoption included time constraints (21% of physicians) as well as lack of evidence that PPAs will reduce drug misuse, and the lack of a uniform, patient-friendly PPA. Based on our survey, clinicians consider the PPA of potential value, but data regarding the utility of such an instrument are lacking.
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Tick-borne encephalitis: Pathogenesis and clinical implications
Czech Academy of Sciences Publication Activity Database
Růžek, Daniel; Dobler, G.; Mantke, O. D.
2010-01-01
Roč. 8, č. 4 (2010), s. 223-232 ISSN 1477-8939 R&D Projects: GA ČR GPP302/10/P438; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tick-borne encephalitis * Tick-borne encephalitis virus * Pathogenesis * Clinical data Subject RIV: EE - Microbiology, Virology
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Mammography - recent technical developments and their clinical potential
Energy Technology Data Exchange (ETDEWEB)
Hemdal, Bengt; Mattsson, Soeren [Malmoe Univ. Hospital (Sweden). Dept. of Radiation Physics; Andersson, Ingvar [Malmoe Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Thilander Klang, Anne [Sahlgrenska Univ. Hospital, Goeteborg (Sweden). Dept. of Medical Physics and Biomedical Engineering; Bengtsson, Gert; Jarlman, O. [Lund Univ. Hospital (Sweden). Dept. of Diagnostic Radiology; Leitz, Wolfram [Swedish Radiation Protection Authority, Stockholm (Sweden); Bjurstam, Nils [Univ. of North Norway, Troms (Norway). Dept. of Radiology
2002-05-01
The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography
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Mammography - recent technical developments and their clinical potential
International Nuclear Information System (INIS)
Hemdal, Bengt; Mattsson, Soeren; Bjurstam, Nils
2002-05-01
The recent technical developments in digital as well as screen-film X-ray mammography have been reviewed in order to evaluate their clinical potential and to analyse possible lines for future development. Material and methods: The scientific literature has been reviewed, conferences covered and contacts with colleagues developed. Companies in the field have been inquired and invited for presentations. Own experience has been gathered from different screen-film and digital mammography systems. Results and conclusions: Although there are important complementary techniques such as ultrasound and magnetic resonance imaging (MRI), X-ray mammography is still the golden standard for breast imaging. It is relatively simple and cost-effective, and it is presently the only realistic technique for screening in a large scale. It is still largely the only technique that can detect breast cancer in a pre invasive stage. Equipment for digital mammography is commercially available both with small area and full field technique (FFDM). The development of FFDM systems is now intense, as well as the development of dedicated workstations and computer-aided detection (CAD). In spite of this, the introduction of digital mammography has been very slow compared to most other X-ray examinations due to high costs and technical challenges to meet the high demands on image quality and dose in mammography as well as the demands on specialised workflow support for screening mammography and suitable display techniques. Film reading of digital mammograms has been the most common display mode so far, but to take full advantage of the digital concept, diagnostic as well as logistic, monitor reading must be applied. There is a potential of FFDM systems for significantly higher image quality or significantly lower dose than screen-film mammography (SFM), or both. Further research is necessary to fully use this potential. The investment costs are much higher for digital than screen-film mammography
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Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use.
Baxter-Holland, Mia; Dass, Crispin R
2018-03-01
The use of doxorubicin, an antineoplastic medication used for the treatment of cancers via mechanisms that prevent replication of cells or lead to their death, can result in damage to healthy cells as well as malignant. Among the affected cells are mesenchymal stem cells (MSCs), which are involved in the maintenance and repair of tissues in the body. This review explores the mechanisms of biological effects and damage attributed to doxorubicin on MSCs. The PubMed database was used as a source of literature for this review. Doxorubicin has the potential to lead to significant and irreversible damage to the human bone marrow environment, including MSCs. The primary known mechanism of these changes is through free radical damage and activation of apoptotic pathways. The presence of MSCs in culture or in vivo appears to either suppress or promote tumour growth. Interactions between doxorubicin and MSCs have the potential to increase chemotherapy resistance. Doxorubicin-induced damage to MSCs is of concern clinically. However, MSCs also have been associated with resistance of tumour cells to drugs including doxorubicin. Further studies, particularly in vivo, are needed to provide consistent results of how the doxorubicin-induced changes to MSCs affect treatment and patient health. © 2018 Royal Pharmaceutical Society.
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Directory of Open Access Journals (Sweden)
Maria Cristina Mendes de Almeida
2015-04-01
Full Text Available OBJECTIVE To assess adherence to clinical appointments by health care workers (HCW and students who suffered accidents with potentially infectious biological material. METHOD A retrospective cross-sectional study that assessed clinical records of accidents involving biological material between 2005 and 2010 in a specialized unit. RESULTS A total of 461 individuals exposed to biological material were treated, of which 389 (84.4% were HCWs and 72 (15.6% students. Of the 461 exposed individuals, 307 (66.6% attended a follow-up appointment. Individuals who had suffered an accident with a known source patient were 29 times more likely to show up to their scheduled follow-up appointments (OR: 29.98; CI95%: 16.09-55.83. CONCLUSION The predictor in both univariate and multivariate analyses for adherence to clinical follow-up appointment was having a known source patient with nonreactive serology for the human immunodeficiency virus and/or hepatitis B and C.
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Virus–Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences
Directory of Open Access Journals (Sweden)
Matthew D. Moore
2018-02-01
Full Text Available Eukaryotic virus–bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus–bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus–bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus–bacteria interactions would likely result in numerous discoveries and beneficial applications.
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Virus-Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences.
Moore, Matthew D; Jaykus, Lee-Ann
2018-02-02
Eukaryotic virus-bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus-bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus-bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus-bacteria interactions would likely result in numerous discoveries and beneficial applications.
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Implications of U.S. electricity deregulation
International Nuclear Information System (INIS)
Gottfried, D.A.
1997-01-01
This article is a concise summary of the potential impacts of electric utility deregulation, including the resolution of stranded costs, impact on electricity rates, reformation of utilities, and reshuffling of the nation's fuel portfolio. The national and state implications of the deregulation of the electricity industry are monumental and overwhelming. The implications occur on many fronts, including monetary, quality, reliability, and environmental issues. Many significant changes will occur as a result--some will be positive and others may be more disturbing
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Zika virus: A review with oral health implications
Directory of Open Access Journals (Sweden)
Ruchika Khanna
2017-01-01
Full Text Available Zika virus was first isolated in the year 1947 from the blood of sentinel rhesus macaque of Uganda. The virus was introduced in Brazil from Pacific Islands and thereon spread rapidly. It was considered the first infectious disease to have birth defects. This review highlights the transmission, clinical aspects, clinical features, diagnosis, and possible implications of the virus for the dental team.
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Principles of three-dimensional printing and clinical applications within the abdomen and pelvis.
Bastawrous, Sarah; Wake, Nicole; Levin, Dmitry; Ripley, Beth
2018-04-04
Improvements in technology and reduction in costs have led to widespread interest in three-dimensional (3D) printing. 3D-printed anatomical models contribute to personalized medicine, surgical planning, and education across medical specialties, and these models are rapidly changing the landscape of clinical practice. A physical object that can be held in one's hands allows for significant advantages over standard two-dimensional (2D) or even 3D computer-based virtual models. Radiologists have the potential to play a significant role as consultants and educators across all specialties by providing 3D-printed models that enhance clinical care. This article reviews the basics of 3D printing, including how models are created from imaging data, clinical applications of 3D printing within the abdomen and pelvis, implications for education and training, limitations, and future directions.
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Walton, Kenneth G; Schneider, Robert H; Salerno, John W; Nidich, Sanford I
2005-01-01
Cardiovascular disease (CVD) remains the leading cause of death in the United States today and a major contributor to total health care costs. Psychosocial stress has been implicated in CVD, and psychosocial approaches to primary and secondary prevention are gaining research support. This third article in the series on psychosocial stress and CVD continues the evaluation of one such approach, the Maharishi Transcendental Meditation program, a psychophysiological approach from the Vedic tradition that is systematically taught by qualified teachers throughout the world. Evidence suggests not only that this program can provide benefits in prevention but also that it may reduce CVD-related and other health care expenses. On the basis of data from the studies available to date, the Transcendental Meditation program may be responsible for reductions of 80% or greater in medical insurance claims and payments to physicians. This article evaluates the implications of research on the Transcendental Meditation program for health care policy and for large-scale clinical implementation of the program. The Transcendental Meditation program can be used by individuals of any ethnic or cultural background, and compliance with the practice regimen is generally high. The main steps necessary for wider adoption appear to be: (1) educating health care providers and patients about the nature and expected benefits of the program, and (2) adjustments in public policies at the state and national levels to allow this program to be included in private and public health insurance plans.
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Directory of Open Access Journals (Sweden)
Elien Segers
2018-03-01
Full Text Available Introduction: Behavioral Parent Training (BPT is often provided for childhood psychiatric disorders. These disorders have been shown to be associated with working memory impairments. BPT is based on operant learning principles, yet how operant principles shape behavior (through the partial reinforcement (PRF extinction effect, i.e., greater resistance to extinction that is created when behavior is reinforced partially rather than continuously and the potential role of working memory therein is scarcely studied in children. This study explored the PRF extinction effect and the role of working memory therein using experimental tasks in typically developing children.Methods: Ninety-seven children (age 6–10 completed a working memory task and an operant learning task, in which children acquired a response-sequence rule under either continuous or PRF (120 trials, followed by an extinction phase (80 trials. Data of 88 children were used for analysis.Results: The PRF extinction effect was confirmed: We observed slower acquisition and extinction in the PRF condition as compared to the continuous reinforcement (CRF condition. Working memory was negatively related to acquisition but not extinction performance.Conclusion: Both reinforcement contingencies and working memory relate to acquisition performance. Potential implications for BPT are that decreasing working memory load may enhance the chance of optimally learning through reinforcement.
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Ma, Di; Feng, Liangshu; Deng, Fang; Feng, Jia-Chun
2017-01-01
Research on attenuating the structural and functional deficits observed following ischemia-reperfusion has become increasingly focused on the therapeutic potential of ischemic postconditioning. In recent years, various methods and animal models of ischemic postconditioning have been utilized. The results of these numerous studies have indicated that the mechanisms underlying the neuroprotective effects of ischemic postconditioning may involve reductions in the generation of free radicals and inhibition of calcium overload, as well as the release of endogenous active substances, alterations in membrane channel function, and activation of protein kinases. Here we review the novel discovery, mechanism, key factors, and clinical application of ischemic postconditioning and discuss its implications for future research and problem of clinical practice.
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Poppers: epidemiology and clinical management of inhaled nitrite abuse.
Romanelli, Frank; Smith, Kelly M; Thornton, Alice C; Pomeroy, Claire
2004-01-01
Commonly referred to as "poppers," inhaled nitrites have a long history of abuse. Poppers are rapid-onset, short-acting potent vasodilators that produce a rush characterized by warm sensations and feelings of dizziness. Poppers sometimes are used to facilitate anal intercourse because of their actions on the anal sphincter. Epidemiologically, the frequent use of nitrites by men who have sex with men has led some experts to implicate these chemicals in the pathogenesis of Kaposi's sarcoma and acquired immunodeficiency syndrome. Controlled clinical trials to examine this potential correlation have not been conducted, and the use of nitrites simply may be a marker for other high-risk behaviors such as unprotected sex. Although regulated in the United States, many nitrite compounds and isomers are sold at various venues including bars, bookstores, and over the Internet. Adverse effects associated with these products vary from mild allergic reactions to life-threatening methemoglobinemia. The potential for drug-drug interactions and a propensity toward unsafe sex also exist. Clinicians should be familiar with the populations most likely to abuse these agents and with the clinical effects and management guidelines for acute ingestions.
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Nguyen, Patricia K; Neofytou, Evgenios; Rhee, June-Wha; Wu, Joseph C
2016-11-01
Although progress continues to be made in the field of stem cell regenerative medicine for the treatment of cardiovascular disease, significant barriers to clinical implementation still exist. To summarize the current barriers to the clinical implementation of stem cell therapy in patients with cardiovascular disease and to discuss potential strategies to overcome them. Information for this review was obtained through a search of PubMed and the Cochrane database for English-language studies published between January 1, 2000, and July 25, 2016. Ten randomized clinical trials and 8 systematic reviews were included. One of the major clinical barriers facing the routine implementation of stem cell therapy in patients with cardiovascular disease is the limited and inconsistent benefit observed thus far. Reasons for this finding are unclear but may be owing to poor cell retention and survival, as suggested by numerous preclinical studies and a small number of human studies incorporating imaging to determine cell fate. Additional studies in humans using imaging to determine cell fate are needed to understand how these factors contribute to the limited efficacy of stem cell therapy. Treatment strategies to address poor cell retention and survival are under investigation and include the following: coadministration of immunosuppressive and prosurvival agents, delivery of cardioprotective factors packaged in exosomes rather than the cells themselves, and use of tissue-engineering strategies to provide structural support for cells. If larger grafts are achieved using these strategies, it will be imperative to carefully monitor for the potential risks of tumorigenicity, immunogenicity, and arrhythmogenicity. Despite important achievements to date, stem cell therapy is not yet ready for routine clinical implementation. Significant research is still needed to address the clinical barriers outlined herein before the next wave of large clinical trials is under way.
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Papagiorgis, Petros Christakis
2016-05-01
Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location.
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Williams, Leanne M; Tsang, Tracey W; Clarke, Simon; Kohn, Michael
2010-10-01
There remains a translational gap between research findings and their implementation in clinical practice that applies to attention-deficit/hyperactivity disorder (ADHD), as well as to other major disorders of brain health in childhood, adolescence and adulthood. Research studies have identified potential 'markers' to support diagnostic, functional assessment and treatment decisions, but there is little consensus about these markers. Of these potential markers, cognitive measures of thinking functions, such as sustaining attention and associated electrical brain activity, show promise in complementing the clinical management process. Emerging evidence highlights the relevance of emotional, as well as thinking, functions to ADHD. Here, we outline an integrative neuroscience framework for ADHD that offers one means to bring together cognitive measures of thinking functions with measures of emotion, and their brain and genetic correlates. Understanding these measures and the relationships between them is a first step towards the development of tools that will help to assess the heterogeneity of ADHD, and aid in tailoring treatment choices.
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DEFF Research Database (Denmark)
Sausen, Mark; Phallen, Jillian; Adleff, Vilmos
2015-01-01
tumour-specific mutations in the circulation of these patients. These analyses reveal somatic mutations in chromatin-regulating genes MLL, MLL2, MLL3 and ARID1A in 20% of patients that are associated with improved survival. We observe alterations in genes with potential therapeutic utility in over...... a third of cases. Liquid biopsy analyses demonstrate that 43% of patients with localized disease have detectable circulating tumour DNA (ctDNA) at diagnosis. Detection of ctDNA after resection predicts clinical relapse and poor outcome, with recurrence by ctDNA detected 6.5 months earlier than with CT...
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Potentially three distinct roles for hypoxic cell sensitizers in the clinic
International Nuclear Information System (INIS)
Chapman, J.D.; Raleigh, J.A.; Pedersen, J.E.; Ngan, J.; Shum, F.Y.
1979-01-01
Nitroaromatic drugs have been applied to radiation therapy on the basis of their effectiveness to enhance radiation damages selectively in hypoxic mammalian cells at nontoxic concentration. Such sensitizers could improve the rate of local tumor control by conventional radiotherapy in such cases that the resistance due to hypoxia in a limiting factor. The selective cytotoxicity of the drug to hypoxic cells is the second distinct action. A third potential role for nitroaromatic drugs could involve their use for the diagnosis of the number and location of hypoxic cells within tumors. The gain in therapeutic ratio by a factor from 5 to 10 is necessary before the full clinical impact of hypoxic cell radiosensitizers can be evaluated. The drugs selected for the use as clinical radiosensitizers were originally developed as the antibacterial agents with selective activity against anaerobes. The hypoxic cells in tumors are usually resistant to chemotherapy as well as resistant to radiation, and this specific drug action of sensitizers combined with that of an agent effective against oxygenated and cycling cells could possibly produce improved tumor cures. Electron-affinitive chemicals become selectively bound to the macromolecules of hypoxic mammalian cells by radiation-induced chemical reaction. This technique was used to identify by autoradiographic procedures the location of the radioactive nitrofurazone bound to hypoxic cells within multicellular spheroids. (Yamashita, S.)
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CSF-1R Inhibitor Development: Current Clinical Status.
Peyraud, Florent; Cousin, Sophie; Italiano, Antoine
2017-09-05
Colony-stimulating factor 1 receptor (CSF-1R) and its ligands, CSF-1 and interleukin 34 (IL-34), regulate the function and survival of tumor-associated macrophages, which are involved in tumorigenesis and in the suppression of antitumor immunity. Moreover, the CSF-1R/CSF-1 axis has been implicated in the pathogenesis of pigmented villonodular synovitis (PVNS), a benign tumor of the synovium. As advanced or metastatic malignant solid tumors and relapsed/refractory PVNS remain unresolved therapeutic problems, new approaches are needed to improve the outcome of patients with these conditions. In solid tumors, targeting CSF-1R via either small molecules or antibodies has shown interesting results in vitro but limited antitumor activity in vivo. Concerning PVNS, clinical trials assessing CSF-1R inhibitors have revealed promising initial outcomes. Blocking CSF-1/CSF-1R signaling represents a promising immunotherapy approach and several new potential combination therapies for future clinical testing.
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Nursing informatics, ethics and decisions: implications for translational research
DEFF Research Database (Denmark)
Kaltoft, Mette Kjer; Nielsen, Jesper Bo; Dowie, Jack
Nursing informatics, ethics and decisions: implications for translational research Objective: To introduce, in the multi-disciplinary contexts of clinical decision making and policy formation, a theory-based decision-analytic framework for the transparent forward translation of research......-calculation with evidence-based ratings for option performance on those criteria to produce a preference-sensitive assessment or opinion. Results: The first example shows the framework connecting nursing informatics and nursing ethics in the clinical context of a nurse’s decision to disclose or not disclose information......, satisfaction, Quality of Life), organization-related (staff and work environment, internal and external communication and relationships) and economics-related (start-up costs, financial implications and externalities)). Conclusion: Web-based decision support can provide nursing with a template, technique...
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Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications
2015-01-01
Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574
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F141. DUTY TO WARN FOR POTENTIAL RISK OF PSYCHOLOGICAL HARM: A CASE REPORT
Zhand, Naista; Attwood, David
2018-01-01
Abstract Background Under the current ethical and legal standards physicians are expected to breach confidentiality when a third party is at risk. However, the law has mainly focused on risk of bodily harm and there is no legal guidance on physicians’ responsibilty when it comes to risk of psychological harm to a potential targeted victim Methods This case report illustrates a clinical dilemma on duty to warn for mental health professionals. Results N/A Discussion This case report illustrates an unconventional perspective on a psychiatrist’s duty to warn: consideration of risk of psychological harm to the potential target of their patient. Psychological trauma can have a potential negative impact on victims, affecting their mental health and well being as well as their physical health. The ethicolegal dilemma discussed in this case has implications for policies related to the care of psychiatric patients.
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Clinical potential of implantable wireless sensors for orthopedic treatments.
Karipott, Salil Sidharthan; Nelson, Bradley D; Guldberg, Robert E; Ong, Keat Ghee
2018-04-01
Implantable wireless sensors have been used for real-time monitoring of chemicals and physical conditions of bones, tendons and muscles to diagnose and study orthopedic diseases and injuries. Due to the importance of these sensors in orthopedic care, a critical review, which not only analyzes the underlying technologies but also their clinical implementations and challenges, will provide a landscape view on their current state and their future clinical role. Areas covered: By conducting an extensive literature search and following the leaders of orthopedic implantable wireless sensors, this review covers the battery-powered and battery-free wireless implantable sensor technologies, and describes their implementation for hips, knees, spine, and shoulder stress/strain monitoring. Their advantages, limitations, and clinical challenges are also described. Expert commentary: Currently, implantable wireless sensors are mostly limited for scientific investigations and demonstrative experiments. Although rapid advancement in sensors and wireless technologies will push the reliability and practicality of these sensors for clinical realization, regulatory constraints and financial viability in medical device industry may curtail their continuous adoption for clinical orthopedic applications. In the next five years, these sensors are expected to gain increased interest from researchers, but wide clinical adoption is still unlikely.
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Leong, Stanley P L; Tseng, William W
2014-01-01
Cancer metastasis may be regarded as a progressive process from its inception in the primary tumor microenvironment to distant sites by way of the lymphovascular system. Although this type of tumor dissemination often occurs in an orderly fashion via the sentinel lymph node (SLN), acting as a possible gateway to the regional lymph nodes, bone marrow, and peripheral blood and ultimately to distant metastatic sites, this is not a general rule as tumor cells may enter the blood and spread to distant sites, bypassing the SLN. Methods of detecting micrometastatic cancer cells in the SLN, bone marrow, and peripheral blood of patients have been established. Patients with cancer cells in their SLN, bone marrow, or peripheral blood have worse clinical outcomes than patients with no evidence of spread to these compartments. The presence of these cells also has important biologic implications for disease progression and the clinician's understanding of the process of cancer metastasis. Further characterization of these micrometastatic cancer cells at each stage and site of metastasis is needed to design novel selective therapies for a more "personalized" treatment. © 2014 American Cancer Society, Inc.
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Directory of Open Access Journals (Sweden)
Samantha M. Brown
2017-09-01
Full Text Available Exposure to stress and early life trauma have been linked to child maltreatment and parental substance misuse. These issues often co-occur, yet few child welfare services target their shared underlying causes in a single intervention. Teaching mindfulness-informed strategies to substance-misusing families in the child welfare system may be one promising trauma-informed approach. As part of a larger pilot study testing the initial efficacy of a mindfulness-informed intervention for parents in public child welfare, this study explored the feasibility, acceptability, and clinical trends of the intervention using weekly reports of stress, coping, and mindfulness. Findings show support for the feasibility and acceptability of the intervention as well as positive responses to the intervention on measures of stress and mindfulness. However, the impact of the intervention varied with regard to improving weekly coping among participants. Implications for the integration of mindfulness into child welfare practice as a trauma-informed approach are discussed.
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Ryan, Christopher James; Callaghan, Sascha; Large, Matthew
2015-08-01
This paper aims to explain the meaning and implications for practice of the High Court of Australia's finding in the negligence case, Hunter and New England Local Health District v McKenna [2014] HCA 44. The facts of the case and the law of negligence are reviewed before reporting the Court's decision. The High Court found that the obligation upon doctors to provide the least restrictive option for care that was imposed by the, then applicable, Mental Health Act 1990 (NSW) was inconsistent with an obligation that might otherwise be imposed by a common law duty to have regard to the interests of those with whom a psychiatric patient may come into contact if not detained. The Court's finding underlines the importance of clinicians documenting their clinical reasoning around why their negotiated management plan was the option least restrictive of the patient's freedom and most protective of his or her human rights. © The Royal Australian and New Zealand College of Psychiatrists 2015.
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HOXA genes cluster: clinical implications of the smallest deletion
Pezzani, Lidia; Milani, Donatella; Manzoni, Francesca; Baccarin, Marco; Silipigni, Rosamaria; Guerneri, Silvana; Esposito, Susanna
2015-01-01
Background HOXA genes cluster plays a fundamental role in embryologic development. Deletion of the entire cluster is known to cause a clinically recognizable syndrome with mild developmental delay, characteristic facies, small feet with unusually short and big halluces, abnormal thumbs, and urogenital malformations. The clinical manifestations may vary with different ranges of deletions of HOXA cluster and flanking regions. Case presentation We report a girl with the smallest deletion reporte...
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The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.
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Chen, Xue; Sheng, Xunlun; Liu, Xiaoxing; Li, Huiping; Liu, Yani; Rong, Weining; Ha, Shaoping; Liu, Wenzhou; Kang, Xiaoli; Zhao, Kanxing; Zhao, Chen
2014-01-01
USH2A mutations have been implicated in the disease etiology of several inherited diseases, including Usher syndrome type 2 (USH2), nonsyndromic retinitis pigmentosa (RP), and nonsyndromic deafness. The complex genetic and phenotypic spectrums relevant to USH2A defects make it difficult to manage patients with such mutations. In the present study, we aim to determine the genetic etiology and to characterize the correlated clinical phenotypes for three Chinese pedigrees with nonsyndromic RP, one with RP sine pigmento (RPSP), and one with USH2. Family histories and clinical details for all included patients were reviewed. Ophthalmic examinations included best corrected visual acuities, visual field measurements, funduscopy, and electroretinography. Targeted next-generation sequencing (NGS) was applied using two sequence capture arrays to reveal the disease causative mutations for each family. Genotype-phenotype correlations were also annotated. Seven USH2A mutations, including four missense substitutions (p.P2762A, p.G3320C, p.R3719H, and p.G4763R), two splice site variants (c.8223+1G>A and c.8559-2T>C), and a nonsense mutation (p.Y3745*), were identified as disease causative in the five investigated families, of which three reported to have consanguineous marriage. Among all seven mutations, six were novel, and one was recurrent. Two homozygous missense mutations (p.P2762A and p.G3320C) were found in one individual family suggesting a potential double hit effect. Significant phenotypic divergences were revealed among the five families. Three families of the five families were affected with early, moderated, or late onset RP, one with RPSP, and the other one with USH2. Our study expands the genotypic and phenotypic variability relevant to USH2A mutations, which would help with a clear insight into the complex genetic and phenotypic spectrums relevant to USH2A defects, and is complementary for a better management of patients with such mutations. We have also
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Mathew, P; Dinter, H; Church, N; Humphries, T J; Kulkarni, R
2016-05-01
The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. © 2016 The Authors. Haemophilia Published by John Wiley & Sons Ltd.
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Implication of snail in metabolic stress-induced necrosis.
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Cho Hee Kim
2011-03-01
Full Text Available Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated.Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis.Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.
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Implications of Clinical Trial Design on Sample Size Requirements
Leon, Andrew C.
2008-01-01
The primary goal in designing a randomized controlled clinical trial (RCT) is to minimize bias in the estimate of treatment effect. Randomized group assignment, double-blinded assessments, and control or comparison groups reduce the risk of bias. The design must also provide sufficient statistical power to detect a clinically meaningful treatment effect and maintain a nominal level of type I error. An attempt to integrate neurocognitive science into an RCT poses additional challenges. Two par...
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Mu, Wei; Shang, Hongcai
2013-01-01
Objective. To define patient values, identify their manifestations in a randomized clinical trial, and investigate the possible implications for clinical research of traditional Chinese medicine. Methods. We categorized patient values manifestations into patient choice, preference, compliance, and patient-reported outcomes and summarized the underlying personal values through purposeful electronic searches for relevant reports. By hypothesizing a set of positive versus negative circumstances occurring in the enrollment, intervention allocation, treatment, and the follow-up stage of a trial, it is possible to discuss the potential implications of patient values manifestation on a trial with traditional Chinese medicine. Results. Patient values and its manifestations are ubiquitous in the process of clinical research with traditional Chinese medicine. These values may provide motivation for participation or engender the internal and external validity of the study. Conclusions. Trialists should attach sufficient importance to the needs and concerns of individual participant. To incorporate patient values into the design and conduct of a clinical study with traditional Chinese medicine, researchers are recommended to adopt participant-friendly design and use patient-reported outcomes, take convenience-for-patients measures, and help foster rational beliefs and behaviors of trial participants.
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Directory of Open Access Journals (Sweden)
Wei Mu
2013-01-01
Full Text Available Objective. To define patient values, identify their manifestations in a randomized clinical trial, and investigate the possible implications for clinical research of traditional Chinese medicine. Methods. We categorized patient values manifestations into patient choice, preference, compliance, and patient-reported outcomes and summarized the underlying personal values through purposeful electronic searches for relevant reports. By hypothesizing a set of positive versus negative circumstances occurring in the enrollment, intervention allocation, treatment, and the follow-up stage of a trial, it is possible to discuss the potential implications of patient values manifestation on a trial with traditional Chinese medicine. Results. Patient values and its manifestations are ubiquitous in the process of clinical research with traditional Chinese medicine. These values may provide motivation for participation or engender the internal and external validity of the study. Conclusions. Trialists should attach sufficient importance to the needs and concerns of individual participant. To incorporate patient values into the design and conduct of a clinical study with traditional Chinese medicine, researchers are recommended to adopt participant-friendly design and use patient-reported outcomes, take convenience-for-patients measures, and help foster rational beliefs and behaviors of trial participants.
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Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N
2018-03-01
Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Excellence in clinical teaching: knowledge transformation and development required.
Irby, David M
2014-08-01
Clinical teachers in medicine face the daunting task of mastering the many domains of knowledge needed for practice and teaching. The breadth and complexity of this knowledge continue to increase, as does the difficulty of transforming the knowledge into concepts that are understandable to learners. Properly targeted faculty development has the potential to expedite the knowledge transformation process for clinical teachers. Based on my own research in clinical teaching and faculty development, as well as the work of others, I describe the unique forms of clinical teacher knowledge, the transformation of that knowledge for teaching purposes and implications for faculty development. The following forms of knowledge for clinical teaching in medicine need to be mastered and transformed: (i) knowledge of medicine and patients; (ii) knowledge of context; (iii) knowledge of pedagogy and learners, and (iv) knowledge integrated into teaching scripts. This knowledge is employed and conveyed through the parallel processes of clinical reasoning and clinical instructional reasoning. Faculty development can facilitate this knowledge transformation process by: (i) examining, deconstructing and practising new teaching scripts; (ii) focusing on foundational concepts; (iii) demonstrating knowledge-in-use, and (iv) creating a supportive organisational climate for clinical teaching. To become an excellent clinical teacher in medicine requires the transformation of multiple forms of knowledge for teaching purposes. These domains of knowledge allow clinical teachers to provide tailored instruction to learners at varying levels in the context of fast-paced and demanding clinical practice. Faculty development can facilitate this knowledge transformation process. © 2014 John Wiley & Sons Ltd.
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Dependence and caring in clinical communication: the relevance of attachment and other theories.
Salmon, Peter; Young, Bridget
2009-03-01
Clinical relationships are usually asymmetric, being defined by patients' dependence and practitioners' care. Our aims are to: (i) identify literature that can contribute to theory for researching and teaching clinical communication from this perspective; (ii) highlight where theoretical development is needed; and (iii) test the utility of the emerging theory by identifying whether it leads to implications for educational practice. Selective and critical review of research concerned with dependence and caring in clinical and non-clinical relationships. Attachment theory helps to understand patients' need to seek safety in relationships with expert and authoritative practitioners but is of limited help in understanding practitioners' caring. Different theories that formulate practitioners' care as altruistic, rewarded by personal connection or as a contract indicate the potential importance of practitioners' emotions, values and sense of role in understanding their clinical communication. Extending the theoretical grounding of clinical communication can accommodate patients' dependence and practitioners' caring without return to medical paternalism. A broader theoretical base will help educators to address the inherent subjectivity of clinical relationships, and researchers to distinguish scientific questions about how patients and clinicians are from normative questions about how they should be.
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Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel
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Fontana E
2014-06-01
Full Text Available Elisa Fontana, Francesco Sclafani, David Cunningham Department of Medicine, The Royal Marsden NHS Foundation Trust, London and Surrey, UK Abstract: The management of pancreatic cancer has historically represented a major challenge for oncologists. The inherent aggressiveness of this tumor and the fibrotic features of the surrounding stromal tissue have significantly limited the impact of standard chemotherapy. Moreover, the paucity of available tumor tissue has hampered a better understanding of the biology of this disease as well as the development of new treatment strategies. Recently, the therapeutic landscape of metastatic pancreatic cancer has been enriched by two new combination regimens (FOLFIRINOX and gemcitabine-nab-paclitaxel which have been demonstrated to improve the outcome in patients with good performance status. Moreover, the peritumoral stroma has been increasingly recognized as a potential therapeutic target for this disease, and several new agents targeting stromal components are currently under investigation. In this paper, we review the current treatment options for advanced pancreatic cancer, highlight the role of the peritumoral stroma, and discuss the clinical potential of nab-paclitaxel and antistromal treatment strategies. Keywords: pancreatic cancer, nab-paclitaxel, stroma, SPARC
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Yanagawa, Yoshimaro; Aoki, Tomoyuki; Morimura, Tadashi; Araki, Osamu; Kimura, Takao; Ogiwara, Takayuki; Kotajima, Nobuo; Yanagawa, Masumi; Murakami, Masami
2014-01-01
In Japanese pediatric patients with thyrotropin (TSH) resistance, the R450H mutation in TSH receptor gene (TSHR) is occasionally observed. We studied the frequency and clinical implication of the R450H mutation in TSHR in the general population of Japanese adults using smart amplification process 2 (SmartAmp2). We designed SmartAmp2 primer sets to detect this mutation using a drop of whole blood. We analyzed thyroid function, antithyroid antibodies, and this mutation in 429 Japanese participants who had not been found to have thyroid disease. Two cases without antithyroid antibodies were heterozygous for the R450H mutation in TSHR. Thus, the prevalence of this mutation was 0.47% in the general population and 0.63% among those without antithyroid antibodies. Their serum TSH concentrations were higher than the average TSH concentration not only in subjects without antithyroid antibodies but also in those with antithyroid antibodies. The R450H mutation in TSHR is relatively common in the Japanese population and potentially affects thyroid function. The present study demonstrates that the SmartAmp2 method is useful to detect the R450H mutation in TSHR, which is one of the common causes of TSH resistance in the Japanese population. PMID:24895636
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Wound healing angiogenesis: The clinical implications of a simple mathematical model
Flegg, Jennifer A.
2012-05-01
Nonhealing wounds are a major burden for health care systems worldwide. In addition, a patient who suffers from this type of wound usually has a reduced quality of life. While the wound healing process is undoubtedly complex, in this paper we develop a deterministic mathematical model, formulated as a system of partial differential equations, that focusses on an important aspect of successful healing: oxygen supply to the wound bed by a combination of diffusion from the surrounding unwounded tissue and delivery from newly formed blood vessels. While the model equations can be solved numerically, the emphasis here is on the use of asymptotic methods to establish conditions under which new blood vessel growth can be initiated and wound-bed angiogenesis can progress. These conditions are given in terms of key model parameters including the rate of oxygen supply and its rate of consumption in the wound. We use our model to discuss the clinical use of treatments such as hyperbaric oxygen therapy, wound bed debridement, and revascularisation therapy that have the potential to initiate healing in chronic, stalled wounds. © 2012 Elsevier Ltd.
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Zwicker, R; Promsawad, A; Zwicker, B M; Laoharojanaphand, S
2010-03-01
Thailand is the number one global exporter and among the top five producers of rice in the world. A significant increase in anthropogenic contamination in agricultural soils over the past few decades has lead to concerns with cadmium and its uptake in rice. The cadmium levels in Thai rice from different sources/areas were determined and used to estimate the potential health risks to consumers. The cadmium concentration in the commercial rice samples ranged from below the detection limit to 0.016 mg/kg. The cadmium concentrations in the contaminated rice samples ranged from a low of 0.007 mg/kg to a high of 0.579 mg/kg. Five of the calculated values exceed the proposed PTWI, with one value almost three times higher and two values almost double. The three highly elevated values are certainly a concern from a health standpoint. Ultimately, action is required to address the health implications resulting from the cadmium contamination in agricultural soils used for rice production in a few select areas of Thailand. Overall, this study indicates that the vast majority of rice produced, consumed and exported by Thailand is safe pertaining to cadmium content.
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Mei Li
2015-01-01
Full Text Available Background: Oocyte vitrification is widely used throughout the world, but its clinical efficacy is inconsistent and depends on the vitrification media. This study compared the developmental potential and clinical results of in vivo matured oocytes cryopreserved with different vitrification media. Methods: This retrospective study involved vitrified-warmed oocytes at one in vitro fertilization laboratory. Vitrification media kits comprised the MC kit (ethylene glycol [EG] plus 1,2-propanediol [PROH], the KT kit (EG plus dimethyl sulphoxide [DMSO], and the Modified kit (EG plus DMSO and PROH kit. Rates of oocyte survival and subsequent developmental potential were recorded and analyzed. The t-test and the Chi-square test were used to evaluate each method′s efficacy. Results: Oocyte survival rate was significantly higher for the Modified kit (92.0% than for the MC kit (88.2% (P 0.05. The high-quality embryo rate per warmed oocyte was significantly higher (23.4% in the Modified kit group than in the other groups (P 0.05. Conclusions: Modified vitrification media are efficient for oocyte vitrification and, with further verification, may be able to replace commercially available media in future clinical applications.
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Tops, Sanne; Habel, Ute; Radke, Sina
2018-03-12
Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles. Copyright © 2018. Published by Elsevier Inc.
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Implications of the behavioral approach to hypnosis.
Starker, S
1975-07-01
The findings of behaviorally oriented research regarding the importance of cognitive-motivational variables in hypnosis are examined and some clinical and theoretical implications are explored. Hypnosis seems usefully conceptualized as a complex configuration or gestalt of interacting variables on several different levels, for example, cognitive, motivational, social, physiologic.
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Klein, Carolina A
2011-01-01
Medical practitioners are revisiting many of the ethics and the legal implications surrounding the clinical frameworks within which we operate. In today's world, distinguishing between virtual and physical reality continues to be increasingly difficult. The physician may be found grappling with the decision of whether to continue to treat a patient who may be obtaining psychotropic medications through the Internet. This article approaches some of the clinical and legal implications and the ethics regarding the availability of prescription psychotropics over the Internet.
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Directory of Open Access Journals (Sweden)
Roberto Bravo
2016-09-01
Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.
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Clinical Implications of TiGRT Algorithm for External Audit in Radiation Oncology.
Shahbazi-Gahrouei, Daryoush; Saeb, Mohsen; Monadi, Shahram; Jabbari, Iraj
2017-01-01
Performing audits play an important role in quality assurance program in radiation oncology. Among different algorithms, TiGRT is one of the common application software for dose calculation. This study aimed to clinical implications of TiGRT algorithm to measure dose and compared to calculated dose delivered to the patients for a variety of cases, with and without the presence of inhomogeneities and beam modifiers. Nonhomogeneous phantom as quality dose verification phantom, Farmer ionization chambers, and PC-electrometer (Sun Nuclear, USA) as a reference class electrometer was employed throughout the audit in linear accelerators 6 and 18 MV energies (Siemens ONCOR Impression Plus, Germany). Seven test cases were performed using semi CIRS phantom. In homogeneous regions and simple plans for both energies, there was a good agreement between measured and treatment planning system calculated dose. Their relative error was found to be between 0.8% and 3% which is acceptable for audit, but in nonhomogeneous organs, such as lung, a few errors were observed. In complex treatment plans, when wedge or shield in the way of energy is used, the error was in the accepted criteria. In complex beam plans, the difference between measured and calculated dose was found to be 2%-3%. All differences were obtained between 0.4% and 1%. A good consistency was observed for the same type of energy in the homogeneous and nonhomogeneous phantom for the three-dimensional conformal field with a wedge, shield, asymmetric using the TiGRT treatment planning software in studied center. The results revealed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy was globally within acceptable standards with no major causes for concern.
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Inherited Retinal Degenerative Clinical Trial Network
2009-10-01
clinical efforts that will impact the NEER network going forward and laid the ground work for the CTECs to participate in ongoing clinical trials for...Clinical Implications: • How will the proposed clinical trial have a significant impact on disease outcome? 34 • How will the clinical trial offer...was 0 041U>< for pat<t!nts NPtS and <H08, 0 4 1ux !01 Ct 110, 1nd 10.0 lux f01 < H13 OJ)Ilo •her on~tion are indiuttd AhtrNtor19 stimuli Wl’f1! pres
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Balajthy, Ernest
1990-01-01
The article examines the potential impact of computer-based text technologies, called hypermedia, on disabled readers. Discussed are hypertext, the hypercard, and implications of metacognitive research (such as author versus user control over text manipulations), instructional implications, and instructional text engineering. (DB)
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Profile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia
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Keller-von Amsberg G
2013-03-01
Full Text Available Gunhild Keller-von Amsberg,1 Steffen Koschmieder21Department of Hematology and Oncology, University Cancer Center Hamburg, University Hospital Hamburg Eppendorf, 2Department of Medicine (Hematology, Oncology, and Stem Cell Transplantation, University Medical Center of Aachen and RWTH Aachen University, Aachen, GermanyAbstract: Bosutinib (SKI-606 is an orally available, once-daily, dual Src and Abl kinase inhibitor with promising clinical potential in first-, second-, and third-line treatment of chronic myeloid leukemia (CML. Bosutinib effectively inhibits wild-type BCR-ABL and most imatinib-resistant BCR-ABL mutations except for V299L and T315I. Low hematologic toxicity is a remarkable characteristic of this novel second-generation tyrosine kinase inhibitor, and this has been ascribed to its minimal activity against the platelet-derived growth factor receptor and KIT. Low-grade, typically self-limiting diarrhea, which usually appears within the first few weeks after treatment initiation, represents the predominant toxicity of bosutinib. Other treatment-associated adverse events are mostly mild to moderate. Bosutinib has been approved by the US Food and Drug Administration for the treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive CML in adult patients with resistance or intolerance to prior therapy. This review summarizes the main properties of bosutinib and the currently available data on its clinical potential in the treatment of CML.Keywords: bosutinib, chronic myeloid leukemia, BCR-ABL, Src/Abl kinase inhibitor, point mutation, imatinib resistance
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Anastasia A
2016-04-01
suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications. Keywords: adjustment disorder, diagnostic criteria, stressor, mobbing, medicolegal
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Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.
Siegal, Tali
2016-01-01
Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.
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Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death
Novaleski, Carolyn K.; Carter, Bruce D.; Sivasankar, M. Preeti; Ridner, Sheila H.; Dietrich, Mary S.; Rousseau, Bernard
2017-01-01
Purpose: Vocal fold diseases affecting the epithelium have a detrimental impact on vocal function. This review article provides an overview of apoptosis, the most commonly studied type of programmed cell death. Because apoptosis can damage epithelial cells, this article examines the implications of apoptosis on diseases affecting the vocal fold…
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Peacock, James; Diaz, Keith M.; Viera, Anthony J.; Schwartz, Joseph E.; Shimbo, Daichi
2014-01-01
‘Masked hypertension’ is defined as having non-elevated clinic blood pressure (BP) with elevated out-of-clinic average BP, typically determined by ambulatory BP monitoring. Approximately 15–30% of adults with non-elevated clinic BP have masked hypertension. Masked hypertension is associated with increased risks of cardiovascular morbidity and mortality compared to sustained normotension (non-elevated clinic and ambulatory BP), which is similar to or approaching the risk associated with sustai...
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Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review
de Rooij, S. E.; Schuurmans, M. J.; van der Mast, R. C.; Levi, M. [=Marcel M.
2005-01-01
Background Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The
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Christou, Anastasis; Agüera, Ana; Bayona, Josep Maria; Cytryn, Eddie; Fotopoulos, Vasileios; Lambropoulou, Dimitra; Manaia, Célia M; Michael, Costas; Revitt, Mike; Schröder, Peter; Fatta-Kassinos, Despo
2017-10-15
The use of reclaimed wastewater (RWW) for the irrigation of crops may result in the continuous exposure of the agricultural environment to antibiotics, antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs). In recent years, certain evidence indicate that antibiotics and resistance genes may become disseminated in agricultural soils as a result of the amendment with manure and biosolids and irrigation with RWW. Antibiotic residues and other contaminants may undergo sorption/desorption and transformation processes (both biotic and abiotic), and have the potential to affect the soil microbiota. Antibiotics found in the soil pore water (bioavailable fraction) as a result of RWW irrigation may be taken up by crop plants, bioaccumulate within plant tissues and subsequently enter the food webs; potentially resulting in detrimental public health implications. It can be also hypothesized that ARGs can spread among soil and plant-associated bacteria, a fact that may have serious human health implications. The majority of studies dealing with these environmental and social challenges related with the use of RWW for irrigation were conducted under laboratory or using, somehow, controlled conditions. This critical review discusses the state of the art on the fate of antibiotics, ARB and ARGs in agricultural environment where RWW is applied for irrigation. The implications associated with the uptake of antibiotics by plants (uptake mechanisms) and the potential risks to public health are highlighted. Additionally, knowledge gaps as well as challenges and opportunities are addressed, with the aim of boosting future research towards an enhanced understanding of the fate and implications of these contaminants of emerging concern in the agricultural environment. These are key issues in a world where the increasing water scarcity and the continuous appeal of circular economy demand answers for a long-term safe use of RWW for irrigation. Copyright © 2017 Elsevier
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The clinical implications of variants of vena cava inferior and aorta on retroperitoneal surgery
Directory of Open Access Journals (Sweden)
S. V. Mukhtarulina
2014-12-01
Full Text Available Objective: to study variants of retroperitoneal vascular structure and its clinical implications on retroperitoneal surgery in patients with cervical cancer IA–IIB stage.Materials and methods. 101 patients who underwent paraaortic and bilateral pelvic lymphadenectomy were included in this study. 10 patients of the first group with anomalies of inferior vena cava, renal arteries and veins, common iliac vein and ovarian vessels were compared with 91 patients of the second group without anomalies.Results. Variants of major retroperitoneal vascular structure were present in 10 (9.9 % patients. Supernumerary renal arteries and veins observed in 5 (4.9 % patients; retroaortic left renal vein type I and II – in 3 (3.0 % patients. Double vena cava inferior detected in 1 (1.0 % patient. Patients with variants of retroperitoneal vascular structures hadn’t vessel injury. There was no difference in intraoperative hemorrhage, transfusion red blood cell, rate of intraoperative hemoglobin and removed paraaortic lymph nodes between the groups. Risk factors for intraoperative bleeding in patients with cervical cancer, depending on the presence or absence of anomalies of retroperitoneal vessels had no significant difference.Conclusion. Despite the fact that the variants of retroperitoneal vascular structures are rare (9.9 %, the success of retroperitoneal surgery is associated with the knowledge of vascular variations which decrease serious, life-threatening complications.
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Greater sage-grouse science (2015–17)—Synthesis and potential management implications
Hanser, Steven E.; Deibert, Patricia A.; Tull, John C.; Carr, Natasha B.; Aldridge, Cameron L.; Bargsten, Travis D.; Christiansen, Thomas J.; Coates, Peter S.; Crist, Michele R.; Doherty, Kevin E.; Ellsworth, Ethan A.; Foster, Lee J.; Herren, Vicki A.; Miller, Kevin H.; Moser, Ann; Naeve, Robin M.; Prentice, Karen L.; Remington, Thomas E.; Ricca, Mark A.; Shinneman, Douglas J.; Truex, Richard L.; Wiechman , Lief A.; Wilson, Dereck C.; Bowen, Zachary H.
2018-02-15
Strategy Actionable Science Plan Team, 2016).In October 2017, after a review of the 2015 Federal plans relative to State sage-grouse plans, in accordance with Secretarial Order 3353, the BLM issued a notice of intent to consider whether to amend some, all, or none of the 2015 land use plans. At that time, the BLM requested the U.S. Geological Survey (USGS) to inform this effort through the development of an annotated bibliography of sage-grouse science published since January 2015 and a report that synthesized and outlined the potential management implications of this new science. Development of the annotated bibliography resulted in the identification and summarization of 169 peer-reviewed scientific publications and reports. The USGS then convened an interagency team (hereafter referred to as the “team”) to develop this report that focuses on the primary topics of importance to the ongoing management of sage-grouse and their habitats.The team developed this report in a three-step process. First, the team identified six primary topic areas for discussion based on the members’ collective knowledge regarding sage-grouse, their habitats, and threats to either or both. Second, the team reviewed all the material in the “Annotated Bibliography of Scientific Research on Greater Sage-Grouse Published since January 2015” to identify the science that addressed the topics. Third, team members discussed the science related to each topic, evaluated the consistency of the science with existing knowledge before 2015, and summarized the potential management implications of this science. The six primary topics identified by the team were:Multiscale habitat suitability and mapping toolsDiscrete anthropogenic activitiesDiffuse activitiesFire and invasive speciesRestoration effectivenessPopulation estimation and genetics
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Women’s involvement in clinical trials: historical perspective and future implications
Directory of Open Access Journals (Sweden)
Liu KA
2016-03-01
Full Text Available The importance of considering the differences between the male and female sex in clinical decision-making is crucial. However, it has been acknowledged in recent decades that clinical trials have not always adequately enrolled women or analyzed sex-specific differences in the data. As these deficiencies have hindered the progress of understanding women’s response to medications, agencies in the United States have worked towards the inclusion of women in clinical trials and appropriate analysis of sex-specific data from clinical trials. This review outlines the history and progress of women’s inclusion in clinical trials for prescription drugs and presents considerations for researchers, clinicians, and academicians on this issue.
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Implications for would healing of patient age and time elapsed since burn injury.
Mountford, E M; Blight, A; Cheshire, I M
1995-01-01
To determine the relationship between growth potential in culture and the age of the patient, skin biopsies were obtained from over 60 patients of varying ages. The relationship between the length of time elapsed since burn injury and growth potential was also examined, using biopsies obtained from patients with burns during their treatment. Keratinocytes were extracted from biopsies and assessed for colony-forming ability by standard methods. Repeated subculture of cells was undertaken to determine the reproductive capacity of cells in vitro. Age had no effect on the colony-forming ability of keratinocytes in primary culture; however age did affect the total number of generations achieved by these cells. The growth potential of keratinocytes from patients with severe burns showed considerable variation according to the amount of time which had elapsed since the injury. This was most apparent around one week post-burn. These results need to be investigated further to understand their clinical implications. The study provides an insight into the influence of age and physiological response on the wound healing process in burn injuries.
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Wells, Ryan S.; Lynch, Cassie M.
2014-01-01
President Obama has proposed a financial aid policy whereby students who complete 100 hours of community service would receive a tax credit of US$4,000 for college. After lawmakers cut this proposal from previous legislation, the administration was tasked with studying the feasibility of implementation. However, the implications of the policy for…
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Reassessing Wind Potential Estimates for India: Economic and Policy Implications
Energy Technology Data Exchange (ETDEWEB)
Phadke, Amol; Bharvirkar, Ranjit; Khangura, Jagmeet
2011-09-15
We assess developable on-shore wind potential in India at three different hub-heights and under two sensitivity scenarios – one with no farmland included, the other with all farmland included. Under the “no farmland included” case, the total wind potential in India ranges from 748 GW at 80m hub-height to 976 GW at 120m hub-height. Under the “all farmland included” case, the potential with a minimum capacity factor of 20 percent ranges from 984 GW to 1,549 GW. High quality wind energy sites, at 80m hub-height with a minimum capacity factor of 25 percent, have a potential between 253 GW (no farmland included) and 306 GW (all farmland included). Our estimates are more than 15 times the current official estimate of wind energy potential in India (estimated at 50m hub height) and are about one tenth of the official estimate of the wind energy potential in the US.
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Optimized non relativistic potential for quarkonium
International Nuclear Information System (INIS)
Rekab, S.; Zenine, N.
2006-01-01
For non relativistic quarkonia description, we consider a wide class of quark antiquark potentials in the form of power law. A systematic study is made by optimizing the potential parameters with a fit on quarkonia vector mesons that lie below the threshold for strong decays. Implications of the obtained results are discussed
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Flanagan, S; Bartizal, K; Minassian, S L; Fang, E; Prokocimer, P
2013-07-01
Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 μM for MAO-A and 5.7 μM for MAO-B and 46.0 and 2.1 μM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459
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Tumour angiogenesis pathways: related clinical issues and implications for nuclear medicine imaging
International Nuclear Information System (INIS)
Wiele, Christophe van de; De Winter, Olivier; Dierckx, Rudi Andre; Oltenfreiter, Ruth; Slegers, Guido; Signore, Alberto
2002-01-01
Tumour angiogenesis is essential for growth, invasion and metastasis. Retrospective studies suggest that it is an independent prognostic factor that merits prospective validation. Furthermore, as tumour blood vessels show many differences from normal vessels and are not genetically unstable, they form a key area for therapy development. However, as anti-angiogenic therapy is primarily cytostatic and not cytotoxic, novel tailor-made specific end-points for treatment monitoring are required. In this regard, suitable molecular parameters for imaging tumour angiogenesis by means of nuclear medicine are being explored. Here we review current knowledge on the multiple pathways controlling tumour angiogenesis and try to assess which are the most clinically relevant for nuclear medicine imaging. Parameters that may influence the imaging potential of radiopharmaceuticals for angiogenesis imaging such as molecular weight and structure, their targeted location within the tumour and their usefulness in terms of specificity and constancy of the targeted molecular pathway are discussed. (orig.)
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Social media in clinical trials.
Thompson, Michael A
2014-01-01
Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.
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Prenatal and perinatal risk factors and the clinical implications on autism spectrum disorder.
Chien, Yi-Ling; Chou, Miao-Chun; Chou, Wen-Jiun; Wu, Yu-Yu; Tsai, Wen-Che; Chiu, Yen-Nan; Gau, Susan Shur-Fen
2018-06-01
Prenatal and perinatal factors may increase the risk of autism spectrum disorder. However, little is known about whether unaffected siblings of probands with autism spectrum disorder also share the phenomenon and whether the prenatal/perinatal factors are related to the clinical severity of autistic symptoms. We compared the frequency of prenatal and perinatal factors among 323 probands with autism spectrum disorder (mean age ± standard deviation, 10.7 ± 3.5 years; males, 91.0%), 257 unaffected siblings (11.7 ± 4.5; 42.8%), and 1504 typically developing controls (8.9 ± 1.6 years; 53.1%); and investigated their effects on the severity of autistic symptoms. We found that probands with autism spectrum disorder and their unaffected siblings had more prenatal/perinatal events than typically developing controls with higher numbers of prenatal/perinatal factors in probands than in unaffected siblings. The prenatal/perinatal events were associated with greater stereotyped behaviors, social-emotional problems, socio-communication deficits, and overall severity. We also found that six prenatal/perinatal factors (i.e. preeclampsia, polyhydramnios, oligoamnios, placenta previa, umbilical cord knot, and gestational diabetes) were associated with the severity of autistic symptoms, particularly stereotyped behaviors and socio-communication deficits. Our findings suggest that prenatal and perinatal factors may potentially moderate the clinical expression of autism spectrum disorder. The underlying mechanism warrants further research.
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Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids.
Huang, Yu-Chi; Hung, Chi-Fa; Lin, Pao-Yen; Lee, Yu; Wu, Chih-Ching; Hsu, Su-Ting; Chen, Chien-Chih; Chong, Mian-Yoon; Lin, Chieh-Hsin; Wang, Liang-Jen
2017-10-01
Past research has indicated gender differences in the clinical characteristics and course of schizophrenia. In this study, we investigated whether gender differences in the manifestation of schizophrenia are correlated with neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone. We further explored the potential relationship between the aforementioned neurosteroids and psychopathology. We recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy control subjects (47 males and 56 females) and obtained blood samples from the subjects in the morning while in a fasting state to determine the serum levels of DHEA, DHEA-S, and pregnenolone. The psychopathology and mood symptoms of patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS) and 17-item Hamilton Depression Rating Scale, respectively. Compared to the male control subjects, male patients with schizophrenia had significantly lower serum levels of DHEA and pregnenolone. In males with schizophrenia, the serum levels of DHEA and DHEA-S were associated with the age of onset and the duration of illness, while pregnenolone levels were associated with general symptoms of the PANSS. However, none of the neurosteroid levels were different between the female patients with schizophrenia and the female controls, and no significant correlation between neurosteroid levels and psychopathology evaluations was found among the schizophrenic females. Neurosteroids, including DHEA, DHEA-S, and pregnenolone, are involved in the pathophysiology of schizophrenia in male patients, but not in female ones. Therefore, our findings suggest that neurosteroids may be associated with gender differences in susceptibility to schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Developments in clinical neuropsychology: implications for school psychological services.
Cleary, Michael J; Scott, Albert J
2011-01-01
According to the 2000 Report of the Surgeon General's Conference on Children's Mental Health, a significant percentage of children and adolescents have emotional or behavioral problems serious enough to merit a mental health diagnosis. The No Child Left Behind Act of 2001 and the Individuals With Disabilities Education Improvement Act of 2004 reemphasized the schools' importance in supporting cognitive and behavioral development in students, particularly those identified with learning problems. In this article, we examine the growing specialty of clinical neuropsychology and provide suggestions for integrating this field into school-based psychological services. This article provides a review of the neuropsychological bases for many childhood learning disorders and addresses how school psychologists can work with clinical neuropsychologists to better address the needs of exceptional children through neuropsychological testing. There is substantial neurological evidence for attention-deficit hyperactivity disorder as well as disorders of reading, language, and mathematics. Close collaborative partnerships between clinical neuropsychologists and school psychologists will help develop assessment protocols that are likely to result in more effective intervention services for students with neuropsychological conditions. Schools are being asked to support the physical, cognitive, and emotional development in students, particularly those identified with chronic physical and mental health challenges. Dissatisfaction with minimal screenings, the growing awareness of the neurology of learning disorders, and the passage of the Individuals With Disabilities Education Improvement Act of 2004 obliges all school-based mental health providers to consider how to fully integrate the tools of clinical neuropsychology into school-based psychological services. © 2011, American School Health Association.
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Clinical implications from monitoring fetal activity.
Rayburn, W F
1982-12-15
The monitoring of fetal motion in high-risk pregnancies has been shown to be worthwhile in predicting fetal distress and impending fetal death. The maternal recording of perceived fetal activity is an inexpensive surveillance technique which is most useful when there is chronic uteroplacental insufficiency or when a stillbirth may be expected. The presence of an active, vigorous fetus is reassuring, but documented fetal inactivity required a reassessment of the underlying antepartum complication and further fetal evaluation with real-time ultrasonography, fetal heart rate testing, and biochemical testing. Fetal distress from such acute changes as abruptio placentae or umbilical cord compression may not be predicted by monitoring fetal motion. Although not used for routine clinical investigation, electromechanical devices such as tocodynamometry have provided much insight into fetal behavioral patterns at many stages of pregnancy and in pregnancies with an antepartum complication.
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Energy Technology Data Exchange (ETDEWEB)
Hermanussen, S.; Gaus, C. [National Research Centre for Environmental Toxicology, Brisbane (Australia); Limpus, C.J. [Queensland Environmental Protection Agency, Brisbane (Australia); Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany); Blanshard, W. [Sea World, Gold Coast (Australia); Connell, D. [School of Public Health, Griffith Univ., Brisbane (Australia)
2004-09-15
Recent investigations have identified elevated concentrations of polychlorinated dibenzo-p-dioxins (dioxins) in marine sediments and wildlife of Queensland, Australia. While it has been demonstrated that the contamination is widespread and predominantly land-based, limited information exists on the pathways and fate of these compounds within the near-shore marine system. This environment supports unique and threatened species including green sea turtles (Chelonia mydas). Adult green turtles are predominantly herbivorous, feeding on seagrass and algae. Apart from initial migration to feeding grounds (at {proportional_to}10 years of age) and intermittent migrations to breeding grounds (at {proportional_to}30-50 years and thereafter), green turtles remain and feed within relatively small home ranges. Long life-span (50 years or more), near-shore feeding grounds and highly specialized food requirements render green turtles potentially vulnerable to contaminant exposure. Recent studies have shown a relationship between PCDD/F concentrations found in herbivorous marine wildlife and concentrations in sediments of their habitats. Hence, the spatial evaluation of sediment PCDD/F distribution may assist the assessment of green turtle exposure and its potential implications. The present study provides baseline information on green turtle PCDD/F concentrations in Queensland, Australia and investigates exposure pathways. In addition, spatial distribution of PCDD/Fs in sediments from known green turtle feeding regions is assessed using geographic information systems. This represents the first stage of a large scale investigation into the exposure and sensitivity of marine reptiles to dioxins and dioxin-like compounds and to evaluate whether poor health status observed in some populations may be related to contaminant exposure.
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Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco
2011-12-01
Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both
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Cassava production and consumption: Health implications
African Journals Online (AJOL)
Mr A. O. Akinpelu
HEALTH IMPLICATIONS OF CASSAVA PRODUCTION AND CONSUMPTION. AKINPELU, A.O. ... huge potential for the export market (Egesi et al., 2007). In urban areas ... farmer's/ household income and economic growth. Stakeholders in ..... dissertation submitted to the school of graduate studies in partial fulfilment of the.
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McKenna, Dennis J
2004-05-01
Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.
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Clinical implications of bile duct injury after transcatheter arterial chemoembolization
International Nuclear Information System (INIS)
Wang Maoqiang; Tang Wenjie; Lin Hanying; Ye Huiyi; Dai Guanghai; Wang Zhiqiang
2005-01-01
Objective: To evaluate the incidence, risk factors , and clinical course of bile duct injury after transcatheter arterial chemoembolization (TACE) for treatment of hepatic malignancy. Methods: A total of 1240 consecutive patients with hepatic malignancies underwent 2680 TACE procedures. None of these patients were found to have any radiographic evidence of biliary abnormalities pre-TACE. Eighteen patients developed bile duct injuries at 3 weeks to 3 months after TACE. A retrospective review of medical records and imaging studies were carried out to evaluate the occurrence of TACE-induced bile duct injury, the clinical outcome, and the statistical significance of potential predisposing factors. Results: The TACE-induced bile duct injuries occurred in 13 of 148 patients with liver metastatic tumors (8.8%), 5 of 1092 patients with HCC (0.5%). Biliary injuries, including focal (n=4) and multiple intrahepatic bile duct dilatation (n=8), and cystic lesion or biloma (n=6), were identified on the follow-up imaging studies after TACE. Three patients with multiple bile duct injuries had mild jaundice at the presentation, two of them responded well to the conservative treatment, one died of irreversible deterioration of liver function at 2 weeks after the onset of jaundice. Four patients with a large biloma had associated serious bacterial infections; 3 of which were treated with percutaneous catheter drainage and antibiotics, 2 of them died of purulent peritonitis due to rupture of the cystic lesions and 1 cured with antibiotic. The remaining 11 patients were asymptomatic. The mortality related to the biliary injury occurred in 3 patients (16.7%). The incidences of bile duct injury were higher in patients with metastatic tumors in non-cirrhotic livers than in patients with hepatocellular carcinoma associated with cirrhosis (P<0.01), higher in patient with hypovascular lesions (P<0.01), and higher in patients using an emulsion of lipiodol-platinum for selective embolization
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Decision Analysis: Engineering Science or Clinical Art
1979-11-01
TECHNICAL REPORT TR 79-2-97 DECISION ANALYSIS: ENGINEERING SCIENCE OR CLINICAL ART ? by Dennis M. Buede Prepared for Defense Advanced Research...APPLICATIONS OF THE ENGINEER- ING SCIENCE AND CLINICAL ART EXTREMES 9 3.1 Applications of the Engineering Science Approach 9 3.1.1 Mexican electrical...DISCUSSION 29 4.1 Engineering Science versus Clinical Art : A Characterization of When Each is Most Attractive 30 4.2 The Implications of the Engineering
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The left ventricle in aortic stenosis--imaging assessment and clinical implications.
Călin, Andreea; Roşca, Monica; Beladan, Carmen Cristiana; Enache, Roxana; Mateescu, Anca Doina; Ginghină, Carmen; Popescu, Bogdan Alexandru
2015-04-29
Aortic stenosis has an increasing prevalence in the context of aging population. In these patients non-invasive imaging allows not only the grading of valve stenosis severity, but also the assessment of left ventricular function. These two goals play a key role in clinical decision-making. Although left ventricular ejection fraction is currently the only left ventricular function parameter that guides intervention, current imaging techniques are able to detect early changes in LV structure and function even in asymptomatic patients with significant aortic stenosis and preserved ejection fraction. Moreover, new imaging parameters emerged as predictors of disease progression in patients with aortic stenosis. Although proper standardization and confirmatory data from large prospective studies are needed, these novel parameters have the potential of becoming useful tools in guiding intervention in asymptomatic patients with aortic stenosis and stratify risk in symptomatic patients undergoing aortic valve replacement.This review focuses on the mechanisms of transition from compensatory left ventricular hypertrophy to left ventricular dysfunction and heart failure in aortic stenosis and the role of non-invasive imaging assessment of the left ventricular geometry and function in these patients.
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Alcohol Use Disorders: Implications for the Clinical Toxicologist
Directory of Open Access Journals (Sweden)
Michael McDonough
2015-03-01
Full Text Available Alcohol use disorders (AUDs are a health problem of high prevalence in most communities and such problems account for 5% of the total burden of disease worldwide. Clinical toxicologists are commonly required to treat patients having AUDs and associated drug/alcohol-related harm. There have been recent changes to some of the diagnostic criteria (notably in DSM V relevant to AUDs, with older terms “alcohol abuse” and “alcohol dependence” no longer being classified. AUDs may sometimes not be clearly recognizable and use of evidence-based screening interventions can help identify such conditions and lead to effective brief interventions (e.g. SBIRT programs in emergency departments. AUDs are viewed as chronic disorders of alcohol consumption occurring across a spectrum of severity. While most AUDs are mild to moderate in severity and usually self-limiting conditions, more severe presentations are more commonly encountered by physicians in emergency settings. Hence, clinical toxicologists are more likely to see patients within the more severe form of disorder, at end of the spectrum of AUDs. Among this group of patients, multi-morbidity and particularly high mortality risk exists, and thus they usually require management collaboration with specialist services. Patients with AUDs are most likely to be recognized by a clinical toxicologist in the following scenarios: following acute heavy alcohol ingestion and subsequently developing acute alcohol intoxication (ethanol toxidrome, following accidental or intentional drug overdosage where alcohol has also been consumed, following acute alcohol consumption that has been associated with behavioral risk-taking and/or self-harming (e.g. poisoning, envenomation, etc., when alcohol withdrawal reactions are severe requiring hospitalization and possibly following an adverse drug reaction.
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Mobile health: the power of wearables, sensors, and apps to transform clinical trials.
Munos, Bernard; Baker, Pamela C; Bot, Brian M; Crouthamel, Michelle; de Vries, Glen; Ferguson, Ian; Hixson, John D; Malek, Linda A; Mastrototaro, John J; Misra, Veena; Ozcan, Aydogan; Sacks, Leonard; Wang, Pei
2016-07-01
Mobile technology has become a ubiquitous part of everyday life, and the practical utility of mobile devices for improving human health is only now being realized. Wireless medical sensors, or mobile biosensors, are one such technology that is allowing the accumulation of real-time biometric data that may hold valuable clues for treating even some of the most devastating human diseases. From wearable gadgets to sophisticated implantable medical devices, the information retrieved from mobile technology has the potential to revolutionize how clinical research is conducted and how disease therapies are delivered in the coming years. Encompassing the fields of science and engineering, analytics, health care, business, and government, this report explores the promise that wearable biosensors, along with integrated mobile apps, hold for improving the quality of patient care and clinical outcomes. The discussion focuses on groundbreaking device innovation, data optimization and validation, commercial platform integration, clinical implementation and regulation, and the broad societal implications of using mobile health technologies. © 2016 New York Academy of Sciences.
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Goic-Barisic, Ivana; Hrenovic, Jasna; Kovacic, Ana; Musić, Martina Šeruga
2016-10-01
Six carbapenem-resistant isolates of Acinetobacter baumannii were recovered from untreated and treated municipal wastewater of the capital city of Zagreb, Croatia. Molecular identification of environmental isolates of A. baumannii was performed by amplification, sequencing, and phylogenetic analyses of rpoB gene. The presence of bla OXA genes encoding OXA-type carbapenemases (OXA-51-like, OXA-23, and OXA-40-like) was confirmed by multiplex PCR and sequencing. Phylogenetic analyses corroborated the affiliation of detected bla OXA genes to three different clusters and showed association of environmental OXAs with those described from clinical isolates. This result suggests that isolates recovered from municipal wastewater are most probably of clinical origin. Furthermore, the presence of OXA-40-like (OXA-72) in an environmental A. baumannii isolate is reported for the first time. Persistence of A. baumannii harboring the clinically important OXAs in the wastewater treatment process poses a potentially significant source for horizontal gene transfer and implications for wider spread of antibiotic resistance genes.
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Implication of novel thiazolo-thiophene derivative (MCD-KV-10) for management of asthma.
Patil, Dhiraj; Dash, Ranjeet Prasad; Thakur, Sandeep Kumar; Pandya, Amit N; Venkatesh, P; Vasu, Kamala K; Nivsarkar, Manish
2015-04-01
Asthma is multifaceted disease where many targets contribute towards its development and progression. Among these, adenosine receptor subtypes play a major role. MCD-KV-10, a novel thiazolo-thiophene was designed and evaluated pre-clinically for its implication in management of asthma. This compound showed good affinity and selectivity towards A(2A)/A3 adenosine receptor (AR) subtypes. Furthermore, MCD-KV-10 was evaluated for in vitro lipoxygenase inhibition activity; in vivo mast cell stabilization potential and in vivo anti-asthmatic activity was done in ovalbumin-induced airway inflammation model in guinea pigs. The compound showed good (>57%) inhibition of lipoxygenase enzyme and also effectively protected mast cell degranulation (>63%). The compound showed good anti-asthmatic activity as inferred from the in vivo studies. These results indicate that MCD-KV-10 has an inhibitory effect on airway inflammation. Though, we have identified a potential candidate for management of asthma, further mechanistic studies are needed.
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Clinical Implications of TiGRT Algorithm for External Audit in Radiation Oncology
Directory of Open Access Journals (Sweden)
Daryoush Shahbazi-Gahrouei
2017-01-01
Full Text Available Background: Performing audits play an important role in quality assurance program in radiation oncology. Among different algorithms, TiGRT is one of the common application software for dose calculation. This study aimed to clinical implications of TiGRT algorithm to measure dose and compared to calculated dose delivered to the patients for a variety of cases, with and without the presence of inhomogeneities and beam modifiers. Materials and Methods: Nonhomogeneous phantom as quality dose verification phantom, Farmer ionization chambers, and PC-electrometer (Sun Nuclear, USA as a reference class electrometer was employed throughout the audit in linear accelerators 6 and 18 MV energies (Siemens ONCOR Impression Plus, Germany. Seven test cases were performed using semi CIRS phantom. Results: In homogeneous regions and simple plans for both energies, there was a good agreement between measured and treatment planning system calculated dose. Their relative error was found to be between 0.8% and 3% which is acceptable for audit, but in nonhomogeneous organs, such as lung, a few errors were observed. In complex treatment plans, when wedge or shield in the way of energy is used, the error was in the accepted criteria. In complex beam plans, the difference between measured and calculated dose was found to be 2%–3%. All differences were obtained between 0.4% and 1%. Conclusions: A good consistency was observed for the same type of energy in the homogeneous and nonhomogeneous phantom for the three-dimensional conformal field with a wedge, shield, asymmetric using the TiGRT treatment planning software in studied center. The results revealed that the national status of TPS calculations and dose delivery for 3D conformal radiotherapy was globally within acceptable standards with no major causes for concern.
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Relational Aggression, Victimization, and Language Development: Implications for Practice
Ostrov, Jamie M.; Godleski, Stephanie A.
2007-01-01
This review explores the development of relational aggression and relational victimization among peers, with specific emphasis on clinical implications for speech-language pathologists. Developmental manifestations of relational aggression and victimization are reviewed from early childhood through emerging adulthood. The concurrent and…
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Horizontal fissure on neonatal plain chest radiographs: clinical implications
International Nuclear Information System (INIS)
Konarzewska, J.; Zawadzka-Kepczynska, A.; Bianek-Bodzak, A.; Kawinska-Kilianczyk, A.; Domzalska-Popadiuk, I.
2005-01-01
Regardless of etiology, pleural fluid, even in small amounts, can be visualized on the neonatal chest x-ray picture within pulmonary fissures. It remains unclear whether a marked horizontal fissure unaccompanied by any other radiological symptoms is of diagnostic value or not. Ninety-one consecutive neonatal chest radiographs with marked horizontal fissure were retrospectively analyzed. The images were made between 1999 and 2005 on 69 newborns admitted to the Neonatology Department, Institute of Obstetrics and Gynecology, Medical University of Gdansk. Analysis of the radiographs was conducted independently by three radiologists based on the following criteria: fissure thickness (marked or thickened), bronchovascular markings (increased or normal), size and shape of the heart (normal or abnormal), presence or absence of pulmonary infiltration, atelectasis, and changes related to wet lung syndrome. Due to divergent interpretations, the ultimate interpretation was established by consensus in 25 cases. The radiological findings were compared with clinical data. The compatibility of the three independent interpreters was statistically significant (p<0.0001). Marked transverse fissure was the only radiological finding on 66 x-rays. In 63 cases (69.2%) the children were asymptomatic as well. In 3 cases (3.3%) clinical symptoms of respiratory tract infection occurred. On the other 25 images, horizontal fissure was accompanied by other radiological symptoms. Chest x-ray results corresponded with clinical symptoms in 24 cases (26.4%). One child (1.1%) with radiological evidence of wet lung syndrome did not present any typical clinical symptoms of it. Horizontal fissure noted on a neonatal chest x-ray seems to be of minor diagnostic value if not accompanied by any other radiological symptoms. (author)
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Koh, Kyungwon; Rubenstein, Ellen; White, Kelvin
2015-01-01
Introduction: This pilot study examined how current information behaviour research addresses the implications and potential impacts of its findings. The goal was to understand what implications and contributions the field has made and how effectively authors communicate implications of their findings. Methods: We conducted a content analysis of 30…
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Ignatowicz, Agnieszka; Slowther, Anne-Marie; Elder, Patrick; Bryce, Carol; Hamilton, Kathryn; Huxley, Caroline; Forjaz, Vera; Sturt, Jackie; Griffiths, Frances
2018-02-23
Digital communication between a patient and their clinician offers the potential for improved patient care, particularly for young people with long term conditions who are at risk of service disengagement. However, its use raises a number of ethical questions which have not been explored in empirical studies. The objective of this study was to examine, from the patient and clinician perspective, the ethical implications of the use of digital clinical communication in the context of young people living with long-term conditions. A total of 129 semi-structured interviews, 59 with young people and 70 with healthcare professionals, from 20 United Kingdom (UK)-based specialist clinics were conducted as part of the LYNC study. Transcripts from five sites (cancer, liver, renal, cystic fibrosis and mental health) were read by a core team to identify explicit and implicit ethical issues and develop descriptive ethical codes. Our subsequent thematic analysis was developed iteratively with reference to professional and ethical norms. Clinician participants saw digital clinical communication as potentially increasing patient empowerment and autonomy; improving trust between patient and healthcare professional; and reducing harm because of rapid access to clinical advice. However, they also described ethical challenges, including: difficulty with defining and maintaining boundaries of confidentiality; uncertainty regarding the level of consent required; and blurring of the limits of a clinician's duty of care when unlimited access is possible. Paradoxically, the use of digital clinical communication can create dependence rather than promote autonomy in some patients. Patient participants varied in their understanding of, and concern about, confidentiality in the context of digital communication. An overarching theme emerging from the data was a shifting of the boundaries of the patient-clinician relationship and the professional duty of care in the context of use of clinical
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Kos, Mark Z; Carless, Melanie A; Peralta, Juan; Curran, Joanne E; Quillen, Ellen E; Almeida, Marcio; Blackburn, August; Blondell, Lucy; Roalf, David R; Pogue-Geile, Michael F; Gur, Ruben C; Göring, Harald H H; Nimgaonkar, Vishwajit L; Gur, Raquel E; Almasy, Laura
2017-12-01
Schizophrenia is a serious mental illness, involving disruptions in thought and behavior, with a worldwide prevalence of about one percent. Although highly heritable, much of the genetic liability of schizophrenia is yet to be explained. We searched for susceptibility loci in multiplex, multigenerational families affected by schizophrenia, targeting protein-altering variation with in silico predicted functional effects. Exome sequencing was performed on 136 samples from eight European-American families, including 23 individuals diagnosed with schizophrenia or schizoaffective disorder. In total, 11,878 non-synonymous variants from 6,396 genes were tested for their association with schizophrenia spectrum disorders. Pathway enrichment analyses were conducted on gene-based test results, protein-protein interaction (PPI) networks, and epistatic effects. Using a significance threshold of FDR < 0.1, association was detected for rs10941112 (p = 2.1 × 10 -5 ; q-value = 0.073) in AMACR, a gene involved in fatty acid metabolism and previously implicated in schizophrenia, with significant cis effects on gene expression (p = 5.5 × 10 -4 ), including brain tissue data from the Genotype-Tissue Expression project (minimum p = 6.0 × 10 -5 ). A second SNP, rs10378 located in TMEM176A, also shows risk effects in the exome data (p = 2.8 × 10 -5 ; q-value = 0.073). PPIs among our top gene-based association results (p < 0.05; n = 359 genes) reveal significant enrichment of genes involved in NCAM-mediated neurite outgrowth (p = 3.0 × 10 -5 ), while exome-wide SNP-SNP interaction effects for rs10941112 and rs10378 indicate a potential role for kinase-mediated signaling involved in memory and learning. In conclusion, these association results implicate AMACR and TMEM176A in schizophrenia risk, whose effects may be modulated by genes involved in synaptic plasticity and neurocognitive performance. © 2017 Wiley Periodicals, Inc.
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Sunagar, Kartik; Undheim, Eivind A B; Scheib, Holger; Gren, Eric C K; Cochran, Chip; Person, Carl E; Koludarov, Ivan; Kelln, Wayne; Hayes, William K; King, Glenn F; Antunes, Agosthino; Fry, Bryan Grieg
2014-03-17
the Catalina Island population appears to have evolved under the constraint of negative selection. Both lectin chains were conspicuously absent in both the proteomics and transcriptomics of the Idyllwild population. Thus, we not only highlight the tremendous biochemical diversity in C. o. helleri's venom-arsenal, but we also show that they experience remarkably variable strengths of evolutionary selection pressures, within each toxin class among populations and among toxin classes within each population. The mapping of geographical venom variation not only provides additional information regarding venom evolution, but also has direct medical implications by allowing prediction of the clinical effects of rattlesnake bites from different regions. Such information, however, also points to these highly variable venoms as being a rich source of novel toxins which may ultimately prove to be useful in drug design and development. These results have direct implications for the treatment of envenomed patients. The variable venom profile of Crotalus oreganus helleri underscores the biodiscovery potential of novel snake venoms. Copyright © 2014 Elsevier B.V. All rights reserved.
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Pharmacogenetics: progress, pitfalls and clinical potential for coronary heart disease.
Humphries, Steve E; Hingorani, Aroon
2006-02-01
Much has been written about the potential of pharmacogenetic testing to inform therapy based on an individual's genetic makeup, and to decide the most effective choice of available drugs, or to avoid dangerous side effects. Currently, there is little hard data for either in the field of cardiovascular disease. The usual approach has been opportunistic use of drug trials in unrelated patients, and to look for differences in response or outcome by "candidate gene" genotype, for example genes coding for drug metabolising enzymes (activators and metabolisers), and enzymes and receptors involved in lipid metabolism, adrenergic response, etc. As with all association studies, initially promising results have often failed the test of replication in larger studies, and the relationship between the CETP Taq-I variant and response to statins has now been disproved. The strongest data to date is the report [Chasman, D.I., Posada, D., Subrahmanyan, L., Cook, N.R., Stanton Jr., V.P., Ridker, P.M., 2004. Pharmacogenetic study of statin therapy and cholesterol reduction. J. Am. Med. Assoc. 291, 2821-2827] of a poorer cholesterol-lowering response to Pravastatin in the 7% of patients carrying a certain haplotype of the HMG CoA reductase gene (14% fall versus 19%), but if this is overcome simply by a higher dose, it is of little clinical relevance. Currently, the best example of avoiding side effects is determining genotype at the CYP2C9 locus with respect of warfarin treatment, since carriers for functional variants (>20% of the population) require lower doses for optimal anticoagulation, and homozygotes, although rare, may well experience serious bleeding if given a usual dose. The full potential of this field will only be realised with much further work.
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Weinfurt, Kevin P; Friedman, Joëlle Y; Allsbrook, Jennifer S; Dinan, Michaela A; Hall, Mark A; Sugarman, Jeremy
2006-09-01
There is little guidance regarding how to disclose researchers' financial interests to potential research participants. To determine what potential research participants want to know about financial interests, their capacity to understand disclosed information and its implications, and the reactions of potential research participants to a proposed disclosure statement. Sixteen focus groups in 3 cities, including 6 groups of healthy adults, 6 groups of adults with mild chronic illness, 1 group of parents of healthy children, 1 group of parents of children with leukemia or brain tumor, 1 group of adults with heart failure, and 1 group of adults with cancer. Focus group discussions covered a range of topics including financial relationships in clinical research, whether people should be told about them, and how they should be told. Audio-recordings of focus groups were transcribed, verified, and coded for analysis. Participants wanted to know about financial interests, whether or not those interests would affect their participation. However, they varied in their desire and ability to understand the nature and implications of financial interests. Whether disclosure was deemed important depended upon the risk of the research. Trust in clinicians was also related to views regarding disclosure. If given the opportunity to ask questions during the consent process, some participants would not have known what to ask; however, after the focus group sessions, participants could identify information they would want to know. Financial interests are important to potential research participants, but obstacles to effective disclosure exist.
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HNF1B-associated clinical phenotypes: the kidney and beyond.
Bockenhauer, Detlef; Jaureguiberry, Graciana
2016-05-01
Mutations in HNF1B, the gene encoding hepatocyte nuclear factor 1β are the most commonly identified genetic cause of renal malformations. HNF1B was first identified as a disease gene for diabetes (MODY5) in 1997, and its involvement in renal disease was subsequently noted through clinical observations in pedigrees affected by MODY5. Since then, a whole spectrum of associated phenotypes have been reported, including genital malformations, autism, epilepsy, gout, hypomagnesaemia, primary hyperparathyroidism, liver and intestinal abnormalities and a rare form of kidney cancer. The most commonly identified mutation, in approximately 50 % of patients, is an entire gene deletion occurring in the context of a 17q12 chromosomal microdeletion that also includes several other genes. Some of the associated phenotypes, especially the neurologic ones, appear to occur only in the context of this microdeletion and thus may not be directly linked to HNF1B. Here we review the spectrum of associated phenotypes and discuss potential implications for clinical management.
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Berghi, Nicolae Ovidiu
2017-08-01
Autoimmunity represents the attack of the immune system of an organism against its own cells and tissues. Autoimmune diseases may affect one organ (Hashimoto thyroiditis) or can be systemic (chronic urticaria). Many factors are implicated in the pathogenesis of autoimmunity (white cells, cytokines, chemokines). Hashimoto thyroiditis has been associated with chronic urticaria in the last 3 decades in a number of clinical studies. Anti-thyroid antibodies have been documented in a proportion ranging from 10% to 30% in chronic urticaria patients in different countries from 3 continents. Two of the factors involved in the mechanism of autoimmunity are present both in the pathophysiology of Hashimoto thyroiditis and chronic urticaria. According to recent studies, IL6 is implicated in the pathogenesis of both diseases. TregsCD4+CD25+Foxp3+ cells have also been implicated in the pathological mechanisms of these 2 entities. This review offers an explanation of the clinical and statistical association between these two diseases from the pathophysiological point of view.
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Visual research in clinical education.
Bezemer, Jeff
2017-01-01
The aim of this paper is to explore what might be gained from collecting and analysing visual data, such as photographs, scans, drawings, video and screen recordings, in clinical educational research. Its focus is on visual research that looks at teaching and learning 'as it naturally occurs' in the work place, in simulation centres and other sites, and also involves the collection and analysis of visual learning materials circulating in these sites. With the ubiquity of digital recording devices, video data and visual learning materials are now relatively cheap to collect. Compared to other domains of education research visual materials are not widely used in clinical education research. The paper sets out to identify and reflect on the possibilities for visual research using examples from an ethnographic study on surgical and inter-professional learning in the operating theatres of a London hospital. The paper shows how visual research enables recognition, analysis and critical evaluation of (1) the hidden curriculum, such as the meanings implied by embodied, visible actions of clinicians; (2) the ways in which clinical teachers design multimodal learning environments using a range of modes of communication available to them, combining, for instance, gesture and speech; (3) the informal assessment of clinical skills, and the intricate relation between trainee performance and supervisor feedback; (4) the potentialities and limitations of different visual learning materials, such as textbooks and videos, for representing medical knowledge. The paper concludes with theoretical and methodological reflections on what can be made visible, and therefore available for analysis, explanation and evaluation if visual materials are used for clinical education research, and what remains unaccounted for if written language remains the dominant mode in the research cycle. Opportunities for quantitative analysis and ethical implications are also discussed. © 2016 John Wiley
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Functional and clinical neuroanatomy of morality.
Fumagalli, Manuela; Priori, Alberto
2012-07-01
-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.
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Clinical implications of lactose malabsorption versus lactose intolerance.
Levitt, Michael; Wilt, Timothy; Shaukat, Aasma
2013-07-01
The majority of the world's adult population and an estimated 80 million Americans are hypolactasic and hence malabsorb ingested lactose. Although lactose malabsorption is easily identified, less readily assessed is the clinically important question of how often does this malabsorption induce symptoms. This review summarizes: (1) knowledge concerning the etiology and diagnosis of hypolactasia and the pathophysiology of the symptoms of lactose malabsorption and (2) the results of well-controlled trials of the symptomatic response of lactose malabsorbers to varying dosages of lactose and the efficacy of therapeutic interventions to alleviate these symptoms. We conclude that the clinical significance of lactose malabsorption has been overestimated by both the lay public and physicians in that commonly ingested doses of lactose (ie, the quantity in a cup of milk) usually do not cause perceptible symptoms when ingested with a meal. Symptoms occur when the lactose dosage exceeds that in a cup of milk or when lactose is ingested without other nutrients. Simple dietary instruction, rather than the use of commercial products to reduce lactose intake, is recommended for the vast majority of lactose-malabsorbing subjects.
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The Chemical Potential of Plasma Membrane Cholesterol: Implications for Cell Biology.
Ayuyan, Artem G; Cohen, Fredric S
2018-02-27
Cholesterol is abundant in plasma membranes and exhibits a variety of interactions throughout the membrane. Chemical potential accounts for thermodynamic consequences of molecular interactions, and quantifies the effective concentration (i.e., activity) of any substance participating in a process. We have developed, to our knowledge, the first method to measure cholesterol chemical potential in plasma membranes. This was accomplished by complexing methyl-β-cyclodextrin with cholesterol in an aqueous solution and equilibrating it with an organic solvent containing dissolved cholesterol. The chemical potential of cholesterol was thereby equalized in the two phases. Because cholesterol is dilute in the organic phase, here activity and concentration were equivalent. This equivalence allowed the amount of cholesterol bound to methyl-β-cyclodextrin to be converted to cholesterol chemical potential. Our method was used to determine the chemical potential of cholesterol in erythrocytes and in plasma membranes of nucleated cells in culture. For erythrocytes, the chemical potential did not vary when the concentration was below a critical value. Above this value, the chemical potential progressively increased with concentration. We used standard cancer lines to characterize cholesterol chemical potential in plasma membranes of nucleated cells. This chemical potential was significantly greater for highly metastatic breast cancer cells than for nonmetastatic breast cancer cells. Chemical potential depended on density of the cancer cells. A method to alter and fix the cholesterol chemical potential to any value (i.e., a cholesterol chemical potential clamp) was also developed. Cholesterol content did not change when cells were clamped for 24-48 h. It was found that the level of activation of the transcription factor STAT3 increased with increasing cholesterol chemical potential. The cholesterol chemical potential may regulate signaling pathways. Copyright © 2018. Published by
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The Future Nuclear Arms Control Agenda and Its Potential Implications for the Air Force
2015-08-01
US AIR FORCE INSTITUTE FOR NATIONAL SECURITY STUDIES USAF ACADEMY, COLORADO INSS OCCASIONAL PAPER AUGUST 2015 70 Dr. Lewis A. Dunn The Future...Implications for the Air Force Dr. Lewis A. Dunn INSS Occasional Paper 70 August 2015 USAF Institute for National Security Studies USAF
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Full Text Available ... take part in a clinical trial. When researchers think that a trial's potential risks are greater than ... care costs for clinical trials. If you're thinking about taking part in a clinical trial, find ...
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Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep
2016-06-01
Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.
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Autoinflammatory diseases in adults. Clinical characteristics and prognostic implications.
González García, A; Patier de la Peña, J L; Ortego Centeno, N
2017-03-01
Autoinflammatory diseases are clinical conditions with inflammatory manifestations that present in a periodic or persistent manner and are caused by acquired or hereditary disorders of the innate immune response. In general, these diseases are more common in childhood, but cases have been reported in adults and are therefore important for all specialists. There are few references on these diseases in adults due to their low prevalence and underdiagnosis. The aim of this study is to review the scientific literature on these disorders to systematise their clinical, prognostic and treatment response characteristics in adults. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.
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Human reporter genes: potential use in clinical studies
Energy Technology Data Exchange (ETDEWEB)
Serganova, Inna [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Ponomarev, Vladimir [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Blasberg, Ronald [Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States); Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 (United States)], E-mail: blasberg@neuro1.mskcc.org
2007-10-15
The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies
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Human reporter genes: potential use in clinical studies
International Nuclear Information System (INIS)
Serganova, Inna; Ponomarev, Vladimir; Blasberg, Ronald
2007-01-01
The clinical application of positron-emission-tomography-based reporter gene imaging will expand over the next several years. The translation of reporter gene imaging technology into clinical applications is the focus of this review, with emphasis on the development and use of human reporter genes. Human reporter genes will play an increasingly more important role in this development, and it is likely that one or more reporter systems (human gene and complimentary radiopharmaceutical) will take leading roles. Three classes of human reporter genes are discussed and compared: receptors, transporters and enzymes. Examples of highly expressed cell membrane receptors include specific membrane somatostatin receptors (hSSTrs). The transporter group includes the sodium iodide symporter (hNIS) and the norepinephrine transporter (hNET). The endogenous enzyme classification includes human mitochondrial thymidine kinase 2 (hTK2). In addition, we also discuss the nonhuman dopamine 2 receptor and two viral reporter genes, the wild-type herpes simplex virus 1 thymidine kinase (HSV1-tk) gene and the HSV1-tk mutant (HSV1-sr39tk). Initial applications of reporter gene imaging in patients will be developed within two different clinical disciplines: (a) gene therapy and (b) adoptive cell-based therapies. These studies will benefit from the availability of efficient human reporter systems that can provide critical monitoring information for adenoviral-based, retroviral-based and lenteviral-based gene therapies, oncolytic bacterial and viral therapies, and adoptive cell-based therapies. Translational applications of noninvasive in vivo reporter gene imaging are likely to include: (a) quantitative monitoring of gene therapy vectors for targeting and transduction efficacy in clinical protocols by imaging the location, extent and duration of transgene expression; (b) monitoring of cell trafficking, targeting, replication and activation in adoptive T-cell and stem/progenitor cell therapies
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Lopresti, Adrian L
2017-06-01
There is growing evidence confirming increased inflammation in a subset of adults with depression. The impact of this relationship has mostly been considered in biologically based interventions; however, it also has potential implications for psychological therapies. Cognitive behaviour therapy is the most commonly used psychological intervention for the treatment of depression with theories around its efficacy primarily based on psychological mechanisms. However, cognitive behaviour therapy may have an effect on, and its efficacy influenced by, physiological processes associated with depression. Accordingly, the purpose of this systematic review was to examine the relationship between cognitive behaviour therapy and inflammation. Studies examining the anti-inflammatory effects of cognitive behaviour therapy in people with depression and other medical conditions (e.g. cancer, diabetes and heart disease) were examined. In addition, the relationship between change in inflammatory markers and change in depressive symptoms following cognitive behaviour therapy, and the influence of pre-treatment inflammation on cognitive behaviour therapy treatment response were reviewed. A total of 23 studies investigating the anti-inflammatory effects of cognitive behaviour therapy were identified. In 14 of these studies, at least one reduction in an inflammatory marker was reported, increases were identified in three studies and no change was found in six studies. Three studies examined the relationship between change in inflammation and change in depressive symptoms following cognitive behaviour therapy. In two of these studies, change in depressive symptoms was associated with a change in at least one inflammatory marker. Finally, three studies examined the influence of pre-treatment inflammation on treatment outcome from cognitive behaviour therapy, and all indicated a poorer treatment response in people with higher premorbid inflammation. Preliminary evidence suggests
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Clinical implications of pleural effusion in patients with acute type B aortic dissection.
Yamada, Yoshihiro; Tanno, Jun; Nakano, Shintaro; Kasai, Takatoshi; Senbonmatsu, Takaaki; Nishimura, Shigeyuki
2016-11-01
Pleural effusion may complicate acute Stanford type B aortic dissection (ABAD). To identify the relationships between the quantity and side of the pleural effusion, biomarkers and outcomes in patients with ABAD. We undertook a retrospective review of 105 patients with ABAD. Their demographics, the data on admission and during hospital stay, the volume of pleural effusion calculated from the area on computed tomography images and clinical outcomes were analysed. The median estimated peak volume (median 6.7 days after onset) was 129 ml (63-192, range 26-514 ml) on the left and 11 ml (6-43, range 2-300 ml) on the right. On univariate analysis, the volume of bilateral effusions was associated with anaemia, hypoalbuminaemia and inflammatory markers, whereas the volume of left-sided effusions was associated with older age, low diastolic blood pressure and maximum aortic diameter. Multivariate analysis revealed that hypoalbuminaemia was independently associated with bilateral effusion volume ( Peffusion volume ( P=0.019). A greater volume of bilateral plural effusion was associated with longer intensive care unit stay. Larger bilateral pleural effusions in patients with ABAD were associated with hypoalbuminaemia and potentially with anaemia and inflammation, and may increase the length of intensive care unit stay. Left-sided effusion volume appears to be influenced by the nature of the aortic dilatation. Multiple mechanisms may underpin the development of pleural effusion in ABAD, and are likely to influence clinical outcomes.