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Sample records for current therapeutic concepts

  1. OSTEOARTHRITIS: CURRENT CLINICAL CONCEPT AND SOME PROMISING THERAPEUTIC APPROACHES

    A. E. Karateev

    2018-01-01

    Full Text Available In recent years, there has been a trend toward changing the clinical concept of osteoarthritis (OA. This disease has been considered as an age-related disease and the long-term result of a current pathological process for a very long time. However, many experts are now inclined to consider it necessary to identify the early, pre-X-ray stage of OA, when adequate treatment may not only halt the progression, but also achieve the regression of joint structural changes. This review deals with a number of pathogenetic and clinical aspects of the early stages of OA, which are important for timely diagnosis and pathogenetic therapy choice. It also considers some therapeutic approaches, both a "classic" and recently actively discussed methods for using platelet-rich plasma and autologous chondrocyte transplantation.

  2. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine

    Koch, Thomas Gadegaard; Berg, Lise Charlotte; Betts, Dean H.

    2009-01-01

    This paper provides a bird's-eye perspective of the general principles of stem-cell therapy and tissue engineering; it relates comparative knowledge in this area to the current and future status of equine regenerative medicine.The understanding of equine stem cell biology, biofactors, and scaffolds...... mesenchymal stromal cells, unless there is proof that they exhibit the fundamental in vivo characteristics of pluripotency and the ability to self-renew. That said, these cells from various tissues hold great promise for therapeutic use in horses. The 3 components of tissue engineering - cells, biological...... factors, and biomaterials - are increasingly being applied in equine medicine, fuelled by better scaffolds and increased understanding of individual biofactors and cell sources.The effectiveness of stem cell-based therapies and most tissue engineering concepts has not been demonstrated sufficiently...

  3. Andropause: Current concepts

    Parminder Singh

    2013-01-01

    Full Text Available Andropause or late-onset hypogonadism is a common disorder which increases in prevalence with advancing age. Diagnosis of late-onset of hypogonadism is based on presence of symptoms suggestive of testosterone deficiency - prominent among them are sexual symptoms like loss of libido, morning penile erection and erectile dysfunction; and demonstration of low testosterone levels. Adequate therapeutic modalities are currently available, but disparate results of clinical trial suggest further evaluation of complex interaction between androgen deficiency and ageing. Before initiating therapy benefits and risk should be discussed with patients and in case of poor response , alternative cause should be investigated.

  4. Intracranial atherosclerosis: current concepts.

    Arenillas, Juan F

    2011-01-01

    The most relevant ideas discussed in this article are described here. Intracranial atherosclerotic disease (ICAD) represents the most common cause of ischemic stroke worldwide. Its importance in whites may have been underestimated. New technical developments, such as high-resolution MRI, allow direct assessment of the intracranial atherosclerotic plaque, which may have a profound impact on ICAD diagnosis and therapy in the near future. Early detection of ICAD may allow therapeutic intervention while the disease is still asymptomatic. The Barcelonès Nord and Maresme Asymptomatic Intracranial Atherosclerosis Study is presented here. The main prognostic factors that characterize the patients who are at a higher risk for ICAD recurrence are classified and discussed. The best treatment for ICAD remains to be established. The Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Study is currently ongoing to address this crucial issue. These and other topics will be discussed at the Fifth International Intracranial Atherosclerosis Conference (Valladolid, Spain, autumn 2011).

  5. Football injuries: current concepts.

    Olson, David E; Sikka, Robby Singh; Hamilton, Abigail; Krohn, Austin

    2011-01-01

    Football is one of the most popular sports in the United States and is the leading cause of sports-related injury. A large focus in recent years has been on concussions, sudden cardiac death, and heat illness, all thought to be largely preventable health issues in the young athlete. Injury prevention through better understanding of injury mechanisms, education, proper equipment, and practice techniques and preseason screening may aid in reducing the number of injuries. Proper management of on-field injuries and health emergencies can reduce the morbidity associated with these injuries and may lead to faster return to play and reduced risk of future injury. This article reviews current concepts surrounding frequently seen football-related injuries.

  6. [Actinic keratosis: New concept and therapeutic update].

    Carmena-Ramón, Rafael; Mateu-Puchades, Almudena; Santos-Alarcón, Sergio; Lucas-Truyols, Sofía

    2017-10-01

    Actinic keratosis (AK) is a common reason for consultation in both Primary Care and Specialised Care. It is the third or fourth most common reason for consultation in dermatology, accounting for up to 5-6% of patients attended. It has also been observed that its prevalence has been increasing in the last 10years, compared to other dermatoses. This is also expected to continue to increase due to longer life expectancy, and by the changes in sun exposure habits since the middle of the last century. The aim of this article is to update the concepts of AK, cancerisation field and to present the currently available therapeutic tools. Copyright © 2017. Publicado por Elsevier España, S.L.U.

  7. Pediatric obesity: Current concepts.

    Greydanus, Donald E; Agana, Marisha; Kamboj, Manmohan K; Shebrain, Saad; Soares, Neelkamal; Eke, Ransome; Patel, Dilip R

    2018-04-01

    This discussion reflects on concepts of obesity in children and adolescents in the early 21st century. It includes reflections on its history, definition, epidemiology, diagnostic perspectives, psychosocial considerations, musculoskeletal complications, endocrine complications and principles of management. In addition to emphasis on diet and exercise, research and clinical applications in the second decade of the 21 st century emphasize the increasing use of pharmacotherapy and bariatric surgery for adolescent and adult populations with critical problems of overweight and obesity. We conclude with a discussion of future directions in pediatric obesity management. Copyright © 2018 Mosby, Inc. All rights reserved.

  8. Marijuana: Current concepts

    Donald eGreydanus

    2013-10-01

    Full Text Available Marijuana (cannabis remains a controversial drug in the 21st century. This paper considers current research on use of Cannabis sativa and its constituents such as the cannabinoids. Topics reviewed include prevalence of cannabis use, other drugs consumed with pot, the endocannabinoid system, use of medicinal marijuana, medical adverse effects of cannabis, and psychiatric adverse effects of cannabis use. Treatment of cannabis withdrawal and dependence is difficult and remains mainly based on psychological therapy; current research on pharmacologic management of problems related to cannabis consumption is also considered. The potential role of specific cannabinoids for medical benefit will be revealed as the 21st century matures. However, potential dangerous adverse effects from smoking marijuana are well known and should be clearly taught to a public often confused by a media-driven, though false message and promise of benign pot consumption.

  9. Transgender youth: current concepts

    2016-01-01

    In many countries throughout the world, increasing numbers of gender nonconforming/transgender youth are seeking medical services to enable the development of physical characteristics consistent with their experienced gender. Such medical services include use of agents to block endogenous puberty at Tanner stage II with subsequent use of cross-sex hormones, and are based on longitudinal studies demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and continue to meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. This review addresses terms and definitions applicable to gender nonconforming youth, studies that shed light on the biologic determinants of gender identity, current clinical practice guidelines for transgender youth, challenges to optimal care, and priorities for research. PMID:28164070

  10. Transgender youth: current concepts

    Stephen M. Rosenthal

    2016-12-01

    Full Text Available In many countries throughout the world, increasing numbers of gender nonconforming/transgender youth are seeking medical services to enable the development of physical characteristics consistent with their experienced gender. Such medical services include use of agents to block endogenous puberty at Tanner stage II with subsequent use of cross-sex hormones, and are based on longitudinal studies demonstrating that those individuals who were first identified as gender dysphoric in early or middle childhood and continue to meet the mental health criteria for being transgender at early puberty are likely to be transgender as adults. This review addresses terms and definitions applicable to gender nonconforming youth, studies that shed light on the biologic determinants of gender identity, current clinical practice guidelines for transgender youth, challenges to optimal care, and priorities for research.

  11. Current concepts of severe asthma

    Raundhal, Mahesh; Oriss, Timothy B.; Ray, Prabir; Wenzel, Sally E.

    2016-01-01

    The term asthma encompasses a disease spectrum with mild to very severe disease phenotypes whose traditional common characteristic is reversible airflow limitation. Unlike milder disease, severe asthma is poorly controlled by the current standard of care. Ongoing studies using advanced molecular and immunological tools along with improved clinical classification show that severe asthma does not identify a specific patient phenotype, but rather includes patients with constant medical needs, whose pathobiologic and clinical characteristics vary widely. Accordingly, in recent clinical trials, therapies guided by specific patient characteristics have had better outcomes than previous therapies directed to any subject with a diagnosis of severe asthma. However, there are still significant gaps in our understanding of the full scope of this disease that hinder the development of effective treatments for all severe asthmatics. In this Review, we discuss our current state of knowledge regarding severe asthma, highlighting different molecular and immunological pathways that can be targeted for future therapeutic development. PMID:27367183

  12. CURRENT CONCEPTS IN ACL RECONSTRUCTION

    Freddie H. Fu

    2008-09-01

    Full Text Available Current Concepts in ACL Reconstruction is a complete reference text composed of the most thorough collection of topics on the ACL and its surgical reconstruction compiled, with contributions from some of the world's experts and most experienced ACL surgeons. Various procedures mentioned throughout the text are also demonstrated in an accompanying video CD-ROM. PURPOSE Composing a single, comprehensive and complete information source on ACL including basic sciences, clinical issues, latest concepts and surgical techniques, from evaluation to outcome, from history to future, editors and contributors have targeted to keep the audience pace with the latest concepts and techniques for the evaluation and the treatment of ACL injuries. FEATURES The text is composed of 27 chapters in 6 sections. The first section is mostly about basic sciences, also history of the ACL, imaging, clinical approach to adolescent and pediatric patients are subjected. In the second section, Graft Choices and Arthroscopy Portals for ACL Reconstruction are mentioned. The third section is about the technique and the outcome of the single-bundle ACL reconstruction. The fourth chapter includes the techniques and outcome of the double-bundle ACL reconstruction. In the fifth chapter revision, navigation technology, rehabilitation and the evaluation of the outcome of ACL reconstruction is subjected. The sixth/the last chapter is about the future advances to reach: What We Have Learned and the Future of ACL Reconstruction. AUDIENCE Orthopedic residents, sports traumatology and knee surgery fellows, orthopedic surgeons, also scientists in basic sciences or clinicians who are studying or planning a research on ACL forms the audience group of this book. ASSESSMENT This is the latest, the most complete and comprehensive textbook of ACL reconstruction produced by the editorial work up of two pioneer and masters "Freddie H. Fu MD and Steven B. Cohen MD" with the contribution of world

  13. Safety pharmacology--current and emerging concepts.

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas; Sidaway, James; Sison-Young, Rowena; Smith, Emma; Stebbings, Richard; Tingle, Yulia; Valentin, Jean-Pierre; Williams, Awel; Williams, Dominic; Park, Kevin; Goldring, Christopher

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Current concepts in the pathophysiology of glaucoma

    Agarwal Renu

    2009-01-01

    Full Text Available Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.

  15. Therapeutic working alliance: From a psychoanalitical to a pantheoretical conception

    Peter Praper

    2004-05-01

    Full Text Available Although the concept of therapeutic working alliance was rooted in psychoanalysis, today it is more prominent in psychoanalytic psychotherapies than psychoanalysis. It is rather surprising that we cannot find the concept in the Laplanche and Pontalis Dictionary. During the last two decades a growing body of empirical research material on therapeutic working alliance was published, confirming the idea of the alliance as a separate dimension of therapeutic relationship with few recognisable components. The dimension of the therapeutic working alliance was examined in several approaches and proved as one of the most important therapeutic factors, regardless of the approach, and it has finally been accepted as a pantheoretical concept.

  16. EXETRA Perspectives: Concepts in Therapeutic Recreation.

    Neal, Larry L.; Edginton, Christopher R.

    Fifteen papers address issues in therapeutic recreation for disabled persons from the perspectives of practitioners, educators, and students. The following papers are presented. "Therapeutic Recreation Service: The Past and Challenging Present" (H. Sessoms); "Therapeutic Recreatiion in an Era of Limits: A Crisis...A Challenge... An Opportunity"…

  17. Chronic Lymphocytic Leukemia: Current Concepts.

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

    2015-10-01

    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  18. Safety pharmacology — Current and emerging concepts

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas

    2013-01-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests

  19. Safety pharmacology — Current and emerging concepts

    Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Atkinson, Jeffrey [Lorraine University Pharmacolor Consultants Nancy PCN (France); Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Delaunois, Annie [UCB Pharma (Belgium); Dermody, Ailsa; Govindappa, Karthik [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Guillon, Jean-Michel [Sanofi-aventis (France); Jenkins, Rosalind [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Kenna, Gerry [Astra-Zeneca (United Kingdom); Lemmer, Björn [Ruprecht-Karls-Universität Heidelberg (Germany); Meecham, Ken [Huntingdon Life Sciences (United Kingdom); Olayanju, Adedamola [MRC Centre for Drug Safety Science, University of Liverpool (United Kingdom); Pestel, Sabine [Boehringer-Ingelheim (Germany); Rothfuss, Andreas [Roche (Switzerland); and others

    2013-12-01

    Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. - Highlights: • SP — mandatory non-clinical risk assessments performed during drug development. • SP organ system studies ensure the safety of clinical participants in FiH trials. • Frontloading in SP facilitates lead candidate drug selection. • Emerging trends: integrating SP-Toxicological endpoints; combined core battery tests.

  20. Current concepts in adult aphasia.

    McNeil, M R

    1984-01-01

    This paper provides a review of recent research from the areas of speech and language pathology, cognitive psychology, psycholinguistics, neurology, and rehabilitation medicine which is used to refine and extend current definitions of aphasia. Evidence is presented from these diverse disciplines, which supports a multimodality, performance-based, verbal and non-verbal, cortical and subcortical, and cognitively multidimensional view of aphasia. A summary of current practice in the assessment and treatment of adult aphasia is summarized.

  1. Current concepts in maxillofacial imaging

    Boeddinghaus, Rudolf [Perth Radiological Clinic, 127 Hamersley Road, Subiaco, Western Australia 6008 (Australia)], E-mail: rboeddinghaus@perthradclinic.com.au; Whyte, Andy [Perth Radiological Clinic, 127 Hamersley Road, Subiaco, Western Australia 6008 (Australia)], E-mail: awhyte@perthradclinic.com.au

    2008-06-15

    A review of state-of-the-art maxillofacial imaging is presented. Current imaging techniques include intra-oral radiographs, dental panoramic tomography, multidetector helical computed tomography, cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI). The commonest conditions encountered in clinical radiological practice are reviewed, including maxillofacial deformities, complicated dental impactions, maxillofacial trauma, jaw lesions (cysts, neoplasms, fibro-osseous lesions (FOLs) and infections), and temporomandibular joint pathology. Pre-operative assessment for dental implant placement is also briefly reviewed.

  2. Burning mouth syndrome: Current concepts

    Cibele Nasri-Heir

    2015-01-01

    Full Text Available Burning mouth syndrome (BMS is a chronic pain condition. It has been described by the International Headache Society as "an intra-oral burning or dysesthetic sensation, recurring daily for more than 2 h/day for more than 3 months, without clinically evident causative lesions." BMS is frequently seen in women in the peri-menopausal and menopausal age group in an average female/male ratio of 7:1. The site most commonly affected is the anterior two-thirds of the tongue. The patient may also report taste alterations and oral dryness along with the burning. The etiopathogenesis is complex and is not well-comprehended. The more accepted theories point toward a neuropathic etiology, but the gustatory system has also been implicated in this condition. BMS is frequently mismanaged, partly because it is not well-known among healthcare providers. Diagnosis of BMS is made after other local and systemic causes of burning have been ruled out as then; the oral burning is the disease itself. The management of BMS still remains a challenge. Benzodiazepines have been used in clinical practice as the first-line medication in the pharmacological management of BMS. Nonpharmacological management includes cognitive behavioral therapy and complementary and alternative medicine (CAM. The aim of this review is to familiarize healthcare providers with the diagnosis, pathogenesis, and general characteristics of primary BMS while updating them with the current treatment options to better manage this group of patients.

  3. Burning mouth syndrome: Current concepts.

    Nasri-Heir, Cibele; Zagury, Julyana Gomes; Thomas, Davis; Ananthan, Sowmya

    2015-01-01

    Burning mouth syndrome (BMS) is a chronic pain condition. It has been described by the International Headache Society as "an intra-oral burning or dysesthetic sensation, recurring daily for more than 2 h/day for more than 3 months, without clinically evident causative lesions." BMS is frequently seen in women in the peri-menopausal and menopausal age group in an average female/male ratio of 7:1. The site most commonly affected is the anterior two-thirds of the tongue. The patient may also report taste alterations and oral dryness along with the burning. The etiopathogenesis is complex and is not well-comprehended. The more accepted theories point toward a neuropathic etiology, but the gustatory system has also been implicated in this condition. BMS is frequently mismanaged, partly because it is not well-known among healthcare providers. Diagnosis of BMS is made after other local and systemic causes of burning have been ruled out as then; the oral burning is the disease itself. The management of BMS still remains a challenge. Benzodiazepines have been used in clinical practice as the first-line medication in the pharmacological management of BMS. Nonpharmacological management includes cognitive behavioral therapy and complementary and alternative medicine (CAM). The aim of this review is to familiarize healthcare providers with the diagnosis, pathogenesis, and general characteristics of primary BMS while updating them with the current treatment options to better manage this group of patients.

  4. Therapeutic communication in nursing students: A Walker & Avant concept analysis

    Abdolrahimi, Mahbobeh; Ghiyasvandian, Shahrzad; Zakerimoghadam, Masoumeh; Ebadi, Abbas

    2017-01-01

    Background and aim Therapeutic communication, the fundamental component of nursing, is a complex concept. Furthermore, the poor encounters between nursing student and patient demonstrate the necessity of instruction regarding therapeutic communication. The aim of this study was to define and clarify this important concept for including this subject in the nursing curriculum with more emphasis. Methods A literature search was conducted using keywords such as “nursing student”, “patient” and “therapeutic communication” and Persian-equivalent words in Persian databases (including Magiran and Medlib) and English databases (including PubMed, ScienceDirect, Scopus and ProQuest) without time limitation. After extracting concept definitions and determining characteristic features, therapeutic communication in nursing students was defined. Then, sample cases, antecedents, consequences and empirical referents of concept were determined. Results After assessing 30 articles, therapeutic communication defining attributes were as follows: “an important means in building interpersonal relationships”, “a process of information transmission”, “an important clinical competency”, “a structure with two different sections” and “a significant tool in patient centered care”. Furthermore, theoretical and clinical education and receiving educators’ feedback regarding therapeutic communication were considered as antecedents of the concept. Improving physical and psychological health status of patient as well as professional development of nursing students were identified as consequences of the concept. Conclusion Nursing instructors can use these results in order to teach and evaluate therapeutic communication in nursing students and train qualified nurses. Also, nursing students may apply the results to improve the quality of their interactions with patients, perform their various duties and meet patients’ diverse needs. PMID:28979730

  5. Aptamer therapeutics: A review of current practice

    Perkins, A.C.; Missailidis, S.

    2007-01-01

    meet the criteria for robust, generic drug discovery technology and open new horizons for the development of future radiopharmaceuticals. We have shown that aptamers directed against the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy, demonstrated high specificity and uniform penetration in tumour xenografts. The future strategy will be to manipulate the molecular weight of the molecules to achieve an optimum balance between the low immunogenicity and excellent tumour penetration for diagnostic imaging and targeted therapy. In this way, a balance can be achieved between the rapid renal clearance and adequate tumour uptake required for diagnostic imaging and targeted therapy. The current work and future prospects for aptamer therapeutics will be described. (author)

  6. [Diagnostic and therapeutic concepts for vesicovaginal and ureterovaginal fistulas].

    Lang, Isabelle Joy; Fisch, Margit; Kluth, Luis Alex

    2018-02-01

     Vesico- and ureterovaginal fistulas are defined as abnormal connections between the urinary tract, on the one side, and the female genital system, on the other. Despite being highly prevalent as an acquired pathology of the urogenital system, there has as yet been no standardized protocol in place for diagnosing and treating these fistulas. This review analyses the current literature concerning vesico- and ureterovaginal fistulas in order to profile common diagnostic and therapeutic concepts.  Literature research was carried out using the data bases of Medline and PubMed. A general internet research was added as well as the subsequent analysis of textbooks. Subsequently 40 scientific publications, four textbooks and one internet source were consulted.  In the diagnostic process of not only vesicovaginal, but also ureterovaginal fistulas a timely vaginal examination followed by a cystoscopy and further imaging by retrograde vaginal methylene blue instillation should be carried out. In order to further the differential diagnosis of ureterovaginal fistulas in particular, additional imaging techniques may be required. However, the therapies of both fistulas manifest essential differences. Ureterovaginal fistulas are closed in a two-stage procedure. At first, a percutaneous nephrostomy is placed to decompress the renal collecting system and further drain the urine, followed by a second intervention, which closes the fistula. The management of vesicovaginal fistulas includes both conservative and surgical concepts, the latter of which may in turn be divided into a transabdominal and/or a transvaginal approach. Essentially, transabdominal fistula surgery should, at first, include the identification of the orifices of both ureters to subsequently splint them as indicated. This should be followed by the excision of the fistula. In the case of large fistulas a flap reconstruction of the area may be considered after the mobilisation of the surrounding tissue. Despite

  7. [Activating therapeutic care in geriatrics : Evaluation of a practice concept].

    Acklau, Stefanie; Gödecker, Lisa; Kaden, Andrea; Jahn, Patrick

    2016-10-01

    The special feature of the concept of activating therapeutic care in geriatrics (ATP-G) is based on the focus of nursing and therapeutic elements specifically related to the elderly. Further significance lies in the bottom-up development of this concept, which shows a close proximity to the nursing practice. The research project targeted the characteristics of ATP-G from a nursing point of view. Furthermore, the resulting elements of professional nursing care understanding for inpatient geriatric rehabilitation were used to build a scientific and theoretical foundation of the ATP-G concept. In this study 12 semi-structured interviews with professional caregivers were realized. The data collection was undertaken in three different facilities of inpatient geriatric (early) rehabilitation, chosen by lot. The data analysis was based on the methodology of qualitative content analysis according to Mayring. The research project showed that the basic elements described in the ATP-G concept are consistent with the view of nursing practitioners and therefore reflect the characteristic features of routine daily practice; nonetheless, some new aspects were found, primarily the importance of interdisciplinary teamwork in geriatric settings. There were also difficulties related to the ATP-G concept which were experienced as restraints by the questioned professionals. Further research should therefore investigate the structures for optimal implementation of the ATP-G concept into standard practice.

  8. Thoracic endometriosis syndrome: Current concept in ...

    Background: Thoracic endometriosis is a rare pathology. The diagnosis is often delayed or missed, however recently, there has been significant advances in the knowledge of this condition and hence, an improvement in the diagnosis and treatment. Objective: To review the current concepts in the pathophysiology and ...

  9. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Vedantam Rajshekhar

    2016-01-01

    Full Text Available Neurocysticercosis (NCC is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues.

  10. Neurocysticercosis: Diagnostic problems & current therapeutic strategies

    Rajshekhar, Vedantam

    2016-01-01

    Neurocysticercosis (NCC) is the most common single cause of seizures/epilepsy in India and several other endemic countries throughout the world. It is also the most common parasitic disease of the brain caused by the cestode Taenia solium or pork tapeworm. The diagnosis of NCC and the tapeworm carrier (taeniasis) can be relatively inaccessible and expensive for most of the patients. In spite of the introduction of several new immunological tests, neuroimaging remains the main diagnostic test for NCC. The treatment of NCC is also mired in controversy although, there is emerging evidence that albendazole (a cysticidal drug) may be beneficial for patients by reducing the number of seizures and hastening the resolution of live cysts. Currently, there are several diagnostic and management issues which remain unresolved. This review will highlight some of these issues. PMID:28139530

  11. [Mass casualty incidents - current concepts and developments].

    Savinsky, Godo; Stuhr, Markus; Kappus, Stefan; Trümpler, Stefan; Wenderoth, Stephan; Wohlers, Jan-Hauke; Paschen, Hans-Richard; Kerner, Thoralf

    2014-12-01

    Medical concepts and strategies are permanently changing. Due to the emergency response in a mass casualty incident everyone who is involved has to work together with different organisations and public authorities, which are not part of the regular emergency medical service. Within the last 25 years throughout the whole country of Germany the role of a "chief emergency physician" has been implemented and in preparation for the FIFA World Cup 2006 mobile treatment units were set up. In 2007, special units of the "Medical Task Force" - funded by the german state - were introduced and have been established by now. They will be a permanent part of regional plannings for mass casualty incidents. This article highlights current concepts and developments in different parts of Germany. © Georg Thieme Verlag Stuttgart · New York.

  12. [Surgical intensive care medicine. Current therapy concepts for septic diseases].

    Niederbichler, A D; Ipaktchi, K; Jokuszies, A; Hirsch, T; Altintas, M A; Handschin, A E; Busch, K H; Gellert, M; Steinau, H-U; Vogt, P M; Steinsträsser, L

    2009-10-01

    The clinical appearance of septic disorders is characterized by an enormous dynamic. The sepsis-induced dysbalance of the immune system necessitates immediate and aggressive therapeutic interventions to prevent further damage progression of the disease to septic shock and multiple organ failure. This includes supportive therapy to normalize and maintain organ and tissue perfusion as well as the identification of the infection focus. In cases where an infectious focus is identified, surgical source control frequently is a key element of the treatment strategy besides pharmacologic and supportive measures. The integrative approach of the management of septic patients requires rapid communication between the involved medical disciplines and the nursing personnel. Therefore, this article outlines current therapeutic concepts of septic diseases as well as central nursing aspects.

  13. Current concepts of salivary gland tumors

    Raj Kumar Badam

    2015-01-01

    Full Text Available The embryonic development of salivary glands is a complex process that creates compact, highly organized secretory organs with functions essential for oral health. The development is an example of branching morphogenesis, recent research found to involve unexpectedly dynamic cell motility, and novel regulatory pathways. Numerous growth factors, extracellular matrix molecules, gene regulatory pathways, and mechanical forces contribute to salivary gland morphogenesis, but local gene regulation and morphological changes appear to play particularly notable roles. Salivary gland tumors are one of the most complex and relatively rare groups of lesions encountered in oral pathology practice. Their complexity is attributed to the heterogeneity of the cells of origin of these lesions. Frequent overlap of microscopic features among various neoplasms makes us sometimes even to differentiate benign and malignant lesions leading to a diagnostic dilemma. Here, we review and summarize the current concepts regarding the histogenetic and morphogenetic concepts of salivary gland tumors and their relevance to routine diagnosis and classification of these lesions.

  14. Current fusion power plant design concepts

    Gore, B.F.; Murphy, E.S.

    1976-09-01

    Nine current U.S. designs for fusion power plants are described in this document. Summary tabulations include a tenth concept, for which the design document was unavailable during preparation of the descriptions. The information contained in the descriptions was used to define an envelope of fusion power plant characteristics which formed the basis for definition of reference first commercial fusion power plant design. A brief prose summary of primary plant features introduces each of the descriptions contained in the body of this document. In addition, summary tables are presented. These tables summarize in side-by-side fashion, plant parameters, processes, combinations of materials used, requirements for construction materials, requirements for replacement materials during operation, and production of wastes

  15. Recent developments and current concepts in medulloblastoma.

    Gerber, N U; Mynarek, M; von Hoff, K; Friedrich, C; Resch, A; Rutkowski, S

    2014-04-01

    Medulloblastoma is the most common malignant brain tumor of childhood. While prognosis has significantly improved in the last decades with multimodal therapy including surgery, radiotherapy, and chemotherapy, one third of patients still succumb to their disease. Further research is needed to find more efficient treatment strategies for prognostically unfavorable patient groups and to minimize long-term sequelae of tumor treatment. This review gives a summary of the current state of treatment concepts including an outlook on the near future. We describe recent advances in the understanding of molecular mechanisms, their potential impact on risk stratification in upcoming clinical trials, and perspectives for the clinical implementation of targeted therapies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Current concepts in urinary tract infections.

    Williams, D H; Schaeffer, A J

    2004-03-01

    Urinary tract infections (UTIs) are common infectious diseases that can be associated with substantial morbidity and significant expenditures. This review highlights the current concepts and recent advances in our understanding and management of this condition. Specific topics include pathogenesis, host factors, antimicrobial resistance, recurrent UTIs in women, diagnosis, treatment of uncomplicated and complicated UTIs, prophylaxis, catheter associated bacteriuria, pregnancy, diabetes, UTIs in men, prostatitis, and the chronic pelvic pain syndrome. UTIs can be viewed as an interaction between specific bacterial virulence factors and the patient. A new model explaining the pathogenesis of recurrent UTIs has been presented. There is a need to reconsider traditional treatment recommendations in the face of local resistance patterns, as well as the need to make better use of drugs that are currently available. Prospects for prevention of recurrent UTI include natural compounds, bacterial interference and immunization. With regard to UTI risk in women, patients can be classified based on age, and functional and hormonal status. Appropriate treatment approaches must be based on this classification. In contrast to uncomplicated UTIs, management of most complicated infections depends on clinical experience and resources at individual institutions rather than on evidence based guidelines. Asymptomatic bacteriuria generally should not be treated except in high-risk catheterized patients and in pregnancy. UTIs in men generally require formal urologic evaluation. Our understanding of the etiologies, diagnostic strategies, and treatment options for prostatitis and the chronic pelvic pain syndrome in men continues to evolve.

  17. Current Concepts on Gastric Carcinoid Tumors

    George C. Nikou

    2012-01-01

    Full Text Available Gastric carcinoid tumors (GCs are rare lesions representing less than 10% of carcinoid tumors and less than 1% of all stomach neoplasms. There are three distinct types of gastric carcinoids; type I includes the vast majority (70–85% of these neoplasms that are closely linked to chronic atrophic gastritis. Type II which accounts for 5–10 %, is associated with Zollinger-Ellison syndrome and often occurs in the context of multiple endocrine neoplasia type 1. Type III, finally, represents 15–25% of gastric carcinoids and is characterized by a far more aggressive course. The optimal clinical approach to GCs remains to be elucidated, depending upon type, size, and number of carcinoids. While there is universal agreement about the surgical treatment of type III GCs, current options for type I and II include simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, or total gastrectomy. Moreover, the introduction of somatostatin analogues could represent another therapeutic option.

  18. [Food allergies in paediatrics: Current concepts].

    Plaza-Martin, Ana María

    2016-07-01

    The concept of allergic reaction currently includes all those where an immunological reaction depends on a reaction mediated by IgE, as well as those that involve other immune mechanisms, such as T-cell regulators. There are many different clinical situations, like the classic immediate reactions (IgE mediated) such as urticaria, angioedema, immediate vomiting, abdominal pain, both upper respiratory (aphonia or rhinitis) and lower (wheezing or dyspnoea) symptom, and cardiovascular symptoms. The reactions that involve more than one organ, such as anaphylaxis, which could be an anaphylactic shock if there is cardiovascular involvement. The clinical signs and symptoms produced by non-IgE mediated reactions are usually more insidious in how they start, such as vomiting hours after the ingestion of food in enterocolitis, diarrhoea after days or weeks from starting food, dermatitis sometime after starting food. In these cases it is more difficult to associate these clinical symptoms directly with food. In this article, we attempt to clarify some concepts such as sensitisation/allergy, allergen/allergenic source, or the relationship of different clinical situations with food allergy, in order to help the paediatrician on the one hand, to prescribe strict diets in case of a suspicion based on the cause/effect relationship with the food, and on the other hand not to introduce unnecessary diets that very often have to last an excessively long time, and could lead to nutritional deficiencies in the children. Copyright © 2016 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  19. Current Biomechanical Concepts for Rotator Cuff Repair

    2013-01-01

    For the past few decades, the repair of rotator cuff tears has evolved significantly with advances in arthroscopy techniques, suture anchors and instrumentation. From the biomechanical perspective, the focus in arthroscopic repair has been on increasing fixation strength and restoration of the footprint contact characteristics to provide early rehabilitation and improve healing. To accomplish these objectives, various repair strategies and construct configurations have been developed for rotator cuff repair with the understanding that many factors contribute to the structural integrity of the repaired construct. These include repaired rotator cuff tendon-footprint motion, increased tendon-footprint contact area and pressure, and tissue quality of tendon and bone. In addition, the healing response may be compromised by intrinsic factors such as decreased vascularity, hypoxia, and fibrocartilaginous changes or aforementioned extrinsic compression factors. Furthermore, it is well documented that torn rotator cuff muscles have a tendency to atrophy and become subject to fatty infiltration which may affect the longevity of the repair. Despite all the aforementioned factors, initial fixation strength is an essential consideration in optimizing rotator cuff repair. Therefore, numerous biomechanical studies have focused on elucidating the strongest devices, knots, and repair configurations to improve contact characteristics for rotator cuff repair. In this review, the biomechanical concepts behind current rotator cuff repair techniques will be reviewed and discussed. PMID:23730471

  20. Current issues of RNAi therapeutics delivery and development.

    Haussecker, D

    2014-12-10

    12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

  1. Current progress in NIF target concepts

    Gobby, P.L.; Foreman, L.R.; Thoma, D.J.; Jacobson, L.A.; Hollis, R.V.; Barrera, J.; Mitchell, M.A.; Salazar, M.A.; Salzer, L.J.

    1996-01-01

    Target concepts for the National Ignition Facility (NIF) require progress in the art and science of target fabrication. Three distinct issues are addressed: beryllium fuel capsules, foam-buffered direct drive, and high-density gas-filled hohlraums. In all cases experiments on the existing Nova laser at LLNL are either in progress or planned for the near future to test the various concepts. Consequently, target fabrication must be able to deliver targets appropriate for each

  2. Current concepts in blood glucose monitoring.

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-12-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  3. Current concepts in blood glucose monitoring

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus. PMID:24910827

  4. Current concepts in blood glucose monitoring

    Kranti Shreesh Khadilkar

    2013-01-01

    Full Text Available Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG and continuous glucose monitoring system (CGMS. It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  5. Current Concepts in Tissue Engineering: Skin and Wound.

    Tenenhaus, Mayer; Rennekampff, Hans-Oliver

    2016-09-01

    Pure regenerative healing with little to no donor morbidity remains an elusive goal for both surgeon and patient. The ability to engineer and promote the development of like tissue holds so much promise, and efforts in this direction are slowly but steadily advancing. Products selected and reviewed reflect historical precedence and importance and focus on current clinically available products in use. Emerging technologies we anticipate will further expand our therapeutic options are introduced. The topic of tissue engineering is incredibly broad in scope, and as such the authors have focused their review on that of constructs specifically designed for skin and wound healing. A review of pertinent and current clinically related literature is included. Products such as biosynthetics, biologics, cellular promoting factors, and commercially available matrices can be routinely found in most modern health care centers. Although to date no complete regenerative or direct identical soft-tissue replacement exists, currently available commercial components have proven beneficial in augmenting and improving some types of wound healing scenarios. Cost, directed specificity, biocompatibility, and bioburden tolerance are just some of the impending challenges to adoption. Quality of life and in fact the ability to sustain life is dependent on our most complex and remarkable organ, skin. Although pure regenerative healing and engineered soft-tissue constructs elude us, surgeons and health care providers are slowly gaining comfort and experience with concepts and strategies to improve the healing of wounds.

  6. Current concepts in blood glucose monitoring

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on t...

  7. Subclinical hyperthyroidism: current concepts and scintigraphic imaging.

    Intenzo, Charles; Jabbour, Serge; Miller, Jeffrey L; Ahmed, Intekhab; Furlong, Kevin; Kushen, Medina; Kim, Sung M; Capuzzi, David M

    2011-09-01

    Subclinical hyperthyroidism is defined as normal serum free thyroxine and a free triiodothyronine level, with a thyroid-stimulating hormone level suppressed below the normal range and is usually undetectable. Although patients with this diagnosis have no or few signs and symptoms of overt thyrotoxicosis, there is sufficient evidence that it is associated with a relatively higher risk of supraventricular arrhythmias as well as the acceleration or the development of osteoporosis. Consequently, the approach to the patient with subclinical hyperthyroidism is controversial, that is, therapeutic intervention versus watchful waiting. Regardless, it is imperative for the referring physician to identify the causative thyroid disorder. This is optimally accomplished by a functional study, namely scintigraphy. Recognition of the scan findings of the various causes of subclinical hyperthyroidism enables the imaging specialist to help in diagnosing the underlying condition causing thyroid-stimulating hormone suppression thereby facilitating the workup and management of this thyroid disorder.

  8. Laryngeal spaces and lymphatics: current anatomic concepts

    Welsh, L.W.; Welsh, J.J.; Rizzo, T.A. Jr.

    1983-01-01

    This investigation evaluates the anatomic concepts of individual spaces or compartments within the larynx by isotope and dye diffusion. The authors identified continuity of spaces particularly within the submucosal planes and a relative isolation within the fixed structures resulting from the longitudinal pattern of fibroelastic tissues, muscle bands, and perichondrium. The historical data of anatomic resistance are refuted by the radioisotope patterns of dispersion and the histologic evidence of tissue permeability to the carbon particles. There is little clinical application of the compartment concept to the perimeter of growth and the configuration of extensive endolaryngeal cancers. The internal and extralaryngeal lymphatic network is presented and the regional associations are identified. The normal ipsilateral relationship is distorted by dispersion within the endolarynx supervening the anatomic midline. The effects of lymphatic obstruction caused by regional lymphadenectomy, tumor fixation, and irradiation-infection sequelae are illustrated; these result in widespread bilateral lymphatic nodal terminals. Finally, the evidence suggests that the internal network is modified by external interruption to accommodate an outflow system in continuity with the residual patent lymphatic channels

  9. Neoplastic stem cells: current concepts and clinical perspectives.

    Schulenburg, Axel; Brämswig, Kira; Herrmann, Harald; Karlic, Heidrun; Mirkina, Irina; Hubmann, Rainer; Laffer, Sylvia; Marian, Brigitte; Shehata, Medhat; Krepler, Clemens; Pehamberger, Hubert; Grunt, Thomas; Jäger, Ulrich; Zielinski, Christoph C; Valent, Peter

    2010-11-01

    Neoplastic stem cells have initially been characterized in myeloid leukemias where NOD/SCID mouse-repopulating progenitors supposedly reside within a CD34+/Lin- subset of the malignant clone. These progenitors are considered to be self-renewing cells responsible for the in vivo long-term growth of neoplastic cells in leukemic patients. Therefore, these cells represent an attractive target of therapy. In some lymphoid leukemias, NOD/SCID mouse-repopulating cells were also reported to reside within the CD34+/Lin- subfraction of the clone. More recently, several attempts have been made to transfer the cancer stem cell concept to solid tumors and other non-hematopoietic neoplasms. In several of these tumors, the cell surface antigens AC133 (CD133) and CD44 are considered to indicate the potential of a cell to initiate permanent tumor formation in vivo. However, several questions concerning the phenotype, self-renewal capacity, stroma-dependence, and other properties of cancer- or leukemia-initiating cells remain to be solved. The current article provides a summary of our current knowledge on neoplastic (cancer) stem cells, with special emphasis on clinical implications and therapeutic options as well as a discussion about conceptual and technical limitations. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  10. Current concepts and future approaches to vestibular rehabilitation.

    Tjernström, Fredrik; Zur, Oz; Jahn, Klaus

    2016-04-01

    Over the last decades methods of vestibular rehabilitation to enhance adaptation to vestibular loss, habituation to changing sensory conditions, and sensory reweighting in the compensation process have been developed. However, the use of these techniques still depends to a large part on the educational background of the therapist. Individualized assessment of deficits and specific therapeutic programs for different disorders are sparse. Currently, vestibular rehabilitation is often used in an unspecific way in dizzy patients irrespective of the clinical findings. When predicting the future of vestibular rehabilitation, it is tempting to foretell advances in technology for assessment and treatment only, but the current intense exchange between clinicians and basic scientists also predicts advances in truly understanding the complex interactions between the peripheral senses and central adaptation mechanisms. More research is needed to develop reliable techniques to measure sensory dependence and to learn how this knowledge can be best used--by playing off the patient's sensory strength or working on the weakness. To be able using the emerging concepts, the neuro-otological community must strive to educate physicians, physiotherapists and nurses to perform the correct examinations for assessment of individual deficits and to look for factors that might impede rehabilitation.

  11. Stereotactic radiosurgery: basic concepts and current status

    Gaur, Maheep Singh

    2016-01-01

    Term Stereotactic Radiosurgery was coined by Prof Lars Leksell in 1951 as concept. Leksell's experimented together with the radiobiologist Borje Larsson in Uppsala, on trying to develop 'stereotactic radiosurgery', aimed at lesioning in the central brain in functional operations such as thalamotomy and capsulotomy. Clinical experiments using a proton beam were initiated at the Gustav Werner Institute in Uppsala, and a few patients had been treated. Experiences from these led Leksell to design a multi-source 'beam knife', which became ready for use in 1967 as the first 'Gamma Knife' and installed at the private hospital Sophiahammet in Stockholm as a clinical research unit. Moving from functional neurosurgery today Gamma knife is used for a wide range on brain tumors, vascular malformations and functional disorders. Introduction of newer technology in navigation and radiation delivery has made it possible to do whole body Radiosurgery. Various technologies, basic principles, radiobiological aspects and applications will be discussed. (author)

  12. Female pattern hair loss: Current treatment concepts

    Quan Q Dinh

    2007-07-01

    Full Text Available Quan Q Dinh, Rodney SinclairDepartment of Dermatology, St Vincent’s Hospital, Fitzroy, Victoria, AustraliaAbstract: Fewer than 45% of women go through life with a full head of hair. Female pattern hair loss is the commonest cause of hair loss in women and prevalence increases with advancing age. Affected women may experience psychological distress and impaired social functioning. In most cases the diagnosis can be made clinically and the condition treated medically. While many women using oral antiandrogens and topical minoxidil will regrow some hair, early diagnosis and initiation of treatment is desirable as these treatments are more effective at arresting progression of hair loss than stimulating regrowth. Adjunctive nonpharmacological treatment modalities such as counseling, cosmetic camouflage and hair transplantation are important measures for some patients. The histology of female pattern hair loss is identical to that of male androgenetic alopecia. While the clinical pattern of the hair loss differs between men, the response to oral antiandrogens suggests that female pattern hair loss is an androgen dependant condition, at least in the majority of cases. Female pattern hair loss is a chronic progressive condition. All treatments need to be continued to maintain the effect. An initial therapeutic response often takes 12 or even 24 months. Given this delay, monitoring for treatment effect through clinical photography or standardized clinical severity scales is helpful.Keywords: female pattern hair loss, androgenetic alopecia

  13. Cardiogenic shock. Current concepts in management.

    Balakumaran, K; Hugenholtz, P G

    1986-10-01

    This article presents a categorisation of circulatory shock and discusses the causes, haemodynamics, and clinical recognition of cardiogenic shock. The first step in the management strategy in cardiogenic shock is to guide the patient from the state of shock to one of managed haemodynamic stability. The therapeutic manoeuvres of this first step constitute the management tactics, which can be grouped under 3 general headings: (a) making the most of a malfunctioning heart; (b) improving the state of the heart; and (c) reducing the demands on the heart. In order to make the most of the heart, i.e. to get the highest possible output at the lowest possible cost, clinicians need to use their judgement in stimulating an overtaxed heart on the one hand, and in manipulating the loads on it (the preload and afterload) on the other, for although these methods may be advantageous, they are not without their pitfalls. Efforts to improve the state of the heart often necessitate surgical (e.g. mitral valve replacement) or semisurgical (e.g. coronary angiography and recanalisation) techniques, although intravenous antithrombotic agents may achieve comparable results in a few cases at the bedside. Reducing the demands on the heart is an active process involving the takeover of at least a part of the work of the heart by ancillary devices such as the intra-aortic balloon pump, and of the work of breathing by intubation and artificial ventilation. The individuality of each case of cardiogenic shock emphasises the need for empirical modulation of therapy based on feedback information obtained by haemodynamic monitoring.

  14. Subclinical Cushing's syndrome: current concepts and trends.

    Zografos, George N; Perysinakis, Iraklis; Vassilatou, Evangeline

    2014-01-01

    Clinically inapparent adrenal masses which are incidentally detected have become a common problem in everyday practice. Approximately 5-20% of adrenal incidentalomas present subclinical cortisol hypersecretion which is characterized by subtle alterations of the hypothalamic-pituitary-adrenal axis due to adrenal autonomy. This disorder has been described as subclinical Cushing's syndrome, since there is no typical clinical phenotype. The diagnosis of subclinical Cushing's syndrome is based on biochemical evaluation; however, there is still no consensus for the biochemical diagnostic criteria. An abnormal 1mg dexamethasone suppression test (DST) as initial screening test in combination with at least one other abnormal test of the hypothalamic-pituitary-adrenal axis has been advocated by most experts for the diagnosis of subclinical Cushing's syndrome. DST is the main method of establishing the diagnosis, while there is inhomogeneity of the information that other tests provide. Arterial hypertension, diabetes mellitus type 2 or impaired glucose tolerance, central obesity, osteoporosis/vertebral fractures and dyslipidemia are considered as detrimental effects of chronic subtle cortisol excess, although there is no proven causal relationship between subclinical cortisol hypersecretion and these morbidities. Therapeutic strategies include careful observation along with medical treatment of morbidities potentially related to subtle cortisol hypersecretion versus laparoscopic adrenalectomy. The optimal management of patients with subclinical Cushing's syndrome is not yet defined. The conservative approach is appropriate for the majority of these patients; however, the duration of follow-up and the frequency of periodical evaluation still remain open issues. Surgical resection may be beneficial for patients with hypertension, diabetes mellitus type 2 or abnormal glucose tolerance and obesity.

  15. Current concepts for chronochemotherapy of cancer.

    Laerum, O D; Smaaland, R; Abrahamsen, J F

    1995-01-01

    In this article, a survey on the concepts and scientific basis for applying chemotherapy against malignant tumors on a circadian schedule is given. The idea is to give the cytostatic drugs at times of the day when optimal effect on the tumor is achieved, but at the same time causing minimal toxic side effects. Following a brief description of the complexity of cancer tissue, some aspects of the present status of cancer chemotherapy in general are reviewed. Applications of chronobiology in cancer treatment are then surveyed together with possibilities to increase cytostatic doses and reduce side effects. When optimal tumor cell kill is achieved, the next step is to address the circadian aspects of normal organs, including the proliferative behavior of tissues with rapid cell renewal. Finally, the question of how regulatory mechanisms responsible for normal circadian rhythms can be interfered with is addressed. Cancer chronochemotherapy today combined with modern infusional technology is a promising field for improving cancer treatment in general and reducing side effects and is expected to make important progress in the near future.

  16. Trochleoplasty in major trochlear dysplasia: current concepts

    Beaufils Philippe

    2012-02-01

    Full Text Available Abstract Trochleoplasty is the theoretical solution to persistent symptoms (pain and/or instability related to trochlear dysplasia where there is not only a trochlear flatness but also a trochlear prominence. The threshold of prominence indicating surgical intervention has as yet not been determined. A bump of 5 mm is generally accepted as the inferior limit. Given the interventional nature of this demanding procedure, it should be proposed in selected cases after considerable discussion with the patient. Trochleoplasty is indicated as a primary procedure for major trochlear dysplasia with a prominence > 5 mm. Stabilization is obtained in most of the cases with the risk of residual mild anterior knee pain. It is also indicated as a salvage procedure when a previous surgery failed. Despite the reputation of the procedure, the published results are encouraging in terms of prevention of re-dislocation, satisfaction index, and radiological outcomes. Post-operative stiffness is the main complication, which may require manipulation under anaesthesia or arthroscopic arthrolysis. There are few other complications reported and to date secondary necrosis of the trochlea has not been reported. Technically speaking, the deepening trochleoplasty is a difficult procedure without reliable landmarks. We propose a recession wedge trochleoplasty which is an easier procedure. It is never undertaken as an isolated procedure, but always in conjunction with other realignment procedures of the extensor apparatus according to the "a la carte" surgery concept.

  17. Esophageal Motility Disorders: Current Concepts of Pathogenesis and Treatment

    Peter J Kahrilas

    2000-01-01

    Full Text Available Current concepts of esophageal motility disorders are summarized. Primary data sources were located via MEDLINE or cross-citation. No attempt was made to be comprehensive or inclusive of the literature because fewer than 10% of citations are discussed. Instead, emphasis was placed on new developments in diagnosis, therapeutics, and practice patterns. Controlled therapeutic trials and pathophysiological observations are emphasized. Achalasia is a rare disease of failed lower sphincter relaxation and aperistalsis. Diffuse esophageal spasm (DES, an equally rare disease, is defined by non-propagated esophageal contractions. Nonspecific motility disorders, including nutcracker esophagus and hypertensive lower esophageal sphincter, are identified only by manometry and are ten times as prevalent. Neuromuscular pathology is evident only with achalasia (myenteric plexus neurons destruction. Pharmacological therapies have limited efficacy with achalasia; more limited with DES; and none with the nonspecific motility disorders. More efficacious therapies for the nonspecific disorders are directed at associated reflux disease or psychiatric disorders. Pneumatic dilation is effective therapy for achalasia 72% of instances, but frequently requires repeat dilation and is complicated by a 3% perforation rate. Surgical myotomy is effective in 88% of achalasics; morbidity from thoracotomy has been the major limitation but this has been sharply reduced with a laparoscopic approach. In conclusion, although it has been suggested that esophageal motility disorders are distinct clinical entities, critical review of the literature supports this only in the case of achalasia, a disease of well defined pathophysiology, functional disturbance, and therapies. This clarity diminishes progressively for DES and non-specific esophageal motility disorders.

  18. SUBCLINICAL HYPOTHYROIDISM CURRENT CONCEPTS & M ANAGEMENT STRATEGEIES

    Radha Krishnan

    2015-05-01

    Full Text Available Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone ( TSH and normal free T3 & T4 , without clinical features of hypothyroidism . Clinical significance of SCH remains uncertain and controversial . Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms . There are still controversies surrounding SCH and associated risk of various cardiovascular diseases ( CVDs , pregnancy outcomes , neuropsychiatric issues , metabolic syndrome , and dyslipidemia . This review will summarize the current data related to the effects of SCH on cardiovascular risk , SCH in pregnancy , in dyslipedemia and clinical guidelines on management of this condition . The evidence has been updated by a Pub med search on the risks and treatment of subclinical hypothyroidism of most recent articles published until March 2015

  19. Partial Thickness Rotator Cuff Tears: Current Concepts

    Matthewson, Graeme; Beach, Cara J.; Nelson, Atiba A.; Woodmass, Jarret M.; Ono, Yohei; Boorman, Richard S.; Lo, Ian K. Y.; Thornton, Gail M.

    2015-01-01

    Partial thickness rotator cuff tears are a common cause of pain in the adult shoulder. Despite their high prevalence, the diagnosis and treatment of partial thickness rotator cuff tears remains controversial. While recent studies have helped to elucidate the anatomy and natural history of disease progression, the optimal treatment, both nonoperative and operative, is unclear. Although the advent of arthroscopy has improved the accuracy of the diagnosis of partial thickness rotator cuff tears, the number of surgical techniques used to repair these tears has also increased. While multiple repair techniques have been described, there is currently no significant clinical evidence supporting more complex surgical techniques over standard rotator cuff repair. Further research is required to determine the clinical indications for surgical and nonsurgical management, when formal rotator cuff repair is specifically indicated and when biologic adjunctive therapy may be utilized. PMID:26171251

  20. Current concepts on the use of IUDs.

    McCarthy, T

    1989-08-01

    IUDs have been used in Singapore since the mid 1960's but acceptance of this contraceptive method has fluctuated widely as a result of misconceptions regarding possible complications. The current generation of copper bearing devices have pregnancy rates below 1 per 100 women per year and this rate falls further with continued use. New developments which hold promise include a device releasing 20 mcg levonorgestrel per day and a copper device without a plastic frame which may reduce menstrual blood loss and dysmenorrhoea. In addition to the well established contra-indications to use, a past history of pelvic inflammatory disease or ectopic pregnancy, promiscuity, nulliparity and age less than 25 are now considered relative contraindications.

  1. Partial Thickness Rotator Cuff Tears: Current Concepts

    Graeme Matthewson

    2015-01-01

    Full Text Available Partial thickness rotator cuff tears are a common cause of pain in the adult shoulder. Despite their high prevalence, the diagnosis and treatment of partial thickness rotator cuff tears remains controversial. While recent studies have helped to elucidate the anatomy and natural history of disease progression, the optimal treatment, both nonoperative and operative, is unclear. Although the advent of arthroscopy has improved the accuracy of the diagnosis of partial thickness rotator cuff tears, the number of surgical techniques used to repair these tears has also increased. While multiple repair techniques have been described, there is currently no significant clinical evidence supporting more complex surgical techniques over standard rotator cuff repair. Further research is required to determine the clinical indications for surgical and nonsurgical management, when formal rotator cuff repair is specifically indicated and when biologic adjunctive therapy may be utilized.

  2. Current Concepts in Sports-Related Concussion.

    Chatterjee, Dipal; Frumberg, David B; Mulchandani, Neil B; Eldib, Ahmed M; Xavier, Fred; Barbash, Scott E; Saha, Subrata; Urban, William P

    2015-01-01

    Traumatic brain injury, specifically concussion, is prevalent in contact sports. In the United States (US) each year, 170 million adults participate in physical recreational activities, and 38 million children and adolescents participate in organized sports. The Centers for Disease Control estimate that in this group ~1.6 to 3.8 million concussions occur annually. Recent class-action lawsuits in the US filed by professional athletes against their respective leagues allege negligence in protecting them from concussions, and this has contributed to the attention received in the popular media. In response, concussion-related publications have increased exponentially during the past several years. Recent studies have challenged earlier assumptions that the effects of concussion are transient. Stronger links between concussion and neurodegenerative processes such as Alzheimer's disease-like conditions, depression, and heightened risk for suicide are being elucidated. In this article, we explore the current knowledge on concussion, including pathophysiology, management, and long-term effects. We conclude that more evidence-based results regarding guidelines for diagnosis, treatment, and return to play (RTP) are needed and should be the focus of future investigations. Attributing the etiology of certain neurodegenerative conditions to a history of concussion has been suggested in the current literature, but additional quantitative data regarding the pathophysiology and causality are needed as well. Bioengineers can have an important role in measuring the dynamic forces encountered during head impacts and their effects on the brain. These results can be effective in designing better helmets as well as improved playing surfaces to reduce the impact of such injuries. At this time, we believe that groups of people with heightened risk for concussion should be followed closely during longer periods of time and compared to matched controls. Such long-term studies are urgently

  3. Ebola virus outbreak, updates on current therapeutic strategies.

    Elshabrawy, Hatem A; Erickson, Timothy B; Prabhakar, Bellur S

    2015-07-01

    Filoviruses are enveloped negative-sense single-stranded RNA viruses, which include Ebola and Marburg viruses, known to cause hemorrhagic fever in humans with a case fatality of up to 90%. There have been several Ebola virus outbreaks since the first outbreak in the Democratic Republic of Congo in 1976 of which, the recent 2013-2015 epidemic in Guinea, Liberia, and Sierra Leone is the largest in recorded history. Within a few months of the start of the outbreak in December 2013, thousands of infected cases were reported with a significant number of deaths. As of March 2015, according to the Centers for Disease Control and Prevention, there have been nearly 25,000 suspected cases, with 15,000 confirmed by laboratory testing, and over 10,000 deaths. The large number of cases and the high mortality rate, combined with the lack of effective Food and Drug Administration-approved treatments, necessitate the development of potent and safe therapeutic measures to combat the current and future outbreaks. Since the beginning of the outbreak, there have been considerable efforts to develop and characterize protective measures including vaccines and antiviral small molecules, and some have proven effective in vitro and in animal models. Most recently, a cocktail of monoclonal antibodies has been shown to be highly effective in protecting non-human primates from Ebola virus infection. In this review, we will discuss what is known about the nature of the virus, phylogenetic classification, genomic organization and replication, disease transmission, and viral entry and highlight the current approaches and efforts, in the development of therapeutics, to control the outbreak. Copyright © 2015 John Wiley & Sons, Ltd.

  4. [Current concepts in pathophysiology of CRPS I].

    Nickel, F T; Maihöfner, C

    2010-02-01

    Knowledge about the pathophysiology underlying the complex regional pain syndrome (CRPS) has increased over the last years. Classically, CRPS has been considered to be mainly driven by sympathetic dysfunction with sympathetically maintained pain being its major pathogenetic mechanism. Currently, the disease is understood as result of a complex interplay between altered somatosensory, motor, autonomic and inflammatory systems. Peripheral and central sensitization is a common feature in CRPS as in other neuropathic pain syndromes. One important mechanism is the sensitization of spinal dorsal horn cells via activation of postsynaptic NMDA-receptors by chronic C-fiber input. Differential activity of endogenous pain modulating systems may play a pivotal role in the development of CRPS, too. Neuronal plasticity of the somatosensory cortex accounts for central sensory signs. Also the motor system is subject to central adaptive changes in patients with CRPS. Calcitonin-gene related peptide (CGRP) and substance P mediate neurogenic inflammation. Additionally other proinflammatory cytokines involved in the inflammatory response in CRPS have been identified. In terms of the sympathetic nervous system, recent evidence rather points to a sensitization of adrenergic receptors than to increased efferent sympathetic activity. Particularly the expression of alpha (1)-adrenoceptors on nociceptive C-fibers may play a major role. These pathophysiological ideas do not exclude each other. In fact they complement one another. The variety of the involved systems may explain the versatile clinical picture of CRPS. Georg Thieme Verlag KG Stuttgart, New York.

  5. Undifferentiated nasopharyngeal cancer (UCNT): current diagnostic and therapeutic aspects

    Altun, M.; Fandi, A.; Dupuis, O.; Cvitkovic, E.; Krajina, Z.; Eschwege, F.

    1995-01-01

    Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoid lineage tumor related to the Epstein Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic aggressiveness is the source of most disease-related demises, because radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Differences in the staging systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and squamous cell carcinoma (SCC) of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin-based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above-mentioned aspects of this fascinating nosologic entity, our own experience, both in metastatic and locoregional disease patients is analyzed

  6. New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window

    Parrish, J.A.

    1981-01-01

    Advances in optics technology, synthetic photochemistry, and the science of photobiology make it possible to think beyond phototherapy and photochemotherapy which is dependent on direct photochemical alteration of metabolites or direct phototoxic insult to cells. This report discusses another gender of photomedicine therapy which includes in vivo photoactivation of medicines, photon-dependent drug delivery, and manipulation of host and exposure source to maximize therapeutic index. These therapeutic manipulations are made possible because the skin is highly overperfused and because non-ionizing electromagnetic radiation that enters skin and blood has adequate photon energy to cause electronic excitation. Radiation of 320-800 nm is not very directly phototoxic, is absorbed by a variety of relatively nontoxic photolabile molecules and has an internal dosimetric depth profile. This radiation can therefore be used to activate, deactivate, bind, release or biotransform medications in vivo in skin or other organs. The photochemist, synthetic chemist and photobiologist can collaborate to significantly increase therapeutic possibilities

  7. Functional polymers as therapeutic agents: concept to market place.

    Dhal, Pradeep K; Polomoscanik, Steven C; Avila, Louis Z; Holmes-Farley, S Randall; Miller, Robert J

    2009-11-12

    Biologically active synthetic polymers have received considerable scientific interest and attention in recent years for their potential as promising novel therapeutic agents to treat human diseases. Although a significant amount of research has been carried out involving polymer-linked drugs as targeted and sustained release drug delivery systems and prodrugs, examples on bioactive polymers that exhibit intrinsic therapeutic properties are relatively less. Several appealing characteristics of synthetic polymers including high molecular weight, molecular architecture, and controlled polydispersity can all be utilized to discover a new generation of therapies. For example, high molecular weight bioactive polymers can be restricted to gastrointestinal tract, where they can selectively recognize, bind, and remove target disease causing substances from the body. The appealing features of GI tract restriction and stability in biological environment render these polymeric drugs to be devoid of systemic toxicity that are generally associated with small molecule systemic drugs. The present article highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer based therapies and biomaterials, including some marketed products.

  8. Opioid withdrawal syndrome: emerging concepts and novel therapeutic targets.

    Rehni, Ashish K; Jaggi, Amteshwar S; Singh, Nirmal

    2013-02-01

    Opioid withdrawal syndrome is a debilitating manifestation of opioid dependence and responds poorly to the available clinical therapies. Studies from various in vivo and in vitro animal models of opioid withdrawal syndrome have led to understanding of its pathobiology which includes complex interrelated pathways leading to adenylyl cyclase superactivation based central excitation. Advancements in the elucidation of opioid withdrawal syndrome mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses the neurobiology of opioid withdrawal syndrome and its therapeutic target recptors like calcitonin gene related peptide receptors (CGRP), N-methyl-D-aspartate (NMDA) receptors, gamma aminobutyric acid receptors (GABA), G-proteingated inwardly rectifying potassium (GIRK) channels and calcium channels. The present review further details the potential role of second messengers like calcium (Ca2+) / calmodulin-dependent protein kinase (CaMKII), nitric oxide synthase, cytokines, arachidonic acid metabolites, corticotropin releasing factor, fos and src kinases in causing opioid withdrawal syndrome. The exploitation of these targets may provide effective therapeutic agents for the management of opioid dependence-induced abstinence syndrome.

  9. Current and novel therapeutic molecules and targets in Alzheimer's disease

    Ashwini Kumar

    2016-01-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline, i.e., dementia. The disease starts with mild symptoms and gradually becomes severe. AD is one of the leading causes of mortality worldwide. Several different hallmarks of the disease have been reported such as deposits of β-amyloid around neurons, hyperphosphorylated tau protein, oxidative stress, dyshomeostasis of bio-metals, low levels of acetylcholine, etc. AD is not simple to diagnose since there is no single diagnostic test for it. Pharmacotherapy for AD currently provides only symptomatic relief and mostly targets cognitive revival. Computational biology approaches have proved to be reliable tools for the selection of novel targets and therapeutic ligands. Molecular docking is a key tool in computer-assisted drug design and development. Docking has been utilized to perform virtual screening on large libraries of compounds, and propose structural hypotheses of how the ligands bind with the target with lead optimization. Another potential application of docking is optimization stages of the drug-discovery cycle. This review summarizes the known drug targets of AD, in vivo active agents against AD, state-of-the-art docking studies done in AD, and future prospects of the docking with particular emphasis on AD.

  10. Current Nondopaminergic Therapeutic Options for Motor Symptoms of Parkinson's Disease

    Juan-Juan Du; Sheng-Di Chen

    2017-01-01

    Objective:The aim of this study was to summarize recent studies on nondopaminergic options for the treatment of motor symptoms in Parkinson's disease (PD).Data Sources:Papers in English published in PubMed,Cochrane,and Ovid Nursing databases between January 1988 and November 2016 were searched using the following keywords:PD,nondopaminergic therapy,adenosine,glutamatergic,adrenergic,serotoninergic,histaminic,and iron chelator.We also reviewed the ongoing clinical trials in the website of clinicaltrials.gov.Study Selection:Articles related to the nondopaminergic treatment of motor symptoms in PD were selected for this review.Results:PD is conventionally treated with dopamine replacement strategies,which are effective in the early stages of PD.Long-term use oflevodopa could result in motor complications.Recent studies revealed that nondopaminergic systems such as adenosine,glutamatergic,adrenergic,serotoninergic,histaminic,and iron chelator pathways could include potential therapeutic targets for motor symptoms,including motor fluctuations,levodopa-induced dyskinesia,and gait disorders.Some nondopaminergic drugs,such as istradefylline and amantadine,are currently used clinically,while most such drugs are in preclinical testing stages.Transitioning of these agents into clinically beneficial strategies requires reliable evaluation since several agents have failed to show consistent results despite positive findings at the preclinical level.Conclusions:Targeting nondopaminergic transmission could improve some motor symptoms in PD,especially the discomfort ofdyskinesia.Although nondopaminergic treatments show great potential in PD treatment as an adjunct therapy to levodopa,further investigation is required to ensure their success.

  11. Is there still a place for the concept of 'therapeutic regression' in psychoanalysis?

    Spurling, Laurence S

    2008-06-01

    The author uses his own failure to find a place for the idea of therapeutic regression in his clinical thinking or practice as the basis for an investigation into its meaning and usefulness. He makes a distinction between three ways the term 'regression' is used in psychoanalytic discourse: as a way of evoking a primitive level of experience; as a reminder in some clinical situations of the value of non-intervention on the part of the analyst; and as a description of a phase of an analytic treatment with some patients where the analyst needs to put aside normal analytic technique in order to foster a regression in the patient. It is this third meaning, which the author terms "therapeutic regression" that this paper examines, principally by means of an extended discussion of two clinical examples of a patient making a so-called therapeutic regression, one given by Winnicott and the other by Masud Khan. The author argues that in these examples the introduction of the concept of therapeutic regression obscures rather than clarifies the clinical process. He concludes that, as a substantial clinical concept, the idea of therapeutic regression has outlived its usefulness. However he also notes that many psychoanalytic writers continue to find a use for the more generic concept of regression, and that the very engagement with the more particular idea of therapeutic regression has value in provoking questions as to what is truly therapeutic in psychoanalytic treatment.

  12. Epistemological beliefs and therapeutic health concepts of physiotherapy students and professionals.

    Bientzle, Martina; Cress, Ulrike; Kimmerle, Joachim

    2014-10-01

    Health knowledge develops fast and includes a lot of ambiguous or tentative information. In their daily routine, both health care students and professionals continuously have to make judgments about the viability of health knowledge. People's epistemological beliefs (EBs) and their therapeutic health concepts are factors that influence how they deal with health knowledge. However, very little is known about the occurrence of these factors at different stages of people's career. The present study examines the EBs and therapeutic health concepts of physiotherapy students in their vocational training and the EBs and therapeutic health concepts of professionals. In a cross-sectional study physiotherapy students and professional physiotherapists filled in a questionnaire that measured their personal EBs about physiotherapy and medicine, as well as their biomedical and biopsychosocial therapeutic health concepts. We compared the participants' EBs regarding both knowledge domains, and their therapeutic health concepts using paired samples t-tests. We also examined the differences between first-year students, advanced students, and professionals regarding their EBs and their therapeutic health concepts using ANOVAs. Eighty-three students and 84 professionals participated in this study, 114/167 (68%) participants were female. EBs as well as therapeutic health concepts differed depending upon the participants' training status. Professionals had more sophisticated EBs than students regarding both knowledge in physiotherapy (F(2, 164) = 6.74, P = 0.002, η(2)(p) = 0.08) and knowledge in medicine (F(2, 164) = 5.93, P = 0.003, η(2)(p) = 0.07). In addition, high values in a biopsychosocial therapeutic health concept already occurred in an early phase of training (F(2, 164) = 5.39, P = 0.005, η(2)(p) = 0.06), whereas increased values in a biomedical concept did not occur until people's professional life (F(2, 164) = 10.99, P students as

  13. Review of the current status of linear hybrid reactor concepts

    Schultz, K.R.

    1977-07-01

    A review was made of the current status of linear fusion-fission hybrid reactor design studies in the USA. The linear hybrid reactor concepts reviewed include the linear theta-pinch hybrid reactor being studied at Los Alamos Scientific Laboratory, the electron beam-heated solenoid hybrid reactor under development at Physics International Co., the laser-heated solenoid hybrid reactor being investigated at Mathematical Sciences Northwest, Inc., and the linear fusion waste burning reactor being studied at General Atomic Company. The discussion addresses confinement and heating mechanisms for each concept, as well as the hybrid blanket designs. The current state of the four reactor designs is summarized and the performance of the various concepts compared

  14. Concepts Concerning 'Disease\\' Causation, Control, and the current ...

    There is an ethical necessity that doctors understand the complex social, political, environmental and economic dynamics involved in infectious disease outbreaks. This article discusses some important concepts concerning 'disease' causation and control with specific reference to the current cholera outbreak in Zimbabwe ...

  15. Augmentation of therapeutic potential of curcumin using nanotechnology: current perspectives.

    Sivasami, Pulavendran; Hemalatha, Thiagarajan

    2018-02-28

    Curcumin, an active principle of Curcuma longa, is extracted from the rhizome. Its therapeutic efficiency has been proved using various in vitro and in vivo models. Inflammatory, neoplastic and preneoplastic diseases are the major targets using curcumin as therapeutic agent. Feasible clinical formulations could not be obtained because of its lack of solubility, stability and higher degradation rate. Recently, many techniques have been evolved to improve the physicochemical properties of pharmacological compounds, thereby increasing their biological activity. Curcumin has been developed using various techniques, particularly micro and nanotechnology to improve its stability and bioavailability. This review focuses on the studies pertaining to the delivery of curcumin in the form of micro and nanosize formulations for the treatment of a variety of diseases.

  16. Clinical and genetic examinations of children with one parent whose gonads were therapeutically irradiated before conception

    Neumeister, K.; Herrmann, T.; Koelling, H.L.; Oelssner, W.; Schoeneich, R.

    1978-01-01

    A systematic program for investigating genetic radiation hazards is outlined. The program is aimed at obtaining clinical, genetic and biochemical data on children with one parent whose gonads were exposed to therapeutic radiation before conception. First results obtained show that there is no contraindication against radiotherapy. However, it is recommended to consult a geneticist in such cases. (author)

  17. Therapeutic drug monitoring in pediatric IBD: current application and future perspectives.

    Lega, Sara; Bramuzzo, Matteo; Dubinsky, Marla

    2017-09-11

    As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies. In the era of biologics, TDM entered the clinical field to assist clinicians managing anti-TNF failure and its role is now moving toward the concept of "proactive" TDM with the goal to optimize drug exposure and prevent loss of response. Research in TDM is rapidly expanding: while the role of TDM with new biologics is under investigation, preliminary data suggest that software-systems support tools could be an opportunity to guide dosing choices and maximize the cost-benefit profile of therapies in the near future. The review discusses the current knowledge that poses the rationale for the use of TDM and the present and future role of TDM-based approaches in the management of pediatric IBD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. The microbiota in inflammatory bowel disease: current and therapeutic insights

    Lane ER

    2017-06-01

    Full Text Available Erin R Lane,1 Timothy L Zisman,2 David L Suskind1 1Division of Gastroenterology and Hepatology, Seattle Children’s Hospital, 2Division of Gastroenterology, University of Washington, Seattle, WA, USA Abstract: Inflammatory bowel disease is a heterogeneous group of chronic disorders that result from the interaction of the intestinal immune system with the gut microbiome. Until recently, most investigative efforts and therapeutic breakthroughs were centered on understanding and manipulating the altered mucosal immune response that characterizes these diseases. However, more recent studies have highlighted the important role of environmental factors, and in particular the microbiota, in disease onset and disease exacerbation. Advances in genomic sequencing technology and bioinformatics have facilitated an explosion of investigative inquiries into the composition and function of the intestinal microbiome in health and disease and have advanced our understanding of the interplay between the gut microbiota and the host immune system. The gut microbiome is dynamic and changes with age and in response to diet, antibiotics and other environmental factors, and these alterations in the microbiome contribute to disease onset and exacerbation. Strategies to manipulate the microbiome through diet, probiotics, antibiotics or fecal microbiota transplantation may potentially be used therapeutically to influence modulate disease activity. This review will characterize the factors involved in the development of the intestinal microbiome and will describe the typical alterations in the microbiota that are characteristic of inflammatory bowel disease. Additionally, this manuscript will summarize the early but promising literature on the role of the gut microbiota in the pathogenesis of inflammatory bowel disease with implications for utilizing this data for diagnostic or therapeutic application in the clinical management of patients with these diseases. Keywords

  19. Current Status of Dengue Therapeutics Research and Development.

    Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

    2017-03-01

    Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  20. Molecular Consortia—Various Structural and Synthetic Concepts for More Effective Therapeutics Synthesis

    Anna Pawełczyk

    2018-04-01

    Full Text Available The design and discovery of novel drug candidates are the initial and most probably the crucial steps in the drug development process. One of the tasks of medicinal chemistry is to produce new molecules that have a desired biological effect. However, even today the search for new pharmaceuticals is a very complicated process that is hard to rationalize. Literature provides many scientific reports on future prospects of design of potentially useful drugs. Many trends have been proposed for the design of new drugs containing different structures (dimers, heterodimers, heteromers, adducts, associates, complexes, biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs, identical or non-identical twin drugs, mixed or combo drugs, supramolecular particles and various nanoindividuals. Recently much attention has been paid to different strategies of molecular hybridization. In this paper, various molecular combinations were described e.g., drug–drug or drug-non-drug combinations which are expressed in a schematic multi-factor form called a molecular matrix, consisting of four factors: association mode, connection method, and the number of elements and linkers. One of the most popular trends is to create small–small molecule combinations such as different hybrids, codrugs, drug–drug conjugates (DDCs and small-large molecule combinations such as antibody-drug conjugates (ADCs, polymer-drug conjugates (PDCs or different prodrugs and macromolecular therapeutics. A review of the structural possibilities of active framework combinations indicates that a wide range of potentially effective novel-type compounds can be formed. What is particularly important is that new therapeutics can be obtained in fast, efficient, and selective methods using current trends in chemical synthesis and the design of drugs such as the “Lego” concept or rational green approach.

  1. The concept of electronegativity. The current state of the problem

    Cherkasov, Artem R; Galkin, Vladimir I; Zueva, Ekaterina M; Cherkasov, Rafael A

    1998-01-01

    A systematic account is given of the current ideas about atomic and group electronegativities and the trends in the development of the concept of electronegativity are analysed. Attention is concentrated on the latest approaches to the definition of electronegativity - the concept of 'orbital' electronegativities and the density functional theory. A procedure is proposed for the determination of 'inductive' electronegativities, which permits a correct theoretical calculation of the electronegativity of a substituent from the electronegativities of individual atoms and the steric structure. It is shown that the approach developed has a series of important advantages - for example, it makes it possible to calculate the group electronegativities of isomeric substituents avoiding the principle of the equalisation of electronegativities. A survey of literature data and generalisation of the method proposed by the authors have made it possible to formulate the concept of electronegativity as an unchanging fundamental immanent characteristic of a chemical element. The bibliography includes 222 references.

  2. Update in Current Diagnostics and Therapeutics of Dry Eye Disease.

    Thulasi, Praneetha; Djalilian, Ali Reza

    2017-11-01

    Dry eye disease (DED) represents a heterogeneous group of conditions with tear film insufficiency and signs and/or symptoms of ocular surface irritation. The clinical manifestations of DED can be highly variable; hence the diagnosis is often based on a combination of symptoms, signs, and clinical tests, given that any one of these alone would miss a significant number of patients. Similarly, the treatment must often be tailored to each patient by targeting the specific mechanisms involved in his or her disease. The purpose of this review is to summarize recent advances that have allowed us to better recognize, categorize, and treat patients with DED. The most notable new diagnostic tests in DED are tear film osmolarity, inflammatory biomarkers, and meibomian gland imaging. Therapeutically, anti-inflammatory therapy, meibomian gland heating and expression, and scleral contact lenses are some of the latest options available for treating DED. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  3. Rectal cancer and Fournier's gangrene - current knowledge and therapeutic options.

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-08-14

    Fournier's gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects.

  4. Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

    Ando, Kosei; Heymann, Marie-Françoise; Stresing, Verena; Mori, Kanji; Rédini, Françoise; Heymann, Dominique

    2013-01-01

    Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies

  5. Non-invasive brain stimulation for Parkinson's disease: Current concepts and outlook 2015.

    Benninger, David H; Hallett, Mark

    2015-01-01

    In advanced Parkinson's disease (PD), the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation as an alternative therapeutic tool. The rationale for its use draws from the concept that reversing abnormalities in brain activity and physiology thought to cause the clinical deficits may restore normal functioning. Currently the best evidence in support of this concept comes from DBS, which improves motor deficits, and modulates brain activity and motor cortex physiology, though whether a causal interaction exists remains largely undetermined. Most trials of non-invasive brain stimulation in PD have applied repetitive transcranial magnetic stimulation (rTMS) targeting the primary motor cortex and cortical areas of the motor circuit. Published studies suggest a possible therapeutic potential of rTMS and transcranial direct current stimulation (tDCS), but clinical effects so far have been small and negligible regarding functional independence and quality of life. Approaches to potentiate the efficacy of rTMS, including increasing stimulation intensity and novel stimulation parameters, derive their rationale from studies of brain physiology. These novel parameters simulate normal firing patterns or act on the hypothesized role of oscillatory activity in the motor cortex and basal ganglia in motor control. There may also be diagnostic potential of TMS in characterizing individual traits for personalized medicine.

  6. Current concepts in the diagnosis and treatment of shoulder impingement

    Bijayendra Singh

    2017-01-01

    Full Text Available Subacromial impingement syndrome (SIS is a very common cause of shoulder pain in the young adults. It can cause debilitating pain, dysfunction, and affects the activities of daily living. It represents a spectrum of pathology ranging from bursitis to rotator cuff tendinopathy which can ultimately lead to degenerative tear of the rotator cuff. Various theories and concepts have been described and it is still a matter of debate. However, most published studies suggest that both extrinsic and intrinsic factors have a role in the development of SIS. The management is controversial as both nonoperative and operative treatments have shown to provide good results. This article aims to provide a comprehensive current concepts review of the pathogenesis, etiologies, clinical diagnosis, appropriate use of investigations, and discussion on the management of SIS.

  7. Recent concepts concerning cerebral ischaemia in man and their implications in therapeutic evaluations

    Depresseux, J C

    1987-06-18

    Recent concepts concerning focal cerebral ischaemia in man and resulting from the data obtained with positron emission tomography are reported. The evolutive steps in the ischaemic process are divided into: perfusion reserve; extraction reserve recruitment; ischaemic penumbra; lesional process and post-lesional developments. Circulatory and metabolic patterns corresponding to these evolutive steps are described and illustrated. The potentials of these data as guide-lines in therapeutic trial methodology are discussed.

  8. Recent concepts concerning cerebral ischaemia in man and their implications in therapeutic evaluations

    Depresseux, J.C.

    1987-01-01

    Recent concepts concerning focal cerebral ischaemia in man and resulting from the data obtained with positron emission tomography are reported. The evolutive steps in the ischaemic process are divided into: perfusion reserve; extraction reserve recruitment; ischaemic penumbra; lesional process and post-lesional developments. Circulatory and metabolic patterns corresponding to these evolutive steps are described and illustrated. The potentials of these data as guide-lines in therapeutic trial methodology are discussed [fr

  9. Lysosomal storage diseases: current diagnostic and therapeutic options

    Malinova, V.; Honzik, T.

    2013-01-01

    Lysosomal storage diseases are rare genetic diseases caused by insufficient activity of some of the lysosomal enzymes and/or transport proteins. Initial symptoms may appear any time from the neonatal period to late adulthood; early forms tend to have a severe course with rapid progression and unfavorable prognosis. There is multisystem involvement with continuous progression of symptoms and involvement of metabolically active organs or tissues – the bone marrow, liver, bones, skeletal muscles, myocardium, or CNS. The diagnosis is definitively confirmed by demonstration of reduced activity of the particular enzyme and by mutation analysis. Some of the storage diseases can be effectively treated by intravenous administration of recombinant enzymes or by limiting the amount of the substrate stored. In a small number of lysosomal storage diseases, bone marrow transplantation is successful. Multidisciplinary collaboration, including genetic counselling and prenatal diagnosis in patient families, is required. The first part of the paper deals with general characteristics of lysosomal storage diseases and the most common diseases that are currently treatable in the Czech Republic (Gaucher’s disease, Pompe disease, Fabry disease, Niemann–Pick disease, cholesterol ester storage disease). The second part of the paper deals with mucopolysaccharidase, another group of rare lysosomal storage diseases. (author)

  10. Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment

    Jaume Folch

    2016-01-01

    Full Text Available Alzheimer’s disease (AD currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC. PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5. Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease.

  11. Ocular Behçet disease: current therapeutic approaches.

    Evereklioglu, Cem

    2011-11-01

    To alert physician to timely recognition and current treatment of recurrent hypopyon iridocyclitis or panuveitis in ocular Behçet disease (OBD). Interferon-α, rituximab, intravitreal triamcinolone, and biological response modifiers by tumor necrosis factor inhibitors such as infliximab and adalimumab are being used increasingly for the treatment of severe sight-threatening ocular inflammation including retinal vasculitis and cystoid macular edema (CME). Biological agents offer tremendous potential in the treatment of OBD. Given that OBD predominantly afflicts the younger adults in their most productive years, dermatologist, rheumatologist, internist, or general practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes should be aware of systemic Behçet disease. Early recognition of ocular involvement is important and such patients should strongly be instructed to visit immediately an ophthalmologist, as uveitis management differs from extraocular involvements with high ocular morbidity from sight-threatening complications due to relapsing inflammatory attacks in the posterior segment of the eye. A single infliximab infusion should be considered for the control of acute panuveitis, whereas repeated long-term infliximab infusions were proved to be more effective in reducing the number of episodes in refractory uveoretinitis with faster regression and complete remission of CME.

  12. Gestational Diabetes Mellitus: a review of current diagnostic strategies concepts

    Juan Sebastián Frías-Ordoñez

    2016-10-01

    Full Text Available Gestational diabetes mellitus (GDM is a state of carbohydrate intolerance that is first recognized during pregnancy. The initial criteria for diagnosis were established more than 50 years ago by O’Sullivan & Mahan, and since then, some modifications have been made. Currently, diagnosis considers two methods: the onestep approach, consisting of an oral glucose tolerance test (OGTT for 2 hours with 75g of glucose, and the two-step approach, which involves an initial screening test with 50g of glucose and OGTT with 100g of glucose if screening is positive. Both diagnostic approaches have been justified by expert consensus; however, an absolute concept about the method to be applied has not been established yet. To select a method, the clinician must take into account various factors. This paper proposes a historical overview and the presentation of the current status of GDM diagnosis.

  13. [Current concepts in perioperative management of children : preface and comments].

    Kuratani, Norifumi; Kikuchi, Hirosato

    2007-05-01

    In the past few years, pediatric anesthesia management changed rapidly to more evidence-based and patient-oriented practice. It has been emphasized that "focused and individualized" pre-anesthesia evaluation is preferred to routine screening of laboratory tests and X-rays. Anesthesia induction should be less stressful for children through the use of various approaches, such as preoperative preparation, sedative premedication, and parent-present induction. Cuffed tracheal tube is becoming popular for small children, and its indication should be considered individually. Laryngeal mask airway is frequently used for simple short cases. Perioperative fluid infusion therapy has been a controversial issue. Traditional therapeutic regimen using hypotonic solution with glucose is criticized as a result of the growing evidence of hyponatremia and hyperglycemia. New ventilatory modes and sedative medications are now available for pediatric patients, and lung-protective ventilatory strategy should be considered to protect immature lung from ventilator-induced lung injury. Emergence agitation from general anesthesia is an evolving problem. Sevoflurane is known to be a major risk factor for stormy wake-up. Pediatric anesthesiologists should pursue high quality of anesthesia emergence. All anesthesia residency programs should include pediatric rotation; otherwise anesthesia residents will lose opportunities to learn basic concepts of pediatric anesthesia.

  14. Persistent hyperinsulinemic hypoglycemia of infancy: An overview of current concepts

    Prabudh Goel

    2012-01-01

    Full Text Available Persistent hyperinsulinemic hypoglycemia of infancy (PHHI is relatively rare but one of the most important causes of severe neonatal hypoglycemia. Recognition of this entity becomes important due to the fact that the hypoglycemia is so severe and frequent that it may lead to severe neurological damage in the infant manifesting as mental or psychomotor retardation or even a life-threatening event if not recognized and treated effectively in time. Near-total pancreatectomy may be required for patients with intractable hypoglycemia despite medical treatment; however, that may result in diabetes mellitus or recurrent postoperative hypoglycemia. This review aims to consolidate the traditional concepts and current information related to the pathogenesis and management of PHHI.

  15. The concept and definition of therapeutic inertia in hypertension in primary care: a qualitative systematic review.

    Lebeau, Jean-Pierre; Cadwallader, Jean-Sébastien; Aubin-Auger, Isabelle; Mercier, Alain; Pasquet, Thomas; Rusch, Emmanuel; Hendrickx, Kristin; Vermeire, Etienne

    2014-07-02

    Therapeutic inertia has been defined as the failure of health-care provider to initiate or intensify therapy when therapeutic goals are not reached. It is regarded as a major cause of uncontrolled hypertension. The exploration of its causes and the interventions to reduce it are plagued by unclear conceptualizations and hypothesized mechanisms. We therefore systematically searched the literature for definitions and discussions on the concept of therapeutic inertia in hypertension in primary care, to try and form an operational definition. A systematic review of all types of publications related to clinical inertia in hypertension was performed. Medline, EMbase, PsycInfo, the Cochrane library and databases, BDSP, CRD and NGC were searched from the start of their databases to June 2013. Articles were selected independently by two authors on the basis of their conceptual content, without other eligibility criteria or formal quality appraisal. Qualitative data were extracted independently by two teams of authors. Data were analyzed using a constant comparative qualitative method. The final selection included 89 articles. 112 codes were grouped in 4 categories: terms and definitions (semantics), "who" (physician, patient or system), "how and why" (mechanisms and reasons), and "appropriateness". Regarding each of these categories, a number of contradictory assertions were found, most of them relying on little or no empirical data. Overall, the limits of what should be considered as inertia were not clear. A number of authors insisted that what was considered deleterious inertia might in fact be appropriate care, depending on the situation. Our data analysis revealed a major lack of conceptualization of therapeutic inertia in hypertension and important discrepancies regarding its possible causes, mechanisms and outcomes. The concept should be split in two parts: appropriate inaction and inappropriate inertia. The development of consensual and operational definitions

  16. Book Review of Relational Patterns, Therapeutic Presence: Concepts and practice of Integrative Psychotherapy by Richard G. Erskine

    Marye O'Reilly-Knapp

    2015-12-01

    Full Text Available Book Review of Relational Patterns, Therapeutic Presence: Concepts and practice of Integrative Psychotherapy by Richard G. Erskine. Published by Karnac Books: London, 2015 Paperback, Pages 366, ISBN 13: 978-1-78220-190-8

  17. Book Review of Relational Patterns, Therapeutic Presence: Concepts and practice of Integrative Psychotherapy by Richard G. Erskine

    Marye O'Reilly-Knapp

    2015-01-01

    Book Review of Relational Patterns, Therapeutic Presence: Concepts and practice of Integrative Psychotherapy by Richard G. Erskine. Published by Karnac Books: London, 2015 Paperback, Pages 366, ISBN 13: 978-1-78220-190-8

  18. Advances in the delivery of RNA therapeutics: from concept to clinical reality.

    Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

    2017-06-27

    The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

  19. [Current treatment concepts for olecranon and prepatellar bursitis in Austria].

    Baumbach, S F; Michel, M; Wyen, H; Buschmann, C T; Kdolsky, R; Kanz, K-G

    2013-04-01

    The limited evidence available on the diagnosis and treatment of olecranon and prepatellar bursitis indicates nationally varying treatment approaches. Therefore the aim of this study was to survey the current treatment concepts of olecranon and prepatellar bursitis in Austria. An online questionnaire comprising of demographic data, questions regarding diagnostics and differentiation between septic bursitis (SB) and non-septic bursitis (NSB) as well as two case reports for therapy appraisal were sent to members of the Austrian Society of Orthopaedics and Orthopaedic Surgery (ÖGO) and the Austrian Society of Traumatology (ÖGU). The overall response rates were 46 % (ÖGU)/12 % (ÖGO). Differentiation between SB and NSB was predominantly based on medical history/clinical presentation (ÖGU: 100 %/ÖGO: 84 %) and blood sampling (ÖGU: 82 %/ÖGO: 77 %). 64/36 % of surveyed members of ÖGO/OGU performed a bursal aspiration. 95/55 % of Austrian ÖGU opinion leaders favoured a surgical treatment approach in cases of SB/NSB. Conversely, ÖGO members rather favoured a conservative treatment approach (28/27 %). Significant differences were found between ÖGO and ÖGU, with the latter favouring a surgical treatment approach in cases of SB and NSB. However, the international literature argues for a conservative treatment approach. Further high quality research is needed to establish an evidence-based treatment approach. Georg Thieme Verlag KG Stuttgart · New York.

  20. Current concepts and controversies on adolescent idiopathic scoliosis: Part I.

    Sud, Alok; Tsirikos, Athanasios I

    2013-03-01

    Adolescent idiopathic scoliosis is the most common spinal deformity encountered by General Orthopaedic Surgeons. Etiology remains unclear and current research focuses on genetic factors that may influence scoliosis development and risk of progression. Delayed diagnosis can result in severe deformities which affect the coronal and sagittal planes, as well as the rib cage, waistline symmetry, and shoulder balance. Patient's dissatisfaction in terms of physical appearance and mechanical back pain, as well as the risk for curve deterioration are usually the reasons for treatment. Conservative management involves mainly bracing with the aim to stop or slow down scoliosis progression during growth and if possible prevent the need for surgical treatment. This is mainly indicated in young compliant patients with a large amount of remaining growth and progressive curvatures. Scoliosis correction is indicated for severe or progressive curves which produce significant cosmetic deformity, muscular pain, and patient discontent. Posterior spinal arthrodesis with Harrington instrumentation and bone grafting was the first attempt to correct the coronal deformity and replace in situ fusion. This was associated with high pseudarthrosis rates, need for postoperative immobilization, and flattening of sagittal spinal contour. Segmental correction techniques were introduced along with the Luque rods, Harri-Luque, and Wisconsin systems. Correction in both coronal and sagittal planes was not satisfactory and high rates of nonunion persisted until Cotrel and Dubousset introduced the concept of global spinal derotation. Development of pedicle screws provided a powerful tool to correct three-dimensional vertebral deformity and opened a new era in the treatment of scoliosis.

  1. Delivery of Therapeutic Proteins Using Electrospun Fibers-Recent Developments and Current Challenges.

    Seif, Salem; Planz, Viktoria; Windbergs, Maike

    2017-10-01

    Proteins play a vital role within the human body by regulating various functions and even serving as structural constituent of many body parts. In this context, protein-based therapeutics have attracted a lot of attention in the last few decades as potential treatment of different diseases. Due to the steadily increasing interest in protein-based therapeutics, different dosage forms were investigated for delivering such complex macromolecules to the human body. Here, electrospun fibers hold a great potential for embedding proteins without structural damage and for controlled release of the protein for therapeutic applications. This review provides a comprehensive overview of the current state of protein-based carrier systems using electrospun fibers, with special emphasis on discussing their potential and key challenges in developing such therapeutic strategies, along with a prospective view of anticipated future directions. © 2017 Deutsche Pharmazeutische Gesellschaft.

  2. Introduction to current and future protein therapeutics: a protein engineering perspective.

    Carter, Paul J

    2011-05-15

    Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies to address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Current concepts and controversies on adolescent idiopathic scoliosis: Part I

    Alok Sud

    2013-01-01

    Full Text Available Adolescent idiopathic scoliosis is the most common spinal deformity encountered by General Orthopaedic Surgeons. Etiology remains unclear and current research focuses on genetic factors that may influence scoliosis development and risk of progression. Delayed diagnosis can result in severe deformities which affect the coronal and sagittal planes, as well as the rib cage, waistline symmetry, and shoulder balance. Patient′s dissatisfaction in terms of physical appearance and mechanical back pain, as well as the risk for curve deterioration are usually the reasons for treatment. Conservative management involves mainly bracing with the aim to stop or slow down scoliosis progression during growth and if possible prevent the need for surgical treatment. This is mainly indicated in young compliant patients with a large amount of remaining growth and progressive curvatures. Scoliosis correction is indicated for severe or progressive curves which produce significant cosmetic deformity, muscular pain, and patient discontent. Posterior spinal arthrodesis with Harrington instrumentation and bone grafting was the first attempt to correct the coronal deformity and replace in situ fusion. This was associated with high pseudarthrosis rates, need for postoperative immobilization, and flattening of sagittal spinal contour. Segmental correction techniques were introduced along with the Luque rods, Harri-Luque, and Wisconsin systems. Correction in both coronal and sagittal planes was not satisfactory and high rates of nonunion persisted until Cotrel and Dubousset introduced the concept of global spinal derotation. Development of pedicle screws provided a powerful tool to correct three-dimensional vertebral deformity and opened a new era in the treatment of scoliosis.

  4. Auricular tachycardia: therapeutic and pathophysiologic news concepts: literature review and casuistic Service presentation

    Horta, J. de; Reyes, W.; Calleriza, F.; Pouso, J.; Besada, E.

    1998-01-01

    The auricular tachycardia are the supraventricular tachycardias whose origin mechanism and maintenance is located at level exclusively auricular. It show diagnostic and therapeutics difficulties.The inadequate handling can cause commitment of the ventricular function and to commit the predict vital.The pharmacological treatment, is more used is few effective.The ablation for catheter with radiofrequency is a new weapon transcendent therapy for the resolution of a significant group of these patients. A review of the concept of auricular tachycardias, it upgrades its classification and the mechanisms pathophysiologic.It describes the techniques of ablation for catheter in these arrhythmias and their results are revised in the literature. In the end it presents the casuistry of the Service in the treatment of the auricular tachycardias focal s,incision ales and atrial flutter by means of ablation for catheter with radiofrequency [es

  5. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

    Pedraza-Chaverri, José; Sánchez-Lozada, Laura G; Osorio-Alonso, Horacio

    2016-01-01

    In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline...... and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies....

  6. Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

    Sproule, Douglas M; Kaufmann, Petra

    2008-10-01

    Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

  7. Current concepts in lung dosimetry. Proceedings of a special workshop

    Fisher, D.R.

    1983-02-01

    The proceedings of the first special workshop on Lung Dosimetry include the presentation of many new concepts and the reassessment of traditional ideas in lung dosimetry and risk evaluation. Separate abstracts were prepared for the 21 papers in the proceedings

  8. Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

    Patel, Ravi Mangal; Denning, Patricia Wei

    2013-01-01

    Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

  9. [Therapeutic Concepts for Treatment of Patients with Non-infectious Uveitis Biologic Disease Modifying Antirheumatic Drugs].

    Walscheid, Karoline; Pleyer, Uwe; Heiligenhaus, Arnd

    2018-04-12

    Biologic disease modifying antirheumatic drugs (bDMARDs) can be highly efficient in the treatment of various non-infectious uveitis entities. Currently, the TNF-α-inhibitor Adalimumab is the only in-label therapeutic option, whereas, all other bDMARDs need to be given as an off-label therapy. bDMARDs are indicated in diseases refractory to conventional synthetic DMARD therapy and/or systemic steroids, or in patients in whom treatment with those is not possible due to side effects. Therapeutic mechanisms currently employed are cytokine-specific (interferons, inhibition of TNF-α or of interleukin [IL]-1-, IL-6- or IL-17-signalling), inhibit T cell costimulation (CTLA-4 fusion protein), or act via depletion of B cells (anti-CD20). All bDMARDs need to be administered parenterally, and therapy is initiated by the treating internal specialist only after interdisciplinary coordination of all treating subspecialties and after exclusion of contraindications. Regular clinical and laboratory monitoring is mandatory for all patients while under bDMARD therapy. Georg Thieme Verlag KG Stuttgart · New York.

  10. Current and future competitiveness of bioenergy - Conceptions about competitiveness

    Ling, E.; Lundgren, K.; Maartensson, Kjell

    1998-01-01

    It is important to visualize the conceptions that guide the behaviour of the actors within the energy system to be able to, in an efficient manner, increase the share of renewable energy in the energy mix. A major issue is to elucidate explicit and implicit presumptions within judgements on the competitiveness of bioenergy. This study focuses on how conceptions of bioenergy in the form of patterns of thinking, influence whether bioenergy can become competitive. The aim of the study is to develop a framework that will enable an increased understanding of the competitiveness of bioenergy today and in the future. The conceptions that the actors of the energy system uphold are studied and analysed. The conceptions of the actors are seen as key factors for the understanding of the function of the energy system and accordingly also for the understanding of the competitiveness of bioenergy. The over-all method perspective in the study is an actor approach. The actors' conceptions have been identified from interviews with 30 significant actors within the energy system. The material from the interviews has been synthesised into nine ideal types of actors. These nine 'model actors' are seen as representing the whole material and form the basis for the further analysis of the competitiveness of bioenergy as depending on patterns of thinking called logics. Three idealized logics are developed. The three logics developed in the study are production logic, market logic and socio-economic logic. (Upholders of the logics rank energy sources after production cost, profitability, and socio-economic legitimacy, respectively.) The logics co-exist within the different parts of the energy system. A single person can even uphold more than one logic. The three logics have however different weight in different organisations and in different parts of the energy system. Finally, the study proposes an enlarged description of the competitiveness of bioenergy in three dimensions: price

  11. Osteoarthritis: A review of old myths and current concepts

    Alexander, C.J.

    1990-01-01

    Radiology is dependent on an accurate understanding of the pathological process. This review of primary osteoarthritis identifies eight areas in which widely held concepts are either demonstrably false or fall short of proof. In some, the concepts have been disproved by the gradual accumulation of evidence. In others, the error is due to readiological misinterpretation while in a third group, the evidence is not in dispute, but the logical framework used in its assessment is flawed. Awareness of these deficiencies simplifies radiological interpretation and clarifies research objectives. (orig.)

  12. Concepts Concerning 'Disease' Causation, Control, and the current ...

    2008-12-02

    Dec 2, 2008 ... practice (and thus disease concepts) is attributable to Michael Foucault who, amongst his other insights, recognises that the development of modern medicine has taken the particular route that it has because it simultaneously constructs its own object of enquiry and comes up with ideas to explain and deal ...

  13. Serotonin syndrome:case report and current concepts.

    Fennell, J

    2005-05-01

    Selective serotonin reuptake inhibitors (SSRI\\'s) are increasingly being used as the first line therapeutic agent for the depression. It is therefore not unusual to see a case of overdose with these agents. More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. The clinical picture of serotonin syndrome (SS) is non-specific and there is no confirmatory test. SS may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.

  14. [Schizoaffective Disorder: Evolution and Current Status of the Concept].

    Padhy, Susanta; Hedge, Aditya

    2015-01-01

    Schizoaffective disorder as a diagnostic entity is of particular present-day relevance; however, the concept of schizoaffective disorder, and its management and prognosis remain contentious. Descriptions of the disorder have varied over time. In this literature review, after tracking the evolution of the concept and nosology of schizoaffective disorder, research findings are summarized. This review takes a broad overview of the epidemiology, neurobiology, clinical presentation, diagnostic validity and stability, treatment, course, and outcome of schizoaffective disorder. Importance is given to the distinctness of schizoaffective disorder, and the overlap with schizophrenia and mood disorders, and problems associated with the construct are examined. Possible ways to treat the construct in the future in the best interest of patients, clinicians, and researchers are discussed.

  15. Unifying concept of serotonin transporter-associated currents.

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H; Sandtner, Walter

    2012-01-02

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents.

  16. New concept of the pathogenesis and therapeutic orientation of acquired communicating hydrocephalus.

    Xu, Hao

    2016-09-01

    Hydrocephalus is a common medical condition characterized by abnormalities in the secretion, circulation and absorption of cerebrospinal fluid (CSF), resulting in ventricle dilatation. For the communicating hydrocephalus, without etiological treatment, its pathogenesis has been considered as a research emphasis. Many factors can damage the CSF system and trigger communicating hydrocephalus, including tumor surgery and hydrocephalus neurological diseases, such as brain trauma, infection, ICH and SAH. But according to our clinical experience, a big proportion of patients do not develop hydrocephalus. That is because the absorbing ability of CSF can compensate within a certain range. If the damage exceeds that range, hydrocephalus will occur. Once it occurs, it is not likely to be reversed, so a shunt surgery is always needed. Therefore, we believe that our orientation could transform the treatment of patient who has already showed hydrocephalus symptoms to the prevention of the occurrence in the patient with high risk of hydrocephalus. Based on the hypothesis above, we first divide the process of hydrocephalus into three stages and we believe that hydrocephalus are possible be reversed or halted in stage 1 and 2. The new concept of the pathogenesis in hydrocephalus will enrich our understanding and provide new insights to the therapeutic orientation. In conclusion, the future research direction should be the prevention of hydrocephalus, which should take a long period from the immediate occurrence of brain injury to several months or even years after the injury.

  17. Halitosis: Current concepts on etiology, diagnosis and management

    Kapoor, Uditi; Sharma, Gaurav; Juneja, Manish; Nagpal, Archna

    2016-01-01

    Halitosis or oral malodor is an offensive odor originating from the oral cavity, leading to anxiety and psychosocial embarrassment. A patient with halitosis is most likely to contact primary care practitioner for the diagnosis and management. With proper diagnosis, identification of the etiology and timely referrals certain steps are taken to create a successful individualized therapeutic approach for each patient seeking assistance. It is significant to highlight the necessity of an interdisciplinary method for the treatment of halitosis to prevent misdiagnosis or unnecessary treatment. The literature on halitosis, especially with randomized clinical trials, is scarce and additional studies are required. This article succinctly focuses on the development of a systematic flow of events to come to the best management of the halitosis from the primary care practitioner's point of view. PMID:27095913

  18. Current Concepts of Hyperinflammation in Chronic Granulomatous Disease

    Nikolaus Rieber

    2012-01-01

    Full Text Available Chronic granulomatous disease (CGD is the most common inherited disorder of phagocytic functions, caused by genetic defects in the leukocyte nicotinamide dinucleotide phosphate (NADPH oxidase. Consequently, CGD phagocytes are impaired in destroying phagocytosed microorganisms, rendering the patients susceptible to bacterial and fungal infections. Besides this immunodeficiency, CGD patients suffer from various autoinflammatory symptoms, such as granuloma formation in the skin or urinary tract and Crohn-like colitis. Owing to improved antimicrobial treatment strategies, the majority of CGD patients reaches adulthood, yet the autoinflammatory manifestations become more prominent by lack of causative treatment options. The underlying pathomechanisms driving hyperinflammatory reactions in CGD are poorly understood, but recent studies implicate reduced neutrophil apoptosis and efferocytosis, dysbalanced innate immune receptors, altered T-cell surface redox levels, induction of Th17 cells, the enzyme indolamine-2,3-dioxygenase (IDO, impaired Nrf2 activity, and inflammasome activation. Here we discuss immunological mechanisms of hyperinflammation and their potential therapeutic implications in CGD.

  19. High current density aluminum stabilized conductor concepts for space applications

    Huang, X.; Eyssa, Y.M.; Hilal, M.A.

    1989-01-01

    Lightweight conductors are needed for space magnets to achieve values of E/M (energy stored per unit mass) comparable to the or higher than advanced batteries. High purity aluminum stabilized NbTi composite conductors cooled by 1.8 K helium can provide a winding current density up to 15 kA/cm/sup 2/ at fields up to 10 tesla. The conductors are edge cooled with enough surface area to provide recovery following a normalizing disturbance. The conductors are designed so that current diffusion time in the high purity aluminum is smaller than thermal diffusion time in helium. Conductor design, stability and current diffusion are considered in detail

  20. Revisiting reflexology: Concept, evidence, current practice, and practitioner training

    Embong, Nurul Haswani; Soh, Yee Chang; Ming, Long Chiau; Wong, Tin Wui

    2015-01-01

    Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and th...

  1. Unifying Concept of Serotonin Transporter-associated Currents*

    Schicker, Klaus; Uzelac, Zeljko; Gesmonde, Joan; Bulling, Simon; Stockner, Thomas; Freissmuth, Michael; Boehm, Stefan; Rudnick, Gary; Sitte, Harald H.; Sandtner, Walter

    2012-01-01

    Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven by ion gradients. The stoichiometry of transported 5-HT and ions is predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for by an uncoupled ion flux. Here, we investigated the mechanistic basis of the uncoupled currents and its relation to the conformational cycle of hSERT. Our observations support the conclusion that the conducting state underlying the uncoupled ion flux is in equilibrium with an inward facing state of the transporter with K+ bound. We identified conditions associated with accumulation of the transporter in inward facing conformations. Manipulations that increased the abundance of inward facing states resulted in enhanced steady-state currents. We present a comprehensive kinetic model of the transport cycle, which recapitulates salient features of the recorded currents. This study provides a framework for exploring transporter-associated currents. PMID:22072712

  2. Osteodensitometry and osteoporosis. Current concepts and strategies for the future

    Restrepo U, Santiago

    1991-01-01

    The osteoporosis is a disease of universal distribution that affects millions of adults in the whole world, producing a high number of fractures, due to insufficiency that generates a significant morbidity and mortality. This condition is especially frequent in post menopause women. Some concepts about the bone structure, and the principal characteristics of the different methods to quantify the bone mass (conventional radiology, radiogrametry, photo densitometry, single photon absorbitometry, dual photon absorbitometry are reviewed. Finally, the advantages, disadvantages, levels of sensibility, precision, of the different techniques are established. An emphasis is made on the special capacity of the quantitative computed axial tomography to detect as a selective way the alterations of the spongiest bone

  3. Rheumatic heart disease screening: Current concepts and challenges

    Dougherty, Scott; Khorsandi, Maziar; Herbst, Philip

    2017-01-01

    Rheumatic heart disease (RHD) is a disease of poverty, is almost entirely preventable, and is the most common cardiovascular disease worldwide in those under 25 years. RHD is caused by acute rheumatic fever (ARF) which typically results in cumulative valvular lesions that may present clinically after a number of years of subclinical disease. Therapeutic interventions, therefore, typically focus on preventing subsequent ARF episodes (with penicillin prophylaxis). However, not all patients with ARF develop symptoms and not all symptomatic cases present to a physician or are correctly diagnosed. Therefore, if we hope to control ARF and RHD at the population level, we need a more reliable discriminator of subclinical disease. Recent studies have examined the utility of echocardiographic screening, which is far superior to auscultation at detecting RHD. However, there are many concerns surrounding this approach. Despite the introduction of the World Heart Federation diagnostic criteria in 2012, we still do not really know what constitutes the most subtle changes of RHD by echocardiography. This poses serious problems regarding whom to treat and what to do with the rest, both important decisions with widespread implications for already stretched health-care systems. In addition, issues ranging from improving the uptake of penicillin prophylaxis in ARF/RHD-positive patients, improving portable echocardiographic equipment, understanding the natural history of subclinical RHD and how it might respond to penicillin, and developing simplified diagnostic criteria that can be applied by nonexperts, all need to be effectively tackled before routine widespread screening for RHD can be endorsed. PMID:28163427

  4. LLNL current meter array--concept and system description

    Mantrom, D.D. [Lawrence Livermore National Lab., CA (United States)

    1994-11-15

    A measurement capability using a horizontal array of 10 S4 current meters mounted on a stiff floating structure with 35 m aperture has been developed to support interpretation of radar imaging of surface effects associated with internal waves. This system has been fielded three times and most recently, has collected data alongside the sea-surface footprint of a land-fixed radar imaging ship-generated internal waves. The underlying need for this measurement capability is described. The specifications resulting from this need are presented and the engineering design and deployment procedures of the platform and systems that resulted are described The current meter data are multiplexed along with meteorological and system status data on board the floating platform and are telemetered to a shore station and on to a data acquisition system. The raw data are recorded, and are then processed to form space-time images of current and strain rate (a spatial derivative of the current field). Examples of raw and processed data associated with ship-generated internal waves are presented.

  5. CURRENT CONCEPTS IN BIOMECHANICAL INTERVENTIONS FOR PATELLOFEMORAL PAIN

    Meira, Erik P.

    2016-01-01

    Patellofemoral pain (PFP) has historically been a complex and enigmatic issue. Many of the factors thought to relate to PFP remain after patients' symptoms have resolved making their clinical importance difficult to determine. The tissue homeostasis model proposed by Dye in 2005 can assist with understanding and implementing biomechanical interventions for PFP. Under this model, the goal of interventions for PFP should be to re-establish patellofemoral joint (PFJ) homeostasis through a temporary alteration of load to the offended tissue, followed by incrementally restoring the envelope of function to the baseline level or higher. High levels of PFJ loads, particularly in the presence of an altered PFJ environment, are thought to be a factor in the development of PFP. Clinical interventions often aim to alter the biomechanical patterns that are thought to result in elevated PFJ loads while concurrently increasing the load tolerance capabilities of the tissue through therapeutic exercise. Biomechanics may play a role in PFJ load modification not only when addressing proximal and distal components, but also when considering the involvement of more local factors such as the quadriceps musculature. Biomechanical considerations should consider the entire kinetic chain including the hip and the foot/ankle complex, however the beneficial effects of these interventions may not be the result of long-term biomechanical changes. Biomechanical alterations may be achieved through movement retraining, but the interventions likely need to be task-specific to alter movement patterns. The purpose of this commentary is to describe biomechanical interventions for the athlete with PFP to encourage a safe and complete return to sport. Level of Evidence 5 PMID:27904791

  6. CONCEPTS OF IMPROVING CURRENT PROTECTION OF POWER-GRID LINES

    F. A. Romaniuk

    2015-01-01

    Full Text Available The  6–35  kV  power-grid  current  protection  serves  to  protect  the  transmission  lines against phase-to-phase short-circuits. The major disadvantage of it lies in the relatively large time delays of the last stages especially in the main sections of the grid owing to the stepped relay characteristics as well as a large number of the steps. A full-fledged protection of the 6–35 kV lines against inter-phase short circuits can be provided by the two-stage current protection: the first stage being the current cutoff without any time delay and the second stage – the maximum current protection where the time delay is linear contingent on the distance between the protection placement and the fault-point location. The article introduces the rating formulae for the time delays of the second-stage and their exemplary graphic presentation. The authors offer a variant for solving the problem with computation of the second-stage time delays in those instances where several feeders diverge from the bus bars of the substation located in the end of the protected line.Improving current protections for the 6–35 kV transmission lines with one-end power supply against interphase short-circuits can be based on the collective application of the following principles: accounting for the type and location of the short-circuit which provides for the high-performance cutoff zone instantaneous expansion and its independence on the mode of failure and the grid operation mode. It also allows increase of the last stage sensitiveness towards asymmetrical short-circuits; detection of the short-circuit location only on the results of fault currents measurement which simplifies the protection implementation; realization of the last (second protection stage with linear-dependent time delay which ensures potentiality of its operation speed increase.

  7. Lessons from the masters current concepts in astronomical image processing

    2013-01-01

    There are currently thousands of amateur astronomers around the world engaged in astrophotography at increasingly sophisticated levels. Their ranks far outnumber professional astronomers doing the same and their contributions both technically and artistically are the dominant drivers of progress in the field today. This book is a unique collaboration of individuals, all world-renowned in their particular area, and covers in detail each of the major sub-disciplines of astrophotography. This approach offers the reader the greatest opportunity to learn the most current information and the latest techniques directly from the foremost innovators in the field today.   The book as a whole covers all types of astronomical image processing, including processing of eclipses and solar phenomena, extracting detail from deep-sky, planetary, and widefield images, and offers solutions to some of the most challenging and vexing problems in astronomical image processing. Recognized chapter authors include deep sky experts su...

  8. Revisiting reflexology: Concept, evidence, current practice, and practitioner training.

    Embong, Nurul Haswani; Soh, Yee Chang; Ming, Long Chiau; Wong, Tin Wui

    2015-10-01

    Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided.

  9. Revisiting reflexology: Concept, evidence, current practice, and practitioner training

    Nurul Haswani Embong

    2015-10-01

    Full Text Available Reflexology is basically a study of how one part of the human body relates to another part of the body. Reflexology practitioners rely on the reflexes map of the feet and hands to all the internal organs and other human body parts. They believe that by applying the appropriate pressure and massage certain spots on the feet and hands, all other body parts could be energized and rejuvenated. This review aimed to revisit the concept of reflexology and examine its effectiveness, practices, and the training for reflexology practitioners. PubMed, SCOPUS, Google Scholar, and SpringerLink databases were utilized to search the following medical subject headings or keywords: foot massage, reflexology, foot reflexotherapy, reflexological treatment, and zone therapy. The articles published for the last 10 years were included. Previous systematic reviews failed to show concrete evidence for any specific effect of reflexology in any conditions. Due to its non-invasive, non-pharmacological complementary nature, reflexology is widely accepted and anecdotal evidence of positive effect reflexology in a variety of health conditions are available. Adequate training for practitioners is necessary to ensure the consistency of service provided.

  10. Current concepts in simulation-based trauma education.

    Cherry, Robert A; Ali, Jameel

    2008-11-01

    The use of simulation-based technology in trauma education has focused on providing a safe and effective alternative to the more traditional methods that are used to teach technical skills and critical concepts in trauma resuscitation. Trauma team training using simulation-based technology is also being used to develop skills in leadership, team-information sharing, communication, and decision-making. The integration of simulators into medical student curriculum, residency training, and continuing medical education has been strongly recommended by the American College of Surgeons as an innovative means of enhancing patient safety, reducing medical errors, and performing a systematic evaluation of various competencies. Advanced human patient simulators are increasingly being used in trauma as an evaluation tool to assess clinical performance and to teach and reinforce essential knowledge, skills, and abilities. A number of specialty simulators in trauma and critical care have also been designed to meet these educational objectives. Ongoing educational research is still needed to validate long-term retention of knowledge and skills, provide reliable methods to evaluate teaching effectiveness and performance, and to demonstrate improvement in patient safety and overall quality of care.

  11. Hypertrophic scars and keloids in surgery: current concepts.

    Song, Colin

    2014-09-01

    Hypertrophic scars and keloids remain a challenge in surgery. We appreciate that our understanding of the process at cellular and molecular level, profound as it is, when it comes to the clinical evidence much is left to be desired. Although the bench to bedside conundrum remains, the science of translational research calls for an even higher level of cooperation between the scientist and the clinician for the impetus to succeed.The clinicians alerted us to the possible theories in the pathogenesis of keloid formation, inter alia, the ischemia theory, mast cell theory, immune theory, transforming growth factor β interaction, mechanical theory, and the melanocyte stimulating hormone theory. All of the above presupposed a stimulus that would result in an uncontrolled upregulation of collagen and extracellular matrix expression in the pathogenesis of the keloid. This bedside to bench initiative, as in true science, realized more ponderables than possibilities.By the same token, research into the epidermal-mesenchymal signaling, molecular biology, genomics, and stem cell research holds much promise in the bench top arena. To assess efficacy, many scar assessment scores exist in the literature. The clinical measurement of scar maturity can aid in determining end points for therapeutics. Tissue oxygen tension and color assessment of scars by standardized photography proved to be useful.In surgery, the use of dermal substitutes holds some promise as we surmise that quality scars that arise from dermal elements, molecular and enzyme behavior, and balance. Although a systematic review shows some benefit for earlier closure and healing of wounds, no such review exists at this point in time for the use of dermal substitutes in scars.Adipose-derived stem cell, as it pertains to scars, will hopefully realize the potential of skin regeneration rather than by repair in which we are familiar with as well as the undesirable scarring as a result of healing through the inflammatory

  12. Concussions in the National Football League: A Current Concepts Review.

    Yengo-Kahn, Aaron M; Johnson, Daniel J; Zuckerman, Scott L; Solomon, Gary S

    2016-03-01

    Significant attention has been directed toward the immediate and long-term effects of sport-related concussions on athletes participating in contact sports, particularly football. The highest level of football, the National Football League (NFL), has received significant attention and criticism regarding player management and safety after mild traumatic brain injury (mTBI). Several review articles have reported data related to concussion in the NFL, but a succinct review and synthesis of data regarding NFL concussions is currently lacking. To (1) review systematically the published data regarding concussion in the NFL and assess limitations of the studies, (2) elucidate areas where further research is needed, and (3) identify methods to improve future investigations of concussion in the NFL. Systematic review of literature. English-language titles and abstracts published between 1900 and September 2014 were searched systematically across electronic databases, and a review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Peer-reviewed journal articles were included if they contained NFL concussion data with or without additional associated long-term effects. Reviews, editorials, letters to the editor, and comments were not included. Of the 344 records screened for review, 88 articles were assessed for eligibility. There were 31 studies that met the inclusion criteria and formed the basis of the evidence synthesis. Included in the current review were 8 case-control studies (Oxford Centre for Evidence-Based Medicine evidence level 3b), 6 descriptive epidemiological studies (level 4), 6 cross-sectional studies (level 4), 6 cohort studies (level 2b), and 5 case series (level 4). The study of concussions in the NFL has been limited by lack of recent empirical data, reliance on self-reported concussion history, and ascertainment bias of brains donated for autopsy studies. The scientific community

  13. Bronchiectasis in Children: Current Concepts in Immunology and Microbiology.

    Pizzutto, Susan J; Hare, Kim M; Upham, John W

    2017-01-01

    Bronchiectasis is a complex chronic respiratory condition traditionally characterized by chronic infection, airway inflammation, and progressive decline in lung function. Early diagnosis and intensive treatment protocols can stabilize or even improve the clinical prognosis of children with bronchiectasis. However, understanding the host immunologic mechanisms that contribute to recurrent infection and prolonged inflammation has been identified as an important area of research that would contribute substantially to effective prevention strategies for children at risk of bronchiectasis. This review will focus on the current understanding of the role of the host immune response and important pathogens in the pathogenesis of bronchiectasis (not associated with cystic fibrosis) in children.

  14. Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations

    Christopher M. Mahoney

    2018-05-01

    Full Text Available Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

  15. Current Therapeutic Strategies for Adipose Tissue Defects/Repair Using Engineered Biomaterials and Biomolecule Formulations.

    Mahoney, Christopher M; Imbarlina, Cayla; Yates, Cecelia C; Marra, Kacey G

    2018-01-01

    Tissue engineered scaffolds for adipose restoration/repair has significantly evolved in recent years. Patients requiring soft tissue reconstruction, caused by defects or pathology, require biomaterials that will restore void volume with new functional tissue. The gold standard of autologous fat grafting (AFG) is not a reliable option. This review focuses on the latest therapeutic strategies for the treatment of adipose tissue defects using biomolecule formulations and delivery, and specifically engineered biomaterials. Additionally, the clinical need for reliable off-the-shelf therapies, animal models, and challenges facing current technologies are discussed.

  16. Current Pathophysiological Aspects and Therapeutic Modalities for Pemphigus Vulgaris : A Review

    J Raviraj

    2007-01-01

    Full Text Available Pemphigus vulgaris (PV is an autoimmune disorder manifesting primarily as blisters involving the mucocutaneous systems. The current medical literature indicates many breakthroughs in the research of pathophysiology and treatment aspects of PV. This article tries to describe some of the novel aspects briefing the role of nondesmoglein antibodies and the role of TNF-alpha in the etiopathogenesis of pemphigus vulgaris and the role of newer therapeutic modalities like Rituximab, Etanercept, intravenous Immunoglobulins, cholinergic drugs, arid the like in the treatment of PV.

  17. Therapeutic options in pediatric non alcoholic fatty liver disease: current status and future directions

    Vajro Pietro

    2012-10-01

    Full Text Available Abstract The epidemics of overweight and obesity has resulted in a significant increase of non alcoholic fatty liver disease (NAFLD, a potentially progressive condition. Currently, obesity related hepatopathy represents therefore the main cause of pediatric chronic liver disease. The first choice treatment at all ages is weight loss and/or lifestyle changes, however compliance is very poor and a pharmacological approach has become necessary. In the present article we present a systematic literature review focusing on established pediatric NALFD drugs (ursodeoxycholic acid, insulin sensitizers, and antioxidants and on innovative therapeutic options as well. Regarding the former ones, a pediatric pilot study highlighted that ursodeoxycholic acid is not efficient on transaminases levels and bright liver. Similarly, a recent large scale, multicenter randomized clinical trial (TONIC study showed that also insulin sensitizers and antioxidant vitamin E have scarce effects on serum transaminase levels. Among a large series of novel therapeutic approaches acting on recently proposed different pathomechanisms, probiotics seem hitherto the most interesting and reasonable option for their safety and tolerability. Toll-like receptors modifiers, Pentoxifylline, and Farnesoid X receptors agonists have been still poorly investigated, and will need further studies before becoming possible promising innovative therapeutic strategies.

  18. Cytomegalovirus infection after liver transplantation: Current concepts and challenges

    Raymund Rabe Razonable

    2008-01-01

    Cytomegalovirus(CMV)is a common viral pathogen that influences the outcome of liver transplantation.In addition to the direct effects of CMV syndrome and tissue-invasive diseases,CMV is associated with an increased predisposition to acute and chronic allograft rejection,accelerated hepatitis C recurrence,and other opportunistic infections,as well as reduced overall patient and allograft survival.Risk factors for CMV disease are often interrelated,and include CMV D+/R-serostatus,acute rejection,female gender,age,use of high-dose mycophenolate mofetil and prednisone,and the overall state of immunity.In addition to the role of CHV-specific CD4+ and CD8+ T lymphocytes,there are data to suggest that functionality of the innate immune system contributes to CMV disease pathogenesis.In one study,liver transplant recipients with a specific polymorphism in innate immune molecules known as Toll-like receptors were more likely to develop higher Ievels of CMV replication and clinical disease.Because of the direct and indirect adverse effects of CMV disease,its prevention,whether through antiviral prophylaxis or preemptive therapy,is an essential component in improving the outcome of liver transplantation.In the majority of transplant centers,antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in CMV-seronegative recipients of liver allografts from CMV-seropositive donors(D+/R-).However,the major drawback of antiviral prophylaxis is the occurrence of delayed-onset primary CMV disease.In several prospective and retrospective studies,the incidence of delayed-onset primary CMV disease ranged from 16% to 47% of CMV D+/R-liver transplant recipients.Current data suggests that delayed-onset CMV disease is associated with increased mortality after liver transplantation.Therefore,optimized strategies for prevention and novel drugs with unique modes of action are needed.Currently,a randomized controlled clinical trial is being

  19. Neonatal posthemorrhagic hydrocephalus from prematurity: pathophysiology and current treatment concepts

    Robinson, Shenandoah

    2013-01-01

    Object Preterm infants are at risk for perinatal complications, including germinal matrix–intraventricular hemorrhage (IVH) and subsequent posthemorrhagic hydrocephalus (PHH). This review summarizes the current understanding of the epidemiology, pathophysiology, management, and outcomes of IVH and PHH in preterm infants. Methods The MEDLINE database was systematically searched using terms related to IVH, PHH, and relevant neurosurgical procedures to identify publications in the English medical literature. To complement information from the systematic search, pertinent articles were selected from the references of articles identifed in the initial search. Results This review summarizes the current knowledge regarding the epidemiology and pathophysiology of IVH and PHH, primarily using evidence-based studies. Advances in obstetrics and neonatology over the past few decades have contributed to a marked improvement in the survival of preterm infants, and neurological morbidity is also starting to decrease. The incidence of IVH is declining, and the incidence of PHH will likely follow. Currently, approximately 15% of preterm infants who suffer severe IVH will require permanent CSF diversion. The clinical presentation and surgical management of symptomatic PHH with temporary ventricular reservoirs (ventricular access devices) and ventriculosubgaleal shunts and permanent ventriculoperitoneal shunts are discussed. Preterm infants who develop PHH that requires surgical treatment remain at high risk for other related neurological problems, including cerebral palsy, epilepsy, and cognitive and behavioral delay. This review highlights numerous opportunities for further study to improve the care of these children. Conclusions A better grasp of the pathophysiology of IVH is beginning to impact the incidence of IVH and PHH. Neonatologists conduct rigorous Class I and II studies to advance the outcomes of preterm infants. The need for well-designed multicenter trials is

  20. Treatment of giant cell tumor of bone: Current concepts.

    Puri, Ajay; Agarwal, Manish

    2007-04-01

    Giant cell tumor (GCT) of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function.Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate.Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance.An accompanying treatment algorithm helps outline the management strategy in GCT.

  1. Treatment of giant cell tumor of bone: Current concepts

    Puri Ajay

    2007-01-01

    Full Text Available Giant cell tumor (GCT of bone though one of the commonest bone tumors encountered by an orthopedic surgeon continues to intrigue treating surgeons. Usually benign, they are locally aggressive and may occasionally undergo malignant transformation. The surgeon needs to strike a balance during treatment between reducing the incidence of local recurrence while preserving maximal function. Differing opinions pertaining to the use of adjuvants for extension of curettage, the relative role of bone graft or cement to pack the defect and the management of recurrent lesions are some of the issues that offer topics for eternal debate. Current literature suggests that intralesional curettage strikes the best balance between controlling disease and preserving optimum function in the majority of the cases though there may be occasions where the extent of the disease mandates resection to ensure adequate disease clearance. An accompanying treatment algorithm helps outline the management strategy in GCT.

  2. Primary Pediatric Hypertension: Current Understanding and Emerging Concepts.

    Tiu, Andrew C; Bishop, Michael D; Asico, Laureano D; Jose, Pedro A; Villar, Van Anthony M

    2017-09-01

    The rising prevalence of primary pediatric hypertension and its tracking into adult hypertension point to the importance of determining its pathogenesis to gain insights into its current and emerging management. Considering that the intricate control of BP is governed by a myriad of anatomical, molecular biological, biochemical, and physiological systems, multiple genes are likely to influence an individual's BP and susceptibility to develop hypertension. The long-term regulation of BP rests on renal and non-renal mechanisms. One renal mechanism relates to sodium transport. The impaired renal sodium handling in primary hypertension and salt sensitivity may be caused by aberrant counter-regulatory natriuretic and anti-natriuretic pathways. The sympathetic nervous and renin-angiotensin-aldosterone systems are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal autocrine/paracrine dopamine system, aberrations of which are involved in the pathogenesis of hypertension, including that associated with obesity. We present updates on the complex interactions of these two systems with dietary salt intake in relation to obesity, insulin resistance, inflammation, and oxidative stress. We review how insults during pregnancy such as maternal and paternal malnutrition, glucocorticoid exposure, infection, placental insufficiency, and treatments during the neonatal period have long-lasting effects in the regulation of renal function and BP. Moreover, these effects have sex differences. There is a need for early diagnosis, frequent monitoring, and timely management due to increasing evidence of premature target organ damage. Large controlled studies are needed to evaluate the long-term consequences of the treatment of elevated BP during childhood, especially to establish the validity of the current definition and treatment of pediatric hypertension.

  3. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

  4. PET/CT and vascular disease: Current concepts

    Cavalcanti Filho, Jose Leite Gondim; Souza Leao Lima, Ronaldo de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Souza Machado Neto, Luiz de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Kayat Bittencourt, Leonardo, E-mail: lkayat@terra.com.br [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Cortes Domingues, Romeu [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Fonseca, Lea Mirian Barbosa da [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil)

    2011-10-15

    Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

  5. Bilateral cochlear implantation: current concepts, indications, and results.

    Basura, Gregory J; Eapen, Rose; Buchman, Craig A

    2009-12-01

    The optimal treatment for bilateral hearing loss continues to evolve as cochlear implant (CI) and hearing aid technologies advance, as does our understanding of the central auditory system. Ongoing discussions continue on the validity and feasibility of bilateral CI in terms of performance, justification of need, medical/surgical safety concerns, and economics. The purpose of this review article is to provide an update on the advantages and disadvantages of bilateral CI and to provide a discussion on timing (simultaneous vs. sequential), technology (bimodal vs. binaural) and feasibility. Binaural advantages are found in both adult and pediatric bilateral CI recipients, the greatest being the head shadow effect and improvements in localization and loudness summation. This theoretically offers an advantage over their unilateral implanted counterparts in terms of improved sound localization and enhanced speech perception under noisy conditions. Most investigators agree that bilateral stimulation during critical periods of development is paramount for optimizing auditory functioning in children. Currently, bilateral CI is widely accepted as a safe and effective means of bilateral auditory stimulation.

  6. Precision medicine in pheochromocytoma and paraganglioma: current and future concepts.

    Björklund, P; Pacak, K; Crona, J

    2016-12-01

    Pheochromocytoma and paraganglioma (PPGL) are rare diseases but are also amongst the most characterized tumour types. Hence, patients with PPGL have greatly benefited from precision medicine for more than two decades. According to current molecular biology and genetics-based taxonomy, PPGL can be divided into three different clusters characterized by: Krebs cycle reprogramming with oncometabolite accumulation or depletion (group 1a); activation of the (pseudo)hypoxia signalling pathway with increased tumour cell proliferation, invasiveness and migration (group 1b); and aberrant kinase signalling causing a pro-mitogenic and anti-apoptotic state (group 2). Categorization into these clusters is highly dependent on mutation subtypes. At least 12 different syndromes with distinct genetic causes, phenotypes and outcomes have been described. Genetic screening tests have a documented benefit, as different PPGL syndromes require specific approaches for optimal diagnosis and localization of various syndrome-related tumours. Genotype-tailored treatment options, follow-up and preventive care are being investigated. Future new developments in precision medicine for PPGL will mainly focus on further identification of driver mechanisms behind both disease initiation and malignant progression. Identification of novel druggable targets and prospective validation of treatment options are eagerly awaited. To achieve these goals, we predict that collaborative large-scale studies will be needed: Pheochromocytoma may provide an example for developing precision medicine in orphan diseases that could ultimately aid in similar efforts for other rare conditions. © 2016 The Association for the Publication of the Journal of Internal Medicine.

  7. Neural synchrony in cortical networks: history, concept and current status

    Peter Uhlhaas

    2009-07-01

    Full Text Available Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, the role of neural synchrony in cortical networks has been expanded to provide a general mechanism for the coordination of distributed neural activity patterns. In the current paper, we present an update of the status of this hypothesis through summarizing recent results from our laboratory that suggest important new insights regarding the mechanisms, function and relevance of this phenomenon. In the first part, we present recent results derived from animal experiments and mathematical simulations that provide novel explanations and mechanisms for zero and nero-zero phase lag synchronization. In the second part, we shall discuss the role of neural synchrony for expectancy during perceptual organization and its role in conscious experience. This will be followed by evidence that indicates that in addition to supporting conscious cognition, neural synchrony is abnormal in major brain disorders, such as schizophrenia and autism spectrum disorders. We conclude this paper with suggestions for further research as well as with critical issues that need to be addressed in future studies.

  8. Current concepts in the management of acute pancreatitis

    Gautham Srinivasan

    2016-01-01

    Full Text Available Guidelines for the management of acute pancreatitis (AP are based on the Western experience, which may be difficult to extrapolate in India due to socioeconomic constraints. Hence, modifications based on the available resources and referral patterns should be introduced so as to ensure appropriate care. We reviewed the current literature on the management of AP available in English on Medline and proposed guidelines locally applicable. Patients of AP presenting with systemic inflammatory response syndrome are at risk of moderate-severe pancreatitis and hence, should be referred to a tertiary center early. The vast majority of patients with AP have mild disease and can be managed at smaller centers. Early aggressive fluid resuscitation with controlled fluid expansion, early enteral nutrition, and culture-directed antibiotics improve outcomes in AP. Infected pancreatic necrosis should be managed in a tertiary care hospital within a multidisciplinary setup. The “step up” approach involving antibiotics, percutaneous drainage, and minimally invasive necrosectomy instituted sequentially based on clinical response has improved the outcomes in this subgroup of patients.

  9. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint.

    Correia, S I; Pereira, H; Silva-Correia, J; Van Dijk, C N; Espregueira-Mendes, J; Oliveira, J M; Reis, R L

    2014-03-06

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving restoration of biological functions and rehabilitation. The mainstream components required to obtain a functional regeneration of tissues may include biodegradable scaffolds, drugs or growth factors and different cell types (either autologous or heterologous) that can be cultured in bioreactor systems (in vitro) prior to implantation into the patient. Particularly in the ankle, which is subject to many different injuries (e.g. acute, chronic, traumatic and degenerative), there is still no definitive and feasible answer to 'conventional' methods. This review aims to provide current concepts of TERM applications to ankle injuries under preclinical and/or clinical research applied to skin, tendon, bone and cartilage problems. A particular attention has been given to biomaterial design and scaffold processing with potential use in osteochondral ankle lesions.

  10. Current concepts on cytomegalovirus infection after liver transplantation.

    Lee, Sang-Oh; Razonable, Raymund R

    2010-09-27

    current state and the future perspectives of prevention and treatment of CMV disease after liver transplantation.

  11. Cutaneous wound healing: Current concepts and advances in wound care

    Kenneth C Klein

    2014-01-01

    Full Text Available A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care. [1] It is a snapshot of a patient′s total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors. [2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT, as used at our institution (CAMC, and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society may vary widely from country to country and payment system. [3] In the USA, CMS (Centers for Medicare and Medicaid Services approved indications for HBOT vary from that of the UHMS for logistical reasons. [1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise.

  12. Cutaneous wound healing: Current concepts and advances in wound care

    Klein, Kenneth C; Guha, Somes Chandra

    2014-01-01

    A non-healing wound is defined as showing no measurable signs of healing for at least 30 consecutive treatments with standard wound care.[1] It is a snapshot of a patient's total health as well as the ongoing battle between noxious factors and the restoration of optimal macro and micro circulation, oxygenation and nutrition. In practice, standard therapies for non-healing cutaneous wounds include application of appropriate dressings, periodic debridement and eliminating causative factors.[2] The vast majority of wounds would heal by such approach with variable degrees of residual morbidity, disability and even mortality. Globally, beyond the above therapies, newer tools of healing are selectively accessible to caregivers, for various logistical or financial reasons. Our review will focus on the use of hyperbaric oxygen therapy (HBOT), as used at our institution (CAMC), and some other modalities that are relatively accessible to patients. HBOT is a relatively safe and technologically simpler way to deliver care worldwide. However, the expense for including HBOT as standard of care for recognized indications per UHMS(Undersea and Hyperbaric Medical Society) may vary widely from country to country and payment system.[3] In the USA, CMS (Centers for Medicare and Medicaid Services) approved indications for HBOT vary from that of the UHMS for logistical reasons.[1] We shall also briefly look into other newer therapies per current clinical usage and general acceptance by the medical community. Admittedly, there would be other novel tools with variable success in wound healing worldwide, but it would be difficult to include all in this treatise. PMID:25593414

  13. CURRENT CONCEPTS ON SELECTION TECHNIQEUS IN FINANCIAL AUDITING

    Munteanu Ciprian

    2015-07-01

    Full Text Available The financial auditor's work evolves around the issue of an independent, professional and objective opinion on the compliance of the client's financial statements with the national accounting rules and principles. At the same time, the auditor will have to express an opinion on the ability of the company to continue its activity. An ideal situation would involve auditing all the components of the yearly accounts, but this would take time, effort and a very high cost. Fortunately, the audit team has some very useful tools for acquiring audit evidence in a fast and conclusive way - selection techniques. These techniques may be used in different phases of the audit and auditors have been using them for a long time, in fact no audit program would function without these techniques. They have become quite common as the auditors make important judgments, such as determining what type of technique to apply, whether to use statistical or nonstatistical techniques, appropriate inputs to determine sample size, and evaluation of results, particularly when errors are detected. This paper aims to theoretically present the main selection techniques, indicating how, why and when to use them. There are six selection techniques and we deal with the most frequent four of them. Our purpose is to present the characteristics and set the limits of these techniques, emphasizing sampling as the most common selection technique currently in use. A commonly held misconception about statistical sampling, for example, is that it removes the need for the use of the professional judgement. While it is true that statistical sampling uses statistical methods to determine the sample size and to select and evaluate audit samples, it is the responsibility of the auditor to consider and specify in advance factors such as materiality, the expected error rate or amount, the risk of over-reliance or the risk of incorrect acceptance, audit risk, inherent risk, control risk, standard

  14. PD-1 and PD-L1 as emerging therapeutic targets in gastric cancer: current evidence

    Tran PN

    2017-05-01

    Full Text Available Phu N Tran,1* Sarmen Sarkissian,1* Joseph Chao,2 Samuel J Klempner3,4 1Division of Hematology-Oncology, University of California Irvine, Orange, 2Department of Medical Oncology and Developmental Therapeutics, City of Hope, Duarte, 3Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, 4The Angeles Clinic and Research Institute, Los Angeles, CA, USA *These authors contributed equally to this work Abstract: Gastric adenocarcinoma is a leading cause of global cancer-related morbidity and mortality, and new therapeutic approaches are needed. Despite the improved outcomes with monoclonal antibodies targeting human epidermal growth factor receptor 2 and vascular endothelial growth factor receptor 2, durable responses are uncommon. Targeting immune checkpoints including PD-1, PD-L1 and CTLA-4 have led to improved survival across several tumor types, frequently characterized by prolonged benefit in responding patients. Tumoral and lymphocyte-derived immunohistochemical staining for PD-1, PD-L1, and tumor mutational burden have shown potential as predictive response biomarkers in several tumor types. Optimal incorporation of immune-mediated therapies into gastric cancer (GC is an area of intense ongoing investigation and benefit has been demonstrated in smaller studies of advanced patients. Important questions of biomarker selection, roles for molecular characterization, optimal combinatorial approaches, and therapeutic sequencing remain. In this study, current data are reviewed for immune checkpoint inhibitors in GC, and putative biomarkers, ongoing trials, and future considerations are discussed. Keywords: immunotherapy, stomach cancer, checkpoint inhibitor, nivolumab, pembrolizumab, tumor mutational burden

  15. Current Opinion on the Role of Neurogenesis in the Therapeutic Strategies for Alzheimer Disease, Parkinson Disease, and Ischemic Stroke; Considering Neuronal Voiding Function

    Myung-Hoon Han

    2016-12-01

    Full Text Available Neurological diseases such as Alzheimer, Parkinson, and ischemic stroke have increased in occurrence and become important health issues throughout the world. There is currently no effective therapeutic strategy for addressing neurological deficits after the development of these major neurological disorders. In recent years, it has become accepted that adult neural stem cells located in the subventricular and subgranular zones have the ability to proliferate and differentiate in order to replace lost or damaged neural cells. There have been many limitations in the clinical application of both endogenous and exogenous neurogenesis for neurological disorders. However, many studies have investigated novel mechanisms in neurogenesis and have shown that these limitations can potentially be overcome with appropriate stimulation and various approaches. We will review concepts related to possible therapeutic strategies focused on the perspective of neurogenesis for the treatment of patients diagnosed with Alzheimer disease, Parkinson disease, and ischemic stroke based on current reports.

  16. Bone Marrow Stem Cell Derived Paracrine Factors for Regenerative Medicine: Current Perspectives and Therapeutic Potential

    Tom J. Burdon

    2011-01-01

    Full Text Available During the past several years, there has been intense research in the field of bone marrow-derived stem cell (BMSC therapy to facilitate its translation into clinical setting. Although a lot has been accomplished, plenty of challenges lie ahead. Furthermore, there is a growing body of evidence showing that administration of BMSC-derived conditioned media (BMSC-CM can recapitulate the beneficial effects observed after stem cell therapy. BMSCs produce a wide range of cytokines and chemokines that have, until now, shown extensive therapeutic potential. These paracrine mechanisms could be as diverse as stimulating receptor-mediated survival pathways, inducing stem cell homing and differentiation or regulating the anti-inflammatory effects in wounded areas. The current review reflects the rapid shift of interest from BMSC to BMSC-CM to alleviate many logistical and technical issues regarding cell therapy and evaluates its future potential as an effective regenerative therapy.

  17. Identifying therapeutic targets in gastric cancer: the current status and future direction

    Yu, Beiqin; Xie, Jingwu

    2016-01-01

    Gastric cancer is the third leading cause of cancer-related death worldwide. Our basic understanding of gastric cancer biology falls behind that of many other cancer types. Current standard treatment options for gastric cancer have not changed for the last 20 years. Thus, there is an urgent need to establish novel strategies to treat this deadly cancer. Successful clinical trials with Gleevec in CML and gastrointestinal stromal tumors have set up an example for targeted therapy of cancer. In this review, we will summarize major progress in classification, therapeutic options of gastric cancer. We will also discuss molecular mechanisms for drug resistance in gastric cancer. In addition, we will attempt to propose potential future directions in gastric cancer biology and drug targets. PMID:26373844

  18. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).

    Lefaucheur, Jean-Pascal; Antal, Andrea; Ayache, Samar S; Benninger, David H; Brunelin, Jérôme; Cogiamanian, Filippo; Cotelli, Maria; De Ridder, Dirk; Ferrucci, Roberta; Langguth, Berthold; Marangolo, Paola; Mylius, Veit; Nitsche, Michael A; Padberg, Frank; Palm, Ulrich; Poulet, Emmanuel; Priori, Alberto; Rossi, Simone; Schecklmann, Martin; Vanneste, Sven; Ziemann, Ulf; Garcia-Larrea, Luis; Paulus, Walter

    2017-01-01

    A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson's disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer's disease, tinnitus, depression, schizophrenia, and craving/addiction. The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10-24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode. It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform t

  19. [Why controlled studies may lead to misleading and unconfirmed therapeutic concepts--a critical view of evidence-based medicine].

    Flachskampf, F A

    2002-03-01

    The concept of evidence-based medicine has gathered widespread support during recent years. While this concept has clear merits in compiling and qualifying up-to-date information for clinical decisions, it should be viewed with caution as the sole valid knowledge source for clinical decision-making. The limitations of such an approach are particularly striking when reviewing two key developments in modern cardiology, fibrinolysis and acute percutaneous intervention in acute myocardial infarction. In both cases, early studies and meta-analyses showed no benefit for these therapeutic interventions over earlier treatment. Only after further refinement (mainly in dosage, time window, concomitant heparin therapy for fibrinolysis, and the introduction of stents and IIb/IIIa inhibitors for acute intervention) did these therapies become universally acknowledged. It is therefore crucial to understand that especially for physicians actively participating in the development of a clinical field clinical decisions cannot be exclusively based on published evidence. Another important problem to consider is the time gap between the emergence of new therapies and the publication and reception by the medical audience, in particular in rapidly evolving fields as cardiology. While it is clear that clinical decision-making must be backed by solid knowledge of the published evidence, in particular the specialist involved in-depth in the field may use not yet proven therapeutic concepts and measures to the patient's advantage.

  20. Current and novel insights into the neurophysiology of migraine and its implications for therapeutics.

    Akerman, Simon; Romero-Reyes, Marcela; Holland, Philip R

    2017-04-01

    Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability. The complex symptomatology of migraine indicates that multiple neuronal systems are involved, including brainstem and diencephalic systems, which function abnormally, resulting in premonitory symptoms, ultimately evolving to affect the dural trigeminovascular system, and the pain phase of migraine. The migraineur also seems to be particularly sensitive to fluctuations in homeostasis, such as sleep, feeding and stress, reflecting the abnormality of functioning in these brainstem and diencephalic systems. Implications for therapeutic development have grown out of our understanding of migraine neurophysiology, leading to major drug classes, such as triptans, calcitonin gene-related peptide receptor antagonists, and 5-HT 1F receptor agonists, as well as neuromodulatory approaches, with the promise of more to come. The present review will discuss the current understanding of the neurophysiology of migraine, particularly migraine headache, and novel insights into the complex neural networks responsible for associated neurological symptoms, and how interaction of these networks with migraine pain pathways has implications for the development of novel therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Current Therapeutic Options for Esophageal Motor Disorders as Defined by the Chicago Classification.

    Zerbib, Frank; Roman, Sabine

    2015-07-01

    With the development of high-resolution manometry and specific metrics to characterize esophageal motility, the Chicago Classification has become the gold standard for the diagnosis of esophageal motor disorders. Major and significant disorders, that is, never observed in healthy subjects, are achalasia, esophagogastric junction outflow obstruction, distal esophageal spasm, absent peristalsis, and hypercontractile (Jackhammer) esophagus. Achalasia subtyping is relevant to predict the response to endoscopic and surgical therapies as several studies suggest that, pneumatic dilation is less effective than Heller myotomy, in type III achalasia. Peroral endoscopic myotomy, initially developed in expert centers, is a promising technique for the treatment of achalasia. The medical therapeutic options for distal esophageal spasm and hypercontractile esophagus are smooth muscle relaxants and pain modulators. Intraesophageal injection of botulinum toxin might be an interesting option for treatment of these disorders but further studies are required to determine the optimal injection protocol and the best candidates based on manometric patterns. The treatment of hypotensive motility disorders is disappointing and relies mainly on dietary and lifestyle changes as no effective esophageal prokinetic is currently available.

  2. Current therapeutic strategies of anti-HER2 treatment in advanced breast cancer patients

    Joanna Huszno

    2016-03-01

    Full Text Available The HER2/neu ( ERBB2 oncogene is amplified and/or overexpressed in approximately 20% of breast cancers, and is a strong prognostic factor for relapse and poor overall survival, particularly in node-positive patients. It is also an important predictor for response to trastuzumab, which has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. Treatment with the anti-HER2 humanized monoclonal antibody – trastuzumab significantly improves progression-free and overall survival among patients with HER2-positive breast cancer. However, in most patients with HER2-positive metastatic breast cancer, the disease progresses occurred, what cause the need for new targeted therapies for advanced disease. In clinical trials, there are tested new drugs to improve the results of treatment for this group of patients. This paper presents new drugs introduced into clinical practice for treatment of advanced breast cancer, whose molecular target are receptors of the HER2 family. In addition, new therapeutic strategies and drugs that are currently in clinical researches are discussed.

  3. Addressing Therapeutic Options for Ebola Virus Infection in Current and Future Outbreaks.

    Haque, Azizul; Hober, Didier; Blondiaux, Joel

    2015-10-01

    Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  4. A concept to transfer a therapeutic splint position into permanent occlusion with a customized lingual appliance.

    Sachse, Tina; Schwestka-Polly, Rainer; Flieger, Stefanie; Wiechmann, Dirk

    2012-05-21

    The role of occlusion concerning temporomandibular disorder is still unclear but seems to be the only component of the stomathognathic system dentists are able to change morphologically. The aim of the paper is to describe the orthodontist's approach for transferring and maintaining a therapeutic splint position into permanent occlusion using a fully customized lingual appliance. Fixed acrylic bite planes on lower molars were used to maintain a symptom-free condyle position prior to orthodontic treatment. Silicone impressions of the arches including the fixed bite planes were used for the Incognito laboratory procedure. Two digital setups were made. One setup represents the target occlusion. A second setup including the bite planes was used to fabricate an additional set of lower molar brackets. In the leveling stage all teeth except the lower molars were settled to maintain the therapeutic condyle position. Finally, the fixed bite planes were stepwise removed and molar brackets were replaced to establish the permanent occlusion planned with the first setup. The advantage of an individual lingual appliance consists in the high level of congruence between the fabricated setups and the final clinical result. Both the individual scope for design and the precision of the appliance were vitally important in the treatment of a patient with a functional disorder of the masticatory system.

  5. A concept to transfer a therapeutic splint position into permanent occlusion with a customized lingual appliance

    Sachse Tina

    2012-05-01

    Full Text Available Abstract Introduction The role of occlusion concerning temporomandibular disorder is still unclear but seems to be the only component of the stomathognathic system dentists are able to change morphologically. The aim of the paper is to describe the orthodontist’s approach for transferring and maintaining a therapeutic splint position into permanent occlusion using a fully customized lingual appliance. Methods Fixed acrylic bite planes on lower molars were used to maintain a symptom-free condyle position prior to orthodontic treatment. Silicone impressions of the arches including the fixed bite planes were used for the Incognito laboratory procedure. Two digital setups were made. One setup represents the target occlusion. A second setup including the bite planes was used to fabricate an additional set of lower molar brackets. In the leveling stage all teeth except the lower molars were settled to maintain the therapeutic condyle position. Finally, the fixed bite planes were stepwise removed and molar brackets were replaced to establish the permanent occlusion planned with the first setup. Results and discussion The advantage of an individual lingual appliance consists in the high level of congruence between the fabricated setups and the final clinical result. Both the individual scope for design and the precision of the appliance were vitally important in the treatment of a patient with a functional disorder of the masticatory system.

  6. Therapeutic applications of Rhenium-188 in nuclear medicine and oncology - Current status and expected future perspectives

    Knapp, F. F. Jr.

    2005-01-01

    Full text: The increasing use of unsealed radioactive targeting agents for cancer treatment requires the routine availability of cost-effective radioisotopes. Rhenium-188 (Re-188; half-life 16.9 hours) is a high-energy beta-emitter (E max 2.12 MeV), readily available no- max carrier-added from the alumina-based tungsten-188 (half-life 69 days)/rhenium-188 generator system. Rhenium-188 also emits a 155 keV (15%) gamma photon, permitting gamma camera imaging for biodistribution and dosimetry evaluation. The versatile chemistry of rhenium allows attachment to a wide variety of targeting molecules for Re-188 applications in nuclear oncology for both palliative metastatic treatment and targeted tumor therapy - radionuclide synovectomy, and coronary restenosis therapy. The long parent half-life and consistent performance provide an indefinite generator shelf-life of several months with high Re-188 elution yields (75-85 %) and consistently low W-188 parent breakthrough ( -6 ). Simple post-elution concentration methods have been developed which provide very high specific volume solution of Re-188 for radiolabeling (> 700 mCi/mL saline/1 Ci generator). Over 60 physician-sponsored clinical trials are currently in progress worldwide with applications in nuclear medicine, nuclear oncology and interventional cardiology. A variety of Re-188-labeled therapeutic radiopharmaceuticals and devices are being developed for clinical trials currently in progress for treatment of both benign and metastatic oncological disorders. Palliation of metastatic bone pain with Re-188-HEDP - prepared from a simple 'kit' - has been demonstrated as a cost-effective alternative to similar agents. Recent studies have in fact demonstrated the enhancement of progression-free interval and survival time by repeated Re-188-HEDP injections to patients with metastatic disease from prostate cancer. The use of the Re-188-labeled antiNCA95 (CD66) antibody in conjunction with external beam irradiation is an

  7. The Impact of Therapeutic Antibodies on the Management of Digestive Diseases: History, Current Practice, and Future Directions.

    Sofia, M Anthony; Rubin, David T

    2017-04-01

    The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.

  8. The translation of product concept to bone products: a partnership of therapeutic effectiveness and commercialization.

    Ratcliffe, Anthony

    2011-12-01

    The fields of tissue engineering and regenerative medicine have the capacity to substantially impact clinical care through the introduction of new products that can address unmet clinical needs, or significantly improve on present therapies. These products will be developed through the demonstration of therapeutic effectiveness, adequate safety, and meeting regulatory requirements. The technology used in the product will dictate the product development and manufacturing costs; the regulatory pathway; and the time taken to complete clinical trials, gain regulatory approval, and become commercialized. A comparison of the required investment of time and funds, with the potential revenue generated, allows for a determination of the likely commercialization opportunity. Ultimately, the long-term success of a product will be dependent on its clinical effectiveness and commercial viability. © Mary Ann Liebert, Inc.

  9. Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept.

    Peyrode, Caroline; Weber, Valérie; Voissière, Aurélien; Maisonial-Besset, Aurélie; Vidal, Aurélien; Auzeloux, Philippe; Gaumet, Vincent; Borel, Michèle; Dauplat, Marie-Mélanie; Quintana, Mercedes; Degoul, Françoise; Rédini, Françoise; Chezal, Jean-Michel; Miot-Noirault, Elisabeth

    2016-11-01

    To date, surgery remains the only option for the treatment of chondrosarcoma, which is radio- and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chondrosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to melphalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosarcoma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scintigraphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the tolerability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma. Mol Cancer Ther; 15(11); 2575-85. ©2016 AACR. ©2016 American Association for Cancer Research.

  10. Current concepts in MRI of rectus femoris musculotendinous (myotendinous) and myofascial injuries in elite athletes

    Kassarjian, A., E-mail: Kassarjian@mac.com [Consultant Radiologist, Corades, S. L., Calle Galeon 2, 28220 Majadahonda, Madrid (Spain); Rodrigo, R.M., E-mail: rmrodrigo@resonanciamagneticabilbao.com [Resonancia Magnetica Bilbao, Hospital San Francisco Javier, Gordoniz 12, 40010 Bilbao, Vizcaya, Basque Country (Spain); Santisteban, J.M., E-mail: j.santisteban@athletic-club.net [Medical Services, Athletic Club Bilbao, Basurto Medical Institute, Faculty of Medicine and Odontology, University of the Basque Country, Barrio de Garaioltza 147, 48197 Lezama, Vizcaya, Basque Country (Spain)

    2012-12-15

    Rectus femoris injuries are extremely common in athletes, particularly in soccer players, rugby player, and sprinters. Magnetic resonance imaging (MRI) plays a key role in diagnosis, prognosis, and rehabilitation of these injuries. The current article discusses current concepts in the diagnosis and treatment of rectus femoris injuries in elite athletes, including a discussion of the less well known myofascial injuries and key prognostic factors as seen at MR imaging.

  11. Current concepts in MRI of rectus femoris musculotendinous (myotendinous) and myofascial injuries in elite athletes

    Kassarjian, A.; Rodrigo, R.M.; Santisteban, J.M.

    2012-01-01

    Rectus femoris injuries are extremely common in athletes, particularly in soccer players, rugby player, and sprinters. Magnetic resonance imaging (MRI) plays a key role in diagnosis, prognosis, and rehabilitation of these injuries. The current article discusses current concepts in the diagnosis and treatment of rectus femoris injuries in elite athletes, including a discussion of the less well known myofascial injuries and key prognostic factors as seen at MR imaging.

  12. [Food addiction: Definition, measurement and limits of the concept, associated factors, therapeutic and clinical implications].

    Cathelain, Sarah; Brunault, Paul; Ballon, Nicolas; Réveillère, Christian; Courtois, Robert

    2016-12-01

    Addictions, which are characterized by the inability to control a behavior despite existence of physical or psychological consequences, have biological, psychological and social determinants. Although the possibility of developing an addiction to some psychoactive substances (e.g. alcohol, tobacco, cannabis) and to gambling (i.e., gambling disorder) is now well demonstrated, the possibility to develop a non-drug addiction (i.e., behavioral addiction) to certain behaviors which provide pleasure (e.g. eating, having sex, buying things) is still in debate. The concept of food addiction, which refers to people who exhibit substance dependence criteria in relation to some high-fat and high-sugar foods, was recently proposed by applying substance dependence DSM criteria to eating behavior. To assess food addiction, the Yale Food Addiction Scale is now the only self-administered questionnaire (diagnosis and estimate of the number of symptoms of food addiction). Prevalence for food addiction is higher in overweight and obese patients, and in patients with certain psychopathological characteristics (i.e., depression, Attention Deficit Hyperactivity Disorder, high impulsivity), in patients who are single and in patients with neurobiological alterations in the reward system. However, it is still unclear whether food addiction is necessary associated with subsequent increase in body weight and/or obesity. An increasing number of studies demonstrated that drug addiction and food addiction shares some similar clinical, neurobiological and psychopathological and sociocultural risk factors. To test the pertinence to include food addiction as an addiction, it would be interesting to conduct future studies in patients who may experience harms related to their food addiction, including not only patients with obesity, but also patients with metabolic syndrome, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis, stroke, or coronary heart disease. Food addiction is a clinical

  13. Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.

    Efferth, Thomas; Koch, Egon

    2011-01-01

    Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on the combined action of a mixture of constituents, offers new treatment opportunities. Because of their biological defence function, plant secondary metabolites act by targeting and disrupting the cell membrane, by binding and inhibiting specific proteins or they adhere to or intercalate into RNA or DNA. Phytotherapeutics may exhibit pharmacological effects by the synergistic or antagonistic interaction of many phytochemicals. Mechanistic reasons for interactions are bioavailability, interference with cellular transport processes, activation of pro-drugs or deactivation of active compounds to inactive metabolites, action of synergistic partners at different points of the same signalling cascade (multi-target effects) or inhibition of binding to target proteins. "-Omics" technologies and systems biology may facilitate unravelling synergistic effects of herbal mixtures.

  14. Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

    Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

    2017-12-01

    Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Civilian Power Program. Part 1, Summary, Current status of reactor concepts

    Author, Not Given

    1959-09-01

    This study group covered the following: delineation of the specific objectives of the overall US AEC civilian power reactor program, technical objectives of each reactor concept, preparation of a chronological development program for each reactor concept, evaluation of the economic potential of each reactor type, a program to encourage the the development, and yardsticks for measuring the development. Results were used for policy review by AEC, program direction, authorization and appropriation requests, etc. This evaluation encompassed civilian power reactors rated at 25 MW(e) or larger and related experimental facilities and R&D. This Part I summarizes the significant results of the comprehensive effort to determine the current technical and economic status for each reactor concept; it is based on the 8 individual technical status reports (Part III).

  16. Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

    Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

    2018-05-17

    The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

  17. Comparing Self-Concept Among Youth Currently Receiving Inpatient Versus Outpatient Mental Health Services.

    Choi, Chris; Ferro, Mark A

    2018-01-01

    This study compared levels of self-concept among youth who were currently receiving inpatient versus outpatient mental health services. Forty-seven youth were recruited from the Child & Youth Mental Health Program at McMaster Children's Hospital. Self-concept was measured using the Self-Perception Profile for Children and Adolescents. The mean age was 14.5 years and most participants were female (70.2%). ANOVAs comparing self-concept with population norms showed large significant effects (d = 0.77 to 1.93) indicating compromised self-concept among youth receiving mental health services. Regression analyses controlling for patient age, sex, family income, and diagnoses of major depressive disorder, generalized social phobia, and generalized anxiety showed that the inpatient setting was a significant predictor of lower global self-worth (β=-.26; p=.035). Compared to outpatients, inpatients generally reported lower self-concept, but differences were significant only for global self-worth. Future research replicating this finding and assessing its clinical significance is encouraged.

  18. New Concept for Assessment of Tidal Current Energy in Jiangsu Coast, China

    Ji-Sheng Zhang

    2013-01-01

    Full Text Available Tidal current energy has attracted more and more attentions of coastal engineers in recent years, mainly due to its advantages of low environmental impact, long-term predictability, and large energy potential. In this study, a two-dimensional hydrodynamic model is applied to predict the distribution of mean density of tidal current energy and to determine a suitable site for energy exploitation in Jiangsu Coast. The simulation results including water elevation and tidal current (speed and direction were validated with measured data, showing a reasonable agreement. Then, the model was used to evaluate the distribution of mean density of tidal current energy during springtide and neap tide in Jiangsu Coast. Considering the discontinuous performance of tidal current turbine, a new concept for assessing tidal current energy is introduced with three parameters: total operating time, dispersion of operating time, and mean operating time of tidal current turbine. The operating efficiency of tidal current turbine at three locations around radial submarine sand ridges was taken as examples for comparison, determining suitable sites for development of tidal current farm.

  19. [From tic disorders to Tourette syndrome: current data, comorbidities, and therapeutic approach in children].

    Fourneret, P; Desombre, H; Broussolle, E

    2014-06-01

    Motor tics are frequently observed in children during development. Usually transient and benign, they can become chronic over time, join various morbid disorders (vocal tics, attention deficit and hyperactivity disorder, and obsessive-compulsive disorders) and move toward genuine Tourette syndrome. In this case, it will be necessary to prevent impacts - mainly in terms of quality of life and emotional and relational problems - using a global therapeutic strategy combining psychoeducational approaches with appropriate medication. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Current perspectives on therapeutic ultrasound in the management of chronic wounds: a review of evidence

    Conner-Kerr T

    2017-07-01

    Full Text Available Teresa Conner-Kerr,1 Mary Ellen Oesterle2 1College of Health Sciences & Professions, 2Department of Physical Therapy, University of North Georgia, Dahlonega, GA, USA Abstract: Although therapeutic ultrasound has been in existence since the 1930s, questions remain as to its effectiveness in promoting tissue healing in various injured tissues. These tissues include soft tissues such as skin, tendons, ligaments, bursae, joint capsules and muscles. Limited evidence exists to support a role for therapeutic ultrasound in closed, soft tissue lesions. However, an evolving literature provides support for the role of therapeutic ultrasound in the treatment of chronic wounds, acute injuries such as fractures and split thickness graft donor sites as well as in the modulation of wound-related pain. Modern technology that uses low-frequency (kilohertz, long wave ultrasound appears promising compared to older, higher frequency ultrasound (megahertz devices. These newer devices appear to have positive effects on healing rates in various wound types, pain levels and the modulation of proinflammatory cytokines. Keywords: low-frequency ultrasound, non-contact ultrasound, KHz, acoustic, healing, cavitation

  1. [Therapeutic strategies. Evolution and current status of the European Guidelines on Cardiovascular disease prevention].

    Guijarro, Carlos; García-Díaz, Juan de Dios

    2013-01-01

    The European Guidelines on Dyslipidaemias (2011) and Cardiovascular Prevention (2012) have incorporated important changes. Firstly, it highlights the identification of a group of "very high risk" patients: patients with atherosclerotic disease in any vascular area, diabetes with associated risk factors, advanced chronic renal failure, or a SCORE estimate >10%. Patients with diabetes and no other risk factors, moderate renal failure, severe hypertension, genetic dyslipidaemias, or a SCORE estimate 5-10%, are considered as "high risk". The HDL cholesterol and triglycerides levels are considered as modulators of risks, but not therapeutic objectives per se. The therapeutic objectives are set at LDL cholesterol levels < 70 mg/dl (or at least a reduction of at least 50%) for patients at very high risk, and an LDL < 100 mg/dl for high risk patients. As well as the changes in lifestyle, pharmacological treatment with statins is the focal point of lipid lowering treatments. Other pharmacological options may be considered if the treatment with the maximum tolerable doses of statins do not achieve the therapeutic objectives. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  2. Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

    Rangel-Castilla, Leonardo; Russin, Jonathan J; Martinez-Del-Campo, Eduardo; Soriano-Baron, Hector; Spetzler, Robert F; Nakaji, Peter

    2014-09-01

    Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

  3. Use of cone beam computed tomography in implant dentistry: current concepts, indications and limitations for clinical practice and research.

    Bornstein, Michael M; Horner, Keith; Jacobs, Reinhilde

    2017-02-01

    Diagnostic radiology is an essential component of treatment planning in the field of implant dentistry. This narrative review will present current concepts for the use of cone beam computed tomography imaging, before and after implant placement, in daily clinical practice and research. Guidelines for the selection of three-dimensional imaging will be discussed, and limitations will be highlighted. Current concepts of radiation dose optimization, including novel imaging modalities using low-dose protocols, will be presented. For preoperative cross-sectional imaging, data are still not available which demonstrate that cone beam computed tomography results in fewer intraoperative complications such as nerve damage or bleeding incidents, or that implants inserted using preoperative cone beam computed tomography data sets for planning purposes will exhibit higher survival or success rates. The use of cone beam computed tomography following the insertion of dental implants should be restricted to specific postoperative complications, such as damage of neurovascular structures or postoperative infections in relation to the maxillary sinus. Regarding peri-implantitis, the diagnosis and severity of the disease should be evaluated primarily based on clinical parameters and on radiological findings based on periapical radiographs (two dimensional). The use of cone beam computed tomography scans in clinical research might not yield any evident beneficial effect for the patient included. As many of the cone beam computed tomography scans performed for research have no direct therapeutic consequence, dose optimization measures should be implemented by using appropriate exposure parameters and by reducing the field of view to the actual region of interest. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Current concepts of chemotherapy and radiotherapy for small cell lung cancer

    Braun, T.J.; Bunn, P.A. Jr.

    1986-01-01

    Small cell lung cancer (SCLC) was projected to account for 20%-25% of the greater than 140,000 newly diagnosed lung cancers in 1985. If considered a separate disease entity, it would be the fourth leading cause of death by cancer. Previous studies have demonstrated distinct clinical and biologic features of small cell lung cancer, and early therapeutic trial results have demonstrated a high sensitivity to both chemotherapy and radiotherapy. More recent results demonstrated a marked survival improvement with the use of combination chemotherapy, which potentially cured a small minority of patients. Unfortunately, in most patients, drug resistance usually develops, as do chronic, often debilitating toxicities in the few long-term survivors. Although therapeutic advances have plateaued, new and important insights into the basic biology of the disease made the last several years offer the possibility of exciting new treatment approaches within the next decade. This chapter addresses our current understanding of therapy for small cell lung cancer, the current therapy questions under investigation, and potential future directions in clinical research

  5. [Infection-induced urinary calculi in children; current therapeutic schedule and prevention of recurrence].

    Bach, D; Brühl, P; Hesse, A

    1988-01-01

    Infection stones have an outstanding position in childhood urolithiasis. In non-infection stones one can mostly find a certain--for example metabolic--causes of stone formation. In infection stones, the urease-producing and thus urea-cleaving properties of some gram-negative bacteria are responsible for alkalization of the urine and lead especially in combination with disturbances of urine transport to the staghorn calculi. Therefore in such children early diagnosis, adequate therapy and consequent maintenance is the crucial point for good life quality in future. Preliminary condition for therapeutic success is a close coworking between pediatric nephrologist, pediatric urologist, family doctor and parents.

  6. Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

    Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

    2016-06-02

    Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

  7. New concepts in the management of diffuse low-grade glioma: Proposal of a multistage and individualized therapeutic approach.

    Duffau, Hugues; Taillandier, Luc

    2015-03-01

    Diffuse low-grade glioma grows, migrates along white matter tracts, and progresses to high-grade glioma. Rather than a "wait and see" policy, an aggressive attitude is now recommended, with early surgery as the first therapy. Intraoperative mapping, with maximal resection according to functional boundaries, is associated with a longer overall survival (OS) while minimizing morbidity. However, most studies have investigated the role of only one specific treatment (surgery, radiotherapy, chemotherapy) without taking a global view of managing the cumulative time while preserving quality of life (QoL) versus time to anaplastic transformation. Our aim is to switch towards a more holistic concept based upon the anticipation of a personalized and long-term multistage therapeutic approach, with online adaptation of the strategy over the years using feedback from clinical, radiological, and histomolecular monitoring. This dynamic strategy challenges the traditional approach by proposing earlier therapy, by repeating treatments, and by reversing the classical order of therapies (eg, neoadjuvant chemotherapy when maximal resection is impossible, no early radiotherapy) to improve OS and QoL. New individualized management strategies should deal with the interactions between the course of this chronic disease, reaction brain remapping, and oncofunctional modulation elicited by serial treatments. This philosophy supports a personalized, functional, and preventive neuro-oncology. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Dhat syndrome: Evolution of concept, current understanding, and need of an integrated approach

    Sujita Kumar Kar

    2015-01-01

    Full Text Available Dhat syndrome has often been construed as a culture-bound sexual neurosis of the Indian subcontinent. Symptoms similar to that of Dhat syndrome has been described in other cultures across different time periods. The present paper looks at the evolution of the concept of Dhat syndrome in India. The review also takes an overview of the current understanding of this syndrome in terms of nosological status as a distinct entity and its "culture-bound" status. The narrative finally attempts to discuss the integrated approach for the treatment of this disorder.

  9. The current theoretical assumptions of the Bobath concept as determined by the members of BBTA.

    Raine, Sue

    2007-01-01

    The Bobath concept is a problem-solving approach to the assessment and treatment of individuals following a lesion of the central nervous system that offers therapists a framework for their clinical practice. The aim of this study was to facilitate a group of experts in determining the current theoretical assumptions underpinning the Bobath concept.A four-round Delphi study was used. The expert sample included all 15 members of the British Bobath Tutors Association. Initial statements were identified from the literature with respondents generating additional statements. Level of agreement was determined by using a five-point Likert scale. Level of consensus was set at 80%. Eighty-five statements were rated from the literature along with 115 generated by the group. Ninety-three statements were identified as representing the theoretical underpinning of the Bobath concept. The Bobath experts agreed that therapists need to be aware of the principles of motor learning such as active participation, opportunities for practice and meaningful goals. They emphasized that therapy is an interactive process between individual, therapist, and the environment and aims to promote efficiency of movement to the individual's maximum potential rather than normal movement. Treatment was identified by the experts as having "change of functional outcome" at its center.

  10. Average current is better than peak current as therapeutic dosage for biphasic waveforms in a ventricular fibrillation pig model of cardiac arrest.

    Chen, Bihua; Yu, Tao; Ristagno, Giuseppe; Quan, Weilun; Li, Yongqin

    2014-10-01

    Defibrillation current has been shown to be a clinically more relevant dosing unit than energy. However, the effects of average and peak current in determining shock outcome are still undetermined. The aim of this study was to investigate the relationship between average current, peak current and defibrillation success when different biphasic waveforms were employed. Ventricular fibrillation (VF) was electrically induced in 22 domestic male pigs. Animals were then randomized to receive defibrillation using one of two different biphasic waveforms. A grouped up-and-down defibrillation threshold-testing protocol was used to maintain the average success rate of 50% in the neighborhood. In 14 animals (Study A), defibrillations were accomplished with either biphasic truncated exponential (BTE) or rectilinear biphasic waveforms. In eight animals (Study B), shocks were delivered using two BTE waveforms that had identical peak current but different waveform durations. Both average and peak currents were associated with defibrillation success when BTE and rectilinear waveforms were investigated. However, when pathway impedance was less than 90Ω for the BTE waveform, bivariate correlation coefficient was 0.36 (p=0.001) for the average current, but only 0.21 (p=0.06) for the peak current in Study A. In Study B, a high defibrillation success (67.9% vs. 38.8%, pcurrent (14.9±2.1A vs. 13.5±1.7A, pcurrent unchanged. In this porcine model of VF, average current was better than peak current to be an adequate parameter to describe the therapeutic dosage when biphasic defibrillation waveforms were used. The institutional protocol number: P0805. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. The Role of Stem Cell Therapeutics in Wound Healing: Current Understanding and Future Directions.

    Sorice, Sarah; Rustad, Kristine C; Li, Alexander Y; Gurtner, Geoffrey C

    2016-09-01

    Chronic wounds present unique challenges for healthcare providers as they place patients at increased risk for various morbidities and mortality. Advances in wound care technology have expanded the treatment options available for wound management, but few products fully address the underlying core deficiencies responsible for the development of poorly healing wounds. In the future, addressing these derangements will undoubtedly play a key role in the treatment of these patients. Broad enthusiasm has surrounded the field of stem cell biology, which has shown great promise in repairing damaged tissues across numerous disease phenotypes. In this review, we provide a comprehensive review of the literature and evaluate the present landscape of wound therapeutics while discussing the rationales and allure behind stem cell-based products. We further propose 2 challenges that remain as new stem cell-based therapies are being developed and as this technology moves toward clinical translation. Given the relatively young age of this newer technology in wound healing, numerous challenges continue to surround its effective use including identifying the ideal population of stem cells to use and determining the optimal cell delivery method. However, significant forward progress has been made, with several clinical trials beginning to demonstrate reliable clinical benefit. The upward trajectory of stem cell technologies provides an exciting opportunity to positively impact patient outcomes through the controlled application of regenerative cell-based therapy.

  12. Prospective Multicentre Study on the Epidemiology and Current Therapeutic Management of Severe Bronchiolitis in Spain

    Jose C. Flores-González

    2017-01-01

    Full Text Available Objective. To determine the epidemiology and therapeutic management of patients with severe acute bronchiolitis (AB admitted to paediatric intensive care units (PICUs in Spain. Design. Descriptive, prospective, multicentre study. Setting. Sixteen Spanish PICUs. Patients. Patients with severe AB who required admission to any of the participating PICUs over 1 year. Interventions. Both epidemiological variables and medical treatment received were recorded. Results. A total of 262 patients were recruited; 143 were male (54.6%, with median age of 1 month (0–23. Median stay in the PICU was 7 days (1–46. Sixty patients (23% received no nebuliser treatment, while the rest received a combination of inhalation therapies. One-quarter of patients (24.8% received corticosteroids and 56.5% antibiotic therapy. High-flow oxygen therapy was used in 14.3% and noninvasive ventilation (NIV was used in 75.6%. Endotracheal intubation was required in 24.4% of patients. Younger age, antibiotic therapy, and invasive mechanical ventilation (IMV were risk factors that significantly increased the stay in the PICU. Conclusions. Spanish PICUs continue to routinely use nebulised bronchodilator treatment and corticosteroid therapy. Despite NIV being widely used in this condition, intubation was required in one-quarter of cases. Younger age, antibiotic therapy, and IMV were associated with a longer stay in the PICU.

  13. Current state of a dual behaviour of antimicrobial peptides-Therapeutic agents and promising delivery vectors.

    Piotrowska, Urszula; Sobczak, Marcin; Oledzka, Ewa

    2017-12-01

    Micro-organism resistance is an important challenge in modern medicine due to the global uncontrolled use of antibiotics. Natural and synthetic antimicrobial peptides (AMPs) symbolize a new family of antibiotics, which have stimulated research and clinical interest as new therapeutic options for infections. They represent one of the most promising antimicrobial substances, due to their broad spectrum of biological activity, against bacteria, fungi, protozoa, viruses, yeast and even tumour cells. Besides, being antimicrobial, AMPs have been shown to bind and neutralize bacterial endotoxins, as well as possess immunomodulatory, anti-inflammatory, wound-healing, angiogenic and antitumour properties. In contrast to conventional antibiotics, which have very defined and specific molecular targets, host cationic peptides show varying, complex and very rapid mechanisms of actions that make it difficult to form an effective antimicrobial defence. Importantly, AMPs display their antimicrobial activity at micromolar concentrations or less. To do this, many peptide-based drugs are commercially available for the treatment of numerous diseases, such as hepatitis C, myeloma, skin infections and diabetes. Herein, we present an overview of the general mechanism of AMPs action, along with recent developments regarding carriers of AMPs and their potential applications in medical fields. © 2017 John Wiley & Sons A/S.

  14. Rectal cancer and Fournier’s gangrene - current knowledge and therapeutic options

    Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

    2015-01-01

    Fournier’s gangrene (FG) is a rapid progressive bacterial infection that involves the subcutaneous fascia and part of the deep fascia but spares the muscle in the scrotal, perianal and perineal region. The incidence has increased dramatically, while the reported incidence of rectal cancer-induced FG is unknown but is extremely low. Pathophysiology and clinical presentation of rectal cancer-induced FG per se does not differ from the other causes. Only rectal cancer-specific symptoms before presentation can lead to the diagnosis. The diagnosis of rectal cancer-induced FG should be excluded in every patient with blood on digital rectal examination, when urogenital and dermatological causes are excluded and when fever or sepsis of unknown origin is present with perianal symptomatology. Therapeutic options are more complex than for other forms of FG. First, the causative rectal tumor should be removed. The survival of patients with rectal cancer resection is reported as 100%, while with colostomy it is 80%. The preferred method of rectal resection has not been defined. Second, oncological treatment should be administered but the timing should be adjusted to the resolution of the FG and sometimes for the healing of plastic reconstructive procedures that are commonly needed for the reconstruction of large perineal, scrotal and lower abdominal wall defects. PMID:26290629

  15. Investigation of students’ intermediate conceptual understanding levels: the case of direct current electricity concepts

    Aktan, D Cobanoglu

    2013-01-01

    Conceptual understanding is one of the main topics in science and physics education research. In the majority of conceptual understanding studies, students’ understanding levels were categorized dichotomously, either as alternative or scientific understanding. Although they are invaluable in many ways, namely developing new instructional materials and assessment instruments, students’ alternative understandings alone are not sufficient to describe students’ conceptual understanding in detail. This paper introduces an example of a study in which a method was developed to assess and describe students’ conceptual understanding beyond alternative and scientific understanding levels. In this study, six undergraduate students’ conceptual understanding levels of direct current electricity concepts were assessed and described in detail by using their answers to qualitative problems. In order to do this, conceptual understanding indicators are described based on science and mathematics education literature. The students’ understanding levels were analysed by assertion analysis based on the conceptual understanding indicators. The results indicated that the participants demonstrated three intermediate understanding levels in addition to alternative and scientific understanding. This paper presents the method and its application to direct current electricity concepts. (paper)

  16. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis

    Cunha, Elen Freitas de Cerqueira; Rocha, Manoel de Souza; Pereira, Fabio Payao; Blasbalg, Roberto; Baroni, Ronaldo Hueb

    2014-01-01

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation - and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients. (author)

  17. Current concepts in the classification, diagnosis and treatment of vascular anomalies

    Ernemann, Ulrike; Kramer, Ulrich; Miller, Stephan; Bisdas, Sotirios; Rebmann, Hans; Breuninger, Helmut; Zwick, Christine; Hoffmann, Juergen

    2010-01-01

    Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise β-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

  18. Walled-off pancreatic necrosis and other current concepts in the radiological assessment of acute pancreatitis

    Cunha, Elen Freitas de Cerqueira [Image Memorial/DASA and Diagnoson Medicina Diagnostica, Salvador, BA (Brazil); Rocha, Manoel de Souza; Pereira, Fabio Payao; Blasbalg, Roberto; Baroni, Ronaldo Hueb [Universidade de Sao Paulo (FM/USPU), Sao Paulo, SP (Brazil). Faculdade de Medicina

    2014-05-15

    Acute pancreatitis is an inflammatory condition caused by intracellular activation and extravasation of inappropriate proteolytic enzymes determining destruction of pancreatic parenchyma and peripancreatic tissues. This is a fairly common clinical condition with two main presentations, namely, endematous pancreatitis - a less severe presentation - and necrotizing pancreatitis - the most severe presentation that affects a significant part of patients. The radiological evaluation, particularly by computed tomography, plays a fundamental role in the definition of the management of severe cases, especially regarding the characterization of local complications with implications in the prognosis and in the definition of the therapeutic approach. New concepts include the subdivision of necrotizing pancreatitis into the following presentations: pancreatic parenchymal necrosis with concomitant peripancreatic tissue necrosis, and necrosis restricted to peripancreatic tissues. Moreover, there was a systematization of the terms acute peripancreatic fluid collection, pseudocyst, post-necrotic pancreatic/peripancreatic fluid collections and walled-off pancreatic necrosis. The knowledge about such terms is extremely relevant to standardize the terminology utilized by specialists involved in the diagnosis and treatment of these patients. (author)

  19. Current concepts in the classification, diagnosis and treatment of vascular anomalies

    Ernemann, Ulrike, E-mail: ulrike.ernemann@med.uni-tuebingen.d [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Kramer, Ulrich; Miller, Stephan [Department of Diagnostic and Interventional Radiology, Radiological Clinic, University Hospital Tuebingen (Germany); Bisdas, Sotirios [Department of Diagnostic and Interventional Neuroradiology, Radiological Clinic, University Hospital Tuebingen, Hoppe-Seyler-Strasse 3, 72076 Tuebingen (Germany); Rebmann, Hans [Department of Paediatrics, Children' s Hospital, University Hospital Tuebingen (Germany); Breuninger, Helmut [Department of Dermatology, University Hospital Tuebingen (Germany); Zwick, Christine [Department of Hand, Plastic, Reconstructive and Burns Surgery, BG Trauma Clinic Tuebingen, University Hospital Tuebingen (Germany); Hoffmann, Juergen [Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen (Germany)

    2010-07-15

    Patients with extended vascular anomalies may suffer from significant aesthetic and functional impairment and represent a challenge to therapeutic planning, which is best met by an interdisciplinary concept. In agreement with the International Society for the Study of Vascular Anomalies (ISSVA), vascular lesions are classified into haemangiomas as proliferating endothelial tumours on the one hand and congenital vascular malformations on the other. According to the preponderant vascular channels and hemodynamic characteristics, malformations are subdivided into low flow (venous, lymphatic and capillary) lesions and high-flow malformations. Diagnostic imaging should be targeted at the specific structural and functional informations required for treatment planning. The imaging modality of choice to provide these informations is magnetic resonance imaging (MRI) supplemented by magnetic resonance angiography (MRA) with high spatial and temporal resolution. Treatment indications for haemangiomas depend on the proliferative behaviour of the lesion and comprise {beta}-blockers in order to induce involution as well as cryotherapy, laser and open surgery. Interventional radiological procedures have evolved as an essential element in an interdisciplinary treatment plan for vascular malformations and include percutaneous sclerotherapy with ethanol and OK-432 for venous and lymphatic malformations and transarterial embolization for high-flow lesions.

  20. Sausage instabilities in the electron current layer and its role in the concept of fast ignition

    Das, Amita; Jain, Neeraj; Kaw, Predhiman; Sengupta, Sudip

    2004-01-01

    The fast ignition concept of laser fusion utilizes hot electrons produced at the surface of the target by an incident intense laser pulse for the creation of the hot spot for ignition. As the hot electrons move inwards to the core of the precompressed target, the electrons from the background plasma provide a return shielding current. Three dimensional PIC simulations have shown that intense Weibel, tearing and coalescence instabilities take place which organize the current distribution into a few current filaments. In each of these filaments the central core region constitutes a current due to the fast electrons propagating inwards towards the pellet core, while the outer cylindrical shell region carries the return shielding current. The presence of instabilities and their subsequent nonlinear development can hinder the propagation of fast electrons towards the core influencing the location of the hot spot for ignition. Earlier studies showing the existence of sausage-like modes were carried out in the nonrelativistic limit and under the assumption of equal electron densities of the fast and the cold electrons. The fast electron density, in general, differs considerably from the background plasma density as it is dependent on the incident laser intensity. This paper incorporates relativistic effects and also studies the dependence of the growth rate on the fast electron density. Finally, nonlinear saturation of the instability and its impact on the stopping of the fast electron motion towards the core have also been investigated using numerical simulations. The simulations have, however, currently been carried out for non-relativistic dynamics. The results show that the sheared velocity profile of the channel gets flattened, causing an effective drop in the inward moving current. (author)

  1. Computationally derived points of fragility of a human cascade are consistent with current therapeutic strategies.

    Deyan Luan

    2007-07-01

    Full Text Available The role that mechanistic mathematical modeling and systems biology will play in molecular medicine and clinical development remains uncertain. In this study, mathematical modeling and sensitivity analysis were used to explore the working hypothesis that mechanistic models of human cascades, despite model uncertainty, can be computationally screened for points of fragility, and that these sensitive mechanisms could serve as therapeutic targets. We tested our working hypothesis by screening a model of the well-studied coagulation cascade, developed and validated from literature. The predicted sensitive mechanisms were then compared with the treatment literature. The model, composed of 92 proteins and 148 protein-protein interactions, was validated using 21 published datasets generated from two different quiescent in vitro coagulation models. Simulated platelet activation and thrombin generation profiles in the presence and absence of natural anticoagulants were consistent with measured values, with a mean correlation of 0.87 across all trials. Overall state sensitivity coefficients, which measure the robustness or fragility of a given mechanism, were calculated using a Monte Carlo strategy. In the absence of anticoagulants, fluid and surface phase factor X/activated factor X (fX/FXa activity and thrombin-mediated platelet activation were found to be fragile, while fIX/FIXa and fVIII/FVIIIa activation and activity were robust. Both anti-fX/FXa and direct thrombin inhibitors are important classes of anticoagulants; for example, anti-fX/FXa inhibitors have FDA approval for the prevention of venous thromboembolism following surgical intervention and as an initial treatment for deep venous thrombosis and pulmonary embolism. Both in vitro and in vivo experimental evidence is reviewed supporting the prediction that fIX/FIXa activity is robust. When taken together, these results support our working hypothesis that computationally derived points of

  2. Off-Axis Driven Current Effects on ETB and ITB Formations based on Bifurcation Concept

    Pakdeewanich, J.; Onjun, T.; Chatthong, B.

    2017-09-01

    This research studies plasma performance in fusion Tokamak system by investigating parameters such as plasma pressure in the presence of an edge transport barrier (ETB) and an internal transport barrier (ITB) as the off-axis driven current position is varied. The plasma is modeled based on the bifurcation concept using a suppression function that can result in formation of transport barriers. In this model, thermal and particle transport equations, including both neoclassical and anomalous effects, are solved simultaneously in slab geometry. The neoclassical coefficients are assumed to be constant while the anomalous coefficients depend on gradients of local pressure and density. The suppression function, depending on flow shear and magnetic shear, is assumed to affect only on the anomalous channel. The flow shear can be calculated from the force balance equation, while the magnetic shear is calculated from the given plasma current. It is found that as the position of driven current peak is moved outwards from the plasma center, the central pressure is increased. But at some point it stars to decline, mostly when the driven current peak has reached the outer half of the plasma. The higher pressure value results from the combination of ETB and ITB formations. The drop in central pressure occurs because ITB stats to disappear.

  3. New Insights into Biology, Prognostic Factors, and Current Therapeutic Strategies in Chronic Lymphocytic Leukemia

    Smolewski, Piotr; Witkowska, Magdalena; Korycka-Wołowiec, Anna

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of mature B lymphocytes. CLL cells show an antiapoptotic profile, suggesting the important role of apoptosis inhibition in the disease development. However, there is some population of proliferating CLL cells, which may also play a role in progression of the disease. There are several newer, biological prognostic factors in CLL. Currently, cytogenetic abnormalities with different prognostic values...

  4. Current therapeutic interventions in the glycation pathway: evidence from clinical studies.

    Engelen, L; Stehouwer, C D A; Schalkwijk, C G

    2013-08-01

    The increased formation of advanced glycation endproducts (AGEs) constitutes a potential mechanism of hyperglycaemia-induced micro- and macrovascular disease in diabetes. In vitro and animal experiments have shown that various interventions can inhibit formation and/or actions of AGEs, in particular the specific AGE inhibitor aminoguanidine and the AGEs crosslink breaker alagebrium, and the B vitamins pyridoxamine and thiamine, and the latter's synthetic derivative, benfotiamine. The potential clinical value of these interventions, however, remains to be established. The present review provides, from the clinical point of view, an overview of current evidence on interventions in the glycation pathway relating to (i) the clinical benefits of specific AGE inhibitors and AGE breakers and (ii) the potential AGE-inhibiting effects of therapies developed for purposes unrelated to the glycation pathway. We found that safety and/or efficacy in clinical studies with the specific AGE inhibitor, aminoguanidine and the AGE breaker, alagebrium, appeared to be a concern. The clinical evidence on the potential AGE-inhibiting effects of B vitamins is still limited. Finally, current evidence for AGE inhibition by therapies developed for purposes unrelated to glycation is limited due to a large heterogeneity in study designs and/or measurement techniques, which have often been sub-optimal. We conclude that, clinical evidence on interventions to inhibit formation and/or action of AGEs is currently weak and unconvincing. © 2012 Blackwell Publishing Ltd.

  5. Clinical proof-of-concept trial to assess the therapeutic effect of sirolimus in patients with autosomal dominant polycystic kidney disease: SUISSE ADPKD study

    Wüthrich Rudolf P

    2007-09-01

    Full Text Available Abstract Background Currently there is no effective treatment available to retard cyst growth and to prevent the progression to end-stage renal failure in patients with autosomal dominant polycystic kidney disease (ADPKD. Evidence has recently been obtained from animal experiments that activation of the mammalian target of rapamycin (mTOR signaling pathway plays a crucial role in cyst growth and renal volume expansion, and that the inhibition of mTOR with rapamycin (sirolimus markedly slows cyst development and renal functional deterioration. Based on these promising results in animals we have designed and initiated the first randomized controlled trial (RCT to examine the effectiveness, safety and tolerability of sirolimus to retard disease progression in ADPKD. Method/design This single center, randomised controlled, open label trial assesses the therapeutic effect, safety and tolerability of the mTOR inhibitor sirolimus (Rapamune® in patients with autosomal dominant polycystic kidney disease and preserved renal function. The primary outcome will be the inhibition of kidney volume growth measured by magnetic resonance imaging (MRI volumetry. Secondary outcome parameters will be preservation of renal function, safety and tolerability of sirolimus. Discussion The results from this proof-of-concept RCT will for the first time show whether treatment with sirolimus effectively retards cyst growth in patients with ADPKD. Trial registration NCT00346918

  6. Mycoplasma genitalium infection: current treatment options, therapeutic failure, and resistance-associated mutations

    Couldwell DL

    2015-05-01

    failure, due to bacteria with coexistent macrolide-associated and fluoroquinolone-associated resistance mutations, were recently published by Australian investigators. Pristinamycin and solithromycin may be of clinical benefit for such multidrug-resistant infections. Further clinical studies are required to determine the optimal therapeutic dosing schedules for both agents to effect clinical cure and minimize the risk of emergent antimicrobial resistance. Continual inappropriate M. genitalium treatments will likely lead to untreatable infections in the future. Keywords: Mycoplasma genitalium, non-gonococcal urethritis, macrolide, fluoroquinolone, resistance, treatment failure

  7. Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

    Distler, Oliver; Cozzio, Antonio

    2016-01-01

    Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

  8. Current therapeutic molecules and targets in neurodegenerative diseases based on in silico drug design.

    Sehgal, Sheikh Arslan; Hammad, Mirza A; Tahir, Rana Adnan; Akram, Hafiza Nisha; Ahmad, Faheem

    2018-03-15

    As the number of elderly persons increases, neurodegenerative diseases are becoming ubiquitous. There is currently a great need for knowledge concerning management of old-age neurodegenerative diseases; the most important of which are: Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis, and Huntington's disease. To summarize the potential of computationally predicted molecules and targets against neurodegenerative diseases. Review of literature published since 1997 against neurodegenerative diseases, utilizing as keywords: in silico, Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis ALS, and Huntington's disease. Due to the costs associated with experimentation and current ethical law, performing experiments directly on living organisms has become much more difficult. In this scenario, in silico techniques have been successful and have become powerful tools in the search to cure disease. Researchers use the Computer Aided Drug Design pipeline which: 1) generates 3-dimensional structures of target proteins through homology modeling 2) achieves stabilization through molecular dynamics simulation, and 3) exploits molecular docking through large compound libraries. Next generation sequencing is continually producing enormous amounts of raw sequence data while neuroimaging is producing a multitude of raw image data. To solve such pressing problems, these new tools and algorithms are required. This review elaborates precise in silico tools and techniques for drug targets, active molecules, and molecular docking studies, together with future prospects and challenges concerning possible breakthroughs in Alzheimer's, Parkinson's, Amyotrophic Lateral Sclerosis, and Huntington's disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Combining Upper Limb Robotic Rehabilitation with Other Therapeutic Approaches after Stroke: Current Status, Rationale, and Challenges

    Stefano Mazzoleni

    2017-01-01

    Full Text Available A better understanding of the neural substrates that underlie motor recovery after stroke has led to the development of innovative rehabilitation strategies and tools that incorporate key elements of motor skill relearning, that is, intensive motor training involving goal-oriented repeated movements. Robotic devices for the upper limb are increasingly used in rehabilitation. Studies have demonstrated the effectiveness of these devices in reducing motor impairments, but less so for the improvement of upper limb function. Other studies have begun to investigate the benefits of combined approaches that target muscle function (functional electrical stimulation and botulinum toxin injections, modulate neural activity (noninvasive brain stimulation, and enhance motivation (virtual reality in an attempt to potentialize the benefits of robot-mediated training. The aim of this paper is to overview the current status of such combined treatments and to analyze the rationale behind them.

  10. Mental and behavioural disorders in the ICD-11: concepts, methodologies, and current status.

    Gaebel, Wolfgang; Zielasek, Jürgen; Reed, Geoffrey M

    2017-04-30

    This review provides an overview of the concepts, methods and current status of the development of the Eleventh Revision of the Mental and Behavioural Disorders chapter of the International Classification of Diseases and Related Health Problems (ICD-11) by the World Health Organization (WHO). Given the global use of the current version (ICD-10) for a wide range of applications in clinical practice and health statistics, a major aim of the development process for ICD-11 has been to increase the utility of the classification system. Expert working groups with responsibility for specific disorder groupings first suggested a set of revised diagnostic guidelines. Then surveys were performed to obtain suggestions for revisions from practicing health professionals. A completely revised structure for the classification of mental and behavioural disorders was developed and major revisions were suggested, for example, for schizophrenia and other primary psychotic disorders, substance use disorders, affective disorders and personality disorders. A new category of "gaming disorder" has been proposed and conditions related to sexual health and gender identity will be classified separately from mental disorders. An ICD-11 beta draft is freely available on the internet and public comments are invited. Field studies of the revised diagnostic guidelines are in process to obtain additional information about necessary improvements. A tabulated crosswalk from previous ICD-10 to then ICD-11 criteria will be necessary to ascertain the continuity of diagnoses for epidemiological and other statistical purposes. The final version of ICD-11 is currently scheduled for release by the World Health Assembly in 2018.

  11. On the concept of e-maintenance: Review and current research

    Muller, Alexandre; Crespo Marquez, Adolfo; Iung, Benoit

    2008-01-01

    The importance of the maintenance function has increased because of its role in keeping and improving system availability and safety, as well as product quality. To support this role, the development of the communication and information technologies has allowed the emergence of the concept of e-maintenance. Within the era of e-manufacturing and e-business, e-maintenance provides the opportunity for a new maintenance generation. As we will discuss later in this paper, e-maintenance integrates existing telemaintenance principles, with Web services and modern e-collaboration principles. Collaboration allows to share and exchange not only information but also knowledge and (e)-intelligence. By means of a collaborative environment, pertinent knowledge and intelligence become available and usable at the right place and time, in order to facilitate reaching the best maintenance decisions. This paper outlines the basic ideas within the e-maintenance concept and then provides an overview of the current research and challenges in this emerging field. An underlying objective is to identify the industrial/academic actors involved in the technological, organizational or management issues related to the development of e-maintenance. Today, this heterogeneous community has to be federated in order to bring up e-maintenance as a new scientific discipline

  12. Implementation of an active instructional design for teaching the concepts of current, voltage and resistance

    Orlaineta-Agüero, S.; Del Sol-Fernández, S.; Sánchez-Guzmán, D.; García-Salcedo, R.

    2017-01-01

    In the present work we show the implementation of a learning sequence based on an active learning methodology for teaching Physics, this proposal tends to promote a better learning in high school students with the use of a comic book and it combines the use of different low-cost experimental activities for teaching the electrical concepts of Current, Resistance and Voltage. We consider that this kind of strategy can be easily extrapolated to higher-education levels like Engineering-college/university level and other disciplines of Science. To evaluate this proposal, we used some conceptual questions from the Electric Circuits Concept Evaluation survey developed by Sokoloff and the results from this survey was analysed with the Normalized Conceptual Gain proposed by Hake and the Concentration Factor that was proposed by Bao and Redish, to identify the effectiveness of the methodology and the models that the students presented after and before the instruction, respectively. We found that this methodology was more effective than only the implementation of traditional lectures, we consider that these results cannot be generalized but gave us the opportunity to view many important approaches in Physics Education; finally, we will continue to apply the same experiment with more students, in the same and upper levels of education, to confirm and validate the effectiveness of this methodology proposal.

  13. Comprehensive management of pressure ulcers in spinal cord injury: Current concepts and future trends

    Kruger, Erwin A.; Pires, Marilyn; Ngann, Yvette; Sterling, Michelle; Rubayi, Salah

    2013-01-01

    Pressure ulcers in spinal cord injury represent a challenging problem for patients, their caregivers, and their physicians. They often lead to recurrent hospitalizations, multiple surgeries, and potentially devastating complications. They present a significant cost to the healthcare system, they require a multidisciplinary team approach to manage well, and outcomes directly depend on patients' education, prevention, and compliance with conservative and surgical protocols. With so many factors involved in the successful treatment of pressure ulcers, an update on their comprehensive management in spinal cord injury is warranted. Current concepts of local wound care, surgical options, as well as future trends from the latest wound healing research are reviewed to aid medical professionals in treating patients with this difficult problem. PMID:24090179

  14. Proposal on ''standardized high current solid targets for cyclotron production of diagnostic and therapeutic radionuclides''

    Suparman, Ibon

    2000-01-01

    The Center for the Development of Radioisotopes and Radiopharmaceuticals - National Nuclear Energy Agency (P2RR-BATAN) has one Cyclotron type CS-30 with maximum 30 MeV proton energy. It is used since 1990 for 201 Tl production. The main use of 201 Tl in Indonesia is for diagnosis and assessment of myocardial ischaemia, especially diagnosis of coronary artery disease, viability of the heart muscle and forecasting the outcome for patients with coronary disease. The Cyclotron facility is supported with a solid target station, two hot cells and the chemical equipment for electroplating. The yield of 201 Tl production currently achieved around 40-50%. The irradiation technique and chemical separation should be improved. We are also very interested in the development of the production of 103 Pd via 103 Rh (p,n) 103 Pd reaction. The objective of this proposal will support the main program of the National Nuclear Energy Agency (BATAN) in enhancement of health care and in providing Cyclotron produced radiopharmaceuticals for hospitals

  15. Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

    Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

    2017-07-01

    Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Current data on extremities chronic osteomyelitis in southwest China: epidemiology, microbiology and therapeutic consequences.

    Wang, Xiaohua; Yu, Shengpeng; Sun, Dong; Fu, Jingshu; Wang, Shulin; Huang, Ke; Xie, Zhao

    2017-11-24

    The current study was designed to explore the epidemiology of extremities chronic osteomyelitis, its prognosis and the complications of the treatment methods being used in southwest China. The data from osteomyelitis patients treated at the Department of Orthopaedics, Southwest Hospital, China between May 2011 and September 2016 were collected and analysed. The study comprised 503 admitted patients, of which 416 males and 87 were females, with an average age of 40.15 ± 5.64 years. Approximately 356 cases were followed for more than 18 months; the average bone union time was 6.24 ± 0.76 months in 94.1% (335) patients, and infections were almost controlled in 93.8% patients. The rate of infection control with the induced membrane technique was higher than with the I-stage free bone graft. Iliac infection was the main complication of the induced membrane technique, and impaired joint activity was the main complication of I-stage free bone grafts. In southwest China, the incidence of haematogenous osteomyelitis, caused mainly by Staphylococcus aureus, remains very high. The speed of bone defect repair and the rate of infection control with the induced membrane technique were superior to those of I-stage free bone grafts. Internal fixation should be given priority because it offers reduced complications with no increase in the recurrence of infection.

  17. [Current antibiotic resistance profile of uropathogenic Escherichia coli strains and therapeutic consequences].

    El Bouamri, M C; Arsalane, L; Kamouni, Y; Yahyaoui, H; Bennouar, N; Berraha, M; Zouhair, S

    2014-12-01

    Urinary tract infections (UTI) are a very common reason for consultation and prescription in current practice. Excessive or inappropriate use of antibiotics in treating urinary tract infections is responsible for the emergence and spread of multiresistant uropathogenic bacteria. To evaluate the isolation frequency and antibiotic resistance of uropathogenic Escherichia coli strains isolated at the Marrakech region. We conducted a retrospective study over a period of three years (from 1st January 2010 to 31 December 2012). It included all non-redundant uropathogenic E. coli strains isolated in the microbiology laboratory of the Avicenne hospital of Marrakech, Morocco. During this study, 1472 uropathogenic enterobacteriaceae were isolated including 924 non-repetitive E. coli strains, an overall isolation frequency of 63%. Antibiotic resistance of isolated E. coli strains showed resistance rates to amoxicillin (65%), sulfamethoxazole-triméthropime (55%), amoxicillin-clavulanic acid (43%), ciprofloxacin (22%), gentamicin (14%), nitrofurans (11%), amikacin (8%) and fosfomycin (7%). The number of E. coli strains resistant to C3G by ESBL production was 67, an average frequency of 4.5% of all isolated uropathogenic enterobacteria. The associated antibiotic resistance in the case of ESBL-producing E. coli were 82% for ciprofloxacin, 76% for sulfamethozole trimethoprim, 66% for gentamicin and 56% for amikacin. No resistance to imipenem was recorded for the isolated E. coli strains, which represents an imipenem sensitivity of 100%. Antibiotic resistance of uropathogenic E. coli strains limits treatment options and therefore constitutes a real public health problem. The regular updating of antibiotic susceptibility statistics of E. coli strains allows a better adaptation of the probabilistic antibiotic therapy to local epidemiological data. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. The Persistence of Prior Concepts about Electric Potential, Current Intensity and Ohm’s Law in Students of Engineering

    María Cristina Periago

    2005-11-01

    Full Text Available The aim of this research was to evaluate and analyze second-year industrial-engineering and chemical-engineering students’ prior knowledge of conceptual aspects of circuit theory. Specifically, we have focused on the basic concepts of electric potential and current intensity and on the fundamental relationship between these as expressed by Ohm’s Law. In order to find out what the students’ prior concepts were, we applied a survey containing nine questions dealing with the most basic concepts of circuit theory. Let us emphasize that there was little information available about the prior concepts of the population type (university students investigated in this research.

  19. Microsurgical reconstruction of the head and neck region: Current concepts of maxillofacial surgery units worldwide.

    Kansy, Katinka; Mueller, Andreas Albert; Mücke, Thomas; Koersgen, Friederike; Wolff, Klaus Dietrich; Zeilhofer, Hans-Florian; Hölzle, Frank; Pradel, Winnie; Schneider, Matthias; Kolk, Andreas; Smeets, Ralf; Acero, Julio; Haers, Piet; Ghali, G E; Hoffmann, Jürgen

    2015-10-01

    Microvascular surgery following tumor resection has become an important field of oral maxillofacial surgery (OMFS). Following the surveys on current reconstructive practice in German-speaking countries and Europe, this paper presents the third phase of the project when the survey was conducted globally. The DOESAK questionnaire has been developed via a multicenter approach with maxillofacial surgeons from 19 different hospitals in Germany, Austria and Switzerland. It was distributed in three different phases to a growing number of maxillofacial units in German-speaking clinics, over Europe and then worldwide. Thirty-eight units from Germany, Austria and Switzerland, 65 remaining European OMFS-departments and 226 units worldwide responded to the survey. There is wide agreement on the most commonly used flaps, intraoperative rapid sections and a trend towards primary bony reconstruction. No uniform concepts can be identified concerning osteosynthesis of bone transplants, microsurgical techniques, administration of supportive medication and postoperative monitoring protocols. Microsurgical reconstruction is the gold standard for the majority of oncologic cases in Europe, but worldwide, only every second unit has access to this technique. The DOESAK questionnaire has proven to be a valid and well accepted tool for gathering information about current practice in reconstructive OMFS surgery. The questionnaire has been able to demonstrate similarities, differences and global inequalities. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

  20. Current and emerging concepts in muscle tension dysphonia: a 30-month review.

    Altman, Kenneth W; Atkinson, Cory; Lazarus, Cathy

    2005-06-01

    The modern theory of hoarseness is that there are multifactorial etiologies contributing to the voice problem. The hypothesis of this study is that muscle tension dysphonia is multifactorial with various contributing etiologies. This project is a retrospective chart review of all patients seen in the Voice Speech and Language Service and Swallowing Center at our institution with a diagnosis of muscle tension (functional hypertensive) dysphonia over a 30-month period. A literature search and review is also performed regarding current and emerging concepts of muscle tension dysphonia. One hundred fifty subjects were identified (60% female, 40% male, with a mean age of 42.3 years). Significant factors in patient history believed to contribute to abnormal voice production were gastroesophageal reflux in 49%, high stress levels in 18%, excessive amounts of voice use in 63%, and excessive loudness demands on voice use in 23%. Otolaryngologic evaluation was performed in 82% of patients, in whom lesions, significant vocal fold edema, or paralysis/paresis was identified in 52.3%. Speech pathology assessment revealed poor breath support, inappropriately low pitch, and visible cervical neck tension in the majority of patients. Inappropriate intensity was observed in 23.3% of patients. This set of multiple contributing factors is discussed in the context of current and emerging understanding of muscle tension dysphonia. Results confirm multifactorial etiologies contributing to hoarseness in the patients identified with muscle tension dysphonia. An interdisciplinary approach to treating all contributing factors portends the best prognosis.

  1. Gender identity disorders in childhood and adolescence: currently debated concepts and treatment strategies.

    Korte, Alexander; Lehmkuhl, Ulrike; Goecker, David; Beier, Klaus Michael; Krude, Heiko; Grüters-Kieslich, Annette

    2008-11-01

    Gender identity disorders (GID) can appear even in early infancy with a variable degree of severity. Their prevalence in childhood and adolescence is below 1%. GID are often associated with emotional and behavioral problems as well as a high rate of psychiatric comorbidity. Their clinical course is highly variable. There is controversy at present over theoretical explanations of the causes of GID and over treatment approaches, particularly with respect to early hormonal intervention strategies. This review is based on a selective Medline literature search, existing national and international guidelines, and the results of a discussion among experts from multiple relevant disciplines. As there have been no large studies to date on the course of GID, and, in particular, no studies focusing on causal factors for GID, the evidence level for the various etiological models that have been proposed is generally low. Most models of these disorders assume that they result from a complex biopsychosocial interaction. Only 2.5% to 20% of all cases of GID in childhood and adolescence are the initial manifestation of irreversible transsexualism. The current state of research on this subject does not allow any valid diagnostic parameters to be identified with which one could reliably predict whether the manifestations of GID will persist, i.e., whether transsexualism will develop with certainty or, at least, a high degree of probability. The types of modulating influences that are known from the fields of developmental psychology and family dynamics have therapeutic implications for GID. As children with GID only rarely go on to have permanent transsexualism, irreversible physical interventions are clearly not indicated until after the individual's psychosexual development ist complete. The identity-creating experiences of this phase of development should not be restricted by the use of LHRH analogues that prevent puberty.

  2. Upper extremity transplantation: current concepts and challenges in an emerging field.

    Elliott, River M; Tintle, Scott M; Levin, L Scott

    2014-03-01

    Loss of an isolated upper limb is an emotionally and physically devastating event that results in significant impairment. Patients who lose both upper extremities experience profound disability that affects nearly every aspect of their lives. While prosthetics and surgery can eventually provide the single limb amputee with a suitable assisting hand, limited utility, minimal haptic feedback, weight, and discomfort are persistent problems with these techniques that contribute to high rates of prosthetic rejection. Moreover, despite ongoing advances in prosthetic technology, bilateral amputees continue to experience high levels of dependency, disability, and distress. Hand and upper extremity transplantation holds several advantages over prosthetic rehabilitation. The missing limb is replaced with one of similar skin color and size. Sensibility, voluntary motor control, and proprioception are restored to a greater degree, and afford better dexterity and function than prosthetics. The main shortcomings of transplantation include the hazards of immunosuppression, the complications of rejection and its treatment, and high cost. Hand and upper limb transplantation represents the most commonly performed surgery in the growing field of Vascularized Composite Allotransplantation (VCA). As upper limb transplantation and VCA have become more widespread, several important challenges and controversies have emerged. These include: refining indications for transplantation, optimizing immunosuppression, establishing reliable criteria for monitoring, diagnosing, and treating rejection, and standardizing outcome measures. This article will summarize the historical background of hand transplantation and review the current literature and concepts surrounding it.

  3. The shaft fractures of the radius and ulna in children: current concepts.

    Sinikumpu, Juha-Jaakko; Serlo, Willy

    2015-05-01

    The incidence of forearm shaft fractures in children has increased in recent years. They are challenging to treat and they can result in several long-lasting complications. The treatment of children's fractures needs to be individualized to their needs. Nonoperative care will be satisfactory for young, preschool children and it is primarily treatment in stable fractures of children at every age. Injury mechanism must be understood to perform appropriate closed reduction. Immobilization using a long-arm cast needs to be focused against the deforming muscle forces - in particular those that rotate - in the forearm, keeping the bones in alignment until bone healing. Operative stabilization by elastic stable intramedullary nailing is the primarily method of treatment in cases of unstable fractures, in particular, in children between preschool age and adolescence. For older children near to skeletal maturity, a rigid plate and screw fixation will be justified. The most common complication after closed treatment is worsening of the alignment and need for repetitive interventions. elastic stable intramedullary nailing results usually in good outcome, and range of forearm rotation is the main feature determining the clinical result. In this article, we report the current concept of paediatric shaft fractures in the radius and ulna.

  4. The current state of knowledge on the use of the benchmark dose concept in risk assessment.

    Sand, Salomon; Victorin, Katarina; Filipsson, Agneta Falk

    2008-05-01

    This review deals with the current state of knowledge on the use of the benchmark dose (BMD) concept in health risk assessment of chemicals. The BMD method is an alternative to the traditional no-observed-adverse-effect level (NOAEL) and has been presented as a methodological improvement in the field of risk assessment. The BMD method has mostly been employed in the USA but is presently given higher attention also in Europe. The review presents a number of arguments in favor of the BMD, relative to the NOAEL. In addition, it gives a detailed overview of the several procedures that have been suggested and applied for BMD analysis, for quantal as well as continuous data. For quantal data the BMD is generally defined as corresponding to an additional or extra risk of 5% or 10%. For continuous endpoints it is suggested that the BMD is defined as corresponding to a percentage change in response relative to background or relative to the dynamic range of response. Under such definitions, a 5% or 10% change can be considered as default. Besides how to define the BMD and its lower bound, the BMDL, the question of how to select the dose-response model to be used in the BMD and BMDL determination is highlighted. Issues of study design and comparison of dose-response curves and BMDs are also covered. Copyright (c) 2007 John Wiley & Sons, Ltd.

  5. Current and emerging basic science concepts in bone biology: implications in craniofacial surgery.

    Oppenheimer, Adam J; Mesa, John; Buchman, Steven R

    2012-01-01

    Ongoing research in bone biology has brought cutting-edge technologies into everyday use in craniofacial surgery. Nonetheless, when osseous defects of the craniomaxillofacial skeleton are encountered, autogenous bone grafting remains the criterion standard for reconstruction. Accordingly, the core principles of bone graft physiology continue to be of paramount importance. Bone grafts, however, are not a panacea; donor site morbidity and operative risk are among the limitations of autologous bone graft harvest. Bone graft survival is impaired when irradiation, contamination, and impaired vascularity are encountered. Although the dura can induce calvarial ossification in children younger than 2 years, the repair of critical-size defects in the pediatric population may be hindered by inadequate bone graft donor volume. The novel and emerging field of bone tissue engineering holds great promise as a limitless source of autogenous bone. Three core constituents of bone tissue engineering have been established: scaffolds, signals, and cells. Blood supply is the sine qua non of these components, which are used both individually and concertedly in regenerative craniofacial surgery. The discerning craniofacial surgeon must determine the proper use for these bone graft alternatives, while understanding their concomitant risks. This article presents a review of contemporary and emerging concepts in bone biology and their implications in craniofacial surgery. Current practices, areas of controversy, and near-term future applications are emphasized.

  6. Skin Wound Healing: An Update on the Current Knowledge and Concepts.

    Sorg, Heiko; Tilkorn, Daniel J; Hager, Stephan; Hauser, Jörg; Mirastschijski, Ursula

    2017-01-01

    The integrity of healthy skin plays a crucial role in maintaining physiological homeostasis of the human body. The skin is the largest organ system of the body. As such, it plays pivotal roles in the protection against mechanical forces and infections, fluid imbalance, and thermal dysregulation. At the same time, it allows for flexibility to enable joint function in some areas of the body and more rigid fixation to hinder shifting of the palm or foot sole. Many instances lead to inadequate wound healing which necessitates medical intervention. Chronic conditions such as diabetes mellitus or peripheral vascular disease can lead to impaired wound healing. Acute trauma such as degloving or large-scale thermal injuries are followed by a loss of skin organ function rendering the organism vulnerable to infections, thermal dysregulation, and fluid loss. For this update article, we have reviewed the actual literature on skin wound healing purposes focusing on the main phases of wound healing, i.e., inflammation, proliferation, epithelialization, angiogenesis, remodeling, and scarring. The reader will get briefed on new insights and up-to-date concepts in skin wound healing. The macrophage as a key player in the inflammatory phase will be highlighted. During the epithelialization process, we will present the different concepts of how the wound will get closed, e.g., leapfrogging, lamellipodial crawling, shuffling, and the stem cell niche. The neovascularization represents an essential component in wound healing due to its fundamental impact from the very beginning after skin injury until the end of the wound remodeling. Here, the distinct pattern of the neovascularization process and the special new functions of the pericyte will be underscored. At the end, this update will present 3 topics of high interest in skin wound healing issues, dealing with scarring, tissue engineering, and plasma application. Although wound healing mechanisms and specific cell functions in wound

  7. Concept Development in Learning Physics: The Case of Electric Current and Voltage Revisited

    Koponen, Ismo T.; Huttunen, Laura

    2013-01-01

    In learning conceptual knowledge in physics, a common problem is the development and differentiation of concepts in the learning process. An important part of this development process is the re-organisation or re-structuring process in which students' conceptual knowledge and concepts change. This study proposes a new view of concept…

  8. Androgen replacement therapy in late-onset hypogonadism: current concepts and controversies - a mini-review.

    Mäkinen, Juuso I; Huhtaniemi, Ilpo

    2011-01-01

    Normal testicular function is essential for the maintenance of male physical strength and behaviour irrespective of age. A new term of late-onset hypogonadism (LOH) has been coined for the condition of decreased testosterone (T) and hypogonadal symptoms in ageing men. The most important testicular hormone, T, is responsible for the gender-specific androgenic-anabolic effects in men. Testicular T production remains stable until around the age of 40 years after which it declines by 1-2% annually. Despite this age-related decline, serum T levels in most older men remain within the reference range of younger men. The decreasing androgen levels are paralleled by well-defined objective biological and nonspecific subjective signs and symptoms of ageing. Because these symptoms are similar to those observed in young men with documented hypogonadism, androgen replacement therapy (ART) has been considered a logical way to treat them. A thorough review of the existing literature was performed to evaluate the current concepts and controversies related to ageing men and ART. Although it is intuitively logical that the symptoms of LOH are due to the ageing-related deficiency of T, and that they can be reversed by ART, the evidence for this is still variable and often weak. In particular, evidence-based information about long-term benefits and risks of ART in ageing men is largely missing. Despite widespread use, evidence-based proof for the objective benefits and side effects of ART of elderly men is still scanty, and such treatments should be considered experimental. Copyright © 2010 S. Karger AG, Basel.

  9. Current concepts and systematic review of vascularized composite allotransplantation of the abdominal wall.

    Berli, Jens U; Broyles, Justin M; Lough, Denver; Shridharani, Sachin M; Rochlin, Danielle; Cooney, Damon S; Lee, W P Andrew; Brandacher, Gerald; Sacks, Justin M

    2013-01-01

    Abdominal wall vascularized composite allotransplantation (AW-VCA) is a rarely utilized technique for large composite abdominal wall defects. The goal of this article is to systematically review the literature and current concepts of AW-VCA, outline the challenges ahead, and provide an outlook for the future. Systematic review of the literature was performed using MEDLINE, EMBASE, and PubMed to identify relevant articles discussing results of AW-VCA. Cadaver and animal studies were excluded from the systematic review, but selectively included in the discussion. The resultant five papers report their results on AW-VCA(Transplantation, 85, 2008, 1607; Am J Transplant, 7, 2007, 1304; Transplant Proc, 41, 2009, 521; Transplant Proc, 36, 2004, 1561; Lancet, 361, 2003, 2173). These papers represent the result of two study groups in which a total of 18 AW-VCA were performed in 17 patients. Two different operative approaches were used. Overall flap/graft survival was 88%. No mortality related to the transplant was reported. One cadaver study and two animal models were identified and separately presented (Transplant Proc, 43, 2011, 1701; Transplantation, 90, 2010, 1590; Journal of Surgical Research, 162, 2010, 314). Literature review reports AW-VCA is technically feasible with low morbidity and mortality. Functional outcomes are not reported and minimally considered. With advancements in vascularized composite allotransplantation research and decreasing toxicity of immunosuppression therapies and immunomodulatory regimens, AW-VCA can be applied in circumstances beyond conjunction with visceral transplantation. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment.

    Huhtaniemi, Ilpo

    2014-01-01

    Although suppressed serum testosterone (T) is common in ageing men, only a small proportion of them develop the genuine syndrome of low T associated with diffuse sexual (e.g., erectile dysfunction), physical (e.g. loss of vigor and frailty) and psychological (e.g., depression) symptoms. This syndrome carries many names, including male menopause or climacterium, andropause and partial androgen deficiency of the ageing male (PADAM). Late-onset hypogonadism (LOH) describes it best and is therefore generally preferred. The decrease of T in LOH is often marginal, and hypogonadism can be either due to primary testicular failure (low T, high luteinizing hormone (LH)) or secondary to a hypothalamic-pituitary failure (low T, low or inappropriately normal LH). The latter form is more common and it is usually associated with overweight/obesity or chronic diseases (e.g., type 2 diabetes mellitus, the metabolic syndrome, cardiovascular and chronic obstructive pulmonary disease, and frailty). A problem with the diagnosis of LOH is that often the symptoms (in 20%-40% of unselected men) and low circulating T (in 20% of men >70 years of age) do not coincide in the same individual. The European Male Ageing Study (EMAS) has recently defined the strict diagnostic criteria for LOH to include the simultaneous presence of reproducibly low serum T (total T treatment of comorbid diseases. T replacement is widely used for the treatment, but evidence-based information about its real benefi ts and short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.

  11. Current concepts in the management of pelvic fracture urethral distraction defects

    Ramanitharan Manikandan

    2011-01-01

    Full Text Available Objectives : Pelvic fracture urethral distraction defect (PFUDD may be associated with disabling complications, such as recurrent stricture, urinary incontinence, and erectile dysfunction. In this article we review the current concepts in the evaluation and surgical management of PFUDD, including redo urethroplasty. Materials and Methods : A PubMedTM search was performed using the keywords "pelvic fracture urethral distraction defect, anastomotic urethroplasty, pelvic fracture urethral stricture, pelvic fracture urethral injuries, and redo-urethroplasty." The search was limited to papers published from 1980 to March 2010 with special focus on those published in the last 15 years. The relevant articles were reviewed with regard to etiology, role of imaging, and the techniques of urethroplasty. Results : Pelvic fracture due to accidents was the most common etiology of PFUDD that usually involved the membranous urethra. Modern cross-sectional imaging, such as sonourethrography and magnetic resonance imaging help assess stricture pathology better, but their precise role in PFUDD management remains undefined. Surgical treatment with perineal anastomotic urethroplasty yields a success rate of more than 90% in most studies. The most important complication of surgical reconstruction is restenosis, occurring in less than 10% cases, most of which can be corrected by a redo anastomotic urethroplasty. The most common complication associated with this condition is erectile dysfunction. Urinary incontinence is a much rarer complication of this surgery in the present day. Conclusions : Anastomotic urethroplasty remains the cornerstone in the management of PFUDD, even in previously failed repairs. Newer innovations are needed to address the problem of erectile dysfunction associated with this condition.

  12. A discussion of current issues and concepts in the practice of skull-photo/craniofacial superimposition.

    Gordon, G M; Steyn, M

    2016-05-01

    A recent review paper on cranio-facial superimposition (CFS) stated that "there have been specific conceptual variances" from the original methods used in the practice of skull-photo superimposition, leading to poor results as far as accuracy is concerned. It was argued that the deviations in the practice of the technique have resulted in the reduced accuracies (for both failure to include and failure to exclude) that are noted in several recent studies. This paper aims to present the results from recent research to highlight the advancement of skull-photo/cranio-facial superimposition, and to discuss some of the issues raised regarding deviations from original techniques. The evolving methodology of CFS is clarified in context with the advancement of technology, forensic science and specifically within the field of forensic anthropology. Developments in the skull-photo/cranio-facial superimposition techniques have largely focused on testing reliability and accuracy objectively. Techniques now being employed by forensic anthropologists must conform to rigorous scientific testing and methodologies. Skull-photo/cranio-facial superimposition is constantly undergoing accuracy and repeatability testing which is in line with the principles of the scientific method and additionally allows for advancement in the field. Much of the research has indicated that CFS is useful in exclusion which is consistent with the concept of Popperian falsifiability - a hypothesis and experimental design which is falsifiable. As the hypothesis is disproved or falsified, another evolves to replace it and explain the new observations. Current and future studies employing different methods to test the accuracy and reliability of skull-photo/cranio-facial superimposition will enable researchers to establish the contribution the technique can have for identification purposes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients.

    Obara, Vitor Yuzo; Zacas, Carolina Petrus; Carrilho, Claudia Maria Dantas de Maio; Delfino, Vinicius Daher Alvares

    2016-01-01

    This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged.

  14. Treatment of displaced intra-articular calcaneal fractures by ligamentotaxis: Current concepts' review

    T. Schepers (Tim); P. Patka (Peter)

    2009-01-01

    textabstractIntroduction: A large variety of therapeutic modalities for calcaneal fractures have been described in the literature. No single treatment modality for displaced intra-articular calcaneal fractures has proven superior over the other. This review describes and compares the different

  15. Treatment of displaced intra-articular calcaneal fractures by ligamentotaxis: current concepts' review

    Schepers, T.; Patka, P.

    2009-01-01

    A large variety of therapeutic modalities for calcaneal fractures have been described in the literature. No single treatment modality for displaced intra-articular calcaneal fractures has proven superior over the other. This review describes and compares the different percutaneous distractional

  16. Current concepts: tissue engineering and regenerative medicine applications in the ankle joint

    Correia, S. I.; Pereira, H.; Silva-Correia, J.; van Dijk, C. N.; Espregueira-Mendes, J.; Oliveira, J. M.; Reis, R. L.

    2014-01-01

    Tissue engineering and regenerative medicine (TERM) has caused a revolution in present and future trends of medicine and surgery. In different tissues, advanced TERM approaches bring new therapeutic possibilities in general population as well as in young patients and high-level athletes, improving

  17. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

    Ilpo Huhtaniemi

    2014-04-01

    short- and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH.

  18. Late-onset hypogonadism: Current concepts and controversies of pathogenesis, diagnosis and treatment

    Huhtaniemi, Ilpo

    2014-01-01

    - and long-term risks, is not yet available. In this review, we will summarize the current concepts and controversies in the pathogenesis, diagnosis and treatment of LOH. PMID:24407185

  19. A Study of Second-Year Engineering Students' Alternative Conceptions about Electric Potential, Current Intensity and Ohm's Law

    Periago, M. Cristina; Bohigas, Xavier

    2005-01-01

    The aim of this research was to evaluate and analyse second-year industrial engineering and chemical engineering students prior knowledge of conceptual aspects of "circuit theory". Specifically, we focused on the basic concepts of electric potential and current intensity and on the fundamental relationship between them as expressed by Ohm's law.…

  20. A new concept of efficient therapeutic drug monitoring using the high-resolution continuum source absorption spectrometry and the surface enhanced Raman spectroscopy

    Xing, Yanlong; Fuss, Harald; Lademann, Jürgen; Huang, Mao Dong; Becker-Ross, Helmut; Florek, Stefan; Patzelt, Alexa; Meinke, Martina C.; Jung, Sora; Esser, Norbert

    2018-04-01

    In this study, a new therapeutic drug monitoring approach has been tested based on the combination of CaF molecular absorption using high-resolution continuum source absorption spectrometry (HR-CSAS) and surface enhanced Raman spectroscopy (SERS). HR-CSAS with mini graphite tube was successfully tested for clinical therapeutic drug monitoring of the fluorine-containing drug capecitabine in sweat samples of cancer patients: It showed advantageous features of high selectivity (no interference from Cl), high sensitivity (characteristic mass of 0.1 ng at CaF 583.069 nm), low sample consumption (down to 30 nL) and fast measurement (no sample pretreatment and less than 1 min of responding time) in tracing the fluorine signal out of capecitabine. However, this technique has the disadvantage of the total loss of the drug's structure information after burning the sample at very high temperature. Therefore, a new concept of combining HR-CSAS with a non-destructive spectroscopic method (SERS) was proposed for the sensitive sensing and specific identification of capecitabine. We tested and succeed in obtaining the molecular characteristics of the metabolite of capecitabine (named 5-fluorouracil) by the non-destructive SERS technique. With the results shown in this work, it is demonstrated that the combined spectroscopic technique of HR-CSAS and SERS will be very useful in efficient therapeutic drug monitoring in the future.

  1. Current liquid metal cooled fast reactor concepts: use of the dry reprocess fuel

    Park, Jee Won; Jeong, C. J.; Yang, M. S.

    2003-03-01

    Recent Liquid metal cooled Fast Reactor (LFR) concepts are reviewed for investigating the potential usability of the Dry Reprocess Fuel (DRF). The LFRs have been categorized into two different types: the sodium cooled and the lead cooled systems. In each category, overall design and engineering concepts are collected which includes those of S-PRISM, AFR300, STAR, ENHS and more. Specially, the nuclear fuel types which can be used in these LFRs, have been summarized and their thermal, physical and neutronic characteristics are tabulated. This study does not suggest the best-matching LFR for the DRF, but shows good possibility that the DRF fuel can be used in future LFRs

  2. Current liquid metal cooled fast reactor concepts: use of the dry reprocess fuel

    Park, Jee Won; Jeong, C. J.; Yang, M. S

    2003-03-01

    Recent Liquid metal cooled Fast Reactor (LFR) concepts are reviewed for investigating the potential usability of the Dry Reprocess Fuel (DRF). The LFRs have been categorized into two different types: the sodium cooled and the lead cooled systems. In each category, overall design and engineering concepts are collected which includes those of S-PRISM, AFR300, STAR, ENHS and more. Specially, the nuclear fuel types which can be used in these LFRs, have been summarized and their thermal, physical and neutronic characteristics are tabulated. This study does not suggest the best-matching LFR for the DRF, but shows good possibility that the DRF fuel can be used in future LFRs.

  3. Measurement and simulation of ionic current as a means of quantifying effects of therapeutic millimeter wave radiation

    Slovinsky, William Stanley

    A "millimeter wave" (MMW) is an electromagnetic oscillation with a wavelength between 1 and 10 mm, and a corresponding frequency of 30 to 300 GHz. In the spectrum of electromagnetic radiation, this band falls above the frequencies of radio waves and microwaves, and below that of infrared radiation. Since the 1950s, frequencies in this regime have been used for short range communications and beginning in the 1970s, a form of therapy known as "millimeter wave therapy" (MWT) , or microwave resonance therapy, in some publications. This form of therapy has been widely used in the republics of the former Soviet Union (FSU). As of 1995, it is estimated that more than one thousand medical centers in the FSU have performed MWT and more than three million patients have received this method of treatment. Despite the abundant use of this form of medicine, very little is known about the mechanisms by which it works. Early accounts of use are limited to Soviet government documents, largely unavailable to the scientific public, and limited translations and oral accounts from FSU scientists and literature reviews . This anecdotal body of evidence lacks the scrutiny of peer-reviewed journal publications. In order to gain more widespread acceptance in Western medicine, the pathway through which this regime of the electromagnetic radiation spectrum affects the human body must be rigorously mapped and quantified. Despite the anecdotal nature of a large portion of the existing research on biological MMW effects, a common link is the idea of an interaction occurring at the skin level, which is transduced into a signal used at a remote location in the body. This study explores a possible mechanism for the generation of this signal. The effects of therapeutic frequency MMW on the ionic currents through two different types of ion transport channels were studied, and the results are discussed with emphasis on how they relate to possible changes in nerve signals used by the body for

  4. Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies

    Hanumantha Rao Madala

    2018-02-01

    Full Text Available Isocitrate dehydrogenases 1 and 2 (IDH1,2, the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs and gain an unusual new activity of reducing the α-ketoglutarate (α-KG to D-2 hydroxyglutarate (D-2HG in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation, JmjC domain-containing KDMs (histone lysine demethylases, and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.

  5. Comparison of three different concepts of high dynamic range and dependability optimised current measurement digitisers for beam loss systems

    Viganò, W; Effinger, E; Venturini, G G; Zamantzas, C

    2012-01-01

    Three Different Concepts of High Dynamic Range and Dependability Optimised Current Measurement Digitisers for Beam Loss Systems will be compared on this paper. The first concept is based on Current to Frequency Conversion, enhanced with an ADC for extending the dynamic range and decreasing the response time. A summary of 3 years’ worth of operational experience with such a system for LHC beam loss monitoring will be given. The second principle is based on an Adaptive Current to Frequency Converter implemented in an ASIC. The basic parameters of the circuit are discussed and compared with measurements. Several measures are taken to harden both circuits against single event effects and to make them tolerant for operation in radioactive environments. The third circuit is based on a Fully Differential Integrator for enhanced dynamic range, where laboratory and test installation measurements will be presented. All circuits are designed to avoid any dead time in the acquisition and have reliability and fail safe...

  6. Border-wide assessment of intelligent transportation system (ITS) technology : current and future concepts.

    2012-07-01

    The purpose of this effort was to conduct a border-wide assessment of the use of intelligent transportation systems (ITS) technologies and operational concepts at and near land border crossings between the U.S. and Mexico. The work focused on tolling...

  7. Environmental Education in Ecuador: Conceptions and Currents in Quito's Private Elementary Schools

    Viteri, Fátima; Clarebout, Geraldine; Crauwels, Marion

    2013-01-01

    While key conceptions and the status of environmental education (EE) have been reported at various international, regional, national and local levels, those in play in the schools of Quito (Ecuador) are still relatively unknown. Of particular interest to this study are private schools: they are considerable in number in Ecuador and elsewhere, yet…

  8. The Therapeutic "Mis"conception: An Examination of its Normative Assumptions and a Call for its Revision.

    Mathews, Debra J H; Fins, Joseph J; Racine, Eric

    2018-01-01

    Dissecting Bioethics, edited by Tuija Takala and Matti Hayry, welcomes contributions on the conceptual and theoretical dimensions of bioethics. The department is dedicated to the idea that words defined by bioethicists and others should not be allowed to imprison people's actual concerns, emotions, and thoughts. Papers that expose the many meanings of a concept, describe the different readings of a moral doctrine, or provide an alternative angle to seemingly self-evident issues are particularly appreciated. To submit a paper or to discuss a suitable topic, contact Tuija Takala at tuija.takala@helsinki.fi.

  9. Modern history of surgical management of lung abscess: from Harold Neuhof to current concepts.

    Schweigert, Michael; Dubecz, Attila; Stadlhuber, Rudolf J; Stein, Hubert J

    2011-12-01

    Harold Neuhof was one of the pioneers of thoracic surgery in the early decades of the last century. Inspired by his preceptor Howard Lilienthal he proposed an entirely new concept for surgery on acute lung abscess. The aim of his one-stage procedure was adequate drainage of the abscess cavity. His approach proved to be the first major breakthrough in the treatment of acute lung abscess. Therapy of pulmonary abscess was again radically changed by the advent of antibiotics in the late 1940s. However, the basic principles of Neuhof's concept still influence modern-day management of putrid lung abscess. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  10. Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage “Switch” Phenotype

    Malyshev, Igor; Malyshev, Yuri

    2015-01-01

    Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-β-, TLR/NF-κB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity. PMID:26366410

  11. PET imaging approaches for inflammatory lung diseases: Current concepts and future directions

    Chen, Delphine L., E-mail: chend@wustl.edu [Divisions of Radiological Sciences and Nuclear Medicine, Mallinckrodt Institute of Radiology, Campus Box 8225, 510S, Kingshighway Blvd, St. Louis, MO (United States); Schiebler, Mark L. [Department of Radiology, UW-Madison School of Medicine and Public Heath, Madison, WI (United States); Goo, Jin Mo [Department of Radiology, Seoul National University, Seoul (Korea, Republic of); Beek, Edwin J.R. van [Clinical Research Imaging Centre, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh (United Kingdom)

    2017-01-15

    Highlights: • Positron emission tomography can provide molecular information inflammatory lung disease mechanisms and assess targeted treatment responses. • {sup 18}F-Fluorodeoxyglucose, {sup 18}F-(+/−)NOS, and {sup 18}F-fluciclatide have potential for serving as biomarkers of inflammation and fibrosis. • PET can complement computed tomography and magnetic resonance imaging to improve our understanding of inflammatory lung disease mechanisms. - Abstract: Inflammatory lung disease is one of the most common clinical scenarios, and yet, it is often poorly understood. Inflammatory lung disorders, such as chronic obstructive pulmonary diseases, which are causing significant mortality and morbidity, have limited therapeutic options. Recently, new treatments have become available for pulmonary fibrosis. This review article will describe the new insights that are starting to be gained from positron emission tomography (PET) methods, by targeting molecular processes using dedicated radiotracers. Ultimately, this should aid in deriving better pathophysiological classification of these disorders, which will ultimately result in better evaluation of novel therapies.

  12. Current quality assurance concepts and considerations for quality control of in-clinic biochemistry testing.

    Lester, Sally; Harr, K E; Rishniw, Mark; Pion, Paul

    2013-01-15

    Quality assurance is an implied concept inherent in every consumer's purchase of a product or service. In laboratory testing, quality assurance encompasses preanalytic (sampling, transport, and handling prior to testing), analytic (measurement), and postanalytic (reporting and interpretation) factors. Quality-assurance programs require that procedures are in place to detect errors in all 3 components and that the procedures are characterized by both documentation and correction of errors. There are regulatory bodies that provide mandatory standards for and regulation of human medical laboratories. No such regulations exist for veterinary laboratory testing. The American Society for Veterinary Clinical Pathology (ASVCP) Quality Assurance and Laboratory Standards Committee was formed in 1996 in response to concerns of ASVCP members about quality assurance and quality control in laboratories performing veterinary testing. Guidelines for veterinary laboratory testing have been developed by the ASVCP. The purpose of this report was to provide an overview of selected quality-assurance concepts and to provide recommendations for quality control for in-clinic biochemistry testing in general veterinary practice.

  13. Improving late life depression and cognitive control through the use of therapeutic video game technology: A proof-of-concept randomized trial.

    Anguera, Joaquin A; Gunning, Faith M; Areán, Patricia A

    2017-06-01

    Existing treatments for depression are known to have only modest effects, are insufficiently targeted, and are inconsistently utilized, particularly in older adults. Indeed, older adults with impaired cognitive control networks tend to demonstrate poor response to a majority of existing depression interventions. Cognitive control interventions delivered using entertainment software have the potential to not only target the underlying cerebral dysfunction associated with depression, but to do so in a manner that is engaging and engenders adherence to treatment protocol. In this proof-of-concept trial (Clinicaltrials.gov #: NCT02229188), individuals with late life depression (LLD) (22; 60+ years old) were randomized to either problem solving therapy (PST, n = 10) or a neurobiologically inspired digital platform designed to enhance cognitive control faculties (Project: EVO™, n = 12). Given the overlapping functional neuroanatomy of mood disturbances and executive dysfunction, we explored the impact of an intervention targeting cognitive control abilities, functional disability, and mood in older adults suffering from LLD, and how those outcomes compare to a therapeutic gold standard. EVO participants demonstrated similar improvements in mood and self-reported function after 4 weeks of treatment to PST participants. The EVO participants also showed generalization to untrained measures of working memory and attention, as well as negativity bias, a finding not evident in the PST condition. Individuals assigned to EVO demonstrated 100% adherence. This study provides preliminary findings that this therapeutic video game targeting cognitive control deficits may be an efficacious LLD intervention. Future research is needed to confirm these findings. © 2016 Wiley Periodicals, Inc.

  14. Radiation therapy for nonmalignant diseases in Germany. Current concepts and future perspectives

    Heinrich Seegenschmiedt, M.; Micke, O.; Willich, N.

    2004-01-01

    Background: radiotherapy (RT) of nonmalignant diseases has a long-standing tradition in Germany. Over the past decade significant theoretical and clinical progress has been made in this field to be internationally recognized as an important segment of clinical RT. This development is reflected in a national patterns-of-care study (PCS) conducted during the years 2001-2002. Material and methods: in 2001 and 2002, a questionnaire was mailed to all RT facilities in Germany to assess equipment, patient accrual, RT indications, and treatment concepts. 146 of 180 institutions (81%) returned all requested data: 23 university hospitals (UNI), 95 community hospitals (COM), and 28 private institutions (PRIV). The specific diseases treated at each institution and the RT concepts were analyzed for frequencies and ratios between the different institution types. All data were compared to the first PCS in 1994-1996. Results: in 137 institutions (94%) 415 megavoltage units (mean 1.7; range 1-4), and in 78 institutions (53%) 112 orthovoltage units (mean 1.1; range 0-2) were available. A mean of 37,410 patients were treated per year in all institutions: 503 (1.3%) for inflammatory disorders, 23,752 (63.5%) for degenerative, 1,252 (3.3%) for hypertrophic, and 11,051 (29.5%) for functional, other and unspecified disorders. In comparison to the first PCS there was a significant increase of patients per year (from 20,082 to 37,410; +86.3%) in most nonmalignant diseases during the past 7-8 years. Most disorders were treated in accordance with the national consensus guidelines: the prescribed dose concepts (single and total doses) varied much less during the period 2001-2002 in comparison with the previous PCS in 1994-1996. Only five institutions (3.4%) received recommendations to change single or total doses and/or treatment delivery. Univariate analysis detected significant institutional differences in the use of RT for various disorders. Conclusion: RT is increasingly accepted in

  15. The high current bus-bars of the LHC from conception to manufacture

    Belova, L; Perinet-Marquet, J-L; Urpin, C

    2006-01-01

    The main magnets of the LHC are series-connected electrically in different excitation circuits by means of superconducting bus-bars, carrying a maximum current of 13 kA. These superconducting bus-bars consist of a superconducting cable thermally and electrically coupled to a copper section all along length. The function of the copper section is essentially to provide an alternative path for the magnet current in case the superconducting cable loses its superconductivity and returns to normal state because of a transient system disturbance or normal zone propagation coming from the neighboring magnets. When a superconducting bus-bar quenches to normal state its temperature must always stay below a safe values of about 100 ° C while the copper is conducting. With regard to that, a quench signal is initiated, which in turn triggers the ramping down of the current from 13000 A to 0....

  16. Summary and viewgraphs from the Q-121 US/Japan advanced current drive concepts workshop

    Bonoli, P.; Porkolab, M.; Chan, V.; Pinsker, R.; Politzer, P.; Darrow, D.; Fukuyama, Atsushi; Imai, Tsuyoshi; Watari, Tetsuo; Itoh, Satoshi; Nakamura, Yukio; James, R.; Logan, G.; Porter, G.; Thomassen, K.; Lyon, J.; Mau, Tak; Tanaka, Hitoshi; Tanaka, Shigetoshi

    1990-01-01

    With the emphasis placed on current drive by ITER, which requires steady state operation in its engineering phase, it is important to bring theory and experiment in agreement for each of the schemes that could be used in that design. Both neutral beam and lower hybrid (LH) schemes are in excellent shape in that regard. Since the projected efficiency of all schemes is marginal it is also important to continue our search for more efficient processes. This workshop featured experimental and theoretical work in each processes. This workshop featured experimental and theoretical work in each of these areas, that is, validation of theory and the search for better ideas. There were a number of notable results to report, the most striking again (as with last year) the long pulse operation of TRIAM-1M. A low current was sustained for over 1 hour with LH waves, using new hall-effect sensors in the equilibrium field circuit to maintain position control. In JT-60, by sharpening the wave spectrum the current drive efficiency was improved to 0.34 x 10 20 m -2 A/W and 1.5 MA of current was driven entirely by the lower hybrid system. Also in that machine, using two different LH frequencies, the H-mode was entered. Finally, by using the LH system for startup they saved 2.5 resistive volt-sec of flux, which if extrapolated to ITER would save 40 volt-sec there. For the first time, and experiment on ECH current drive showed reasonable agreement with theory. Those experiments are reported here by James (LLNL) on the D3-D machine. Substantially lower ECH current drive than expected theoretically was observed on WT-3, but if differed by being in a low absorption regime. Nonetheless, excellent physics results were achieved in the WT-3 experiments, notably in having careful measurements of the parallel velocity distributions

  17. Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

    K Gautam

    2015-03-01

    Full Text Available Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2 cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it difficult to take clinical decisions. Newer technologies were introduced for the antibody detection to ensure high sensitivity and specificity. This article intends to provide an overview of the concepts on ANA testing, the different diagnostic methods available, the various patterns and clinical utility, the clinical guidelines to be followed, the drawbacks and what lies ahead in the future of ANA testing.Journal of Pathology of Nepal (2015 Vol. 5, 766-773

  18. Current concepts in the pathogenesis and treatment of chronic suppurative otitis media

    Mittal, Rahul; Lisi, Christopher V.; Gerring, Robert; Mittal, Jeenu; Mathee, Kalai; Narasimhan, Giri; Azad, Rajeev K.; Yao, Qi; Grati, M'hamed; Yan, Denise; Eshraghi, Adrien A.; Angeli, Simon I.; Telischi, Fred F.

    2015-01-01

    Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval window of the inner ear, causing conductive hearing loss. In addition, the inflammatory mediators generated during CSOM can penetrate into the inner ear through the round window. This can cause the loss of hair cells in the cochlea, leading to sensorineural hearing loss. Pseudomonas aeruginosa and Staphylococcus aureus are the most predominant pathogens that cause CSOM. Although the pathogenesis of AOM is well studied, very limited research is available in relation to CSOM. With the emergence of antibiotic resistance as well as the ototoxicity of antibiotics and the potential risks of surgery, there is an urgent need to develop effective therapeutic strategies against CSOM. This warrants understanding the role of host immunity in CSOM and how the bacteria evade these potent immune responses. Understanding the molecular mechanisms leading to CSOM will help in designing novel treatment modalities against the disease and hence preventing the hearing loss. PMID:26248613

  19. Pancreatic Cysts: Current Concepts of Pathogenesis, Diagnosis and Diagnostic and Treatment Approach

    V.М. Ratchik

    2014-09-01

    Full Text Available The relevance of pancreatic cyst treatment is determined by the increase in the incidence of pancreatitis, a considerable number of complications and high mortality rate. In recent decades, there has been steady growth of destructive forms of pancreatitis, respectively the number of pancreatic cysts increases. Pancreatic cysts in 18–68 % of cases cause various complications (suppuration, perforation, bleeding, internal and external fistulas, malignant transformation that define high mortality — 9.2–53 %. The nature and extent of surgery depend on the etiology, the presence or absence of the cyst connection with ductal system, the presence of complications. Surgical treatment for pancreatic cysts remains the method of choice. Minimally invasive surgical procedures became widely used. High prevalence of cystic lesions of the pancreas, the difficulty of choosing the optimal method of treatment require the creation of a rational, convenient for clinical practice diagnostic and therapeutic algorithm. Dissatisfaction with the results of treatment and a large number of complications lead to the search for a new, so called gold standard for treatment of patients and determine the real place of minimally invasive and open surgical techniques.

  20. Role of Ureaplasma Respiratory Tract Colonization in Bronchopulmonary Dysplasia Pathogenesis: Current Concepts and Update.

    Viscardi, Rose Marie; Kallapur, Suhas G

    2015-12-01

    Respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and Ureaplasma urealyticum in preterm infants is a significant risk factor for bronchopulmonary dysplasia (BPD). Recent studies of the ureaplasmal genome, animal infection models, and human infants have provided a better understanding of specific virulence factors, pathogen-host interactions, and variability in genetic susceptibility that contribute to chronic infection, inflammation, and altered lung development. This review provides an update on the current evidence supporting a causal role of ureaplasma infection in BPD pathogenesis. The current status of antibiotic trials to prevent BPD in Ureaplasma-infected preterm infants is also reviewed. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Role of Ureaplasma Respiratory Tract Colonization in BPD Pathogenesis: Current Concepts and Update

    Viscardi, Rose Marie; Kallapur, Suhas G.

    2015-01-01

    SYNOPSIS Respiratory tract colonization with the genital mycoplasma species Ureaplasma parvum and U. urealyticum in preterm infants is a significant risk factor for BPD. Recent studies of the ureaplasmal genome, animal infection models, and human infants have provided a better understanding of specific virulence factors, pathogen-host interactions, and variability in genetic susceptibility that contribute to chronic infection, inflammation, and altered lung development. This review will provide an update on the current evidence supporting a causal role of Ureaplasma infection in BPD pathogenesis. The current status of antibiotic trials to prevent BPD in Ureaplasma-infected preterm infants is also reviewed. PMID:26593075

  2. Current status of temporomandibular joint disorders and the therapeutic system derived from a series of biomechanical, histological, and biochemical studies

    Kazuo Tanne

    2015-01-01

    Full Text Available This article was designed to report the current status of temporomandibular joint disorders (TMDs and the therapeutic system on the basis of a series of clinical, biomechanical, histological and biochemical studies in our research groups. In particular, we have focused on the association of degenerative changes of articular cartilage in the mandibular condyle and the resultant progressive condylar resorption with mechanical stimuli acting on the condyle during the stomatognathic function. In a clinical aspect, the nature and prevalence of TMDs, association of malocclusion with TMDs, association of condylar position with TMDs, association of craniofacial morphology with TMDs, and influences of TMDs, TMJ-osteoarthritis (TMJ-OA in particular, were examined. In a biomechanical aspect, the nature of stress distribution in the TMJ from maximum clenching was analyzed with finite element method. In addition, the pattern of stress distribution was examined in association with varying vertical discrepancies of the craniofacial skeleton and friction between the articular disk and condyle. The results demonstrated an induction of large compressive stresses in the anterior and lateral areas on the condyle by the maximum clenching and the subsequent prominent increases in the same areas of the mandibular condyle as the vertical skeletal discrepancy became more prominent. Increase of friction at the articular surface was also indicated as a cause of larger stresses and the relevant disk displacement, which further induced an increase in stresses in the tissues posterior to the disks, indicating an important role of TMJ disks as a stress absorber. In a histological or biological aspect, increase in TMJ loading simulated by vertical skeletal discrepancy, which has already been revealed by the preceding finite element analysis or represented by excessive mouth opening, produced a decrease in the thickness of cartilage layers, an increase in the numbers of

  3. Measuring currents, ice drift, and waves from space: the Sea surface KInematics Multiscale monitoring (SKIM) concept

    Ardhuin, Fabrice; Aksenov, Yevgueny; Benetazzo, Alvise; Bertino, Laurent; Brandt, Peter; Caubet, Eric; Chapron, Bertrand; Collard, Fabrice; Cravatte, Sophie; Delouis, Jean-Marc; Dias, Frederic; Dibarboure, Gérald; Gaultier, Lucile; Johannessen, Johnny; Korosov, Anton; Manucharyan, Georgy; Menemenlis, Dimitris; Menendez, Melisa; Monnier, Goulven; Mouche, Alexis; Nouguier, Frédéric; Nurser, George; Rampal, Pierre; Reniers, Ad; Rodriguez, Ernesto; Stopa, Justin; Tison, Céline; Ubelmann, Clément; van Sebille, Erik; Xie, Jiping

    2018-05-01

    We propose a satellite mission that uses a near-nadir Ka-band Doppler radar to measure surface currents, ice drift and ocean waves at spatial scales of 40 km and more, with snapshots at least every day for latitudes 75 to 82°, and every few days for other latitudes. The use of incidence angles of 6 and 12° allows for measurement of the directional wave spectrum, which yields accurate corrections of the wave-induced bias in the current measurements. The instrument's design, an algorithm for current vector retrieval and the expected mission performance are presented here. The instrument proposed can reveal features of tropical ocean and marginal ice zone (MIZ) dynamics that are inaccessible to other measurement systems, and providing global monitoring of the ocean mesoscale that surpasses the capability of today's nadir altimeters. Measuring ocean wave properties has many applications, including examining wave-current interactions, air-sea fluxes, the transport and convergence of marine plastic debris and assessment of marine and coastal hazards.

  4. Measuring currents, ice drift, and waves from space: the Sea surface KInematics Multiscale monitoring (SKIM concept

    F. Ardhuin

    2018-05-01

    Full Text Available We propose a satellite mission that uses a near-nadir Ka-band Doppler radar to measure surface currents, ice drift and ocean waves at spatial scales of 40 km and more, with snapshots at least every day for latitudes 75 to 82°, and every few days for other latitudes. The use of incidence angles of 6 and 12° allows for measurement of the directional wave spectrum, which yields accurate corrections of the wave-induced bias in the current measurements. The instrument's design, an algorithm for current vector retrieval and the expected mission performance are presented here. The instrument proposed can reveal features of tropical ocean and marginal ice zone (MIZ dynamics that are inaccessible to other measurement systems, and providing global monitoring of the ocean mesoscale that surpasses the capability of today's nadir altimeters. Measuring ocean wave properties has many applications, including examining wave–current interactions, air–sea fluxes, the transport and convergence of marine plastic debris and assessment of marine and coastal hazards.

  5. The dynomak: An advanced spheromak reactor concept with imposed-dynamo current drive and next-generation nuclear power technologies

    Sutherland, D.A., E-mail: das1990@uw.edu; Jarboe, T.R.; Morgan, K.D.; Pfaff, M.; Lavine, E.S.; Kamikawa, Y.; Hughes, M.; Andrist, P.; Marklin, G.; Nelson, B.A.

    2014-04-15

    A high-β spheromak reactor concept has been formulated with an estimated overnight capital cost that is competitive with conventional power sources. This reactor concept utilizes recently discovered imposed-dynamo current drive (IDCD) and a molten salt (FLiBe) blanket system for first wall cooling, neutron moderation and tritium breeding. Currently available materials and ITER-developed cryogenic pumping systems were implemented in this concept from the basis of technological feasibility. A tritium breeding ratio (TBR) of greater than 1.1 has been calculated using a Monte Carlo N-Particle (MCNP5) neutron transport simulation. High temperature superconducting tapes (YBCO) were used for the equilibrium coil set, substantially reducing the recirculating power fraction when compared to previous spheromak reactor studies. Using zirconium hydride for neutron shielding, a limiting equilibrium coil lifetime of at least thirty full-power years has been achieved. The primary FLiBe loop was coupled to a supercritical carbon dioxide Brayton cycle due to attractive economics and high thermal efficiencies. With these advancements, an electrical output of 1000 MW from a thermal output of 2486 MW was achieved, yielding an overall plant efficiency of approximately 40%.

  6. New IES scheme for power conditioning at ultra-high currents: from concept to MHD modeling and first experiments

    Chuvatin, Alexandre S.; Aranchuk, Leonid E.; Rudakov, Leonid I.; Kokshenev, Vladimir A.; Kurmaev, Nikolai E.; Fursov, Fiodor I.; Huet, Dominique; Gasilov, Vladimir A.; Krukovskii, Alexandre Yu.

    2002-01-01

    This work introduces an inductive energy storage (IES) scheme which aims pulsed-power conditioning at multi- MJ energies. The key element of the scheme represents an additional plasma volume, where a magnetically accelerated wire array is used for inductive current switching. This plasma acceleration volume is connected in parallel to a microsecond capacitor bank and to a 100-ns current ruse-time useful load. Simple estimates suggest that optimized scheme parameters could be reachable even when operating at ultra-high currents. We describe first proof-of-principle experiments carried out on GIT12 generator at the wire-array current level of 2 MA. The obtained confirmation of the concept consists in generation of a 200 kV voltage directly at an inductive load. This load voltage value can be already sufficient to transfer the available magnetic energy into kinetic energy of a liner at this current level. Two-dimensional modeling with the radiational MHD numerical tool Marple confirms the development of inductive voltage in the system. However, the average voltage increase is accompanied by short-duration voltage drops due to interception of the current by the low-density upstream plasma. Upon our viewpoint, this instability of the current distribution represents the main physical limitation to the scheme performance

  7. A novel concept of fault current limiter based on saturable core in high voltage DC transmission system

    Yuan, Jiaxin; Zhou, Hang; Gan, Pengcheng; Zhong, Yongheng; Gao, Yanhui; Muramatsu, Kazuhiro; Du, Zhiye; Chen, Baichao

    2018-05-01

    To develop mechanical circuit breaker in high voltage direct current (HVDC) system, a fault current limiter is required. Traditional method to limit DC fault current is to use superconducting technology or power electronic devices, which is quite difficult to be brought to practical use under high voltage circumstances. In this paper, a novel concept of high voltage DC transmission system fault current limiter (DCSFCL) based on saturable core was proposed. In the DCSFCL, the permanent magnets (PM) are added on both up and down side of the core to generate reverse magnetic flux that offset the magnetic flux generated by DC current and make the DC winding present a variable inductance to the DC system. In normal state, DCSFCL works as a smoothing reactor and its inductance is within the scope of the design requirements. When a fault occurs, the inductance of DCSFCL rises immediately and limits the steepness of the fault current. Magnetic field simulations were carried out, showing that compared with conventional smoothing reactor, DCSFCL can decrease the high steepness of DC fault current by 17% in less than 10ms, which verifies the feasibility and effectiveness of this method.

  8. Cyber stalking victimisation of women: Evaluating the effectiveness of current laws in India from restorative justice and therapeutic jurisprudential perspectives

    Halder Debarati

    2015-01-01

    Full Text Available Victimisation of women through cyber stalking is one of the most serious crimes against women. Many countries including India have developed laws regulating cyber stalking. This article argues that since both, restorative justice (RJ and therapeutic jurisprudence (TJ are victim oriented, the issue of cyber stalking of women may be dealt with by RJ process and the laws in this regard must be analysed by the legal actors with a background in RJ and TJ philosophy. India had earlier taken up therapeutic punishment policy to enforce rights of the accused. But the modern principles of TJ have still not been considered in the RJ background in cyber stalking cases. This article therefore examines whether RJ and TJ principles can replace retributive principles for cyber stalking victimisation. It also examines the Indian cyber stalking law from RJ and TJ perspectives to assess its effectiveness for victims.

  9. Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets.

    Sun, Na; Keep, Richard F; Hua, Ya; Xi, Guohua

    2016-10-01

    Sphingolipids are a series of cell membrane-derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition, and migration. Sphingosine-1-phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function, and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as poststroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether the sphingolipid pathway could be a novel therapeutic target in stroke. The sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

  10. Theory of Digital Natives in the Light of Current and Future E-Learning Concepts

    Bodo von der Heiden

    2011-06-01

    Full Text Available The digital generation has many names: Net Generation, Generation@ or Digital Natives. The meaning behind these terms is, that the current generation of students is digitally and media literate, technology-savvy and are able to use other learning approaches than former generations. But these topics are discussed controversial and even the cause-effect-relationship is not as clear as it seems. Did the digital generation really have other learning approaches, or do they have only the possibility to live other learning modes? Against this background this article tries to shed some light on this debate. Therefore we use current and future projects performed at RWTH Aachen University to illustrate the relevance, value and significance due to the theory of the digital natives.

  11. Current Concepts for Injury Prevention in Athletes After Anterior Cruciate Ligament Reconstruction

    Hewett, Timothy E.; Di Stasi, Stephanie L.; Myer, Gregory D.

    2012-01-01

    Ligament reconstruction is the current standard of care for active patients with an anterior cruciate ligament (ACL) rupture. Although the majority of ACL reconstruction (ACLR) surgeries successfully restore the mechanical stability of the injured knee, postsurgical outcomes remain widely varied. Less than half of athletes who undergo ACLR return to sport within the first year after surgery, and it is estimated that approximately 1 in 4 to 1 in 5 young, active athletes who undergo ACLR will g...

  12. On the concept of virtual current as a means to enhance verification of electromagnetic flowmeters

    Baker, Roger C

    2011-01-01

    Electromagnetic flowmeters are becoming increasingly widely used in the water industry and other industries which handle electrically conducting liquids. When installed they are often difficult to remove for calibration without disturbing the liquid flow. Interest has therefore increased in the possibility of in situ calibration. The result has been the development of verification which attempts to approach calibration. However, while it checks on magnetic field and amplification circuits, it does not check adequately on the internals of the flowmeter pipe. This paper considers the use of the virtual voltage, a key element of the weight function theory of the flowmeter, to identify changes which have occurred in the flow tube and its liner. These could include a deformed insulating liner to the flow tube, or a deposit in the tube resulting from solids in the flow. The equation for virtual voltage is solved using a finite difference approach and the results are checked using a tank to simulate the flow tube, and tests on a flow rig. The concept is shown to be promising as a means of approaching verification of calibration

  13. Transcranial Direct Current Stimulation Effects on Athletes’ Cognitive Performance: An Exploratory Proof of Concept Trial

    Davimar Borduchi

    2016-11-01

    Full Text Available Among the 2016 Olympic and Paralympic Games unforgettable moments, one could not overlook performances by Phelps and Bolt, which challenge old premises about the maximum extension of individual supremacism in ultracompetitive modalities and the doping scandals. Different media channels resonated these two trends, with an unseen rise on discussions about traits and practices that may set ultrahigh performance athletes apart from the more ordinary ones. Yet, some key issues remain undebated. This paper aims to add to this debate, with a proof of concept trial, which investigates whether tDCS may serve as an aid for professional athletes. Ten professional athletes of three different modalities of (judo, N=4 athletes, swimming, N=3 athletes and rhythmic gymnastics, N=3 athletes received anodal stimulation (2mA for 20 minutes on the left dorsolateral prefrontal cortex for ten consecutive weekdays. We observed a positive effect of tDCS in their cognitive performance, including a significant improvement in alternated, sustained and divided attention and in memory scores. We also observed a decrease in Beck Depression Inventory scores (4.50 points in this non-clinical population. These preliminary results suggest that tDCS sessions may translate into competitive advantages for professional athletes and recommend the deepening of the discussion on its ethical use in sports, which is ultimately tied to the wider debate around the risks and opportunities that neuromodulation brings to the table.

  14. Imaging biomarkers in Parkinson's disease and Parkinsonian syndromes: current and emerging concepts.

    Saeed, Usman; Compagnone, Jordana; Aviv, Richard I; Strafella, Antonio P; Black, Sandra E; Lang, Anthony E; Masellis, Mario

    2017-01-01

    transporters and postsynaptic dopamine D2 receptors), and cerebral perfusion, 5) positron emission tomography for gauging nigrostriatal functions, glucose metabolism, amyloid and tau molecular imaging, as well as neuroinflammation, 6) myocardial scintigraphy for dysautonomia, and 7) transcranial sonography for measuring substantia nigra and lentiform nucleus echogenicity. Imaging biomarkers, using the 'multimodal approach', may aid in making early, accurate and objective diagnostic decisions, highlight neuroanatomical and pathophysiological mechanisms, as well as assist in evaluating disease progression and therapeutic responses to drugs in clinical trials.

  15. F-actin-based Ca signaling-a critical comparison with the current concept of Ca signaling.

    Lange, Klaus; Gartzke, Joachim

    2006-11-01

    A short comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect, the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating endoplasmic/sarcoplasmic reticulum-derived vesicles equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive channel-receptors for Ca-release. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of actin filaments. Cellular sites of F-actin-based Ca storage are microvilli and the submembrane cytoskeleton. Several specific features of Ca signaling such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release (CICR), which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling. Copyright 2006 Wiley-Liss, Inc.

  16. Current concepts of metabolic abnormalities in HIV patients: focus on lipodystrophy.

    Kolter, Donald P

    2003-12-01

    HIV infection is associated with a number of metabolic abnormalities, including lipodystrophy, a difficult-to-define disorder whose characteristics include hyperlipidemia, insulin resistance, and fat redistribution. Current data suggest that lipodystrophy is caused by multiple factors. Dual-nucleoside reverse transcriptase inhibitor therapy combined with protease inhibitor therapy has been shown to increase the risk of metabolic abnormalities, but susceptibility independent of drug effects has also been shown. While many of the treatments for the broad range of signs and symptoms of lipodystrophy bring about improvements in patient status, none have been demonstrated to bring about a return to baseline levels.

  17. Non-contact ACL injuries in female athletes: an International Olympic Committee current concepts statement

    Renstrom, P; Ljungqvist, A; Arendt, E

    2008-01-01

    clinicians and scientists to (1) review current evidence including data from the new Scandinavian ACL registries; (2) critically evaluate high-quality studies of injury mechanics; (3) consider the key elements of successful prevention programmes; (4) summarise clinical management including surgery...... and conservative management; and (5) identify areas for further research. Risk factors for female athletes suffering ACL injury include: (1) being in the preovulatory phase of the menstrual cycle compared with the postovulatory phase; (2) having decreased intercondylar notch width on plain radiography; and (3...

  18. Comparative investigation of the economics of seawater desalting based on current and advanced distillation concepts

    Glueckstern, P.; Reed, S.A.

    1976-01-01

    A reassessment of desalting plant design and product water cost based on current technology and energy and equipment costs has been made. Plant sizes in the range of 1 to 200 Mgd utilizing the multistage flash (MSF) and the vertical tube evaporator (VTE) were investigated. Process steam was assumed to be supplied by large nuclear dual-purpose plants or from fossil-fired low-pressure boilers. Plants applying the pH control method versus the threshold pretreatment method were compared. The potential benefits of applying low cost aluminum tubing in low-temperature VTE plants were also investigated

  19. Current and future competitiveness of renewable energy carriers - Conceptions about competitiveness

    Lundgren, K.

    1998-01-01

    The dissertation draws attention to the fact that in the world today 80% of the resources that are used are limited - non renewable energy carriers - and because of the long time between planning and doing (carrying out) within the energy sector, it is worthwhile from the long-term perspective to steer early on towards more sustainable solutions, such as renewable energy carriers. The State and the market have begun to adjust to concepts such as 'competitiveness', which can be viewed as containing both feasibility and legitimacy aspects - the state through different regulations and environmental taxes and environmental fees, and actors on the market that marginally produce/choose renewable energy carriers. The overlying methodology in the dissertation is an actor's viewpoint. This viewpoint brings forth, in turn, two different views, the analytical and the interpretative. The dissertation presents different stances within the energy sector: commercial production logic, commercial sustainability logic, and the socio-economic sustainability logic. By drawing one's attention to how one has the possibility to create (enact) his own reality, it is possible to highlight how organisations can increase their competitiveness by being conscious of their own view and others, logic, which in turn forms their views about competitiveness, which in turn determines which projects will materialize. Enterprises and individuals create a description of reality together through a dialectic process, i.e. by developing an environmental management system that contains elements of environmental auditing, environmental performance indicators, and environmental labelling, which 'reveal' the production conditions that lie behind the actualization of the final product. An example is the product, 'green' electricity, which, in spite of the fact that the final product - electricity - is identical irrespective of the production method, just at the moment can be sold at different prices according

  20. Sleep and memory in the making. Are current concepts sufficient in children?

    Peigneux, P

    2014-01-01

    Memory consolidation is an active process wired in brain plasticity. How plasticity mechanisms develop and are modulated after learning is at the core of current models of sleep-dependent memory consolidation. Nowadays, two main classes of sleep-related memory consolidation theories are proposed, namely system consolidation and synaptic homeostasis. However, novel models of consolidation emerge, that might better account for the highly dynamic and interactive processes of encoding and memory consolidation. Processing steps can take place at various temporal phases and be modulated by interactions with prior experiences and ongoing events. In this perspective, sleep might support (or not) memory consolidation processes under specific neurophysiological and environmental circumstances leading to enduring representations in long-term memory stores. We outline here a discussion about how current and emergent models account for the complexity and apparent inconsistency of empirical data. Additionally, models aimed at understanding neurophysiological and/or cognitive processes should not only provide a satisfactory explanation for the phenomena at stake, but also account for their ontogeny and the conditions that disrupt their organisation. Looking at the available literature, this developmental condition appears to remain unfulfilled when trying to understand the relationships between sleep, learning and memory consolidation processes, both in healthy children and in children with pathological conditions.

  1. Towards an ankle neuroprosthesis for hybrid robotics: Concepts and current sources for functional electrical stimulation.

    Casco, S; Fuster, I; Galeano, R; Moreno, J C; Pons, J L; Brunetti, F

    2017-07-01

    Hybrid rehabilitation robotics combine neuro-prosthetic devices (close-loop functional electrical stimulation systems) and traditional robotic structures and actuators to explore better therapies and promote a more efficient motor function recovery or compensation. Although hybrid robotics and ankle neuroprostheses (NPs) have been widely developed over the last years, there are just few studies on the use of NPs to electrically control both ankle flexion and extension to promote ankle recovery and improved gait patterns in paretic limbs. The aim of this work is to develop an ankle NP specifically designed to work in the field of hybrid robotics. This article presents early steps towards this goal and makes a brief review about motor NPs and Functional Electrical Stimulation (FES) principles and most common devices used to aid the ankle functioning during the gait cycle. It also shows a current sources analysis done in this framework, in order to choose the best one for this intended application.

  2. Augmented Reality in Neurosurgery: A Review of Current Concepts and Emerging Applications.

    Guha, Daipayan; Alotaibi, Naif M; Nguyen, Nhu; Gupta, Shaurya; McFaul, Christopher; Yang, Victor X D

    2017-05-01

    Augmented reality (AR) superimposes computer-generated virtual objects onto the user's view of the real world. Among medical disciplines, neurosurgery has long been at the forefront of image-guided surgery, and it continues to push the frontiers of AR technology in the operating room. In this systematic review, we explore the history of AR in neurosurgery and examine the literature on current neurosurgical applications of AR. Significant challenges to surgical AR exist, including compounded sources of registration error, impaired depth perception, visual and tactile temporal asynchrony, and operator inattentional blindness. Nevertheless, the ability to accurately display multiple three-dimensional datasets congruently over the area where they are most useful, coupled with future advances in imaging, registration, display technology, and robotic actuation, portend a promising role for AR in the neurosurgical operating room.

  3. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  4. Current Concepts in Pediatric Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia

    Bernt, Kathrin M.; Hunger, Stephen P.

    2014-01-01

    The t(9;22)(q34;q11) or Philadelphia chromosome creates a BCR–ABL1 fusion gene encoding for a chimeric BCR–ABL1 protein. It is present in 3–4% of pediatric acute lymphoblastic leukemia (Ph+ ALL), and about 25% of adult ALL cases. Prior to the advent of tyrosine kinase inhibitors (TKI), Ph+ ALL was associated with a very poor prognosis despite the use of intensive chemotherapy and frequently hematopoietic stem-cell transplantation (HSCT) in first remission. The development of TKIs revolutionized the therapy of Ph+ ALL. Addition of the first generation ABL1 class TKI imatinib to intensive chemotherapy dramatically increased the survival for children with Ph+ ALL and established that many patients can be cured without HSCT. In parallel, the mechanistic understanding of Ph+ ALL expanded exponentially through careful mapping of pathways downstream of BCR–ABL1, the discovery of mutations in master regulators of B-cell development such as IKZF1 (Ikaros), PAX5, and early B-cell factor (EBF), the recognition of the complex clonal architecture of Ph+ ALL, and the delineation of genomic, epigenetic, and signaling abnormalities contributing to relapse and resistance. Still, many important basic and clinical questions remain unanswered. Current clinical trials are testing second generation TKIs in patients with newly diagnosed Ph+ ALL. Neither the optimal duration of therapy nor the optimal chemotherapy backbone are currently defined. The role of HSCT in first remission and post-transplant TKI therapy also require further study. In addition, it will be crucial to continue to dig deeper into understanding Ph+ ALL at a mechanistic level, and translate findings into complementary targeted approaches. Expanding targeted therapies hold great promise to decrease toxicity and improve survival in this high-risk disease, which provides a paradigm for how targeted therapies can be incorporated into treatment of other high-risk leukemias. PMID:24724051

  5. Feedbacks between geomorphology and biota controlling Earth surface processes and landforms: A review of foundation concepts and current understandings

    Corenblit, Dov; Baas, Andreas C. W.; Bornette, Gudrun; Darrozes, José; Delmotte, Sébastien; Francis, Robert A.; Gurnell, Angela M.; Julien, Frédéric; Naiman, Robert J.; Steiger, Johannes

    2011-06-01

    This review article presents recent advances in the field of biogeomorphology related to the reciprocal coupling between Earth surface processes and landforms, and ecological and evolutionary processes. The aim is to present to the Earth Science community ecological and evolutionary concepts and associated recent conceptual developments for linking geomorphology and biota. The novelty of the proposed perspective is that (1) in the presence of geomorphologic-engineer species, which modify sediment and landform dynamics, natural selection operating at the scale of organisms may have consequences for the physical components of ecosystems, and particularly Earth surface processes and landforms; and (2) in return, these modifications of geomorphologic processes and landforms often feed back to the ecological characteristics of the ecosystem (structure and function) and thus to biological characteristics of engineer species and/or other species (adaptation and speciation). The main foundation concepts from ecology and evolutionary biology which have led only recently to an improved conception of landform dynamics in geomorphology are reviewed and discussed. The biogeomorphologic macroevolutionary insights proposed explicitly integrate geomorphologic niche-dimensions and processes within an ecosystem framework and reflect current theories of eco-evolutionary and ecological processes. Collectively, these lead to the definition of an integrated model describing the overall functioning of biogeomorphologic systems over ecological and evolutionary timescales.

  6. Methadone, QTc prolongation and torsades de pointes: Current concepts, management and a hidden twist in the tale?

    Mujtaba, Sobia; Romero, Jorge; Taub, Cynthia C

    2013-12-01

    Methadone is a drug that has found widespread utility in the management of opioid addiction and pain. Along with its popularity, methadone has also earned an infamous reputation for causing prolongation of the QT interval and an increased risk of torsades de pointes. In this article we will give a brief overview of the long QT syndromes, followed by an in-depth look at the current pathophysiologic mechanisms of methadone induced QT prolongation, a review of the existing literature and the current concepts regarding the prevention and management of methadone induced torsades de pointes. In addition, we explore the idea and implications of a genetic link between methadone induced prolongation of the QT interval and torsades de pointes.

  7. Ab initio molecular dynamics: basic concepts, current trends and novel applications

    Tuckerman, Mark E

    2002-01-01

    The field of ab initio molecular dynamics (AIMD), in which finite temperature molecular dynamics (MD) trajectories are generated with forces obtained from accurate 'on the fly' electronic structure calculations, is a rapidly evolving and growing technology that allows chemical processes in condensed phases to be studied in an accurate and unbiased way. This article is intended to present the basics of the AIMD method as well as to provide a broad survey of the state of the art of the field and showcase some of its capabilities. Beginning with a derivation of the method from the Born-Oppenheimer approximation, issues including the density functional representation of electronic structure, basis sets, calculation of observables and the Car-Parrinello extended Lagrangian algorithm are discussed. A number of example applications, including liquid structure and dynamics and aqueous proton transport, are presented in order to highlight some of the current capabilities of the approach. Finally, advanced topics such as inclusion of nuclear quantum effects, excited states and scaling issues are addressed. (topical review)

  8. De Quervain’s thyroiditis: current concepts and a report of four cases

    Roberto Boni

    2013-03-01

    Full Text Available Introduction: De Quervain’s subacute thyroiditis is a self-limiting granulomatous inflammatory disorder, which is thought to be virally induced in genetically predisposed individuals. It is characterized by thyroid pain and thyrotoxicosis, as well as by systemic symptoms like fever, hepatic cytolysis, and an elevated erythrocyte sedimentation rate. It is often mistaken for an upper respiratory tract infection. Materials and methods: The authors review recent advances in the understanding of the pathogenesis and pathophysiology of De Quervain’s subacute thyroiditis; risk factors for complications, with emphasis on relapses and end-stage hypothyroidism; differential diagnosis and the exclusion of other subtypes of thyroiditis; and current treatment options. Four cases of De Quervain’s thyroiditis are then analyzed and compared with cases in the literature. Discussion: In three of the patients, onset occurred in June and was probably related to a small, seasonal epidemic cluster. These cases were quite different from the fourth one, which occurred in October, suggesting that two distinct viruses might be involved. One of the patients presented a very rare complication, vocal-cord paralysis, which responded well to glucocorticoid therapy. Another presented with an even rarer post-partum form of painful thyroiditis.

  9. Current Concepts in the Mandibular Condyle Fracture Management Part II: Open Reduction Versus Closed Reduction

    Yang, Jung-Dug; Chung, Ho-Yun; Cho, Byung-Chae

    2012-01-01

    In the treatment of mandibular condyle fracture, conservative treatment using closed reduction or surgical treatment using open reduction can be used. Management of mandibular condylar fractures remains a source of ongoing controversy in oral and maxillofacial trauma. For each type of condylar fracture,the treatment method must be chosen taking into consideration the presence of teeth, fracture height, patient'sadaptation, patient's masticatory system, disturbance of occlusal function, and deviation of the mandible. In the past, closed reduction with concomitant active physical therapy conducted after intermaxillary fixation during the recovery period had been mainly used, but in recent years, open treatment of condylar fractures with rigid internal fixation has become more common. The objective of this review was to evaluate the main variables that determine the choice of an open or closed method for treatment of condylar fractures, identifying their indications, advantages, and disadvantages, and to appraise the current evidence regarding the effectiveness of interventions that are used in the management of fractures of the mandibular condyle. PMID:22872831

  10. Organ Preservation: Current Concepts and New Strategies for the Next Decade

    Guibert, Edgardo E.; Petrenko, Alexander Y.; Balaban, Cecilia L.; Somov, Alexander Y.; Rodriguez, Joaquín V.; Fuller, Barry J.

    2011-01-01

    Summary Organ transplantation has developed over the past 50 years to reach the sophisticated and integrated clinical service of today through several advances in science. One of the most important of these has been the ability to apply organ preservation protocols to deliver donor organs of high quality, via a network of organ exchange to match the most suitable recipient patient to the best available organ, capable of rapid resumption of life-sustaining function in the recipient patient. This has only been possible by amassing a good understanding of the potential effects of hypoxic injury on donated organs, and how to prevent these by applying organ preservation. This review sets out the history of organ preservation, how applications of hypothermia have become central to the process, and what the current status is for the range of solid organs commonly transplanted. The science of organ preservation is constantly being updated with new knowledge and ideas, and the review also discusses what innovations are coming close to clinical reality to meet the growing demands for high quality organs in transplantation over the next few years. PMID:21566713

  11. Current Concepts in the Mandibular Condyle Fracture Management Part II: Open Reduction Versus Closed Reduction

    Kang-Young Choi

    2012-07-01

    Full Text Available In the treatment of mandibular condyle fracture, conservative treatment using closedreduction or surgical treatment using open reduction can be used. Management of mandibularcondylar fractures remains a source of ongoing controversy in oral and maxillofacial trauma.For each type of condylar fracture,the treatment method must be chosen taking intoconsideration the presence of teeth, fracture height, patient’sadaptation, patient’s masticatorysystem, disturbance of occlusal function, and deviation of the mandible. In the past, closedreduction with concomitant active physical therapy conducted after intermaxillary fixationduring the recovery period had been mainly used, but in recent years, open treatment ofcondylar fractures with rigid internal fixation has become more common. The objectiveof this review was to evaluate the main variables that determine the choice of an open orclosed method for treatment of condylar fractures, identifying their indications, advantages,and disadvantages, and to appraise the current evidence regarding the effectiveness ofinterventions that are used in the management of fractures of the mandibular condyle.

  12. Current Concepts in the Mandibular Condyle Fracture Management Part II: Open Reduction Versus Closed Reduction

    Kang-Young Choi

    2012-07-01

    Full Text Available In the treatment of mandibular condyle fracture, conservative treatment using closed reduction or surgical treatment using open reduction can be used. Management of mandibular condylar fractures remains a source of ongoing controversy in oral and maxillofacial trauma. For each type of condylar fracture,the treatment method must be chosen taking into consideration the presence of teeth, fracture height, patient'sadaptation, patient's masticatory system, disturbance of occlusal function, and deviation of the mandible. In the past, closed reduction with concomitant active physical therapy conducted after intermaxillary fixation during the recovery period had been mainly used, but in recent years, open treatment of condylar fractures with rigid internal fixation has become more common. The objective of this review was to evaluate the main variables that determine the choice of an open or closed method for treatment of condylar fractures, identifying their indications, advantages, and disadvantages, and to appraise the current evidence regarding the effectiveness of interventions that are used in the management of fractures of the mandibular condyle.

  13. Current Concepts in Diabetes Mellitus and Chronic Liver Disease: Clinical Outcomes, Hepatitis C Virus Association, and Therapy.

    García-Compeán, Diego; González-González, José Alberto; Lavalle-González, Fernando Javier; González-Moreno, Emmanuel Irineo; Villarreal-Pérez, Jesús Zacarías; Maldonado-Garza, Héctor J

    2016-02-01

    Hereditary type 2 diabetes mellitus is a risk factor for chronic liver disease, and ~30 % of patients with liver cirrhosis develop diabetes. Diabetes mellitus has been associated with cirrhotic and non-cirrhotic hepatitis C virus liver infection, can aggravate the course the liver infection, and can induce a lower sustained response to antiviral treatment. Evidences that HCV may induce metabolic and autoimmune disturbances leading to hypobetalipoproteinemia, steatosis, insulin resistance, impaired glucose tolerance, thyroid disease, and gonadal dysfunction have been found. Prospective studies have demonstrated that diabetes increases the risk of liver complications and death in patients with cirrhosis. However, treatment of diabetes in these patients is complex, as antidiabetic drugs can promote hypoglycemia and lactic acidosis. There have been few therapeutic studies evaluating antidiabetic treatments in patients with liver cirrhosis published to date; thus, the optimal treatment for diabetes and the impact of treatment on morbidity and mortality are not clearly known. As numbers of patients with chronic liver disease and diabetes mellitus are increasing, largely because of the global epidemics of obesity and nonalcoholic fatty liver disease, evaluation of treatment options is becoming more important. This review discusses new concepts on hepatogenous diabetes, the diabetes mellitus–hepatitis C virus association, and clinical implications of diabetes mellitus in patients with chronic liver disease. In addition, the effectiveness and safety of old and new antidiabetic drugs, including incretin-based therapies, will be described.

  14. Rapid assessment of health needs in mass emergencies: review of current concepts and methods.

    Guha-Sapir, D

    1991-01-01

    The increase in the number of natural disasters and their impact on population is of growing concern to countries at risk and agencies involved in health and humanitarian action. The numbers of persons killed or disabled as a result of earthquakes, cyclones, floods and famines have reached record levels in the last decade. Population density, rampant urbanization and climatic changes have brought about risk patterns that are exposing larger and larger sections of populations in developing countries to life-threatening natural disasters. Despite substantial spending on emergency relief, the approaches to relief remain largely ad hoc and amateurish, resulting generally in inappropriate and/or delayed action. In recent years, mass emergencies of the kind experienced in Bangladesh or the Sahelian countries have highlighted the importance of rapid assessment of health needs for better allocation of resources and relief management. As a result, the development of techniques for rapid assessment of health needs has been identified as a priority for effective emergency action. This article sketches the health context of disasters in terms of mortality and morbidity patterns; it describes initial assessment techniques currently used and their methodological biases and constraints; it also discusses assessment needs which vary between different types of disasters and the time frame within which assessments are undertaken. Earthquakes, cyclones, famines, epidemics or refugees all have specific risk profiles and emergency conditions which differ for each situation. Vulnerability to mortality changes according to age and occupation, for earthquakes and famines. These risk factors then have significant implications for the design of rapid assessment protocols and checklists. Experiences from the field in rapid survey techniques and estimation of death rates are discussed, with emphasis on the need for a reliable denominator even for the roughest assessment. Finally, the

  15. Tribology and total hip joint replacement: current concepts in mechanical simulation.

    Affatato, S; Spinelli, M; Zavalloni, M; Mazzega-Fabbro, C; Viceconti, M

    2008-12-01

    Interest in the rheology and effects of interacting surfaces is as ancient as man. This subject can be represented by a recently coined word: tribology. This term is derived from the Greek word "tribos" and means the "science of rubbing". Friction, lubrication, and wear mechanism in the common English language means the precise field of interest of tribology. Wear of total hip prosthesis is a significant clinical problem that involves, nowadays, a too high a number of patients. In order to acquire further knowledge on the tribological phenomena that involve hip prosthesis wear tests are conducted on employed materials to extend lifetime of orthopaedic implants. The most basic type of test device is the material wear machine, however, a more advanced one may more accurately reproduce some of the in vivo conditions. Typically, these apparatus are called simulators, and, while there is no absolute definition of a joint simulator, its description as a mechanical rig used to test a joint replacement, under conditions approximating those occurring in the human body, is acceptable. Simulator tests, moreover, can be used to conduct accelerated protocols that replicate/simulate particularly extreme conditions, thus establishing the limits of performance for the material. Simulators vary in their level of sophistication and the international literature reveals many interpretations of the design of machines used for joint replacement testing. This paper aims to review the current state of the art of the hip joint simulators worldwide. This is specified through a schematic overview by describing, in particular, constructive solutions adopted to reproduce in vivo conditions. An exhaustive commentary on the evolution and actually existing simulation standards is proposed by the authors. The need of a shared protocol among research laboratories all over the world could lead to a consensus conference.

  16. First meeting on the CRP 'standardized high current solid targets for cyclotron production of diagnostic and therapeutic radionuclides'

    Winkel, P. van den

    2000-01-01

    The Cyclotron Department of the VUB has three groups performing research in the field of target development, production of radionuclides and their application in nuclear medicine. 1. The Physics Group is busy on the optimization of beam parameters, on the determination of cross sections and on neutron spectrometry. 2. The Inorganic Radiochemistry Group performs research on solid target electroplating (Tl, Zn, Cd, Rh ... ), on optimisation of target carrier geometry and cooling and on automated PC-controlled radiochemistry (Tl-201, Ga-67, In-111) and recovery systems and the associated software written in Modula-2 and Visual Basic. 3. The Organic Radiochemistry Group develops new techniques for radiolabelling of organic molecules (fatty acids, neuroleptics, synthetic polypeptides...) useful in diagnostic and therapeutic nuclear medicine. All three groups take part in bulk productions of radionuclides

  17. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Catherine Tomaro-Duchesneau

    2013-01-01

    Full Text Available Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed.

  18. Microencapsulation for the Therapeutic Delivery of Drugs, Live Mammalian and Bacterial Cells, and Other Biopharmaceutics: Current Status and Future Directions

    Saha, Shyamali; Malhotra, Meenakshi; Kahouli, Imen; Prakash, Satya

    2013-01-01

    Microencapsulation is a technology that has shown significant promise in biotherapeutics, and other applications. It has been proven useful in the immobilization of drugs, live mammalian and bacterial cells and other cells, and other biopharmaceutics molecules, as it can provide material structuration, protection of the enclosed product, and controlled release of the encapsulated contents, all of which can ensure efficient and safe therapeutic effects. This paper is a comprehensive review of microencapsulation and its latest developments in the field. It provides a comprehensive overview of the technology and primary goals of microencapsulation and discusses various processes and techniques involved in microencapsulation including physical, chemical, physicochemical, and other methods involved. It also summarizes the state-of-the-art successes of microencapsulation, specifically with regard to the encapsulation of microorganisms, mammalian cells, drugs, and other biopharmaceutics in various diseases. The limitations and future directions of microencapsulation technologies are also discussed. PMID:26555963

  19. Current progress and future perspectives in the development of anti-polo-like kinase 1 therapeutic agents [version 1; referees: 4 approved

    Jung-Eun Park

    2017-06-01

    Full Text Available Although significant levels of side effects are often associated with their use, microtubule-directed agents that primarily target fast-growing mitotic cells have been considered to be some of the most effective anti-cancer therapeutics. With the hope of developing new-generation anti-mitotic agents with reduced side effects and enhanced tumor specificity, researchers have targeted various proteins whose functions are critically required for mitotic progression. As one of the highly attractive mitotic targets, polo-like kinase 1 (Plk1 has been the subject of an extensive effort for anti-cancer drug discovery. To date, a variety of anti-Plk1 agents have been developed, and several of them are presently in clinical trials. Here, we will discuss the current status of generating anti-Plk1 agents as well as future strategies for designing and developing more efficacious anti-Plk1 therapeutics.

  20. The role of stress and beta-adrenergic system in melanoma: current knowledge and possible therapeutic options.

    Colucci, Roberta; Moretti, Silvia

    2016-05-01

    The aim of the present review was to discuss recent findings on the role of beta-adrenergic system in melanoma, in order to provide information on the biological responses elicited by its activation and its potential application for melanoma treatment. A literature search was performed, and evidences regarding the involvement of stress and beta-adrenergic system in cancer and melanoma were found and discussed. Our search pointed out that beta-adrenergic system is a key regulator of important biological processes involved in the onset and progression of some solid tumors. In the last decade, functional beta-adrenoceptors have been also identified on melanoma cells, as well as on their microenvironment cells. Similarly to other common cancers too, the activation of such adrenoceptors by catecholamines, usually released under stress conditions, has been found to trigger pro-tumorigenic pathways contributing to cell proliferation and motility, immune system regulation, apoptosis, epithelial-mesenchymal transition, invasion and neoangiogenesis. The biological evidences we found clarify and sustain the clinical evidences reporting the involvement of chronic stress in melanoma onset and progression. In such scenario, it is conceivable that a therapeutic approach targeting beta-adrenergic system could constitute a novel and promising strategy for melanoma treatment.

  1. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  2. An Official American Thoracic Society Research Statement : Current Challenges Facing Research and Therapeutic Advances in Airway Remodeling

    Prakash, Y S; Halayko, Andrew J; Gosens, Reinoud; Panettieri Jr., Reynold A; Camoretti-Mercado, Blanca; Penn, Raymond B; Burgess, Janette K

    2017-01-01

    BACKGROUND: Airway remodeling (AR) is a prominent feature of asthma and other obstructive lung diseases that is minimally affected by current treatments. The goals of this Official American Thoracic Society (ATS) Research Statement are to discuss the scientific, technological, economic, and

  3. Neuropathic pain - Current concepts

    Department of Family Medicine, University of Pretoria and Kalafong Hospital ... The aim of treatment is to assist the patient in managing the pain and to improve function ..... The incidence of true addiction to strong opioids in the management.

  4. Percutaneous nephrolithotomy: Current concepts

    Fabio C Vicentini

    2009-01-01

    Although the evolution of the technique in the last 20 years, urologists must continue to improve their skills and develop new technologies to offer to the patients more and more a safe and effective option to treat large renal stones.

  5. Current Concepts of Bruxism.

    Manfredini, Daniele; Serra-Negra, Junia; Carboncini, Fabio; Lobbezoo, Frank

    Bruxism is a common phenomenon, and emerging evidence suggests that biologic, psychologic, and exogenous factors have greater involvement than morphologic factors in its etiology. Diagnosis should adopt the grading system of possible, probable, and definite. In children, it could be a warning sign of certain psychologic disorders. The proposed mechanism for the bruxism-pain relationship at the individual level is that stress sensitivity and anxious personality traits may be responsible for bruxism activities that may lead to temporomandibular pain, which in turn is modulated by psychosocial factors. A multiple-P (plates, pep talk, psychology, pills) approach involving reversible treatments is recommended, and adult prosthodontic management should be based on a common-sense cautionary approach.

  6. Laparoscopic splenectomy: Current concepts

    Misiakos, Evangelos P; Bagias, George; Liakakos, Theodore; Machairas, Anastasios

    2017-01-01

    Since early 1990’s, when it was inaugurally introduced, laparoscopic splenectomy has been performed with excellent results in terms of intraoperative and postoperative complications. Nowadays laparoscopic splenectomy is the approach of choice for both benign and malignant diseases of the spleen. However some contraindications still apply. The evolution of the technology has allowed though, cases which were considered to be absolute contraindications for performing a minimal invasive procedure to be treated with modified laparoscopic approaches. Moreover, the introduction of advanced laparoscopic tools for ligation resulted in less intraoperative complications. Today, laparoscopic splenectomy is considered safe, with better outcomes in comparison to open splenectomy, and the increased experience of surgeons allows operative times comparable to those of an open splenectomy. In this review we discuss the indications and the contraindications of laparoscopic splenectomy. Moreover we analyze the standard and modified surgical approaches, and we evaluate the short-term and long-term outcomes. PMID:28979707

  7. Amide proton transfer imaging in clinics: Basic concepts and current and future use in brain tumors and stoke

    Park, Ji Eun [Dept. of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul (Korea, Republic of); Jahng, Geon Ho [Dept. of Radiology, Kyung Hee University Hospital at Gangdong, College of Medicine, Kyung Hee University, Seoul (Korea, Republic of); Jeong, Ha Kyu [Philips Korea, Seoul (Korea, Republic of)

    2016-12-15

    Amide proton transfer (APT) imaging is gaining attention as a relatively new in vivo molecular imaging technique that has higher sensitivity and spatial resolution than magnetic resonance spectroscopy imaging. APT imaging is a subset of the chemical exchange saturation transfer mechanism, which can offer unique image contrast by selectively saturating protons in target molecules that get exchanged with protons in bulk water. In this review, we describe the basic concepts of APT imaging, particularly with regard to the benefit in clinics from the current literature. Clinical applications of APT imaging are described from two perspectives: in the diagnosis and monitoring of the treatment response in brain glioma by reflecting endogenous mobile proteins and peptides, and in the potential for stroke imaging with respect to tissue acidity.

  8. Moored current meter and wind recorder measurement near Point Conception, California: The 1983 OPUS Observations, from 1983-04-01 to 1983-07-29 (NODC Accession 8600041)

    National Oceanic and Atmospheric Administration, Department of Commerce — The OPUS (Organization of Persistent Upwelling Structures) program deployed two current meter (VMCM) moorings near Point Conception, California, during April - July...

  9. Hydroxychloroquine reduces heart rate by modulating the hyperpolarization-activated current If: Novel electrophysiological insights and therapeutic potential

    Capel, Rebecca A.; Herring, Neil; Kalla, Manish; Yavari, Arash; Mirams, Gary R.; Douglas, Gillian; Bub, Gil; Channon, Keith; Paterson, David J.; Terrar, Derek A.; Burton, Rebecca-Ann B.

    2015-01-01

    Background Bradycardic agents are of interest for the treatment of ischemic heart disease and heart failure, as heart rate is an important determinant of myocardial oxygen consumption. Objectives The purpose of this study was to investigate the propensity of hydroxychloroquine (HCQ) to cause bradycardia. Methods We assessed the effects of HCQ on (1) cardiac beating rate in vitro (mice); (2) the “funny” current (If) in isolated guinea pig sinoatrial node (SAN) myocytes (1, 3, 10 µM); (3) heart rate and blood pressure in vivo by acute bolus injection (rat, dose range 1–30 mg/kg), (4) blood pressure and ventricular function during feeding (mouse, 100 mg/kg/d for 2 wk, tail cuff plethysmography, anesthetized echocardiography). Results In mouse atria, spontaneous beating rate was significantly (P < .05) reduced (by 9% ± 3% and 15% ± 2% at 3 and 10 µM HCQ, n = 7). In guinea pig isolated SAN cells, HCQ conferred a significant reduction in spontaneous action potential firing rate (17% ± 6%, 1 μM dose) and a dose-dependent reduction in If (13% ± 3% at 1 µM; 19% ± 2% at 3 µM). Effects were also observed on L-type calcium ion current (ICaL) (12% ± 4% reduction) and rapid delayed rectifier potassium current (IKr) (35% ± 4%) at 3 µM. Intravenous HCQ decreased heart rate in anesthetized rats (14.3% ± 1.1% at 15mg/kg; n = 6) without significantly reducing mean arterial blood pressure. In vivo feeding studies in mice showed no significant change in systolic blood pressure nor left ventricular function. Conclusions We have shown that HCQ acts as a bradycardic agent in SAN cells, in atrial preparations, and in vivo. HCQ slows the rate of spontaneous action potential firing in the SAN through multichannel inhibition, including that of If. PMID:26025323

  10. Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

    Renato De Vecchis

    2016-10-01

    Full Text Available In the congestive heart failure (CHF setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

  11. Current concepts on oxidative/carbonyl stress, inflammation and epigenetics in pathogenesis of chronic obstructive pulmonary disease

    Yao Hongwei; Rahman, Irfan

    2011-01-01

    Chronic obstructive pulmonary disease (COPD) is a global health problem. The current therapies for COPD are poorly effective and the mainstays of pharmacotherapy are bronchodilators. A better understanding of the pathobiology of COPD is critical for the development of novel therapies. In the present review, we have discussed the roles of oxidative/aldehyde stress, inflammation/immunity, and chromatin remodeling in the pathogenesis of COPD. An imbalance of oxidants/antioxidants caused by cigarette smoke and other pollutants/biomass fuels plays an important role in the pathogenesis of COPD by regulating redox-sensitive transcription factors (e.g., NF-κB), autophagy and unfolded protein response leading to chronic lung inflammatory response. Cigarette smoke also activates canonical/alternative NF-κB pathways and their upstream kinases leading to sustained inflammatory response in lungs. Recently, epigenetic regulation has been shown to be critical for the development of COPD because the expression/activity of enzymes that regulate these epigenetic modifications have been reported to be abnormal in airways of COPD patients. Hence, the significant advances made in understanding the pathophysiology of COPD as described herein will identify novel therapeutic targets for intervention in COPD.

  12. INVASIVE CANDIDA INFECTIONS IN PATIENTS WITH HAEMATOLOGICAL MALIGNANCIES AND HEMATOPOIETIC STEM CELL TRANSPLANT RECIPIENTS: CURRENT EPIDEMIOLOGY AND THERAPEUTIC OPTIONS.

    Corrado Girmenia

    2011-03-01

    Full Text Available In the last decades, the global epidemiological impact of invasive candidiasis (IC in patients with hematologic malignancies (HM and in hematopoietic stem cell transplant (HSCT recipients has decreased and the incidence of invasive aspergillosis  exceeded that of Candida infections. The use of prevention strategies, first of all antifungal prophylaxis with triazoles,  contributed to the reduction of IC in these populations as demonstrated by several  epidemiological studies. However, relatively little is known about the current epidemiological patterns of IC in HM and HSCT populations, because recent epidemiological data almost exclusively derive from retrospective experiences and few prospective data are available. Several prospective, controlled studies in the prophylaxis of invasive fungal diseases have been conducted in both the HM and HSCT setting. On the contrary, most of the prospective controlled trials that demonstrated the efficacy of the antifungal drugs echinocandins and voriconazole in the treatment of candidemia and invasive candidiasis mainly involved  patients with underlying conditions other than HM or  HSCT.  For these reasons, international guidelines provided specific indications for the prophylaxis strategies in HM and HSCT patients, whereas the  recommendations on therapy of documented Candida infections are based on the results observed in the general population and should be considered with caution.

  13. A Systemic View of the Learning and Differentiation of Scientific Concepts: The Case of Electric Current and Voltage Revisited

    Koponen, Ismo T.; Kokkonen, Tommi

    2014-01-01

    In learning conceptual knowledge in physics, a common problem is the incompleteness of a learning process, where students' personal, often undifferentiated concepts take on more scientific and differentiated form. With regard to such concept learning and differentiation, this study proposes a systemic view in which concepts are considered as…

  14. Modulation of the activity of N-methyl-D-aspartate receptors as a novel treatment option for depression: current clinical evidence and therapeutic potential of rapastinel (GLYX-13

    Vasilescu AN

    2017-03-01

    Full Text Available Andrei-Nicolae Vasilescu,1,* Nina Schweinfurth,2,* Stefan Borgwardt,2,* Peter Gass,1 Undine E Lang,2,* Dragos Inta,1,2,* Sarah Eckart2,* 1Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; 2Department of Psychiatry (Universitäre Psychiatrische Kliniken, University of Basel, Basel, Switzerland *These authors contributed equally to this work Abstract: Classical monoaminergic antidepressants show several disadvantages, such as protracted onset of therapeutic action. Conversely, the fast and sustained antidepressant effect of the N-methyl-d-aspartate receptor (NMDAR antagonist ketamine raises vast interest in understanding the role of the glutamate system in mood disorders. Indeed, numerous data support the existence of glutamatergic dysfunction in major depressive disorder (MDD. Drawback to this short-latency therapy is its side effect profile, especially the psychotomimetic action, which seriously hampers the common and widespread clinical use of ketamine. Therefore, there is a substantial need for alternative glutamatergic antidepressants with milder side effects. In this article, we review evidence that implicates NMDARs in the prospective treatment of MDD with focus on rapastinel (formerly known as GLYX-13, a novel synthetic NMDAR modulator with fast antidepressant effect, which acts by enhancing NMDAR function as opposed to blocking it. We summarize and discuss current clinical and animal studies regarding the therapeutic potential of rapastinel not only in MDD but also in other psychiatric disorders, such as obsessive–compulsive disorder and posttraumatic stress disorder. Additionally, we discuss current data concerning the molecular mechanisms underlying the antidepressant effect of rapastinel, highlighting common aspects as well as differences to ketamine. In 2016, rapastinel received the Breakthrough Therapy designation for the treatment

  15. A brief overview of current relationships of geography, statistics, and taxonomy with the classical integrated control concept

    A classic paper on the integrated control concept appeared in the later part of the 1950’s, led by Vernon Stern, Ray Smith, Robert van den Bosch, and Kenneth Hagen. Numerous concepts and definitions were formulated at that time. In this presentation, a short philosophical summary will be presented...

  16. New concepts of nuclear reactors and fuel cycles: performing agile technometric studies to understand the promises and the current reality

    Reis Junior, Jose S.B.; Barroso, Antonio C.O., E-mail: jsreis@ipen.br, E-mail: barroso@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    The progress of previous projects pointed out the need to face some problems of software for detecting emerging research and development trends from databases of scientific publication. Given the lack of efficient computing applications dedicated to this purpose that we consider to be an artifact of great usefulness to better planning R and D programs in institutions, which are obliged to manage and develop, with limited resources and within the realm of complex and multidisciplinary technology fields as is the case of the Brazilian nuclear sector. We performed a review of the currently available software in such a way that we could clearly delineate the opportunity to develop new tools. As a result, we developed a software called Cite snake, which was especially designed to help the detection and study of emerging trends from the analysis of networks of various types extracted from the scientific databases. Using this powerful and stable computational tool, we performed preliminary analyzes of emerging research and development trends in a few thematic fields. The case that concerns this paper is the one devoted to the eld of Generation IV Nuclear Power Generation Systems. We analyzed the productivity of authors, co-authorship networks, co-citation networks, development structure and emerging sub-areas of research. The idea was to nd what reactors and fuel cycles have evolved more over the past ten years, in such a way to compare the what from the most promising concepts selected from the Generation Four Initiative have better evolved to fulfill some of their promises. (author)

  17. New concepts of nuclear reactors and fuel cycles: performing agile technometric studies to understand the promises and the current reality

    Reis Junior, Jose S.B.; Barroso, Antonio C.O.

    2013-01-01

    The progress of previous projects pointed out the need to face some problems of software for detecting emerging research and development trends from databases of scientific publication. Given the lack of efficient computing applications dedicated to this purpose that we consider to be an artifact of great usefulness to better planning R and D programs in institutions, which are obliged to manage and develop, with limited resources and within the realm of complex and multidisciplinary technology fields as is the case of the Brazilian nuclear sector. We performed a review of the currently available software in such a way that we could clearly delineate the opportunity to develop new tools. As a result, we developed a software called Cite snake, which was especially designed to help the detection and study of emerging trends from the analysis of networks of various types extracted from the scientific databases. Using this powerful and stable computational tool, we performed preliminary analyzes of emerging research and development trends in a few thematic fields. The case that concerns this paper is the one devoted to the eld of Generation IV Nuclear Power Generation Systems. We analyzed the productivity of authors, co-authorship networks, co-citation networks, development structure and emerging sub-areas of research. The idea was to nd what reactors and fuel cycles have evolved more over the past ten years, in such a way to compare the what from the most promising concepts selected from the Generation Four Initiative have better evolved to fulfill some of their promises. (author)

  18. Effective translation of current dietary guidance: understanding and communicating the concepts of minimal and optimal levels of dietary protein.

    Rodriguez, Nancy R; Miller, Sharon L

    2015-04-29

    Dietitians and health care providers have critical roles in the translation of the dietary guidance to practice. The protein content of diets for adults can be based on the Recommended Dietary Allowance (RDA) of 0.80 g/kg per day. Alternatively, the most recent Dietary Reference Intakes (DRIs) for macronutrients reflect expanded guidance for assessing protein needs and consider the relative relation of absolute amounts of protein, carbohydrate, and fat to total energy intake in the context of chronic disease prevention. The Acceptable Macronutrient Distribution Range (AMDR) reflects the interrelation between the macronutrients and affords dietitians and clinicians additional flexibility in diet planning. Accounting for the caloric value of RDAs for carbohydrate and fat, "flexible calories" emerge as an opportunity to create varied eating plans that provide for protein intakes in excess of the RDA but within the AMDR. Protein Summit 2.0 highlighted the growing body of scientific evidence documenting the benefits of higher protein intakes at amounts approximating twice the RDA, which include promotion of healthy body weight and preservation of lean body mass and functional ability with age. The essential amino acid (EAA) density of a food also emerged as a novel concept analogous to "nutrient density," which can enable the practitioner to calculate the caloric cost associated with a specific protein source to attain the daily requirement of EAAs to accomplish various health outcomes because these indispensable nutrients have a significant role in protein utilization and metabolic regulation. Tailoring recommendations unique to an individual's varying goals and needs remains a challenge. However, flexibility within the application of DRIs to include consideration of the AMDR provides a sound framework to guide practitioners in effective translation of current dietary guidance with a specific regard for the documented benefits of higher protein intakes. © 2015

  19. Level conceptual change pre-service elementary teachers on electric current conceptions through visual multimedia supported conceptual change

    Hermita, N.; Suhandi, A.; Syaodih, E.; Samsudin, A.; Marhadi, H.; Sapriadil, S.; Zaenudin, Z.; Rochman, C.; Mansur, M.; Wibowo, F. C.

    2018-05-01

    Now a day, conceptual change is the most valuable issues in the science education perspective, especially in the elementary education. Researchers have already dialed with the aim of the research to increase level conceptual change process on the electric conceptions through Visual Multimedia Supported Conceptual Change Text (VMMSCCText). We have ever utilized research and development method namely 3D-1I stands for Define, Design, Development, and Implementation. The 27 pre-service elementary teachers were involved in the research. The battery function in circuit electric conception is the futuristic concept which should have been learned by the students. Moreover, the data which was collected reports that static about 0%, disorientation about 0%, reconstruction about 55.6%, and construction about 25.9%. It can be concluded that the implementation of VMMSCCText to pre-service elementary teachers are increased to level conceptual change categories.

  20. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

    Rooney, Terence

    2012-02-01

    OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

  1. New concepts in sickle cell anemia | Chiabi | Clinics in Mother and ...

    New concepts in sickle cell anemia. ... Abstract. Current knowledge on the pathophysiology of sickle cell anemia is reviewed and potential therapeutic options are reviewed and ... Clinics in Mother and Child Health Vol. ... HOW TO USE AJOL.

  2. Understanding Key Mechanisms of Exercise-Induced Cardiac Protection to Mitigate Disease: Current Knowledge and Emerging Concepts.

    Bernardo, Bianca C; Ooi, Jenny Y Y; Weeks, Kate L; Patterson, Natalie L; McMullen, Julie R

    2018-01-01

    The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation. This includes cardiac excitation and contraction, mitochondrial adaptations, cellular stress responses to promote survival (heat shock response, ubiquitin-proteasome system, autophagy-lysosomal system, endoplasmic reticulum unfolded protein response, DNA damage response), extracellular matrix, inflammatory response, and organ-to-organ crosstalk. We summarize therapeutic strategies targeting known regulators of exercise-induced protection and the challenges translating findings from bench to bedside. We conclude that technological advancements that allow for in-depth profiling of the genome, transcriptome, proteome and metabolome, combined with animal and human studies, provide new opportunities for comprehensively defining the signaling and regulatory aspects of cell/organelle functions that underpin the protective properties of exercise. This is likely to lead to the identification of novel biomarkers and therapeutic targets for heart disease.

  3. A critical comparison of the current view of Ca signaling with the novel concept of F-actin-based Ca signaling.

    Lange, Klaus; Gartzke, Joachim

    2006-01-01

    A detailed comparative survey on the current idea of Ca signaling and the alternative concept of F-actin-based Ca signaling is given. The two hypotheses differ in one central aspect - the mechanism of Ca storage. The current theory rests on the assumption of Ca-accumulating vesicles derived from the endoplasmic/ sarcoplasmic reticulum, which are equipped with an ATP-dependent Ca pump and IP3- or ryanodine-sensitive Ca-release channels/receptors. The alternative hypothesis proceeds from the idea of Ca storage at the high-affinity binding sites of F-actin subunits. Several prominent features of Ca signaling, which are not adequately described by the current concept, are inherent properties of the F-actin system and its dynamic state of treadmilling. F-actin is the only known biological Ca-binding system that has been proven by in vitro experiments to work within the physiological range of Ca concentrations and the only system that meets all necessary conditions to function as receptor-operated Ca store and as a coupling device between the Ca store and the store-operated Ca influx pathway. The most important properties of Ca signaling, such as store-channel coupling, quantal Ca release, spiking and oscillations, biphasic and "phasic" uptake kinetics, and Ca-induced Ca release, turn out to be systematic features of the new concept but remain unexplained by the classical vesicle storage hypothesis. A number of novel findings, specifically recent reports about direct effects of actin-specific toxins on Ca stores, have strengthened the new concept. The concept of F-actin-based Ca signaling combined with the notion of microvillar regulation of ion and substrate fluxes opens new aspects and far-reaching consequences, not only for cellular Ca signaling but also for various other cell functions, and represents an opportunity to connect several fields of cell physiology on the basis of a common mechanism.

  4. Policies for Resource Efficient and Effective Solutions : A review of concepts, current policy landscape and future policy considerations for the transition to a Circular Economy

    Milios, Leonidas

    2016-01-01

    This report presents basic concepts around resources, resource efficiency and the Circular Economy. The limitations and the opportunities within the Circular Economy are identified and clearly presented. The current policy landscape in the EU as well as in Sweden is thoroughly analysed and a set of policy areas with a significant untapped potential for resource efficiency is identified. The policy areas which have been underutilised so far include policies for re-use, repair and remanufacturi...

  5. Cystic Fibrosis Transmembrane Conductance Regulator Potentiation as a Therapeutic Strategy for Pulmonary Edema: A Proof-of-Concept Study in Pigs.

    Li, Xiaopeng; Vargas Buonfiglio, Luis G; Adam, Ryan J; Stoltz, David A; Zabner, Joseph; Comellas, Alejandro P

    2017-12-01

    To determine the feasibility of using a cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor (VX-770/Kalydeco, Vertex Pharmaceuticals, Boston, MA), as a therapeutic strategy for treating pulmonary edema. Prospective laboratory animal investigation. Animal research laboratory. Newborn and 3 days to 1 week old pigs. Hydrostatic pulmonary edema was induced in pigs by acute volume overload. Ivacaftor was nebulized into the lung immediately after volume overload. Grams of water per grams of dry lung tissue were determined in the lungs harvested 1 hour after volume overload. Ivacaftor significantly improved alveolar liquid clearance in isolated pig lung lobes ex vivo and reduced edema in a volume overload in vivo pig model of hydrostatic pulmonary edema. To model hydrostatic pressure-induced edema in vitro, we developed a method of applied pressure to the basolateral surface of alveolar epithelia. Elevated hydrostatic pressure resulted in decreased cystic fibrosis transmembrane conductance regulator activity and liquid absorption, an effect which was partially reversed by cystic fibrosis transmembrane conductance regulator potentiation with ivacaftor. Cystic fibrosis transmembrane conductance regulator potentiation by ivacaftor is a novel therapeutic approach for pulmonary edema.

  6. Metal is not inert: role of metal ions released by biocorrosion in aseptic loosening--current concepts.

    Cadosch, Dieter; Chan, Erwin; Gautschi, Oliver P; Filgueira, Luis

    2009-12-15

    Metal implants are essential therapeutic tools for the treatment of bone fractures and joint replacements. The metals and metal alloys used in contemporary orthopedic and trauma surgery are well tolerated by the majority of patients. However, complications resulting from inflammatory and immune reactions to metal implants have been well documented. This review briefly discusses the different mechanisms of metal implant corrosion in the human body, which lead to the release of significant levels of metal ions into the peri-implant tissues and the systemic blood circulation. Additionally, this article reviews the effects of the released ions on bone metabolism and the immune system and discusses their involvement in the pathophysiological mechanisms of aseptic loosening and metal hypersensitivity in patients with metal implants.

  7. Therapeutic cloning in the mouse

    Mombaerts, Peter

    2003-01-01

    Nuclear transfer technology can be applied to produce autologous differentiated cells for therapeutic purposes, a concept termed therapeutic cloning. Countless articles have been published on the ethics and politics of human therapeutic cloning, reflecting the high expectations from this new opportunity for rejuvenation of the aging or diseased body. Yet the research literature on therapeutic cloning, strictly speaking, is comprised of only four articles, all in the mouse. The efficiency of derivation of embryonic stem cell lines via nuclear transfer is remarkably consistent among these reports. However, the efficiency is so low that, in its present form, the concept is unlikely to become widespread in clinical practice. PMID:12949262

  8. The integrated control concept and its relevance to current integrated pest management in California fresh market grapes.

    Bentley, Walter J

    2009-12-01

    The foundation of an integrated pest management program involves valid treatment thresholds, accurate and simple monitoring methods, effective natural controls, selective pesticides and trained individuals who can implement the concept. The Integrated Control Concept written by Stern, Smith, van den Bosch and Hagen elucidated each of these points in an alfalfa ecosystem. Alfalfa hay (Medicago sativa L.) has a low per acre value, requires little hand labor and is primarily marketed in the USA. In contrast, fresh market table grape (Vitis vinifera L.) has a high per acre value, requires frequent hand labor operations, suffers unacceptable cosmetic damage and is marketed throughout both the USA and the world. Each of the components of a working IPM program is present in table grape production. Marketing grapes to foreign countries presents special problems with pests considered invasive and where residue tolerances for some selective insecticides are lacking. However, fresh market grape farmers are still able to deal with these special problems and utilize an IPM program that has resulted in a 42% reduction in broad-spectrum insecticide use from 1995 to 2007. (c) 2009 Society of Chemical Industry.

  9. [The current conception of the unconscious - empirical results of neurobiology, cognitive sciences, social psychology and emotion research].

    Schüssler, Gerhard

    2002-01-01

    The influence of the unconscious on psychosomatic medicine and psychotherapy: a comprehensive concept of unconscious processes based on empirical evidence. The theory of the Unconscious constitutes the basis of psychoanalysis and of psychodynamic therapy. The traditional description of the Unconscious as given by Freud is of historical significance and not only gained widespread acceptance but also attracted much criticism. The most important findings of neurobiology, the cognitive sciences, social psychology and emotion research in relation to the Unconscious are compared with this traditional definition. Empirical observations on defence mechanisms are of particular interest in this context. A comprehensive concept of unconscious processes is revealed: the fundamental process of brain function is unconscious. Parts of the symbolic-declarative and emotional-procedural processing by the brain are permanently unconscious. Other parts of these processing procedures are conscious or can be brought to the conscious or alternatively, can also be excluded from the conscious. Unconscious processes exert decisive influence on experience and behaviour; for this reason, every form of psychotherapy should take into account such unconscious processes.

  10. Narcotic analgesic utilization amongst injured workers: using concept mapping to understand current issues from the perspectives of physicians and pharmacists

    Fortin Claire

    2011-10-01

    Full Text Available Abstract Background Work-related injuries result in considerable morbidity, as well as social and economic costs. Pain associated with these injuries is a complex, contested topic, and narcotic analgesics (NA remain important treatment options. Factors contributing to NA utilization patterns are poorly understood. This qualitative study sought to characterize the factors contributing to NA utilization amongst injured workers from the perspectives of physicians and pharmacists. Methods The study employed concept mapping methodology, a structured process yielding a conceptual framework of participants' views on a particular topic. A visual display of the ideas/concepts generated is produced. Eligible physicians and pharmacists (n = 22 serving injured workers in the province of Ontario (Canada were recruited via purposive sampling, and participated in concept mapping activities (consisting of brainstorming, sorting, rating, and map exploration. Participants identified factors influencing NA utilization, and sorted these factors into categories (clusters. Next, they rated the factors on two scales: 'strength of influence on NA over-utilization' and 'amenability to intervention'. During follow-up focus groups, participants refined the maps and discussed the findings and their implications. Results 82 factors were sorted into 7 clusters: addiction risks, psychosocial issues, social/work environment factors, systemic-third party factors, pharmacy-related factors, treatment problems, and physician factors. These clusters were grouped into 2 overarching categories/regions on the map: patient-level factors, and healthcare/compensation system-level factors. Participants rated NA over-utilization as most influenced by patient-level factors, while system-level factors were rated as most amenable to intervention. One system-level cluster was rated highly on both scales (treatment problems - e.g. poor continuity of care, poor interprofessional communication

  11. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

    Tucci S

    2010-05-01

    Full Text Available Sonia A Tucci, Emma J Boyland, Jason CG HalfordKissileff Laboratory for the Study of Human Ingestive Behaviour, School of Psychology, University of Liverpool, Liverpool, UKAbstract: Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon.Keywords: lipase, amylase, saccharidases, overweight, orlistat, Alli®, digestion, body weight

  12. Current concepts in combination therapy for the treatment of hypertension: combined calcium channel blockers and RAAS inhibitors

    Alberto F Rubio-Guerra

    2009-11-01

    Full Text Available Alberto F Rubio-Guerra1, David Castro-Serna2, Cesar I Elizalde Barrera2, Luz M Ramos-Brizuela21Metabolic and Research Clinic, 2Internal Medicine Department, Hospital General de Ticomán SS DF, MéxicoAbstract: Recent guidelines for the management of hypertension recommend target blood pressures <140/90 mmHg in hypertensive patients, or <130/80 mmHg in subjects with diabetes, chronic kidney disease, or coronary artery disease. Despite the availability and efficacy of antihypertensive drugs, most hypertensive patients do not reach the recommended treatment targets with monotherapy, making combination therapy necessary to achieve the therapeutic goal. Combination therapy with 2 or more agents is the most effective method for achieving strict blood pressure goals. Fixed-dose combination simplifies treatment, reduces costs, and improves adherence. There are many drug choices for combination therapy, but few data are available about the efficacy and safety of some specific combinations. Combination therapy of calcium antagonists and inhibitors of the renin-angiotensin-aldosterone system (RAAS are efficacious and safe, and have been considered rational by both the JNC 7 and the 2007 European Society of Hypertension – European Society of Cardiology guidelines for the management of arterial hypertension. The aim of this review is to discuss some relevant issues about the use of combinations with calcium channel blockers and RAAS inhibitors in the treatment of hypertension.Keywords: hypertension, calcium channel blockers, renin-angiotensin-aldosterone system inhibitors, fixed-dose combination, adherence

  13. [Current modalities and concepts on access and use of biospecimen samples and associated data for research from human biobanks].

    Siddiqui, Roman; Semler, Sebastian Claudius

    2016-03-01

    It is accepted worldwide that biospecimen and data sharing (BDS) play an essential role for the future of medical research to improve diagnostics and prognostics, e.g. by validated biomarkers. BDS is also pivotal to the development of new therapeutic treatments and for the improvement of population health. Human biobanks can generate an added value to this need by providing biospecimens and/or associated data to researchers. An inspection of several examples of epidemiological as well as clinical/disease-oriented biobanks in Germany shows that best practice procedures (BPP) that are internationally agreed on are being installed for biospecimen and/or data access. In general, fair access is aimed at requiring a written application by the requesting scientist, which is then peer-reviewed for scientific and ethical validity by the Biobank. Applied BPP take into account (i) patient education/agreement according to the informed consent model, (ii) privacy protection, (iii) intellectual property rights, the (iv) notification obligation of health-related findings (including incidental findings), the (v) use of material (MTA) and data transfer agreements (DTA) for mutual legal security, the avoidance of conflicts of interests, as well as for cost recovery/fee for service as a basis for sustainability of the biobank. BPP are rooted in the self-regulation efforts of life sciences and are supported by parent ethics committees in Germany. Central biobank registries displaying aggregated information on biospecimens stored and the research foci constitute an important tool to make biobanks that are scattered across the country visible to each other, and, can thus promote access to hitherto unknown biospecimen and data resources.

  14. Nonlinear State of Sausage-like Instability of Electron Current Channels in Fast Ignition Concept of Inertial Fusion

    Jain, Neeraj; Das, Amita; Kaw, Predhiman; Sengupta, Sudip

    2003-01-01

    This paper deals with a detailed fluid simulation study of linear and nonlinear aspects of the velocity shear modes in electron current channels in a two dimensional geometry. Simulation results clearly show the flattening of flow profile and the development of sausage like structures (kink structures, which are intrinsically three dimensional excitations, are ruled out in the present simulations) which grow linearly and eventually saturate by nonlinear effects. An analytic understanding of the nonlinear saturation mechanism is also provided

  15. Concept - or no concept

    Thorsteinsson, Uffe

    1999-01-01

    Discussion about concept in industrial companies. A method for mapping of managerial concept in specific area is shown......Discussion about concept in industrial companies. A method for mapping of managerial concept in specific area is shown...

  16. Diagnosed, identified, current and complete depression among patients attending primary care in southern Catalonia: different aspects of the same concept.

    Montesó-Curto, Pilar; Ferré-Grau, Carme; Lleixà-Fortuño, Mar; Albacar-Riobóo, Nuria; Lejeune, Marylene

    2014-02-01

    The aims of this study were to explore the prevalence and the conceptualizations of depression detected by the healthcare system, identified by the patient or classified/identified in the validated Goldberg's questionnaire in a community. We conducted a cross-sectional evaluation of 317 patients. The different types of depression diagnosed, identified, current or total were stratified by age and gender groups. The difference in the conceptualization of depression from the medical or ordinary people point of view indicate that depression care requires the understanding of the lifestyle, beliefs, attitudes, family and social networks of the people the physicians and nurses care for. © 2014.

  17. Current and future competitiveness of renewable energy carriers - Conceptions about competitiveness; Foernyelsebara energibaerares nuvarande och framtida konkurrenskraft - foerestaellningar om konkurrenskraft

    Lundgren, K.

    1998-05-01

    The dissertation draws attention to the fact that in the world today 80% of the resources that are used are limited - non renewable energy carriers - and because of the long time between planning and doing (carrying out) within the energy sector, it is worthwhile from the long-term perspective to steer early on towards more sustainable solutions, such as renewable energy carriers. The State and the market have begun to adjust to concepts such as `competitiveness`, which can be viewed as containing both feasibility and legitimacy aspects - the state through different regulations and environmental taxes and environmental fees, and actors on the market that marginally produce/choose renewable energy carriers. The overlying methodology in the dissertation is an actor`s viewpoint. This viewpoint brings forth, in turn, two different views, the analytical and the interpretative. The dissertation presents different stances within the energy sector: commercial production logic, commercial sustainability logic, and the socio-economic sustainability logic. By drawing one`s attention to how one has the possibility to create (enact) his own reality, it is possible to highlight how organisations can increase their competitiveness by being conscious of their own view and others, logic, which in turn forms their views about competitiveness, which in turn determines which projects will materialize. Enterprises and individuals create a description of reality together through a dialectic process, i.e. by developing an environmental management system that contains elements of environmental auditing, environmental performance indicators, and environmental labelling, which `reveal` the production conditions that lie behind the actualization of the final product. An example is the product, `green` electricity, which, in spite of the fact that the final product - electricity - is identical irrespective of the production method, just at the moment can be sold at different prices according

  18. The Brazilian equipment for photovoltaic systems industry: current concepts; A industria brasileira de equipamentos para sistemas fotovoltaicos: panorama atual

    Varella, Fabiana Karla de Oliveira Martins; Cavaliero, Carla Kazue Nakao [Universidade Estadual de Campinas (DE/FEM/UNICAMP), SP (Brazil). Fac. de Engenharia Mecanica. Dept. de Energia], e-mail: fkv@fem.unicamp.br, e-mail: cavaliero@fem.unicamp.br; Silva, Ennio Peres da [Universidade Estadual de Campinas (DFA/IFGW/UNICAMP), SP (Brazil). Inst. de Fisica Gleb Wataghin. Dept. de Fisica Aplicada], e-mail: lh2ennio@ifi.unicamp.br

    2008-07-01

    The use of renewable alternative sources of energy in the world has been growing in the last few decades due to concerns about dependence on fossil sources and to environmental reasons, related to climatic change and its effects on mankind. Tax and/or financial incentives have been instituted for the population, to have access to renewable source technologies, and for the local equipment industry, to develop more quickly. In Brazil, the PV (photovoltaic) equipment to convert solar into electricity is more often used in low income rural communities, located distant from the grid network. However, since there is no currently specific regulatory incentive mechanism for this source in the country, the Brazilian PV equipment industry has not made great advances and the market is largely dominated by multinationals. Against this background, this work has as objective to analyze the current PV equipment industry in Brazil, in such way that the obtained information can aid in a future elaboration of a national program development to promote the use of this technology, stimulating the domestic industry and reducing the dependence on imported equipment. (author)

  19. Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 1: Biologics Overview, Ligament Injury, Tendinopathy.

    LaPrade, Robert F; Geeslin, Andrew G; Murray, Iain R; Musahl, Volker; Zlotnicki, Jason P; Petrigliano, Frank; Mann, Barton J

    2016-12-01

    Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries. This series of current concepts reviews reports the summary of the scientific presentations, roundtable discussions, and recommendations from this think tank. © 2016 The Author(s).

  20. Low-level radioactive waste disposal in the United States: An overview of current commercial regulations and concepts

    Kennedy, W.E. Jr.

    1993-08-01

    Commercial low-level radioactive waste disposal in the United States is regulated by the US Nuclear Regulatory Commission (NRC) under 10 CFR 61 (1991). This regulation was issued in 1981 after a lengthy and thorough development process that considered the radionuclide concentrations and characteristics associated with commercial low-level radioactive waste streams; alternatives for waste classification; alternative technologies for low-level radioactive waste disposal; and data, modeling, and scenario analyses. The development process also included the publication of both draft and final environmental impact statements. The final regulation describes the general provisions; licenses; performance objectives; technical requirements for land disposal; financial assurances; participation by state governments and Indian tribes; and records, reports, tests, and inspections. This paper provides an overview of, and tutorial on, current commercial low-level radioactive waste disposal regulations in the United States

  1. The role of gene-environment interplay in occupational and environmental diseases: current concepts and knowledge gaps.

    Kwo, Elizabeth; Christiani, David

    2017-03-01

    The interplay between genetic susceptibilities and environmental exposures in the pathogenesis of a variety of diseases is an area of increased scientific, epidemiologic, and social interest. Given the variation in methodologies used in the field, this review aims to create a framework to help understand occupational exposures as they currently exist and provide a foundation for future inquiries into the biological mechanisms of the gene-environment interactions. Understanding of this complex interplay will be important in the context of occupational health, given the public health concerns surrounding a variety of occupational exposures. Studies found evidence that suggest genetics influence the progression of disease postberyllium exposure through genetically encoded major histocompatibility complex, class II, DP alpha 2 (HLA-DP2)-peptide complexes as it relates to T-helper cells. This was characterized at the molecular level by the accumulation of Be-responsive CD4 T cells in the lung, which resulted in posttranslational change in the HLA-DPB1 complex. These studies provide important evidence of gene-environment association, and many provide insights into specific pathogenic mechanisms. The following includes a review of the literature regarding gene-environment associations with a focus on pulmonary diseases as they relate to the workplace.

  2. Haematopoietic stem cell transplantation as first-line treatment in myeloma: a global perspective of current concepts and future possibilities

    Catriona Elizabeth Mactier

    2012-10-01

    Full Text Available Stem cell transplantation forms an integral part of the treatment for multiple myeloma. This paper reviews the current role of transplantation and the progress that has been made in order to optimize the success of this therapy. Effective induction chemotherapy is important and a combination regimen incorporating the novel agent bortezomib is now favorable. Adequate induction is a crucial adjunct to stem cell transplantation and in some cases may potentially postpone the need for transplant. Different conditioning agents prior to transplantation have been explored: high-dose melphalan is most commonly used and bortezomib is a promising additional agent. There is no well-defined superior transplantation protocol but single or tandem autologous stem cell transplantations are those most commonly used, with allogeneic transplantation only used in clinical trials. The appropriate timing of transplantation in the treatment plan is a matter of debate. Consolidation and maintenance chemotherapies, particularly thalidomide and bortezomib, aim to improve and prolong disease response to transplantation and delay recurrence. Prognostic factors for the outcome of stem cell transplant in myeloma have been highlighted. Despite good responses to chemotherapy and transplantation, the problem of disease recurrence persists. Thus, there is still much room for improvement. Treatments which harness the graft-versus-myeloma effect may offer a potential cure for this disease. Trials of novel agents are underway, including targeted therapies for specific antigens such as vaccines and monoclonal antibodies.

  3. Current concepts on selected plant secondary metabolites with promising inhibitory effects against enzymes linked to Alzheimer's disease.

    Orhan, I Erdogan

    2012-01-01

    Alzheimer's disease (AD) has become one of the deadliest diseases for human beings with special incidence in elderly population. It is a progressive neurodegenerative disease and the most prevalent cause of dementia. The neuropathology of AD has not been fully elucidated yet, however, cholinergic hypothesis is the most accepted theory nowadays, resulting from the cholinergic deficit emerging in the brains of AD patients. Shortage of the neurotransmitters, acetylcholine and butyrylcholine has been demonstrated, and therefore, inhibition of the enzymes; acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) that break down acetylcholine and butyrylcholine has become a standard approach for AD treatment. However, cholinesterase inhibitors are only effective in symptomatic treatment and have no ability to impede the disease. The pathogenesis of AD is highly complex and another hypothesis is the formation of amyloid plaques containing beta-amyloid peptide, which causes neurolesions in the brains of AD patients. Beta-amyloid peptide is generated after the sequential cleavage of amyloid precursor protein, especially by the beta- and gamma-secretase in the amyloidogenic pathway. The secretases involved in the processing of amyloid precursor protein are of particular interest and, consequently, the inhibition of secretase enzyme family of protease type has become another desired treatment strategy for AD. On the other hand, medicinal plants are attractive sources for drug research and development as they produce chemically-varying molecules with preferred biological activities. The aim of this article is to review the available data on selected inhibitors from plant secondary metabolites with emphasis on cholinesterase, prolyl endopeptidase, and secretase enzyme families as being the current treatments of AD.

  4. Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management.

    Lee, B B; Baumgartner, I; Berlien, H P; Bianchini, G; Burrows, P; Do, Y S; Ivancev, K; Kool, L S; Laredo, J; Loose, D A; Lopez-Gutierrez, J C; Mattassi, R; Parsi, K; Rimon, U; Rosenblatt, M; Shortell, C; Simkin, R; Stillo, F; Villavicencio, L; Yakes, W

    2013-02-01

    care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

  5. Therapeutic options to enhance coma arousal after traumatic brain injury: state of the art of current treatments to improve coma recovery.

    Cossu, Giulia

    2014-04-01

    Traumatic brain injury is a leading cause of death and disability. Optimizing the recovery from coma is a priority in seeking to improve patients' functional outcomes. Standards of care have not been established: pharmacological interventions, right median nerve and sensory stimulation, dorsal column stimulation (DCS), deep brain stimulation, transcranial magnetic stimulation, hyperbaric oxygen therapy and cell transplantation have all been utilized with contrasting results. The aim of this review is to clarify the indications for the various techniques and to guide the clinical practice towards an earlier coma arousal. A systematic bibliographic search was undertaken using the principal search engines (Pubmed, Embase, Ovid and Cochrane databases) to locate the most pertinent studies. Traumatic injury is a highly individualized process, and subsequent impairments are dependent on multiple factors: this heterogeneity influences and determines therapeutic responses to the various interventions.

  6. Positioning end-of-life care education within the pre-registration therapeutic radiography curriculum: A survey of current practices amongst UK higher education institutions

    White, N.

    2017-01-01

    Aim: It is essential that all health professionals who come into contact with patients with terminal diagnoses are equipped to effectively and competently provide end of life care. This study aims to investigate the manner in which Higher Education Institutions address this requirement with their programmes of pre-registration therapeutic radiography education. Method: A structured survey was administered electronically to all UK universities with responsibility for therapeutic radiography education. The scope of the survey addressed mode and duration of end of life care education, its location, curricular assessment, identifiable barriers and best practice. Results: All respondents confirmed the presence of dedicated end of life care education within their curriculum. Variation in the duration and location of this education is reported as are approaches to assessment of associated skills and knowledge. Analysis of respondent commentary has identified three themes-preparedness for the clinical role, dissonance between technology and care, and holistic approaches to course design. Conclusion: Respondents have highlighted the importance of end of life care instruction with their programmes of study and identified aspects of the mode and duration of its delivery. Inclusion of this aspect of study may be problematic in the face of competing demands arising from the volume and complexity of the curriculum. Practical experience of end of life care predominantly occurs within the radiotherapy department, although there is scope to explore opportunities within the hospice and community care setting. - Highlights: • Effective end of life care training within radiotherapy radiography programmes is necessary. • Universities confirm the inclusion of end of life care training in their curriculum. • Variations in contact time and mode of delivery are reported. • The majority of end of life care practice experience is gained within the radiotherapy department. • Wider

  7. Current concepts on integrative safety assessment of active substances of botanical, mineral or chemical origin in homeopathic medicinal products within the European regulatory framework.

    Buchholzer, Marie-Luise; Werner, Christine; Knoess, Werner

    2014-03-01

    For active substances of botanical, mineral or chemical origin processed in homeopathic medicinal products for human use, the adequate safety principles as with other human medicinal products are applied in line with the European regulatory framework. In homeopathy, nonclinical safety assessment is facing a particular challenge because of a multitude and diversity of source materials used and due to rarely available toxicological data. Thus, current concepts applied by the national regulatory authority in Germany (BfArM) on integrative safety assessment of raw materials used in homeopathic medicinal products involve several evaluation approaches like the use of the Lowest Human Recommended Dose (LHRD), toxicological limit values, Threshold of Toxicological Concern (TTC), data from food regulation or the consideration of unavoidable environmental or dietary background exposure. This publication is intended to further develop and clarify the practical use of these assessment routes by exemplary application on selected homeopathic preparations. In conclusion, the different approaches are considered a very useful scientific and simultaneously pragmatic procedure in differentiated risk assessment of homeopathic medicinal products. Overall, this paper aims to increase the visibility of the safety issues in homeopathy and to stimulate scientific discussion of worldwide existing regulatory concepts on homeopathic medicinal products. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Hairy cell leukemia: current concepts.

    Cannon, Timothy; Mobarek, Dalia; Wegge, Julia; Tabbara, Imad A

    2008-10-01

    Hairy cell Leukemia (HCL) is a chronic lymphoproliferative disorder that was characterized in the late 1950s. HCL is defined, according to the WHO classification, as a mature (peripheral) B-cell neoplasm (1). HCL accounts for between 2-3% of all leukemia cases, with about 600 new cases diagnosed in the U.S. each year (1). HCL occurs more commonly in males, with an overall male to female ratio of approximately 4:1. The median age of onset is 52 years. This disease is seen more commonly in Caucasians and appears to be especially frequent in Ashkenazi Jewish males, with rare occurrence in persons of Asian and African descents (1). Hairy cells are distinct, clonal B cells arrested at a late stage of maturation. They are small B lymphoid cells that possess oval nuclei and abundant cytoplasm with characteristic micro-filamentous ("hairy") projections. They strongly express CD103, CD22, and CD11c (2). These cells typically infiltrate the bone marrow, the spleen, and to a lesser extent the liver, lymph nodes, and skin. Many patients present with splenomegaly and pancytopenia. Other clinical manifestations include recurrent opportunistic infections and vasculitis. Historically, HCL was considered uniformly fatal (2). However, recent treatment advances, using purine analogues such as Cladribine and Pentostatin, led to a significant improvement in prognosis with achievement of high response rates and durable remissions (2).

  9. Burning mouth syndrome: Current concepts

    Nasri-Heir, Cibele; Zagury, Julyana Gomes; Thomas, Davis; Ananthan, Sowmya

    2015-01-01

    Burning mouth syndrome (BMS) is a chronic pain condition. It has been described by the International Headache Society as "an intra-oral burning or dysesthetic sensation, recurring daily for more than 2 h/day for more than 3 months, without clinically evident causative lesions." BMS is frequently seen in women in the peri-menopausal and menopausal age group in an average female/male ratio of 7:1. The site most commonly affected is the anterior two-thirds of the tongue. The patient may also rep...

  10. CURRENT CONCEPTS OF PLYOMETRIC EXERCISE.

    Davies, George; Riemann, Bryan L; Manske, Robert

    2015-11-01

    As knowledge regarding rehabilitation science continues to increase, exercise programs following musculoskeletal athletic injury continue to evolve. Rehabilitation programs have drastically changed, especially in the terminal phases of rehabilitation, which include performance enhancement, development of power, and a safe return to activity. Plyometric exercise has become an integral component of late phase rehabilitation as the patient nears return to activity. Among the numerous types of available exercises, plyometrics assist in the development of power, a foundation from which the athlete can refine the skills of their sport. Therefore, the purpose of this clinical commentary is to provide an overview of plyometrics including: definition, phases, the physiological, mechanical and neurophysiological basis of plyometrics, and to describe clinical guidelines and contraindications for implementing plyometric programs.

  11. Current concepts in multiple sclerosis

    Wiethoelter, Horst; Dichgans, Johannes

    1991-01-01

    This volume contains 9 articles dealing with the use of nuclear magnetic resonance imaging and positron emitted tomography in the diagnosis and staging of multiple sclerosis. (H.W.). refs.; figs.; tabs

  12. Current Concepts in Graves' Disease

    Girgis, Christian M.; Champion, Bernard L.; Wall, Jack R.

    2011-01-01

    Graves' disease is the most common cause of hyperthyroidism in the developed world. It is caused by an immune defect in genetically susceptible individuals in whom the production of unique antibodies results in thyroid hormone excess and glandular hyperplasia. When unrecognized, Graves' disease impacts negatively on quality of life and poses serious risks of psychosis, tachyarrhythmia and cardiac failure. Beyond the thyroid, Graves' disease has diverse soft-tissue effects that reflect its systemic autoimmune nature. Thyroid eye disease is the most common of these manifestations and is important to recognise given its risk to vision and potential to deteriorate in response to radioactive iodine ablation. In this review we discuss the investigation and management of Graves' disease, the recent controversy regarding the hepatotoxicity of propylthiouracil and the emergence of novel small-molecule thyroid-stimulating hormone (TSH) receptor ligands as potential targets in the treatment of Graves' disease. PMID:23148179

  13. Abfraction lesions reviewed: current concepts

    Adriana de Fátima Vasconcelos Pereira

    2008-01-01

    Full Text Available Non-carious cervical lesions are characterized by structural loss near the cementoenamel junction, without the presence of caries. Anumber of theories have arisen to explain the etiology of such lesions, although the real causes remain obscure, as is reflected by the contradictory terminology used in the literature. In addition to describing acidic and abrasive processes documented as etiological factors, attention is given to the role of mechanical stress from occlusal load, which is the most accepted theory for the development of abfraction lesions. Considering that tensile stress leads to the failure of restorations in the cervical region and that this is a fruitful area for future research, the present study has highlighted diagnosis, prognosis and the criteria for treatment.

  14. Current Concepts in Filler Injection.

    Moradi, Amir; Watson, Jeffrey

    2015-11-01

    When evaluating the face in thirds, the upper face, midface, and lower face, one may assume the lateral the temple, midface, and lateral mandible as the pillars of these subdivisions. Many of our facial aesthetic procedures address these regions, including the lateral brow lift, midface lift, and lateral face lift. As the use of facial fillers has advanced, more emphasis is placed on the correction of the temples, midlateral face, and lateral jaw line. This article is dedicated to these facial aesthetic pillars. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Craniosynostosis: current conceptions and misconceptions

    Cristiane Sá Roriz Fonteles

    2016-04-01

    Full Text Available Cranial bones articulate in areas called sutures that must remain patent until skull growth is complete. Craniosynostosis is the condition that results from premature closure of one or more of the cranial vault sutures, generating facial deformities and more importantly, skull growth restrictions with the ability to severely affect brain growth. Typically, craniosynostosis can be expressed as an isolated event, or as part of syndromic phenotypes. Multiple signaling mechanisms interact during developmental stages to ensure proper and timely suture fusion. Clinical outcome is often a product of craniosynostosis subtypes, number of affected sutures and timing of premature suture fusion. The present work aimed to review the different aspects involved in the establishment of craniosynostosis, providing a close view of the cellular, molecular and genetic background of these malformations.

  16. Current concepts in cancer research

    Ivan Kok Seng Yap; Ammu Kutty Radhakrishnan; Chee Onn Leong

    2013-01-01

    Cancer research is an extremely broadtopic covering many scientific disciplines includingbiology (e.g. biochemistry and signal transduction),chemistry (e.g. drug discover and development),physics (e.g. diagnostic devices) and even computerscience (e.g. bioinformatics). Some would argue thatcancer research will continue in much the same wayas it is by adding further layers of complexity to thescientific knowledge that is already complex and almostbeyond measure. But we anticipate that cancer r...

  17. Schizophrenia : Current concepts in aetiology

    P S Bhat

    2014-01-01

    Full Text Available Schizophrenia is perhaps the most devastating neuropsychiatric illness. Worldwide, its prevalence rate is about 1%. Schizophrenia is considered a neurodevelopmental disorder involving the interplay of susceptibility genes and environmental factors. There is a wide range of pathologic findings, but there is no specific or diagnostic laboratory abnormality. Till date, the aetiology, neuropathology, and pathophysiology of schizophrenia remain elusive. Over the last forty years, the dopaminergic model has been the leading neurochemical hypothesis of schizophrenia. Yet it remains unlikely that dopaminergic dysfunction, on its own. Glutamatergic models provide an alternate approach for conceptualizing the brain abnormalities associated with schizophrenia. New pharmacological and behavioral approaches aimed at potentiating glutamatergic neurotransmission, offer new hopeforfuture clinical development

  18. Fournier's gangrene--current concepts.

    Wróblewska, Marta; Kuzaka, Bolesław; Borkowski, Tomasz; Kuzaka, Piotr; Kawecki, Dariusz; Radziszewski, Piotr

    2014-01-01

    Fournier's gangrene (FG) is a rapidly progressive form of infective necrotising fasciitis of the perineal, genital, or perianal regions, leading to thrombosis of the small subcutaneous vessels and necrosis of the overlying skin. It is believed that the occurrence of the disease in women is underreported and may be unrecognised by some clinicians. Fournier's gangrene is a life-threatening condition, constituting an urological emergency. Many patients with Fournier's gangrene have medical or surgical conditions, which are predisposing factors to this disease or its more severe or fatal course. These comprise diabetes mellitus, hypertension, alcoholism and advanced age. Recent reports in the literature point to changes in the epidemiology of FG, comprising an increasing age of patients. Several authors reported that the mean age of FG patients is at present 53-55 years. Prognosis in FG patients is based on FGSI (Fournier's gangrene severity index) score. Despite the progress in medical care for FG patients, the mortality rate reported in the literature remains high--most often 20-40%, but ranges from 4% to 80%. The most common isolates cultured from FG lesions are both Gram-positive and Gram-negative, as well as strictly anaerobic bacteria. Recently community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an etiological agent of FG with severe clinical course and even fulminant sepsis. Rarely FG may have a fungal etiology, being caused by yeast-like fungi Candida spp. or by moulds. Antibiotics should be administered parenterally and in doses high enough to reach an effective concentration in the infected tissues.

  19. The role of imaging in the diagnosis and management of thoracolumbar burst fractures: current concepts and a review of the literature

    Saifuddin, A.; Noordeen, H.; Taylor, B.A.; Bayley, I.

    1996-01-01

    The burst fracture of the spine was first described by Holdsworth in 1963 and redefined by Denis in 1983 as being a fracture of the anterior and middle columns of the spine with or without an associated posterior column fracture. This injury has received much attention in the literature as regards its radiological diagnosis and also its clinical managment. The purpose of this article is to review the way that imaging has been used both to diagnose the injury and to guide management. Current concepts of the stability of this fracture are presented and our experience in the use of magnetic resonance imaging in deciding treatment options is discussed. (orig.). With 18 figs., 2 tabs

  20. Study of the input-side subsurface reorganization vs. the outside current density in hydrogen permeation under constant cell voltage through iron membrane according to RHC concept

    DePetris-Wery, M.; Wery, S.; Catonne, J.C.

    2010-01-01

    In this work, hydrogen permeation tests were performed on pure iron membrane in 1 M sodium hydroxide at 298 K, subjected to hydrogen charging under 'quasi-potentiostatic' polarization conditions, i.e. constant cell voltage applied between the cathode (membrane entry side) and the anode (counter electrode), which is a typical situation during metal electrodeposition or cathodic degreasing on steel in metal finishing industry. Two consecutive charging-discharging runs were carried out. Prolonged hydrogen charging under quasi-potentiostatic polarization was investigated and the change of cathodic current density (i in ) chg and electrode potential (E in ) chg as well as permeation current density (i out ) chg were analysed. Three singularities were underlined for each experiment: (i) the curve (i in ) chg = f((E in ) chg ), illustrating the inverse of hydrogen charge resistance R HC -1 evolution which was negative, equal to zero and then became positive; (ii) quasi-periodic instabilities during the R HC -1 zero period, probably induced by atomic reorganizing due to subsurface hydrogen insertion in the input-side; (iii) the same ratio (i out ) chg /(i in ) chg = -6 x 10 -5 . During discharge runs, both sides of the membrane were polarized at the same potential (E in ) dischg = (E out ) dischg = -0.285 V/Hg/HgO/NaOH 1 M and the current densities, (i in ) dischg and (i out ) dischg which corresponded to the desorption rates of hydrogen, were measured. The following correlation (i out ) dischg vs.(i in ) dischg = -6 x 10 -5 was confirmed leading us to introduce the R HC -1 mirror concept to observe the input-side subsurface reorganization by the survey of its potential vs. outside current density during the hydrogen charge. Thus, this R HC -1 mirror concept showed: (i) a non-stop and irreversible progress in the subsurface reorganization during the two permeations; (ii) a probable structural evolution to a stable subsurface structure, the only condition of a real steady

  1. Macromolecular therapeutics.

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Current status of therapeutic drug monitoring in Australia and New Zealand: a need for improved assay evaluation, best practice guidelines, and professional development.

    Norris, Ross L; Martin, Jennifer H; Thompson, Erin; Ray, John E; Fullinfaw, Robert O; Joyce, David; Barras, Michael; Jones, Graham R; Morris, Raymond G

    2010-10-01

    The measurement of drug concentrations, for clinical purposes, occurs in many diagnostic laboratories throughout Australia and New Zealand. However, the provision of a comprehensive therapeutic drug monitoring (TDM) service requires the additional elements of pre- and postanalytical advice to ensure that concentrations reported are meaningful, interpretable, and clinically applicable to the individual patient. The aim of this project was to assess the status of TDM services in Australia and New Zealand. A range of professions involved in key aspects of TDM was surveyed by questionnaire in late 2007. Information gathered included: the list of drugs assayed; analytical methods used; interpretation services offered; interpretative methods used; and further monitoring advice provided. Fifty-seven responses were received, of which 42% were from hospitals (public and/or private); 11% a hospital (public and/or private) and pathology provider; and 47% a pathology provider only (public and/or private). Results showed that TDM is applied to a large number of different drugs. Poorly performing assay methods were used in some cases, even when published guidelines recommended alternative practices. Although there was a wide array of assays available, the evidence suggested a need for better selection of assay methods. In addition, only limited advice and/or interpretation of results was offered. Of concern, less than 50% of those providing advice on aminoglycoside dosing in adults used pharmacokinetic tools with six of 37 (16.2%) respondents using Bayesian pharmacokinetic tools, the method recommended in the Australian Therapeutic Guidelines: Antibiotic. In conclusion, the survey highlighted deficiencies in the provision of TDM services, in particular assay method selection and both quality and quantity of postanalytical advice. A range of recommendations, some of which may have international implications, are discussed. There is a need to include measures of impact on clinical

  3. Therapeutic Nanodevices

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  4. Individualised care for women with assisted conception pregnancies and midwifery practice implications: An analysis of the existing research and current practice.

    Younger, Mimi; Hollins-Martin, Caroline; Choucri, Lesley

    2015-02-01

    the aim is to explore the psychosocial needs of women who are pregnant after assisted conception, specifically in vitro Fertilisation and whether their needs are being addressed within the current maternity care service. critical review of the literature using a narrative approach. 15 papers were identified. These included both qualitative and quantitative studies, literature reviews and surveys. The findings of this limited narrative review imply that women who undergo assistive reproductive techniques to achieve pregnancy have higher levels of anxiety in pregnancy and may have some difficulties in the transition to parenthood leading to perinatal morbidity. It appears that for this group of women it is important that their history in achieving pregnancy is known to the care providers, to enable the alleviation of some of the anxieties they face. Various aspects of antenatal care have been identified as possible areas which if addressed may reduce these levels of anxiety leading to a reduction in perinatal morbidity. currently, there is insufficient evidence to suggest that providing specialist midwifery care reduces morbidity in these women. However, maternity service providers should consider offering additional antenatal and postnatal services to meet the needs of this group in advance of further research in this area. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Purinergic Signalling: Therapeutic Developments

    Geoffrey Burnstock

    2017-09-01

    Full Text Available Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

  6. Desarrollo Conceptual: Perspectivas Actuales en la Adquisición Temprana de Conceptos Conceptual Development: Current Approaches to Children's Early Concept Acquisition

    Andrea Sabina Taverna

    2009-01-01

    Full Text Available Se examinan cuatro propuestas teóricas actuales acerca de la formación y desarrollo temprano de conceptos: aproximaciones innatistas, enfoques asociacionistas, teorías del conocimiento nuclear y perspectivas socio-culturales. Las propuestas concuerdan en que los conceptos cumplen un rol importante en el desarrollo cognitivo, pero difieren marcadamente en el modo de explicar su adquisición y desarrollo temprano. Estas divergencias reeditan debates filosóficos clásicos acerca del lugar de la naturaleza, la experiencia, la razón y la cultura en el desarrollo del conocimiento. Se discute la necesidad de reconsiderar el desarrollo conceptual a la luz de modelos teóricos más inclusivos, si se pretende avanzar críticamente en una aproximación teórica general acerca de la formación y desarrollo de conceptos en la infancia.Four current theoretical proposals about early conceptual acquisition and development are examined: nativist perspectives, associationist views, core-knowledge theories, and socio-cultural approaches. The proposals agree that concepts play an important role in children's cognitive development, but they differ in their explanation as to how these are acquired and their early development. These differences date back to classical philosophical debates about the role of nature, experience, reason, and culture in the development of knowledge. The need to revisit conceptual development with a more inclusive theoretical approach is discussed, if critical advancement towards a general theoretical approach for understanding the formation and development of concepts in early childhood is to be achieved.

  7. An ingested mobile phone in the stomach may not be amenable to safe endoscopic removal using current therapeutic devices: A case report.

    Obinwa, Obinna; Cooper, David; O'Riordan, James M

    2016-01-01

    This case report is intended to inform clinicians, endoscopists, policy makers and industry of our experience in the management of a rare case of mobile phone ingestion. A 29-year-old prisoner presented to the Emergency Department with vomiting, ten hours after he claimed to have swallowed a mobile phone. Clinical examination was unremarkable. Both initial and repeat abdominal radiographs eight hours later confirmed that the foreign body remained in situ in the stomach and had not progressed along the gastrointestinal tract. Based on these findings, upper endoscopy was performed under general anaesthesia. The object could not be aligned correctly to accommodate endoscopic removal using current retrieval devices. Following unsuccessful endoscopy, an upper midline laparotomy was performed and the phone was delivered through an anterior gastrotomy, away from the pylorus. The patient made an uneventful recovery and underwent psychological counselling prior to discharge. In this case report, the use of endoscopy in the management when a conservative approach fails is questioned. Can the current endoscopic retrieval devices be improved to limit the need for surgical interventions in future cases? An ingested mobile phone in the stomach may not be amenable for removal using the current endoscopic retrieval devices. Improvements in overtubes or additional modifications of existing retrieval devices to ensure adequate alignment for removal without injuring the oesophagus are needed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. A critical view on singular therapeutic projects

    Fernando Sfair Kinker

    2016-04-01

    Full Text Available This article discusses the issue of unique therapeutic projects within the mental health services built in the Brazilian psychiatric reform process. Starting from the concepts that have gained strength in both the psychiatric reform as in the collective health, this study proposes that current notions of the therapeutic project still are influenced by biological, psychological or social paradigms that simplify the complexity of the experience suffered by the subjects. Despite therapeutic projects are an essential achievement for the qualification of mental health care, it is still necessary to produce an epistemological rupture in the relationship with mental suffering so that they can achieve the greatest potential for transformation. Therefore, the article suggests that the practice of therapeutic projects should hold discussions with the reality of users life of and their relationships in the territories of existence, to transform the relations of power and knowledge that reproduce the subjects annulment. Thus, it is possible to dialogue with the complexity of the mental suffering experience, producing changes in the scenes that produce it.

  9. Volume 42, Issue5 (May 2005)Articles in the Current Issue:Developmental growth in students' concept of energy: Analysis of selected items from the TIMSS database

    Liu, Xiufeng; McKeough, Anne

    2005-05-01

    The aim of this study was to develop a model of students' energy concept development. Applying Case's (1985, 1992) structural theory of cognitive development, we hypothesized that students' concept of energy undergoes a series of transitions, corresponding to systematic increases in working memory capacity. The US national sample from the Third International Mathematics and Science Study (TIMSS) database was used to test our hypothesis. Items relevant to the energy concept in the TIMSS test booklets for three populations were identified. Item difficulty from Rasch modeling was used to test the hypothesized developmental sequence, and percentage of students' correct responses was used to test the correspondence between students' age/grade level and level of the energy concepts. The analysis supported our hypothesized sequence of energy concept development and suggested mixed effects of maturation and schooling on energy concept development. Further, the results suggest that curriculum and instruction design take into consideration the developmental progression of students' concept of energy.

  10. Taking Sides: An Integrative Review of the Impact of Laterality and Polarity on Efficacy of Therapeutic Transcranial Direct Current Stimulation for Anomia in Chronic Poststroke Aphasia

    Sandars, Margaret; Cloutman, Lauren; Woollams, Anna M.

    2016-01-01

    Anomia is a frequent and persistent symptom of poststroke aphasia, resulting from damage to areas of the brain involved in language production. Cortical neuroplasticity plays a significant role in language recovery following stroke and can be facilitated by behavioral speech and language therapy. Recent research suggests that complementing therapy with neurostimulation techniques may enhance functional gains, even amongst those with chronic aphasia. The current review focuses on the use of transcranial Direct Current Stimulation (tDCS) as an adjunct to naming therapy for individuals with chronic poststroke aphasia. Our survey of the literature indicates that combining therapy with anodal (excitatory) stimulation to the left hemisphere and/or cathodal (inhibitory) stimulation to the right hemisphere can increase both naming accuracy and speed when compared to the effects of therapy alone. However, the benefits of tDCS as a complement to therapy have not been yet systematically investigated with respect to site and polarity of stimulation. Recommendations for future research to help determine optimal protocols for combined therapy and tDCS are outlined. PMID:26819777

  11. Ultrasound and MRI of nerves for monitoring disease activity and treatment effects in chronic dysimmune neuropathies - Current concepts and future directions.

    Décard, Bernhard F; Pham, Mirko; Grimm, Alexander

    2018-01-01

    New imaging modalities like high-resolution-ultrasound (HRUS) and MR-Neurography (MRN) are increasingly used for the evaluation of the peripheral nervous system. The increasing knowledge on morphological changes observed in different neuropathies has led to a better understanding of underlying pathophysiological processes. The diagnosis of acquired chronic dysimmune neuropathies (CDN) like chronic inflammatory demyelinating polyneuropathy (CIDP), Lewis-Sumner Syndrome (LSS) or multifocal motor neuropathy (MMN) can be challenging. The current diagnostic criteria and outcome parameters are mainly based on clinical and electrophysiological parameters. Especially in CDN cases with atypical presentation or during early disease stages, the diagnostic accuracy is low and standardized protocols for the evaluation of disease activity and treatment response are lacking. The establishment of combined diagnostic criteria for CDN including imaging modalities could help to improve the diagnostic accuracy, allow a better differentiation of subtypes and facilitate the follow-up of disease course. The appropriate selection of eligible patients and sensitive monitoring of treatment response is mandatory future in treatment trials. In this article, we briefly summarize the clinical presentations and pathophysiological concepts of different CDN like CIDP, LSS and MMN. Furthermore, this review focuses on the diagnostic value of HRUS/MRN and its potential role for the monitoring of disease activity. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  12. A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: current research and opinion

    Mitchell AJ

    2013-01-01

    Full Text Available Álvaro Sánchez-Ferro,1–4 Julián Benito-León,1–3 Alex J Mitchell,5 Félix Bermejo-Pareja1–31Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain; 2Department of Medicine, Complutense University, Madrid, Spain; 3Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain; 4Instituto de Salud Carlos III, Madrid, Spain; 5Department of Psycho-oncology, Leicestershire Partnership NHS Trust and University of Leicester, Leicester, UKAbstract: Alzheimer’s disease is one of the most prevalent neurodegenerative disorders. However, there is no current treatment, which definitively influences disease progression over a sustained period. Numerous studies linking an increase in serum cholesterol, mainly during midlife, with the pathogenic process of Alzheimer’s disease have been published. Therefore, the role of statins as a therapy in this disorder may be of great interest. The aim of the present review is to summarize of the role of statins in the treatment of Alzheimer’s disease.Keywords: animal models, epidemiology, HMGCoA-inhibitors, clinical trials, prevention, cognitive function

  13. Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption.

    Benéitez, M Cristina; Gil-Alegre, M Esther

    2017-01-01

    Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. A systematic search on the common databases of relevant papers published until 2016 inclusive. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

  14. Opioid Addiction: Social Problems Associated and Implications of Both Current and Possible Future Treatments, including Polymeric Therapeutics for Giving Up the Habit of Opioid Consumption

    M. Cristina Benéitez

    2017-01-01

    Full Text Available Background. Detoxification programmes seek to implement the most secure and compassionate ways of withdrawing from opiates so that the inevitable withdrawal symptoms and other complications are minimized. Once detoxification has been achieved, the next stage is to enable the patient to overcome his or her drug addiction by ensuring consumption is permanently and completely abandoned, only after which can the subject be regarded as fully recovered. Methods. A systematic search on the common databases of relevant papers published until 2016 inclusive. Results and Conclusion. Our study of the available oral treatments for opioid dependence has revealed that no current treatment can actually claim to be fully effective. These treatments require daily oral administration and, consequently, regular visits to dispensaries, which in most cases results in a lack of patient compliance, which causes fluctuations in drug plasma levels. We then reviewed alternative treatments in the available scientific literature on polymeric sustained release formulations. Research has been done not only on release systems for detoxification but also on release systems for giving up the habit of taking opioids. These efforts have obtained the recent authorization of polymeric systems for use in patients that could help them to reduce their craving for drugs.

  15. Therapeutic ultrasound

    Crum, Lawrence A

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques. (amum lecture)

  16. Therapeutic targets in liver fibrosis.

    Fallowfield, Jonathan A

    2011-05-01

    Detailed analysis of the cellular and molecular mechanisms that mediate liver fibrosis has provided a framework for therapeutic approaches to prevent, slow down, or even reverse fibrosis and cirrhosis. A pivotal event in the development of liver fibrosis is the activation of quiescent hepatic stellate cells (HSCs) to scar-forming myofibroblast-like cells. Consequently, HSCs and the factors that regulate HSC activation, proliferation, and function represent important antifibrotic targets. Drugs currently licensed in the US and Europe for other indications target HSC-related components of the fibrotic cascade. Their deployment in the near future looks likely. Ultimately, treatment strategies for liver fibrosis may vary on an individual basis according to etiology, risk of fibrosis progression, and the prevailing pathogenic milieu, meaning that a multiagent approach could be required. The field continues to develop rapidly and starts to identify exciting potential targets in proof-of-concept preclinical studies. Despite this, no antifibrotics are currently licensed for use in humans. With epidemiological predictions for the future prevalence of viral, obesity-related, and alcohol-related cirrhosis painting an increasingly gloomy picture, and a shortfall in donors for liver transplantation, the clinical urgency for new therapies is high. There is growing interest from stakeholders keen to exploit the market potential for antifibrotics. However, the design of future trials for agents in the developmental pipeline will depend on strategies that enable equal patient stratification, techniques to reliably monitor changes in fibrosis over time, and the definition of clinically meaningful end points.

  17. Imbalances in the Development of Muscle and Tendon as Risk Factor for Tendinopathies in Youth Athletes: A Review of Current Evidence and Concepts of Prevention

    Falk Mersmann

    2017-12-01

    Full Text Available Tendons feature the crucial role to transmit the forces exerted by the muscles to the skeleton. Thus, an increase of the force generating capacity of a muscle needs to go in line with a corresponding modulation of the mechanical properties of the associated tendon to avoid potential harm to the integrity of the tendinous tissue. However, as summarized in the present narrative review, muscle and tendon differ with regard to both the time course of adaptation to mechanical loading as well as the responsiveness to certain types of mechanical stimulation. Plyometric loading, for example, seems to be a more potent stimulus for muscle compared to tendon adaptation. In growing athletes, the increased levels of circulating sex hormones might additionally augment an imbalanced development of muscle strength and tendon mechanical properties, which could potentially relate to the increasing incidence of tendon overload injuries that has been indicated for adolescence. In fact, increased tendon stress and strain due to a non-uniform musculotendinous development has been observed recently in adolescent volleyball athletes, a high-risk group for tendinopathy. These findings highlight the importance to deepen the current understanding of the interaction of loading and maturation and demonstrate the need for the development of preventive strategies. Therefore, this review concludes with an evidence-based concept for a specific loading program for increasing tendon stiffness, which could be implemented in the training regimen of young athletes at risk for tendinopathy. This program incorporates five sets of four contractions with an intensity of 85–90% of the isometric voluntary maximum and a movement/contraction duration that provides 3 s of high magnitude tendon strain.

  18. O papel do estresse oxidativo na DPOC: conceitos atuais e perspectivas The role of oxidative stress in COPD: current concepts and perspectives

    Antonio George de Matos Cavalcante

    2009-12-01

    Full Text Available A DPOC é uma causa importante de morbidade e mortalidade em escala global. As manifestações clínicas e funcionais da DPOC resultam de danos pulmonares provocados por um conjunto de mecanismos, incluindo o estresse oxidativo, a inflamação, o desequilíbrio do sistema protease-antiprotease e a apoptose. O estresse oxidativo é central na gênese da DPOC, pois além de provocar dano direto às estruturas pulmonares, amplifica os demais mecanismos. Os eventos celulares e moleculares responsáveis pelo dano pulmonar antecedem em muito a expressão clínica e funcional da DPOC. Os broncodilatadores, principais drogas empregadas atualmente no tratamento da DPOC, não são eficazes em reduzir a progressão da doença. Avanços na compreensão da patogênese da DPOC aliados a esforços renovados na pesquisa básica e clínica deverão permitir sua detecção na fase pré-clínica e possibilitar um monitoramento mais adequado de sua atividade, além de permitir a introdução de novas modalidades de agentes terapêuticos capazes de impedir eficazmente sua progressão.Worldwide, COPD is a major cause of morbidity and mortality. The clinical and functional manifestations of COPD result from lung injury occurring through various mechanisms, including oxidative stress, inflammation, protease-antiprotease imbalance and apoptosis. Oxidative stress is central to the pathogenesis of COPD, since it can directly damage lung structures and exacerbate the other mechanisms involved. The cellular and molecular events involved in such lung injury are believed to occur long before the clinical and functional expression of COPD. Although the use of bronchodilators is currently the principal treatment for COPD, bronchodilators have little or no effect on disease progression. A better understanding of the pathogenesis of COPD, together with renewed efforts in basic and clinical research, will allow the diagnosis of COPD at a pre-clinical stage and provide more

  19. [Current therapeutic indications of thalidomide and lenalidomide].

    Ordi-Ros, Josep; Cosiglio, Francisco Javier

    2014-04-22

    Thalidomide is a synthetic glutamic acid derivative first introduced in 1956 in Germany as an over the counter medications. It was thought to be one of the safest sedatives ever produced as it was effective in small doses, was not addictive, and did not have acute side-effects such as motor impairment, but was quickly removed from market after it was linked to cases of severe birth defects. The Food and Drug Administration approved use in the treatment of erythema nodosum leprosum. Further, it was shown its effectiveness in unresponsive dermatological conditions such as actinic prurigo, adult Langerhans cell hystiocytosis, aphthous stomatitis, Behçet syndrome, graft-versus-host disease, cutaneous sarcoidosis, erythema multiforme, Jessner-Kanof lymphocytic infiltration of the skin, Kaposi sarcoma, lichen planus, lupus erythematosus, melanoma, prurigo nodularis, pyoderma gangrenosum and others. In May 2006, it was approved for the treating multiple myeloma. New thalidomide analogues have been developed but lack clinical experience. This paper is a review of the history, pharmacology, mechanism of action, clinical applications and side effects of thalidomide and its analogues. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  20. Evolution and current situation of the quality and industrial safety. Concepts, laws and regulations; Evolucion y situacion actual de la calidad y seguridad industrial. Conceptos, leyes y reglamentos

    Munoz, A.

    2013-06-01

    The aim of this article is to show the difference between the concepts of quality and industrial safety and how in the legislation of products and industrial installation there is a very close relationship between both concepts. So, that Spanish companies could place in the market not only safe products but also reliable ones that meet the society's demand regarding quality. (Author)

  1. Key concepts in glioblastoma therapy

    Bartek, Jiri; Ng, Kimberly; Bartek, Jiri

    2012-01-01

    principles that drive the formulation of therapeutic strategies in glioblastoma. Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed....

  2. [End therapeutic nihilism towards COPD].

    Juergens, Uwe R

    2007-03-15

    Prevention of COPD requires appropriate patient education, especially of adolescents, as well as the establishment of an effective national health policy. The new GOLD guidelines represent the current standard of knowledge on the management of chronic, progressive, obstructive pulmonary diseases. It points out that COPD is avoidable and treatable,and hence, there is no reason for therapeutic nihilism. Chronic bronchitis preceding a progressive respiratory obstruction cannot be improved with the presently available respiratory therapeutics. For this reason, therapeutic measures concentrate on the avoidance of exacerbations, which are primarily responsible for the severity of the course of COPD.

  3. A new therapeutic community: development of a compassion-focussed and contextual behavioural environment.

    Veale, David; Gilbert, Paul; Wheatley, Jon; Naismith, Iona

    2015-01-01

    Social relationships and communities provide the context and impetus for a range of psychological developments, from genetic expression to the development of core self-identities. This suggests a need to think about the therapeutic changes and processes that occur within a community context and how communities can enable therapeutic change. However, the 'therapeutic communities' that have developed since the Second World War have been under-researched. We suggest that the concept of community, as a change process, should be revisited within mainstream scientific research. This paper briefly reviews the historical development of therapeutic communities and critically evaluates their current theory, practice and outcomes in a systematic review. Attention is drawn to recent research on the nature of evolved emotion regulation systems, the way these are entrained by social relationships, the importance of affiliative emotions in the regulation of threat and the role of fear of affiliative emotions in psychopathology. We draw on concepts from compassion-focussed therapy, social learning theory and functional analytical psychotherapy to consider how members of a therapeutic community can be aware of each other's acts of courage and respond using compassion. Living in structured and affiliative-orientated communities that are guided by scientific models of affect and self-regulation offers potential therapeutic advantages over individual outpatient therapy for certain client groups. This conclusion should be investigated further. Key Practitioner Message Current therapeutic community practice is not sufficiently evidence based and may not be maximizing the potential therapeutic value of a community. Compassion-focussed therapy and social learning theory offer new approaches for a therapeutic environment, involving an understanding of the role, nature and complexities of compassionate and affiliative relationships from staff and members, behavioural change guided by

  4. PYTHIOSIS: A THERAPEUTIC APPROACH

    C. M. C. Falcão

    2015-10-01

    Full Text Available Pythiosis, a disease caused by the oomycete Pythium insidiosum, often presents inefficient response to chemotherapy. It is a consensus that, in spite the several therapeutic protocols, a combination of surgery, chemotherapy and immunotherapy should be used. Surgical excision requires the removal of the entire affected area, with a wide margin of safety. The use of antifungal drugs has resulted in variable results, both in vitro and in vivo, and presents low therapeutic efficiency due to differences in the agent characteristics, which differ from true fungi. Immunotherapy is a non-invasive alternative for the treatment of pythiosis, which aims at modifying the immune response of the host, thereby producing an effective response to the agent. Photodynamic therapy has emerged as a promising technique, with good activity against P. insidiosum in vitro and in vivo. However, more studies are necessary to increase the efficiency of the current treatment protocols and consequently improve the cure rates. This paper aims to conduct a review covering the conventional and recent therapeutic methods against P. insidiosum infections

  5. The myeloma stem cell concept, revisited: From phenomenology to operational terms

    H.E. Johnsen (Hans); M. Bøgsted (Martin); A. Schmitz; Bødker, J.S. (Julie Støve); El-Galaly, T.C. (Tarec Christoffer); Johansen, P. (Preben); P. Valent (Peter); Zojer, N. (Niklas); E. van Valckenborgh (Els); Vanderkerken, K. (Karin); M. van Duin (Mark); P. Sonneveld (Pieter); M. Perez-Andres; A. Orfao (Alberto); K. Dybkær (Karen)

    2016-01-01

    textabstractThe concept of the myeloma stem cell may have important therapeutic implications, yet its demonstration has been hampered by a lack of consistency in terms and definitions. Here, we summarize the current documentation and propose single-cell in vitro studies for future translational

  6. Evolução do conceito e controvérsias atuais sobre o transtorno bipolar do humor Bipolar disorder: evolution of the concept and current controversies

    José Alberto Del Porto

    2004-10-01

    Full Text Available O autor revê o conceito de transtorno bipolar como um processo em evolução. Suas raízes podem ser encontradas no trabalho de Araeteus da Capadócia, que assumia serem a melancolia e a mania duas formas da mesma doença. A compreensão atual da doença bipolar começou na França, através dos trabalhos de Falret (1851 e Baillarguer (1854. Os conceitos fundamentais de Kraepelin mudaram as bases da nosologia psiquiátrica, e o conceito unitário de Kraepelin sobre a insanidade maníaco-depressiva passou a ser amplamente aceito. Depois de Kraepelin, no entanto, as idéias de Kleist e Leonhard, na Alemanha, e o trabalho subseqüente de Angst, Perris e Winokur enfatizaram a distinção entre as formas monopolares e bipolares da depressão. Mais recentemente a ênfase mudou novamente para o espectro bipolar, que em suas formas leves expande-se às bordas dos temperamentos normais. Finalizando, o autor sumariza os aspectos polêmicos da nosologia da doença bipolar e seus limites com as esquizofrenias, a doença esquizoafetiva e as psicoses ciclóides.The author reviews the evolution of the concept of bipolar disorder as an ongoing process. Its roots can be found in the work of Araeteus of Capadocia, who assumed that melancholia and mania were two forms of the same disease. The modern understanding of bipolar disorder began in France, through the work of Falret (1851 and Baillarger (1854. The pivotal concepts of Emil Kraepelin changed the basis of psychiatric nosology, and Kraepelin's unitary concept of manic-depressive insanity was largely accepted. Kraepelin and Weigandt's ideas on mixed states were the cornerstone of this unitary concept. After Kraepelin, however, the ideas of Kleist and Leonhard, in Germany, as well as the work of Angst, Perris and Winokur, emphasized the distinction between unipolar and bipolar forms of depression. More recently, the emphasis has shifted again to the bipolar spectrum, which, in its mild forms, expanded to the

  7. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

    Kirchgesner, J; Lemaitre, M; Rudnichi, A; Racine, A; Zureik, M; Carbonnel, F; Dray-Spira, R

    2017-01-01

    Management of inflammatory bowel disease (IBD) has evolved in the last decade. To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected. © 2016 John Wiley & Sons Ltd.

  8. Alpha-fetoprotein in the routine clinical laboratory: evaluation of a simple radioimmunoassay and review of current concepts in its clinical application

    Brummund, W.; Mennuti, M.T.; Arvan, D.A.; Starkovsky, N.A.

    1980-01-01

    The authors have assessed the clinical utility of a radioimmunoassay for alpha-fetoprotein (AFP). The method, which relies on ammonium sulfate precipitation for the separation of 'bound' and 'free' radiolabeled antigen, can be completed in one working day. The assay is specific for AFP, has a sensitivity of <10 ng/ml, and has intra- and inter-assay precision of 5-8% and 9-11%, respectively. They have conducted a three-year study of 472 pregnancies in which physicians wished to detect neural tube defects, and of 400 non-pregnant patients to assess the value of serum AFP as a marker for certain benign and malignant diseases. Six of 6 fetal open neural-tube defects (NTD'S) and 3 of 3 intrauterine fetal deaths were correctly identified by their association with marked AFP elevations in both maternal serum and amniotic fluid. Thirty non-pregnant patients were found to have AFP elevations greater than 20 ng/ml. Malignancies associated with these elevations were hepatoma, germ cell tumors, Wilms' tumor, and carcinoma of unknown origin. Carcinoma metastatic to the liver was not associated with AFP elevations. In AFP-associated tumors they found serial measurements of serum AFP to be of value in assessing therapeutic response. (Auth.)

  9. [Are the current concepts of obsessive disorders a novelty? From Westphal (1877) and Thomsen (1895) to ICD-10 and DSM-5].

    Oberbeck, A; Steinberg, H

    2015-09-01

    In German-speaking countries it was Carl Westphal who in 1877 offered the first precise definition of obsessive ideas and distinguished obsessive compulsive disorder (OCD) as an independent disorder in its own right. The criteria mentioned by him for establishing OCD gave rise to a debate on the character and classification of OCD but were not fully acknowledged by his colleagues at the time. In 1895 Westphal's student Robert Thomsen tried to substantiate all points in his teacher's theory that had raised criticism. Thus the works by Westphal and Thomsen are most relevant for the current conceptualization and definition of OCD, for they laid the basis for the present phenomenology, definition and classification of OCD according to ICD-10 and DSM-5. Apart from phenomenologically differentiating between obsessions (i.e. obsessive thoughts and impulses) and compulsions (i.e. compulsive actions and inhibitions), Westphal and Thomsen also laid the basis for most of the current diagnostic criteria. Thomsen led the way to current classifications by subdifferentiating OCD as an illness on its own on the one hand and obsessions and compulsions as symptoms accompanying other conditions on the other.

  10. [The inner barrier: how health psychology concepts contribute to the explanation of prehospital delays in acute myocardial infarction: a systematic analysis of the current state of knowledge].

    Ladwig, Karl-Heinz; Gärtner, Cornelia; Walz, Linda Maria; Smenes, Kerstin Regina; Ronel, Joram

    2009-12-01

    During onset of an acute myocardial infarction (AMI), less than 20 % of patients reach the hospital within an optimal time window. About 75 % of pre-hospital delay time is caused by deficits in the patients' subjective decision making. To date, little is known about the course of threat appraisal during AMI. We aim to show here that health psychology related concepts offer an attractive conceptual frame to understand paradoxical reactions of AMI patients during this life threatening phase of their life. Only if patients overcome a complex network of barriers in perception and interpretation of symptoms, AMI symptoms will become effective as cues-to-action. Perception of symptoms may be compromised by a wide range of nociceptive stimuli originating from the heart. Symptom vagueness and a mismatch between expected and perceived symptoms may limit interpretation of the threat, yet active misattributing coping strategies may be even more present. Negative outcome expectancies and an impaired perceived self-efficacy, predominately in subjects with co-morbid negative affectivity are likely to contribute to delay.

  11. Current concepts on ventricular fibrillation: A Vicious Circle of Cardiomyocyte Calcium Overload in the Initiation, Maintenance, and Termination of Ventricular Fibrillation

    Christian E. Zaugg

    2004-04-01

    Full Text Available Based on recent experimental studies, this review article introduces the novel concept that cardiomyocyte Ca2+ and ventricular fibrillation (VF are mutually related, forming a self-maintaining vicious circle in the initiation, maintenance, and termination of VF. On the one hand, elevated myocyte Ca2+ can cause delayed afterdepolarizations, triggered activity, and consequently life-threatening ventricular tachyarrhythmias in various pathological conditions such as digitalis toxicity, myocardial ischemia, or heart failure. On the other hand, VF itself directly and rapidly causes progressive myocyte Ca2+ overload that maintains VF and renders termination of VF increasingly difficult. Accordingly, energy levels for successful electrical defibrillation (defibrillation thresholds increase as both VF and Ca2+ overload progress. Furthermore, VF-induced myocyte Ca2+ overload can promote re-induction of VF after defibrillation and/or postfibrillatory myocardial dysfunction (postresuscitation stunning due to reduced myofilament Ca2+ responsiveness. The probability of these adverse events is best reduced by early detection and rapid termination of VF to prevent or limit Ca2+ overload. Early additional therapy targeting transsarcolemmal Ca2+ entry, particularly during the first 2 min of VF, may partially prevent myocyte Ca2+ overload and thus, increase the likelihood of successful defibrillation as well as prevent postfibrillatory myocardial dysfunction.

  12. Targeted Therapeutic Nanoparticles: An Immense Promise to Fight against Cancer

    Sheikh Tasnim Jahan

    2017-01-01

    Full Text Available In nanomedicine, targeted therapeutic nanoparticle (NP is a virtual outcome of nanotechnology taking the advantage of cancer propagation pattern. Tying up all elements such as therapeutic or imaging agent, targeting ligand, and cross-linking agent with the NPs is the key concept to deliver the payload selectively where it intends to reach. The microenvironment of tumor tissues in lymphatic vessels can also help targeted NPs to achieve their anticipated accumulation depending on the formulation objectives. This review accumulates the application of poly(lactic-co-glycolic acid (PLGA and polyethylene glycol (PEG based NP systems, with a specific perspective in cancer. Nowadays, PLGA, PEG, or their combinations are the mostly used polymers to serve the purpose of targeted therapeutic NPs. Their unique physicochemical properties along with their biological activities are also discussed. Depending on the biological effects from parameters associated with existing NPs, several advantages and limitations have been explored in teaming up all the essential facts to give birth to targeted therapeutic NPs. Therefore, the current article will provide a comprehensive review of various approaches to fabricate a targeted system to achieve appropriate physicochemical properties. Based on such findings, researchers can realize the benefits and challenges for the next generation of delivery systems.

  13. Evolution/Creationism Controversy: Analysis of Past and Current Policies in Public Schools and the Practice of Allowing Students to Opt Out of Learning Evolution Concepts

    Speake, Jacquelyn Hoffmann

    2011-07-01

    Recent anti-evolution legislation, in the form of Academic Freedom bills, has been introduced in many state legislatures over the last three years. The language in the proposed Academic Freedom bills may allow different interpretations of what can be taught in the science classrooms, and possibly spur parents to take advantage of their perceived parental rights to request their child be opted-out of class when the scientific theory of evolution is taught. Five research questions guided the analysis of participant responses to questions and perception statements focusing on secondary school administrators' actions, perceptions, and awareness as they relate to their decision to allow or not allow a student to opt out of academics, specifically evolution, through the collection of data using a web-based survey. Opt out policies are typically invoked to excuse students from activities to which they or their parents may have religious objections (Scott & Branch, 2008). Florida statutes allow parents to opt out their child from human sexuality and animal dissection. The population consisted of 281 Florida public secondary school administrators, who were divided into two subgroups based on whether they have allowed or would allow a student to opt out of evolution, or have not allowed or would not allow a student to opt out of class when the scientific theory of evolution is taught. Results found that over 70% of the administrators who completed the survey have allowed or would allow parents to opt out their child from learning about the scientific theory of evolution. There was a significant relationship between the decision to allow opt out and the following variables: (a) Free and Reduced Lunch population, (b) grade level served, (c) support for teaching evolution and alternative theories, and (d) the perception that parent rights supersede state statute requiring students to learn evolution. In Florida, any scientific concept that is based on empirical evidence is

  14. Concepts of formal concept analysis

    Žáček, Martin; Homola, Dan; Miarka, Rostislav

    2017-07-01

    The aim of this article is apply of Formal Concept Analysis on concept of world. Formal concept analysis (FCA) as a methodology of data analysis, information management and knowledge representation has potential to be applied to a verity of linguistic problems. FCA is mathematical theory for concepts and concept hierarchies that reflects an understanding of concept. Formal concept analysis explicitly formalizes extension and intension of a concept, their mutual relationships. A distinguishing feature of FCA is an inherent integration of three components of conceptual processing of data and knowledge, namely, the discovery and reasoning with concepts in data, discovery and reasoning with dependencies in data, and visualization of data, concepts, and dependencies with folding/unfolding capabilities.

  15. [Therapeutic education didactic techniques].

    Valverde, Maite; Vidal, Mercè; Jansa, Margarida

    2012-10-01

    This article includes an introduction to the role of Therapeutic Education for Diabetes treatment according to the recommendations of the American Diabetes Association (ADA), the Diabetes Education Study Group (DESG) of the "European Association for Study of Diabetes (EASD) and the clinical Practice Guidelines (CPG) of the Spanish Ministry of Health. We analyze theoretical models and the differences between teaching vs. learning as well as current trends (including Internet), that can facilitate meaningful learning of people with diabetes and their families and relatives. We analyze the differences, similarities, advantages and disadvantages of individual and group education. Finally, we describe different educational techniques (metaplan, case method, brainstorming, role playing, games, seminars, autobiography, forums, chats,..) applicable to individual, group or virtual education and its application depending on the learning objective.

  16. Atresia das vias biliares extra-hepáticas: conhecimentos atuais e perspectivas futuras Extrahepatic biliary atresia: current concepts and future directions

    Elisa de Carvalho

    2007-04-01

    mainly on its etiopathogenesis, diagnosis, treatment and prognosis. SOURCES: MEDLINE and PubMed databases were searched using the following keywords: biliary atresia,etiopathogenesis, diagnosis, treatment, prognosis, children. SUMMARY OF THE FINDINGS: Extrahepatic biliary atresia is the main indication for liver transplantation among pediatric patients. As to its etiology, cytomegalovirus, reovirus and rotavirus have been widely investigated as possible triggers of the immunomediated obstruction of the biliary tree. The immune response, especially the predominant TH1 and interferon-gamma responses, genetic susceptibility and disorders related to the embryonic development of the biliary tree can play a role in the etiopathogenesis of extrahepatic biliary atresia. Yet today, portoenterostomy is the only available treatment, with better results when performed in the first 2 months of life. As to prognosis, all untreated children eventually die due to complications resulting from portal hypertension and liver cirrhosis, and most treated children have to undergo liver transplantation. CONCLUSIONS: Extrahepatic biliary atresia is still the major indication for pediatric liver transplantation, and to change this scenario some more light should be shed upon the etiopathogenesis of biliary atresia in different disease phenotypes. Future research into the role of interferon-gamma and of other cytokines is necessary in order to assess whether these aspects should be potential targets for therapeutic intervention.

  17. Z-pinch driven hohlraums design for the 100 nanoseconds current time scale; Conception de cavites radiatives chauffees par plasma de striction magnetique en regime 100ns

    Hamann, F

    2003-12-15

    This work estimates Z-pinch driven hohlraums capabilities to obtain high temperatures (>200 eV). Simple models are proposed to calculate the performances offered by currents of 5 to 100 MA in 100 ns. The one dimensional physics of the Z-pinch at the length scale of its thickness and the hydrodynamics instabilities are studied. Then the enhancement of hohlraums performances with double nested Z-pinches or the use of an axial magnetic field is analysed. Z-pinch direct drive approach for inertial confinement fusion is finally considered. All the presented results are based on theoretical and 2D numerical approach and on the analysis of experimental results which were obtained on the american 'Z' generator. Annexes recall radiation MHD equations and check their validity for Z-pinch implosion. (author)

  18. Modern concepts for basic radiobiological factors characterizing tumor tissue radiosensitivity

    Gocheva, L.; Sergieva, K.

    2002-01-01

    Traditionally radiotherapy is prescribed at doses consistent with the expected therapeutic response and tolerance of tumor and normal tissues without consideration to individual differences in radiosensitivity. However, the basic radiobiological knowledge and clinical experience along this line point to significant variations in the observed therapeutic results. It has been established that cells and tissues under experimental and clinical conditions manifest a wide spectrum of individual radiosensitivity. The aim of this survey is to outline the current concepts for the basic radiobiological factors influencing tumor radiosensitivity. A thorough discussion is done of the essence, mechanisms of action, methods of determination and measurement, and effect on the prognosis in patients with malignant diseases of a number of radiobiological factors, such as: tumor-cell proliferation, apoptosis, tumor hypoxia and neovascularization. Although the knowledge of the mechanisms of radiosensitivity is constantly expanding, its clinical implementation is still rather limited. The true role of radiosensitivity in predicting the therapeutic response should be more accurately defined. (authors)

  19. Models for mature T-cell lymphomas--a critical appraisal of experimental systems and their contribution to current T-cell tumorigenic concepts.

    Warner, Kathrin; Crispatzu, Giuliano; Al-Ghaili, Nabil; Weit, Nicole; Florou, Vaia; You, M James; Newrzela, Sebastian; Herling, Marco

    2013-12-01

    Mature T-cell lymphomas/leukemias (MTCL) have been understudied lymphoid neoplasms that currently receive growing attention. Our historically rudimentary molecular understanding and dissatisfactory interventional success in this complex and for the most part poor-prognostic group of tumors is only slightly improving. A major limiting aspect in further progress in these rare neoplasms is the lack of suitable model systems that would substantially facilitate pathogenic studies and pre-clinical drug evaluations. Such representations of MTCL have thus far not been systematically appraised. We therefore provide an overview on existing models and point out their particular advantages and limitations in the context of the specific scientific questions. After addressing issues of species-specific differences and classifications, we summarize data on MTCL cell lines of human as well as murine origin, on murine strain predispositions to MTCL, on available models of genetically engineered mice, and on transplant systems. From an in-silico meta-analysis of available primary data of gene expression profiles on human MTCL we cross-reference genes reported to transform T-cells in mice and reflect on their general vs entity-restricted relevance and on target-promoter influences. Overall, we identify the urgent need for new models of higher fidelity to human MTCL with respect to their increasingly recognized diversity and to predictions of drug response. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. Potential therapeutic applications of biosurfactants.

    Gudiña, Eduardo J; Rangarajan, Vivek; Sen, Ramkrishna; Rodrigues, Lígia R

    2013-12-01

    Biosurfactants have recently emerged as promising molecules for their structural novelty, versatility, and diverse properties that are potentially useful for many therapeutic applications. Mainly due to their surface activity, these molecules interact with cell membranes of several organisms and/or with the surrounding environments, and thus can be viewed as potential cancer therapeutics or as constituents of drug delivery systems. Some types of microbial surfactants, such as lipopeptides and glycolipids, have been shown to selectively inhibit the proliferation of cancer cells and to disrupt cell membranes causing their lysis through apoptosis pathways. Moreover, biosurfactants as drug delivery vehicles offer commercially attractive and scientifically novel applications. This review covers the current state-of-the-art in biosurfactant research for therapeutic purposes, providing new directions towards the discovery and development of molecules with novel structures and diverse functions for advanced applications. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. RNAi Therapeutics in Autoimmune Disease

    Seunghee Cha

    2013-03-01

    Full Text Available Since the discovery of RNA interference (RNAi, excitement has grown over its potential therapeutic uses. Targeting RNAi pathways provides a powerful tool to change biological processes post-transcriptionally in various health conditions such as cancer or autoimmune diseases. Optimum design of shRNA, siRNA, and miRNA enhances stability and specificity of RNAi-based approaches whereas it has to reduce or prevent undesirable immune responses or off-target effects. Recent advances in understanding pathogenesis of autoimmune diseases have allowed application of these tools in vitro as well as in vivo with some degree of success. Further research on the design and delivery of effectors of RNAi pathway and underlying molecular basis of RNAi would warrant practical use of RNAi-based therapeutics in human applications. This review will focus on the approaches used for current therapeutics and their applications in autoimmune diseases, including rheumatoid arthritis and Sjögren’s syndrome.

  2. Factores y riesgos laborales psicosociales: conceptualización, historia y cambios actuales Factors and occupational psychosocial risks: concept, history and current changes

    Bernardo Moreno Jiménez

    2011-01-01

    Full Text Available El trabajo ha sido históricamente un riesgo para la salud. Las condiciones laborales han supuesto habitualmente una amenaza a la salud que han ocasionado accidentes y enfermedades relacionadas con la salud de todo tipo. La imagen popular l asociada al trabajo ha sido claramente negativa. Los tiempos han cambiado de forma muy importante, pero las condiciones laborales siguen siendo preocupantes. La preocupación por los riesgos laborales se ha centrado históricamente en los riesgos físicos y ambientales, pero se ha producido una atención creciente en los riesgos psicosociales que exigen un mayor esfuerzo de definición en sus diferentes formas. En los tiempos actuales, debido a la expansión del mercado de servicios y a la globalización los riesgos psicosociales se han incrementado e intensificado. Los datos actuales muestran que sus efectos sobre la salud son amplios e importantes. Por ello, una atención integral a la salud laboral necesita cuidar de forma especial atención a los factores y riesgos psicosociales.Work has been historically a health risk. Working conditions have usually been a threat to health causing accidents and many kind of health-related diseases. The popular image associated with work has clearly been negative. Times have changed very significantly, but working conditions remain a concern. Concern about occupational risks has historically focused on environmental and physical risks, but there has been increasing attention on psychosocial risks which require a greater effort to be defined. In modern times, due to services market expansion and globalization, psychosocial risks have increased and intensified. Current data show that psychosocial risks cause important health effects. Therefore, it is important make special attention to psychosocial factors and risks.

  3. Brain-computer interface training combined with transcranial direct current stimulation in patients with chronic severe hemiparesis: Proof of concept study.

    Kasashima-Shindo, Yuko; Fujiwara, Toshiyuki; Ushiba, Junichi; Matsushika, Yayoi; Kamatani, Daiki; Oto, Misa; Ono, Takashi; Nishimoto, Atsuko; Shindo, Keiichiro; Kawakami, Michiyuki; Tsuji, Tetsuya; Liu, Meigen

    2015-04-01

    Brain-computer interface technology has been applied to stroke patients to improve their motor function. Event-related desynchronization during motor imagery, which is used as a brain-computer interface trigger, is sometimes difficult to detect in stroke patients. Anodal transcranial direct current stimulation (tDCS) is known to increase event-related desynchronization. This study investigated the adjunctive effect of anodal tDCS for brain-computer interface training in patients with severe hemiparesis. Eighteen patients with chronic stroke. A non-randomized controlled study. Subjects were divided between a brain-computer interface group and a tDCS- brain-computer interface group and participated in a 10-day brain-computer interface training. Event-related desynchronization was detected in the affected hemisphere during motor imagery of the affected fingers. The tDCS-brain-computer interface group received anodal tDCS before brain-computer interface training. Event-related desynchronization was evaluated before and after the intervention. The Fugl-Meyer Assessment upper extremity motor score (FM-U) was assessed before, immediately after, and 3 months after, the intervention. Event-related desynchronization was significantly increased in the tDCS- brain-computer interface group. The FM-U was significantly increased in both groups. The FM-U improvement was maintained at 3 months in the tDCS-brain-computer interface group. Anodal tDCS can be a conditioning tool for brain-computer interface training in patients with severe hemiparetic stroke.

  4. Modeling plant density and ponding water effects on flooded rice evapotranspiration and crop coefficients: critical discussion about the concepts used in current methods

    Aschonitis, Vassilis; Diamantopoulou, Maria; Papamichail, Dimitris

    2018-05-01

    The aim of the study is to propose new modeling approaches for daily estimations of crop coefficient K c for flooded rice ( Oryza sativa L., ssp. indica) under various plant densities. Non-linear regression (NLR) and artificial neural networks (ANN) were used to predict K c based on leaf area index LAI, crop height, wind speed, water albedo, and ponding water depth. Two years of evapotranspiration ET c measurements from lysimeters located in a Mediterranean environment were used in this study. The NLR approach combines bootstrapping and Bayesian sensitivity analysis based on a semi-empirical formula. This approach provided significant information about the hidden role of the same predictor variables in the Levenberg-Marquardt ANN approach, which improved K c predictions. Relationships of production versus ET c were also built and verified by data obtained from Australia. The results of the study showed that the daily K c values, under extremely high plant densities (e.g., for LAI max > 10), can reach extremely high values ( K c > 3) during the reproductive stage. Justifications given in the discussion question both the K c values given by FAO and the energy budget approaches, which assume that ET c cannot exceed a specific threshold defined by the net radiation. These approaches can no longer explain the continuous increase of global rice yields (currently are more than double in comparison to the 1960s) due to the improvement of cultivars and agriculture intensification. The study suggests that the safest method to verify predefined or modeled K c values is through preconstructed relationships of production versus ET c using field measurements.

  5. Enactments in Psychoanalysis: Therapeutic Benefits.

    Stern, Stanley

    The therapeutic benefits of enactments are addressed. Relevant literature reveals disparate conceptions about the nature and use of enactments. Clarification of the term is discussed. This analyst's theoretical and technical evolution is addressed; it is inextricably related to using enactments. How can it not be? A taxonomy of enactments is presented. The article considers that enactments may be fundamental in the evolution from orthodox to contemporary analytic technique. Assumptions underlying enactments are explored, as are guidelines for using enactments. Finally, the article posits that enactments have widened the scope of analysis and contributed to its vitality.

  6. Molecularly targeted therapeutic radiopharmaceuticals

    Saw, M.M.

    2007-01-01

    Full text: It is generally agreed that current focus of nuclear medicine development should be on molecular imaging and therapy. Though, the widespread use of the terminology 'molecular imaging' is quite recent, nuclear medicine has used molecular imaging techniques for more than 20 years ago. A variety of radiopharmaceuticals have been introduced for the internal therapy of malignant and inflammatory lesions in nuclear medicine. In the field of bio/medical imaging, nuclear medicine is one of the disciplines which has the privilege of organized and well developed chemistry/ pharmacy section; radio-chemistry/radiopharmacy. Fundamental principles have been developed more than 40 years ago and advanced research is going well into postgenomic era. The genomic revolution and dramatically increased insight in the molecular mechanisms underlying pathology have led to paradigm shift in drug development. Likewise does in the nuclear medicine. Here, the author will present current clinical and pre-clinical therapeutic radiopharmaceuticals based on molecular targets such as membrane-bound receptors, enzymes, nucleic acids, sodium iodide symporter, etc, in correlation with fundamentals of radiopharmacy. (author)

  7. The effects of therapeutic touch on pain.

    Monroe, Carolyn Magdalen

    2009-06-01

    To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

  8. Sinigrin and Its Therapeutic Benefits

    Anisha Mazumder

    2016-03-01

    Full Text Available Sinigrin (allyl-glucosinolate or 2-propenyl-glucosinolate is a natural aliphatic glucosinolate present in plants of the Brassicaceae family, such as broccoli and brussels sprouts, and the seeds of Brassica nigra (mustard seeds which contain high amounts of sinigrin. Since ancient times, mustard has been used by mankind for its culinary, as well as medicinal, properties. It has been systematically described and evaluated in the classical Ayurvedic texts. Studies conducted on the pharmacological activities of sinigrin have revealed anti-cancer, antibacterial, antifungal, antioxidant, anti-inflammatory, wound healing properties and biofumigation. This current review will bring concise information about the known therapeutic activities of sinigrin. However, the information on known biological activities is very limited and, hence, further studies still need to be conducted and its molecular mechanisms also need to be explored. This review on the therapeutic benefits of sinigrin can summarize current knowledge about this unique phytocompounds.

  9. Reactor-produced therapeutic radioisotopes

    Knapp, F.F. Jr.

    2002-01-01

    contribution will focus on the issues associated with the reactor-production of therapeutic radioisotopes of current and projected interest

  10. Current concepts in C3 glomerulopathy

    S Thomas

    2014-01-01

    Full Text Available Complement component 3 glomerulopathy (C3G is a recently defined entity comprising of dense deposit disease and C3 glomerulonephritis. The key histological feature is the presence of isolated C3 deposits without immunoglobulins. Often masqueradng as some of the common glomerulonephritides this is a prototype disorder occurring from dysregulated alternate complement pathway with recently identified genetic defects and autoantibodies. We review the pathophysiology, clinical features, and diagnostic and treatment strategies.

  11. Nelson syndrome: historical perspectives and current concepts.

    Hornyak, Mark; Weiss, Martin H; Nelson, Don H; Couldwell, William T

    2007-01-01

    The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958. The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels. The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy. Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well. In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity. The authors describe the history of the diagnosis and treatment of Nelson syndrome. In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.

  12. Congenital anophthalmia: current concepts in management.

    Quaranta-Leoni, Francesco M

    2011-09-01

    The introduction of hydrogel socket and orbital expanders has modified the approach towards the rehabilitation of congenital anophthalmia. This study highlights the most recent advances for the treatment of congenital anophthalmia based on personal experience and the review of recent literature. Hydrogel socket expanders may be positioned as an out-patient procedure with topical anaesthesia, using cyanoacrylate glue as opposed to temporary tarsorraphy. Increased orbital volume has been confirmed by computed tomography (CT) scan or magnetic resonance imaging (MRI) following early dermis-fat graft in children with congenital anophthalmia. An orbital tissue expander made of an inflatable silicone globe sliding on a titanium T-plate and secured to the lateral orbital rim appears to be effective to stimulate orbital bone growth and development. Congenital anophthalmia has a complex cause with both genetic and environmental factors involved. The ideal treatment is simultaneous expansion of the eyelids, socket and orbital bones, and it should begin after birth as soon as possible. Socket expansion with self-inflating expanders is a useful technique, although custom-made conformers may produce similar results. Dermis-fat grafts are another reasonable option as an orbital implant, following adequate lid and socket expansion.

  13. Maxillary reconstruction: Current concepts and controversies

    Subramania Iyer

    2014-01-01

    Full Text Available Maxillary reconstruction is still an evolving art when compared to the reconstruction of the mandible. The defects of maxilla apart from affecting the functions of the speech, swallowing and mastication also cause cosmetic disfigurement. Rehabilitation of the form and function in patients with maxillary defects is either by using an obturator prosthesis or by a surgical reconstruction. Literature is abundant with a variety of reconstructive methods. The classification systems are also varied, with no universal acceptance of any one of them. The oncologic safety of these procedures is still debated, and conclusive evidence in this regard has not emerged yet. Management of the orbit is also not yet addressed properly. Tissue engineering, that has been hyped to be one of the possible solutions for this vexing reconstructive problem, has not come out with reliable and reproducible results so far. This review article discusses the rationale and oncological safety of the reconstructing the maxillary defects, critically analyzes the classification systems, offers the different reconstructive methods and touches upon the controversies in this subject. The management of the retained and exenterated orbit associated with maxillectomy is reviewed. The surgical morbidity, complications and the recent advances in this field are also looked into. An algorithm, based on our experience, is presented.

  14. Maxillary reconstruction: Current concepts and controversies

    Iyer, Subramania; Thankappan, Krishnakumar

    2014-01-01

    Maxillary reconstruction is still an evolving art when compared to the reconstruction of the mandible. The defects of maxilla apart from affecting the functions of the speech, swallowing and mastication also cause cosmetic disfigurement. Rehabilitation of the form and function in patients with maxillary defects is either by using an obturator prosthesis or by a surgical reconstruction. Literature is abundant with a variety of reconstructive methods. The classification systems are also varied, with no universal acceptance of any one of them. The oncologic safety of these procedures is still debated, and conclusive evidence in this regard has not emerged yet. Management of the orbit is also not yet addressed properly. Tissue engineering, that has been hyped to be one of the possible solutions for this vexing reconstructive problem, has not come out with reliable and reproducible results so far. This review article discusses the rationale and oncological safety of the reconstructing the maxillary defects, critically analyzes the classification systems, offers the different reconstructive methods and touches upon the controversies in this subject. The management of the retained and exenterated orbit associated with maxillectomy is reviewed. The surgical morbidity, complications and the recent advances in this field are also looked into. An algorithm, based on our experience, is presented. PMID:24987199

  15. Fibrosis imaging : Current concepts and future directions

    Baues, Maike; Dasgupta, Anshuman; Ehling, Josef; Prakash, Jai; Boor, Peter; Tacke, Frank; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Fibrosis plays an important role in many different pathologies. It results from tissue injury, chronic inflammation, autoimmune reactions and genetic alterations, and it is characterized by the excessive deposition of extracellular matrix components. Biopsies are routinely employed for fibrosis

  16. Bone island (enostosis): current concept - a review

    Greenspan, A.

    1995-01-01

    A bone island can be virtually diagnosed based on its characteristic clinical and radiologic features. Typically asymptomatic, the lesion is usually an incidental finding, with a preference for the pelvis, femur, and other long bones, although it may be found anywhere in the skeleton, including the spine. Plain radiography reveals a homogeneously dense, sclerotic focus in the cancellous bone with distinctive radiating bony streaks (''thorny radiation'') that blend with the trabeculae of the host bone, creating a feathered or brush-like border. On CT scan, a bone island appears as a low-attenuation focus, and on MRI sequences it shows low signal intensity like cortical bone. A distinguishing feature of bone islands is that they are usually ''cold'' on skeletal scintigraphy. Thus, bone scan has been and continues to be the means of differentiating bone islands from the more aggressive entities. However, reports of histologically confirmed bone islands that were scintigraphically active have raised a note of caution about relying on this modality in the differential consideration of lesions otherwise characteristic of bone islands. Guides to the correct diagnosis should be looked for in the individual clinical situation and in the morphologic features of the lesion on plain radiography, CT, and MRI, without regard to the lesion's activity on bone scan. If such a lesion, however, is symptomatic and ''hot'' on scintigraphy, it demands close observation with follow-up imaging studies. (orig./VHE)

  17. Current concepts review: Fractures of the patella

    Gwinner, Clemens; Märdian, Sven; Schwabe, Philipp; Schaser, Klaus-D.; Krapohl, Björn Dirk; Jung, Tobias M.

    2016-01-01

    Fractures of the patella account for about 1% of all skeletal injuries and can lead to profound impairment due to its crucial function in the extensor mechanism of the knee. Diagnosis is based on the injury mechanism, physical examination and radiological findings. While the clinical diagnosis is often distinct, there are numerous treatment options available. The type of treatment as well as the optimum timing of surgical intervention depends on the underlying fracture type, the associated soft tissue damage, patient factors (i.e. age, bone quality, activity level and compliance) and the stability of the extensor mechanism. Regardless of the treatment method an early rehabilitation is recommended in order to avoid contractures of the knee joint capsule and cartilage degeneration. For non-displaced and dislocated non-comminuted transverse patellar fractures (2-part) modified anterior tension band wiring is the treatment of choice and can be combined – due to its biomechanical superiority – with cannulated screw fixation. In severe comminuted fractures, open reduction and fixation with small fragment screws or new angular stable plates for anatomic restoration of the retropatellar surface and extension mechanism results in best outcome. Additional circular cerclage wiring using either typical metal cerclage wires or resorbable PDS/non-resorbable FiberWires increases fixation stability and decreases risk for re-dislocation. Distal avulsion fractures should be fixed with small fragment screws and should be protected by a transtibial McLaughlin cerclage. Partial or complete patellectomy should be regarded only as a very rare salvage operation due to its severe functional impairment. PMID:26816667

  18. SUBCLINICAL HYPOTHYROIDISM CURRENT CONCEPTS & M ANAGEMENT STRATEGEIES

    Radha Krishnan; Soumini; Adithya

    2015-01-01

    Subclinical hypothyroidism is a biochemical diagnosis characterized by raised thyroid stimulating hormone ( TSH ) and normal free T3 & T4 , without clinical features of hypothyroidism . Clinical significance of SCH remains uncertain and controversial . Symptoms of SCH may vary from being asymptomatic to having mild nonspecific symptoms . There are still controversies surrounding SCH and associated risk of ...

  19. Current conceptions of industrial quality assurance

    Zeller, H.

    1978-01-01

    In the electrical engineering industry quality assurance is mainly oriented in accordance with the customers', users', and consumers' requirements concerning the quality of products (including reliability). These requirements are as manifold as the range of products itself. They do not only comprise functional criteria, but also safety against malfunctions, bodily injury or property damage. Quality assurance is embedded in the overall activities of a company; the peripheral conditions, such as organization, profitability, qualification, and responsibility of staff have to be considered. Thus, quality assurance in the electrical engineering industry proceeds in efficient systems which are adapted to the individual forms of production. These systems may include planning, testing, feedback of quality data, statistical procedures, costs and profitability. Their obvious interaction is based on the system of coordinates of integrated quality control. The paper will illustrate the basic features of this interaction by reference to various examples. (orig.) [de

  20. Patellofemoral anatomy and biomechanics: current concepts

    ZAFFAGNINI, STEFANO; DEJOUR, DAVID; GRASSI, ALBERTO; BONANZINGA, TOMMASO; MUCCIOLI, GIULIO MARIA MARCHEGGIANI; COLLE, FRANCESCA; RAGGI, FEDERICO; BENZI, ANDREA; MARCACCI, MAURILIO

    2013-01-01

    The patellofemoral joint, due to its particular bone anatomy and the numerous capsuloligamentous structures and muscles that act dynamically on the patella, is considered one of the most complex joints in the human body from the biomechanical point of view. The medial patellofemoral ligament (MPFL) has been demonstrated to contribute 60% of the force that opposes lateral displacement of the patella, and MPFL injury results in an approximately 50% reduction in the force needed to dislocate the patella laterally with the knee extended. For this reason, recent years have seen a growing interest in the study of this important anatomical structure, whose aponeurotic nature has thus been demonstrated. The MPFL acts as a restraint during motion, playing an active role under conditions of laterally applied stress, but an only marginal role during natural knee flexion. However, it remains extremely difficult to clearly define the anatomy of the MPFL and its relationships with other anatomical structures. PMID:25606512

  1. Current Concepts in Restorative Implant Dentistry

    Prof.Marchack

    2009-01-01

    Patients today are incteasingly aware of dental implants.and their expectations are for esthetically and functionally pleasingimplant restorations that mimic natural teeth.This presentation will give both the experienced and novice practitioner a better understand-ing of how restorative implant dentistry has evolved.Treatment planning and restorative options for single implants.multiple implants andfully edentulons arches will be discussed,and the use of modern materials and CADCAM technology in fabricating the most contemporaryfixed implant supported prostheses will be demonstrated.

  2. Perfusion MRI in CNS disease: current concepts

    Essig, M.; Giesel, F.; Le-Huu, M.; Stieltjes, B.; Tengg, H. von; Weber, M.-A.

    2004-01-01

    Today there are several indications for cerebral perfusion MRI. The major indications routinely used in increasing numbers of imaging centers include cerebrovascular disease, tumor imaging and recently psychiatric disorders. Perfusion MRI is based on the injection of a gadolinium chelate and the rapid acquisition of images as the bolus of contrast agent passes through the blood vessels in the brain. The contrast agent causes a signal change; this signal change over time can be analysed to measure cerebral hemodynamics. The quality of brain perfusion studies is very dependent on the contrast agent used: a robust and strong signal decrease with a compact bolus is needed. MultiHance (gadobenate dimeglumine, Gd-BOPTA) is the first of a new class of paramagnetic MR contrast agents with a weak affinity for serum proteins. Due to the interaction of Gd-BOPTA with serum albumin, MultiHance presents with significantly higher T1- and T2-relaxivities enabling a sharper bolus profile. This article reviews the indications of perfusion MRI and the performance of MultiHance in MR perfusion of different diseases. Previous studies using perfusion MRI for a variety of purposes required the use of double dose of contrast agent to achieve a sufficiently large signal drop to enable the acquisition of a clear input function and the calculation of perfusion rCBV and rCBF maps of adequate quality. Recent studies with Multi-Hance suggest that only a single dose of this agent is needed to cause a signal drop of about 30% which is sufficient to allow the calculation of high quality rCBV and rCBF maps. (orig.)

  3. Extended trochanteric osteotomy: current concepts review.

    Sambandam, Senthil Nathan; Duraisamy, Gopinath; Chandrasekharan, Jayadev; Mounasamy, Varatharaj

    2016-04-01

    Revision total hip arthroplasty is a technically demanding procedure which has gained importance for more than two decades. It was a nightmare for revision surgeons during its initial years of inception before the advent of extended trochanteric osteotomy (ETO). This technique gains access to the femoral medullary canal without compromising the bone stock and aids removal of primary implant and cement mantle without further damaging the parent bone. Like any other surgery, ETO does have certain limitations and complications as reported by various authors. Though it has been routinely used by revision surgeons, thorough knowledge of technical details of ETO is still lacking. So this review article is aimed at addressing the indications, surgical procedure, fixation technique, implant selection and complication of ETO which has been presented over a period of years by various authors. We searched in the most commonly used portals like MEDLINE (PubMed) and Google scholar using appropriate terminologies for the literature regarding the various preoperative, intraoperative and postoperative clinical scenarios in which revision surgeons utilized ETO. ETO is an important tool in the revision surgeon's armamentarium and can be used in variety of clinical scenarios and for various intraoperative needs and goals. Awareness about biomechanics of ETO, indications, implants selection, fixation techniques and complications is paramount for good intraoperative and postoperative outcome. ETO by posterior approach continues to be a work horse approach for most revision surgeons all over the world.

  4. Current concepts in chronic inflammatory diseases

    Garn, Holger; Bahn, Sabine; Baune, Bernhard T

    2016-01-01

    Recent research indicates that chronic inflammatory diseases, including allergies and autoimmune and neuropsychiatric diseases, share common pathways of cellular and molecular dysregulation. It was the aim of the International von-Behring-Röntgen Symposium (October 16-18, 2014, in Marburg, Germany...

  5. Adolescent patellar instability: current concepts review.

    Clark, D; Metcalfe, A; Wogan, C; Mandalia, V; Eldridge, J

    2017-02-01

    Patellar instability most frequently presents during adolescence. Congenital and infantile dislocation of the patella is a distinct entity from adolescent instability and measurable abnormalities may be present at birth. In the normal patellofemoral joint an increase in quadriceps angle and patellar height are matched by an increase in trochlear depth as the joint matures. Adolescent instability may herald a lifelong condition leading to chronic disability and arthritis. Restoring normal anatomy by trochleoplasty, tibial tubercle transfer or medial patellofemoral ligament (MPFL) reconstruction in the young adult prevents further instability. Although these techniques are proven in the young adult, they may cause growth arrest and deformity where the physis is open. A vigorous non-operative strategy may permit delay of surgery until growth is complete. Where non-operative treatment has failed a modified MPFL reconstruction may be performed to maintain stability until physeal closure permits anatomical reconstruction. If significant growth remains an extraosseous reconstruction of the MPFL may impart the lowest risk to the physis. If minor growth remains image intensifier guided placement of femoral intraosseous fixation may impart a small, but acceptable, risk to the physis. This paper presents and discusses the literature relating to adolescent instability and provides a framework for management of these patients. Cite this article: Bone Joint J 2017;99-B:159-70. ©2017 The British Editorial Society of Bone & Joint Surgery.

  6. Aneurysmal disease – current management concepts

    abdominal pulsation or present with one of the complications of .... cardiopulmonary and renal co-morbidities. (ASA III .... extending into the common iliac arteries (a), requiring an aortobi-iliac (b) or aortobi-femoral (c) bypass using a bifurcated.

  7. Shoulder Stiffness : Current Concepts and Concerns

    Itoi, Eiji; Arce, Guillermo; Bain, Gregory I.; Diercks, Ronald L.; Guttmann, Dan; Imhoff, Andreas B.; Mazzocca, Augustus D.; Sugaya, Hiroyuki; Yoo, Yon-Sik

    Shoulder stiffness can be caused by various etiologies such as immobilization, trauma, or surgical interventions. The Upper Extremity Committee of ISAKOS defined the term "frozen shoulder" as idiopathic stiff shoulder, that is, without a known cause. Secondary stiff shoulder is a term that should be

  8. Current concepts in nuclear pore electrophysiology.

    Bustamante, José Omar

    2006-01-01

    Over 4 decades ago, microelectrode studies of in situ nuclei showed that, under certain conditions, the nuclear envelope (NE) behaves as a barrier opposing the nucleocytoplasmic flow of physiological ions. As the nuclear pore complexes (NPCs) of the NE are the only pathways for direct nucleocytoplasmic flow, those experiments implied that the NPCs are capable of restricting ion flow. These early studies validated electrophysiology as a useful approach to quantify some of the mechanisms by which NPCs mediate gene activity and expression. Since electron microscopy (EM) and other non-electrophysiological investigations, showed that the NPC lumen is a nanochannel, the opinion prevailed that the NPC could not oppose the flow of ions and, therefore, that electrophysiological observations resulted from technical artifacts. Consequently, the initial enthusiasm with nuclear electrophysiology faded out in less than a decade. In 1990, nuclear electrophysiology was revisited with patch-clamp, the most powerful electrophysiological technique to date. Patch-clamp has consistently demonstrated that the NE has intrinsic ion channel activity. Direct demonstrations of the NPC on-off ion channel gating behavior were published for artificial conditions in 1995 and for intact living nuclei in 2002. This on-off switching/gating behavior can be interpreted in terms of a metastable energy barrier. In the hope of advancing nuclear electrophysiology, and to complement the other papers contained in this special issue of the journal, here I review some of the main technical, experimental, and theoretical issues of the field, with special focus on NPCs.

  9. COMET concept

    Alsmeyer, H.; Tromm, W.

    1995-01-01

    Studies of the COMET core catcher concept developed for a future PWR have been continued. The concept is based on the spreading of a core melt on a sacrificial layer and its erosion, until a subsequent addition of water from below causes a fragmentation of the melt. A porous solidification of the melt would then admit a complete flooding within a short period. (orig.)

  10. Concept Mapping

    Technology & Learning, 2005

    2005-01-01

    Concept maps are graphical ways of working with ideas and presenting information. They reveal patterns and relationships and help students to clarify their thinking, and to process, organize and prioritize. Displaying information visually--in concept maps, word webs, or diagrams--stimulates creativity. Being able to think logically teaches…

  11. Management concepts.

    Bittner, Rhonda

    2006-01-01

    Management concepts evolve through time. Health care managers can learn new concepts by evaluating classical management strategies, as well as modern-day strategies. Focusing on quality improvement and team building can help managers align the goals of their departments with the goals of the organization, consequently improving patient care.

  12. Therapeutic radionuclides: Making the right choice

    Srivastava, S.C.

    1996-01-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

  13. Innovative confinement concepts workshop

    Kirkpatrick, R.C.

    1998-01-01

    The Innovative Confinement Concepts Workshop occurred in California during the week preceding the Second Symposium on Current Trends in International Fusion Research. An informal report was made to the Second Symposium. A summary of the Workshop concluded that some very promising ideas were presented, that innovative concept development is a central element of the restructured US DOE. Fusion Energy Sciences program, and that the Workshop should promote real scientific progress in fusion

  14. Lateral Concepts

    Gad, Christopher; Bruun Jensen, casper

    2016-01-01

    This essay discusses the complex relation between the knowledges and practices of the researcher and his/her informants in terms of lateral concepts. The starting point is that it is not the prerogative of the (STS) scholar to conceptualize the world; all our “informants” do it too. This creates...... the possibility of enriching our own conceptual repertoires by letting them be inflected by the concepts of those we study. In a broad sense, the lateral means that there is a many-to-many relation between domains of knowledge and practice. However, each specific case of the lateral is necessarily immanent...... to a particular empirical setting and form of inquiry. In this sense lateral concepts are radically empirical since it locates concepts within the field. To clarify the meaning and stakes of lateral concepts, we first make a contrast between lateral anthropology and Latour’s notion of infra-reflexivity. We end...

  15. Concept theory

    Hjørland, Birger

    2009-01-01

      Concept theory is an extremely broad, interdisciplinary and complex field of research related to many deep fields with very long historical traditions without much consensus. However, information science and knowledge organization cannot avoid relating to theories of concepts. Knowledge...... organizing systems (e.g. classification systems, thesauri and ontologies) should be understood as systems basically organizing concepts and their semantic relations. The same is the case with information retrieval systems. Different theories of concepts have different implications for how to construe......, evaluate and use such systems. Based on "a post-Kuhnian view" of paradigms this paper put forward arguments that the best understanding and classification of theories of concepts is to view and classify them in accordance with epistemological theories (empiricism, rationalism, historicism and pragmatism...

  16. Concept Analysis: Music Therapy.

    Murrock, Carolyn J; Bekhet, Abir K

    2016-01-01

    Down through the ages, music has been universally valued for its therapeutic properties based on the psychological and physiological responses in humans. However, the underlying mechanisms of the psychological and physiological responses to music have been poorly identified and defined. Without clarification, a concept can be misused, thereby diminishing its importance for application to nursing research and practice. The purpose of this article was for the clarification of the concept of music therapy based on Walker and Avant's concept analysis strategy. A review of recent nursing and health-related literature covering the years 2007-2014 was performed on the concepts of music, music therapy, preferred music, and individualized music. As a result of the search, the attributes, antecedents, and consequences of music therapy were identified, defined, and used to develop a conceptual model of music therapy. The conceptual model of music therapy provides direction for developing music interventions for nursing research and practice to be tested in various settings to improve various patient outcomes. Based on Walker and Avant's concept analysis strategy, model and contrary cases are included. Implications for future nursing research and practice to use the psychological and physiological responses to music therapy are discussed.

  17. German emergency management concept

    Burkart, K.

    1993-01-01

    The advantages and disadvantages of the margin and start-up value concepts (according to ICRP 40 and EU-ordinances) are explained, and it is demonstrated that the two concepts are combinable. The combined concept has the advantage of immediately providing, if required, intervention levels for the various measures to be taken, and of obliging those persons concerned with emergency protection to study and quantify, already at the planning stage, the influence of a range of accident conditions on the decision on measures. In this context, the use of computerized decision support systems which are currently being developed is indispensable. (orig./DG) [de

  18. The concept of psychical trauma: a bridge in interdisciplinary space.

    Tutté, Juan Carlos

    2004-08-01

    The concept of trauma currently occupies a central position in interdisciplinary dialogue. Using the concept of psychical trauma as a bridge, the author attempts an interdisciplinary dialogue with psychiatry, biology and neuroscience. Beginning with the concept of psychical trauma in Freud, the author reviews the evolution of Freud's thinking, and links it with the ideas of Ferenczi and post-Freudian psychoanalytical authors. From a different framework, he considers the present state of research on post-traumatic stress disorder in current psychiatric nosography and attempts an interdisciplinary approximation to the concept of psychical trauma. Interesting ideas like the traumatic situation, trauma spectrum and psychopathological spectrum emerge, which enable a better understanding of the concept of psychical trauma through its relatedness, as a bridge connecting a broad psychopathological range extending from normality to psychosis. The ensuing possible relative loss of nosographical rigour is more than compensated by the resulting increased understanding and enlarged therapeutic possibilities. In the second part of the paper, the author attempts a dialogue with neuroscience, taking into account new advances in current research on emotion and memory, and making them compatible with the psychoanalytical concept of trauma. In this sense, the paper underlines the importance of emotion and crucially of memory, regarded as a fundamental axis of the subject explored in this paper. Here a substantial distinction which is pertinent for analytical work appears: declarative memories versus non-declarative or procedural memories. In a concluding discussion the author argues that, taking into account the implications of these current notions regarding a number of theoretical and technical aspects, psychoanalysis currently holds a privileged position, both in its potential for prevention and regarding the treatment of patients, in so far as, through interdisciplinary dialogue

  19. Novel approach to cancer therapeutics using comparative cancer biology

    Revi, Bhindu

    2018-01-01

    Developing personalized cancer therapies based on cancer genomics methodologies forms the basis for future cancer therapeutics. A genomics platform was developed based on canine cancer to produce a proof-of-concept for personalized genomics led therapeutic choices but also developing personalized therapeutics for canine cancer patients themselves. The platform identified the genetic state of a canine cancer patient within two drugable pathways; p53 and HSP90/IRF1. The former ge...

  20. Student Wellbeing and the Therapeutic Turn in Education

    Wright, Katie

    2014-01-01

    This article considers current concerns with promoting student mental health and wellbeing against the backdrop of critiques of the "therapeutic turn" in education. It begins by situating accounts of "therapeutic education" within broader theorisation of therapeutic culture. In doing so, the importance of this work is…

  1. Travelling Concepts

    Simonsen, Karen-Margrethe

    2013-01-01

    Review of "Travelling Concepts, Metaphors, and Narratives: Literary and Cultural Studies in an Age of Interdisciplinary Research" ed. by Sibylle Baumgarten, Beatrice Michaelis and Ansagar Nünning, Trier; Wissenschaftlicher Verlag Trier, 2012......Review of "Travelling Concepts, Metaphors, and Narratives: Literary and Cultural Studies in an Age of Interdisciplinary Research" ed. by Sibylle Baumgarten, Beatrice Michaelis and Ansagar Nünning, Trier; Wissenschaftlicher Verlag Trier, 2012...

  2. Therapeutic approaches for celiac disease

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  3. Dental therapeutic systems.

    Iqbal, Zeenat; Jain, Nilu; Jain, Gaurav K; Talegaonkar, Sushama; Ahuja, Alka; Khar, Roop K; Ahmad, Farhan J

    2008-01-01

    The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in

  4. Unexplored therapeutic opportunities in the human genome

    Oprea, Tudor I; Bologa, Cristian G; Brunak, Søren

    2018-01-01

    A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially d...... as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development....

  5. Current management of overactive bladder.

    Cartwright, Rufus; Renganathan, Arasee; Cardozo, Linda

    2008-10-01

    The concept of overactive bladder has helped us address the problem of urgency and urge incontinence from a symptomatic perspective. In this review, we provide a critical summary of clinically relevant recent publications, focusing in particular on advances in our understanding of assessment methods and therapeutic interventions for overactive bladder in women. According to current definitions, the prevalence of overactive bladder in western nations is now estimated as 13.0%. Although the prevalence increases with age, the symptoms of overactive bladder may follow a relapsing and remitting course. There has been a proliferation of validated symptom and quality of life measures and increasing sophistication in the analysis of bladder diaries. The role of urodynamics in the evaluation of urgency remains uncertain, with many trials showing limited benefit as a preoperative investigation. Fluid restriction and bladder retraining remain important first-line interventions. Many new anticholinergic medications have been licensed, with limited benefits compared with existing preparations. Intravesical botulinum toxin has become a popular alternative for patients who fail oral therapies. Although there have been few important therapeutic innovations, recent publications have led to greater sophistication in assessment methods and a clearer understanding of the role of existing interventions.

  6. Basic concepts in oceanography

    Small, L.F.

    1997-01-01

    Basic concepts in oceanography include major wind patterns that drive ocean currents, and the effects that the earth's rotation, positions of land masses, and temperature and salinity have on oceanic circulation and hence global distribution of radioactivity. Special attention is given to coastal and near-coastal processes such as upwelling, tidal effects, and small-scale processes, as radionuclide distributions are currently most associated with coastal regions. (author)

  7. Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 2: Role of Growth Factors in Normal and Pathological Wound Healing: Therapeutic Potential and Methods of Delivery

    Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

    2012-01-01

    This is the second of 2 articles that discuss the biology and pathophysiology of wound healing, reviewing the role that growth factors play in this process and describing the current methods for growth factor delivery into the wound bed. PMID:22820962

  8. Sound Search Engine Concept

    2006-01-01

    Sound search is provided by the major search engines, however, indexing is text based, not sound based. We will establish a dedicated sound search services with based on sound feature indexing. The current demo shows the concept of the sound search engine. The first engine will be realased June...

  9. Conotoxins that confer therapeutic possibilities

    Essack, Magbubah

    2012-06-04

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  10. Diagnostic and therapeutic peroral cholangioscopy

    Jong Ho Moon

    2012-01-01

    Full Text Available Peroral cholangioscopy (POC provides direct visualization of the bile duct and facilitates diagnostic or therapeutic intervention. The currently available single-operator POC systems are "Mother-baby" scope system, SpyGlass direct visualization system, and direct POC using a regular ultra-slim upper endoscope. Direct POC using an ultra-slim upper endoscope having a larger 2-mm working channel can provide a valuable and economic solution for evaluating bile-duct lesions. Main diagnostic procedures under direct POC are visual characterization and optically guided target biopsy for the indeterminate bile duct lesion. Image-enhanced endoscopy such as narrow-band imaging has shown promise for more detailed evaluation of mucosal abnormality and can be performed under direct POC. Intracorporeal lithotripsy such as electrohydraulic lithotripsy or laser lithotripsy is a main therapeutic intervention of direct POC for patients with bile duct stones that are resistant to conventional endoscopic stone-removal procedures. Besides, tumor ablation therapy, such as photodynamic therapy and argon plasma coagulation may be also performed using direct POC. Further developments of the endoscope and specialized accessories or devices are expected to facilitate diagnostic and therapeutic role of this cholangioscopic procedure.

  11. Conotoxins that confer therapeutic possibilities

    Essack, Magbubah; Bajic, Vladimir B.; Archer, John A.C.

    2012-01-01

    Cone snails produce a distinctive repertoire of venom peptides that are used both as a defense mechanism and also to facilitate the immobilization and digestion of prey. These peptides target a wide variety of voltage- and ligand-gated ion channels, which make them an invaluable resource for studying the properties of these ion channels in normal and diseased states, as well as being a collection of compounds of potential pharmacological use in their own right. Examples include the United States Food and Drug Administration (FDA) approved pharmaceutical drug, Ziconotide (Prialt; Elan Pharmaceuticals, Inc.) that is the synthetic equivalent of the naturally occurring ?-conotoxin MVIIA, whilst several other conotoxins are currently being used as standard research tools and screened as potential therapeutic drugs in pre-clinical or clinical trials. These developments highlight the importance of driving conotoxin-related research. A PubMed query from 1 January 2007 to 31 August 2011 combined with hand-curation of the retrieved articles allowed for the collation of 98 recently identified conotoxins with therapeutic potential which are selectively discussed in this review. Protein sequence similarity analysis tentatively assigned uncharacterized conotoxins to predicted functional classes. Furthermore, conotoxin therapeutic potential for neurodegenerative disorders (NDD) was also inferred. 2012 by the authors; licensee MDPI.

  12. Ancient Indian concepts about phenomenology, biology, and therapeutics of epilepsy.

    Arya, Ravindra

    2018-01-01

    This article discusses etiology, pathogenesis, symptoms, and treatment of epilepsy, as described in Charaka Samhitā (translation: Charaka's Compendium) and Sushruta Samhitā, the two core texts of Ayurveda, an ancient system of medicine. Ayurveda emphasized amnesia and loss of consciousness as core features of epileptic seizures (Sanskrit: apasmar; translation: apa negation, smaran memory) and recognized that seizures occur due to a disturbance in brain function or flow of "humors" to the brain. Semiology of various seizure types was well described. Epilepsy was attributed to both internal and multiple exogenous factors. Treatment of epilepsy with formulations of naturally occurring substances, their compounding and use, is described in remarkable detail. Lifestyle modifications to protect people with epilepsy are also documented. Cognitive comorbidities of epilepsy were recognized. Although none of the Ayurveda formulations have any empirical evidence supporting their safety or efficacy in the treatment of epilepsy, studies are needed to generate relevant evidence, to recognize their hazards, and to integrate traditional and complementary systems of medicine with modern health care in an informed and safe manner.

  13. New insights into cannabis consumption; abuses and possible therapeutic effects

    Daniela Luiza Baconi

    2014-10-01

    Full Text Available Cannabis is one of the oldest psychotropic drugs known to humanity. The paper assesses the current knowledge on the cannabis, including the mechanisms of action and the therapeutic potential of cannabinoids. Three varieties of Cannabis plant are recognised: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. The variety indica is used predominantly to obtain the drugs. Cannabis herb is usually named marijuana, while the cannabis oleoresin secreted by the glandular hairs found mainly on the flowering or fruiting tops of the plant is known as hashish. More than 400 known chemicals are present in cannabis, at least 70 of which are called cannabinoids. The major psychoactive constituent in cannabis is delta-9-tetrahydrocannabinol (Δ9-THC. It is now recognized that there are three types of cannabinoids: natural (phytocannabinoids, endogenous cannabinoids, and synthetic cannabioids. Cannabinoids exert their actions by binding to specific membrane protein, the cannabinoid receptor. To date, two subtypes of cannabinoid receptors, named cannabinoid-1 (CB1, most abundantly expressed in the central nervous system and cannabinoid-2 (CB2 receptors, found predominantly in peripheral tissues with immune functions have been cloned. Therefore, the concept of endogenous cannabinoid system (endocannabinoid system, SEC has been developed. Based on the current scientific evidence, there are several effects of cannabinoids with potential therapeutic use: antiemetic, analgesic in cancerous pains, and chronic neuropathic pain, in multiple sclerosis or spinal cord injuries. Cannabis consume can result in a state of drug dependency and cannabis withdrawal has been included in DSM-V. Cannabis plant remains controversial in the twenty-first century and the potential therapeutic of specific cannabinoid compounds and medical marijuana remains under active medical research.

  14. Concept of „long centric"

    Martinović Željko; Obradović-Đuričić Kosovka; Teodorović Nevenka S.; Živković Rade

    2004-01-01

    The objective of this paper was to show the historical perspective of the „long centric" occlusal concept and its importance in the modern dentistry, especially from the gnathological aspect. The „long centric" concept represents therapeutic modality used in modern dentistry and occlusal adjustment in all patients showing differences in strong and weak closure of the lower jaw starting from the position of physiological rest/long centric" concept is applied only for anterior teeth and occlusa...

  15. Basic concepts

    Dorner, B.

    1999-01-01

    The basic concepts of neutron scattering as a tool for studying the structure and the dynamics of condensed matter. Theoretical aspects are outlined, the two different cases of coherent and incoherent scattering are presented. The issue of resolution, coherence volume and the role of monochromators are also discussed. (K.A.)

  16. Simple Concepts

    Materna, Pavel

    2013-01-01

    Roč. 28, č. 3 (2013), s. 295-319 ISSN 0353-5150 R&D Projects: GA ČR(CZ) GAP401/10/0792 Institutional support: RVO:67985955 Keywords : concept * constructions * set-theoretical paradigm Subject RIV: AA - Philosophy ; Religion

  17. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

    Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

    2013-02-01

    Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

  18. CONCEPT-5 user's manual

    Hudson, C.R. II.

    1979-01-01

    The CONCEPT computer code package was developed to provide conceptual capital cost estimates for nuclear-fueled and fossil-fired power plants. Cost estimates can be made as a function of plant type, size, location, and date of initial operation. The output includes a detailed breakdown of the estimate into direct and indirect costs similar to the accounting system described in document NUS--531. Cost models are currently provided in CONCEPT 5 for single- and multiunit pressurized-water reactors, boiling-water reactors, and cost-fired plants with and without flue gas desulfurization equipment

  19. Astrophysical Concepts

    Harwit, Martin

    2006-01-01

    This classic text, aimed at senior undergraduates and beginning graduate students in physics and astronomy, presents a wide range of astrophysical concepts in sufficient depth to give the reader a quantitative understanding of the subject. Emphasizing physical concepts, the book outlines cosmic events but does not portray them in detail: it provides a series of astrophysical sketches. For this fourth edition, nearly every part of the text has been reconsidered and rewritten, new sections have been added to cover recent developments, and others have been extensively revised and brought up to date. The book begins with an outline of the scope of modern astrophysics and enumerates some of the outstanding problems faced in the field today. The basic physics needed to tackle these questions are developed in the next few chapters using specific astronomical processes as examples. The second half of the book enlarges on these topics and shows how we can obtain quantitative insight into the structure and evolution of...

  20. Polyzystisches Ovarsyndrom – ein aktueller Überblick über therapeutische Ansätze bei Kinderwunsch und metabolischen Komorbiditäten // PCOS – A Current Overview of Therapeutic Options for Infertility and Metabolic Co-Morbidities

    Lunger F

    2017-01-01

    Full Text Available The diagnosis of the polycystic ovary syndrome continues to be made based on the 2003 Rotterdam criteria which include oligo- or anovulation, hyperandrogenemia and/ or clinical signs of androgen excess, and polycystic ovaries on ultrasound. Nonetheless, the diagnosis is not always clear. In cases where one is unsure whether a woman ovulates, a progesterone level in the mid-luteal phase of the cycle can confirm ovulation. Clinical signs of hyperandrogenemia are strongly influenced by ethnicity, which should be considered during the assessment, although no ethnicity- related norms have been published. Recent studies have shown that AMH in combination with LH can aid in differentiating sonographically observed PCO morphology (a common entity in younger women from true PCOS. For women desiring pregnancy, the first therapeutic step is weight reduction as part of a lifestyle modification. Ovulation induction in these anovulatory women can be accomplished with clomiphene or low-dose gonadotropins, and may be combined with metformin. Clomiphene continues to be the first-line treatment because of its ease of administration, low costs and success rates. Low-dose gonadotropins may have an even higher success rate of ovulation and pregnancy, especially in clomipheneresistant women, but are much more expensive. Metabolic co-morbidities are very common in women with PCOS and should be diagnosed and treated in order to prevent or reduce future consequences. International recommendations include screening women with PCOS for dia betes with fasting glucose and oral glucose tolerance test, especially those with adiposity, anovulation and positive family history. Fasting insulin or HOMA Index can be used to assess for IR. Targeted thera pies for the metabolic aspects of PCOS include diet and exercise as part of lifestyle modification, treatment of hypertension and hypercholesterolemia with appropriate medications, and the use of insulin sensitizers for insulin

  1. Therapeutic HIV Peptide Vaccine

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  2. Introductory concepts

    Barnes, W.E.

    1983-01-01

    Physical theories are commonly classified as being either ''classical'' or ''modern''. The reasons for this distinction are both historical and substantive. Limited in the sophistication of their measuring instruments, early scientists proposed theories appropriate for the description of the simplest and most accessible physical phenomena, e.g., the trajectories of the planets. Because of the class of phenomena observed, certain beliefs came to underlie all classical theories with regard to the nature of time, space, matter, etc. For example, the idea was undisputed that an object has at all times both a definite position and velocity. Not until the interior of the atom and the nature of electromagnetic radiation were explored was it discovered that the concepts of classical physics are inadequate to deal with many phenomena. A reassessment of fundamental postulates led to the formulation of modern physics which, it is believed, successfully treats the behavior of all physical systems. To gain an understanding of the rudiments of modern physics, one proceeds as the early scientists did by first mastering the classical concepts that emerge from their intuitive picture of the world. Modifications of these concepts are subsequently introduced which allow a more accurate treatment of physical phenomena, particularly atomic and nuclear systems

  3. A concept analysis of befriending.

    Balaam, Marie-Clare

    2015-01-01

    To report an analysis of the concept of befriending. Befriending is an intervention used in a range of nursing, health and social care settings to provide support for individuals who are socially isolated or lack social support. However, in many cases befriending and its impact remains poorly understood and under researched. Concept analysis provides clarification of the concept and basis for further research and development. Concept analysis. AMED, Psyc Articles, Psych Info, Medline, MedlinePlus, Social Science Index and CINHAL databases were searched for literature published between 1993-2013 using the search term Befriending. Walker and Avant's method of concept analysis was chosen. This combined with insights from Risjord's work produced a theoretical concept analysis which focused on the concept in peer reviewed academic literature. There are currently several ways the mechanisms of befriending and its effects on individuals and communities are understood. It is possible however to identify key attributes which define the concept and differentiate it from related concepts, such as peer support and mentoring. Key attributes are that it is an organised intervention, involving the creation of an emotionally connected friend-like relationship, where there is a negotiation of power. This concept analysis has clarified current understandings and uses of befriending. It provides the basis for widening the focus of research into the effectiveness and impact of befriending on those who are befriended, those who befriend and the communities where befriending takes place. © 2014 John Wiley & Sons Ltd.

  4. The future of antibody therapeutics: ADCs bi-specifics and RIT

    Reichert, J.

    2015-01-01

    Full text of publication follows. Antibodies are widely accepted as remarkably versatile therapeutic agents. As evidence of this, the ∼ 30 antibody products marketed worldwide had total global sales of more than 50 billion dollars in 2012, and the commercial clinical pipeline currently comprises over 350 antibody-based product candidates. In a testament to scientific ingenuity, the investigational molecules (clinical and preclinical) are notably diverse in their composition of matter and include antibodies conjugated to a variety of agents (drugs, radioisotopes), bi-specific antibodies, and fragments or domains of antibodies. The concepts that form the basis of these agents were established decades ago, but advances in technology are now allowing new opportunities for their development. In this presentation, future directions in antibody therapeutics development will be discussed, with a focus on antibody-drug conjugates, bi-specific antibodies and radioimmunotherapy. (author)

  5. Exosomes as a tumor immune escape mechanism: possible therapeutic implications

    Hanley Harold H

    2008-07-01

    Full Text Available Abstract Advances in cancer therapy have been substantial in terms of molecular understanding of disease mechanisms, however these advances have not translated into increased survival in the majority of cancer types. One unsolved problem in current cancer therapeutics is the substantial immune suppression seen in patients. Conventionally, investigations in this area have focused on antigen-nonspecific immune suppressive molecules such as cytokines and T cell apoptosis inducing molecules such as Fas ligand. More recently, studies have demonstrated nanovesicle particles termed exosomes are involved not only in stimulation but also inhibition of immunity in physiological conditions. Interestingly, exosomes secreted by cancer cells have been demonstrated to express tumor antigens, as well as immune suppressive molecules such as PD-1L and FasL. Concentrations of exosomes from plasma of cancer patients have been associated with spontaneous T cell apoptosis, which is associated in some situations with shortened survival. In this paper we place the "exosome-immune suppression" concept in perspective of other tumor immune evasion mechanisms. We conclude by discussing a novel therapeutic approach to cancer immune suppression by extracorporeal removal of exosomes using hollow fiber filtration technology

  6. Marketing therapeutic recreation services.

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  7. Therapeutic Recombinant Monoclonal Antibodies

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  8. Therapeutic applications of radiopharmaceuticals

    Baker, W.J.; Datz, F.L.; Beightol, R.W.

    1987-01-01

    Whether a radiopharmaceutical has diagnostic or therapeutic application depends on both the isotope and pharmaceutical used. For diagnostic applications, the isotope should undergo only γ-decay, since usually only γ-radiation is detected by nuclear medicine cameras. The half-life should be just long enough to allow the procedure to be performed. In contrast, the isotope needed for therapeutic purposes should have particulate radiation, such as a β-particle (electron), since these are locally absorbed an increase the local radiation dose. γ-Radiation, which penetrates the tissues, produces less radiation dose than do Β-particles. Several references dealing with radioactive decay, particulate interactions, and diagnostic and therapeutic applications of radiopharmaceuticals are available. Radiopharmaceuticals can legally be used only by physicians who are qualified by specific training in the safe handling of radionuclides. The experience and training of these physicians must be approved by the Nuclear Regulatory Commission or Agreement State Agency authorized to license the use of radiopharmaceuticals. A list of all byproduct material and procedures is available in the Code of Federal Regulations. Of the many radiopharmaceuticals available for diagnostic and therapeutic use, only those commonly used are discussed in this chapter

  9. The Current State of Music Therapy Theory?

    Bonde, Lars Ole

    2015-01-01

    An essay on themes from Ken Aigen (2014): "The Study of Music Therapy. Current Issues and Concepts"......An essay on themes from Ken Aigen (2014): "The Study of Music Therapy. Current Issues and Concepts"...

  10. ITER concept definition. V.2

    1989-01-01

    Volume II of the two volumes describing the concept definition of the International Thermonuclear Experimental Reactor deals with the ITER concept in technical depth, and covers all areas of design of the ITER tokamak. Included are an assessment of the current database for design, scoping studies, rationale for concepts selection, performance flexibility, the ITER concept, the operations and experimental/testing program, ITER parameters and design phase schedule, and research and development specific to ITER. This latter includes a definition of specific research and development tasks, a division of tasks among members, specific milestones, required results, and schedules. Figs and tabs

  11. Students’ conceptions analysis on several electricity concepts

    Saputro, D. E.; Sarwanto, S.; Sukarmin, S.; Ratnasari, D.

    2018-05-01

    This research is aimed to analyse students’ conceptions on several electricity concept. This is a descriptive research with the subjects of new students of Sebelas Maret University. The numbers of the subject were 279 students that consisted of several departments such as science education, physics education, chemistry education, biology education and mathematics education in the academic year of 2017/2018. The instrument used in this research was the multiple-choice test with arguments. Based on the result of the research and analysis, it can be concluded that most of the students still find misconceptions and do not understand electricity concept on sub-topics such as electric current characteristic in the series and parallel arrangement, the value of capacitor capacitance, the influence of the capacitor charge and discharge towards the loads, and the amount of capacitor series arrangement. For the future research, it is suggested to improve students’ conceptual understanding with appropriate learning method and assessment instrument because electricity is one of physics material that closely related with students’ daily life.

  12. Aflatoxinas: conceitos sobre mecanismos de toxicidade e seu envolvimento na etiologia do câncer hepático celular Aflatoxins in foodstuffs: current concepts on mechanisms of toxicity and its involvement in the etiology of hepatocellular carcinoma

    Carlos Augusto Fernandes de Oliveira

    1997-08-01

    Full Text Available Foram revistos os conceitos de maior relevância sobre mecanismos de toxicidade e evidências do envolvimento das aflatoxinas na etiologia do câncer hepático humano. A aflatoxina B1 (AFB1, principal metabólito produzido por fungos do gênero Aspergillus, manifesta seus efeitos tóxicos após conversão hepática em AFB1-epóxido, o qual reage com macromoléculas celulares, incluindo proteínas, RNA (ácido ribonucléico e DNA (ácido desoxirribonucléico. A reação com o DNA ocorre através da ligação com guaninas, ao nível do códon 249, do gene supressor de tumores p53. Em seres humanos, estudos de biomonitoramento individual de derivados AFB1-N7-guanina tem demonstrado que as aflatoxinas constituem importantes fatores de risco, com uma provável interação sinergística com o vírus da hepatite B, para o desenvolvimento do carcinoma hepatocelular em populações expostas. Considerando-se a ocorrência freqüente das aflatoxinas em produtos alimentícios, no Brasil, ressalta-se a necessidade de estudos que avaliem criteriosamente o impacto dos níveis de exposição a estas toxinas sobre a saúde humana.Current concepts derived from intensive research over the last decade, on biotransformation, mechanisms of toxicity and evidences for the involvement of aflatoxins in the etiolgy of human liver cancer are summarily presented. Aflatoxin B1(AFB1, the main metabolite produced by moulds of genus Aspergillus, exerts its effects after conversion to the reactive compound AFB1-epoxide, by the action of cytochrome P450-dependent enzymes. This epoxide can form derivatives with cellular macromolecules, including proteins, RNA and DNA. The reaction with DNA occurs with guanines in the códon 249 of tumor suppressor gene p53. Primary biotransformation of AFB1 also produces hydroxylated and less toxic derivatives, such as aflatoxins Q1 and P1. Differences intra and interspecies in the pathways of activation/detoxification are directly related to the

  13. Changing Emotion: The Use of Therapeutic Storytelling

    Parker, Trent S.; Wampler, Karen S.

    2006-01-01

    Even though using metaphors in a therapeutic context is common, there are very few studies that address their effects. This study examines the effects of storytelling in therapy. After discussing a problem in a current relationship, 42 female participants were randomly assigned to receive either a story or psychoeducational information. Results…

  14. Therapeutic genes for anti-HIV/AIDS gene therapy.

    Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca

    2013-01-01

    The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.

  15. Acute Organophosphate Poisonings: Therapeutic Dilemmas and New Potential Therapeutic Agents

    Vucinic, S.; Jovanovic, D.; Vucinic, Z.; Todorovic, V.; Segrt, Z.

    2007-01-01

    It has been six decades since synthesis of organophosphates, but this chapter has not yet come to a closure. Toxic effects of organophosphates are well known and the current therapeutic scheme includes supportive therapy and antidotes. There is a dilemma on whether and when to apply gastric lavage and activated charcoal. According to Position Statement (by EAPCCT) it should be applied only if the patient presents within one hour of ingestion, with potentially lethal ingested dose. Atropine, a competitive antagonist of acetylcholine at m-receptors, which antagonizes bronchosecretion and bronchoconstriction, is the corner stone of acute organophosphate poisoning therapy. There were many attempts to find a more efficient drug, including glycopyrrolate which has been used even in clinical trials, but it still can not replace atropine. The only dilemma about atropine usage which still exists, concerns usage of high atropine dose and scheme of application. The most efficient atropinization is achieved with bolus doses of 1-2mg of atropine i.v push, with repeating the dose on each 5 minutes until signs of atropinization are registered. Diazepam, with its GABA stabilizing effect, reduces central nervous system damage and central respiratory weakness. Oximes reactivate phosphorylated acetylcholinesterase, which still has not gone ageing, reducing acetylcholine concentration and cholinergic crisis. These effects are clearly demonstrated in experimental conditions, but the clinical significance of oximes is still unclear and there are still those who question oxime therapy. For those who approve it, oxime dosage, duration of therapy, the choice of oxime for certain OP is still an open issue. We need new, more efficient antidotes, and those that are in use are only the small part of the therapy which could be used. Experimental studies show favorable therapeutic effect of many agents, but none of them has been introduced in standard treatment of OPI poisoning in the last 30

  16. Diverticular disease: A therapeutic overview

    Tursi, Antonio

    2010-01-01

    Formation of colonic diverticula, via herniation of the colonic wall, is responsible for the development of diverticulosis. When diverticulosis becomes symptomatic, it becomes diverticular disease. Diverticular disease is common in Western and industrialized countries, and it is associated with numerous abdominal symptoms (including pain, bloating, nausea, diarrhea, and constipation). Standard medical therapies with antibiotics are currently recommended for patients affected by diverticular disease. However, changing concepts on the pathophysiology of the disease suggest that diverticular disease may share many of the hallmarks of inflammatory bowel diseases. On this basis, the addition of therapies using mesalazine and probiotics may enhance treatment efficacy by shortening the course of the disease and preventing recurrences. PMID:21577292

  17. Report on the 1st research co-ordination meeting of the co-ordinated research project on standardized high current solid targets for cyclotron production of diagnostic and therapeutic radionuclides

    2000-01-01

    of deposition of the oxide on the metal target plate, 2) the stability of the oxide layer during storage and irradiation, 3) the thermal characteristics of the oxide layer especially during irradiation, 4) methods of radioiodine recovery such as dry distillation, and 5) reprocessing of the targets. For the electrodeposited tellurium targets, the improvement of the existing deposition method and the presently used recovery process (wet chemistry) will be done. (ii) to prepare a target for the production of Thallium-201 which will withstand high beam currents in the range of 100 μA or more This will be accomplished through the transfer of the technology available on the electrodeposition of Thallium onto copper plates to produce a smooth, stable surface. The techniques will include the preparation of the targets before irradiation, extraction of the desired radioisotope, and the processing and recovery of the enriched materials after irradiation. Furthermore, a standard procedure for the preparation of trivalent Tl-201 ( 201 Tl + ) suitable for polypeptide labelling can be developed. (iii) to prepare a target for the production of Pd-103 from Rhodium. This will be accomplished by transferring the existing technology for the electrodeposition of Rh onto metal plates. The chemical removal of Rh will also be investigated as an integral goal of the CRP. Attempts will be made to investigate the production and quality control methods for the preparation of sealed sources for the treatment of prostate cancer

  18. Stem cell transplantation for amyotrophic lateral sclerosis: therapeutic potential and perspectives on clinical translation.

    Faravelli, Irene; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Zanetta, Chiara; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

    2014-09-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by degeneration of upper and lower motor neurons. There are currently no clinically impactful treatments for this disorder. Death occurs 3-5 years after diagnosis, usually due to respiratory failure. ALS pathogenesis seems to involve several pathological mechanisms (i.e., oxidative stress, inflammation, and loss of the glial neurotrophic support, glutamate toxicity) with different contributions from environmental and genetic factors. This multifaceted combination highlights the concept that an effective therapeutic approach should counteract simultaneously different aspects: stem cell therapies are able to maintain or rescue motor neuron function and modulate toxicity in the central nervous system (CNS) at the same time, eventually representing the most comprehensive therapeutic approach for ALS. To achieve an effective cell-mediated therapy suitable for clinical applications, several issues must be addressed, including the identification of the most performing cell source, a feasible administration protocol, and the definition of therapeutic mechanisms. The method of cell delivery represents a major issue in developing cell-mediated approaches since the cells, to be effective, need to be spread across the CNS, targeting both lower and upper motor neurons. On the other hand, there is the need to define a strategy that could provide a whole distribution without being too invasive or burdened by side effects. Here, we review the recent advances regarding the therapeutic potential of stem cells for ALS with a focus on the minimally invasive strategies that could facilitate an extensive translation to their clinical application.

  19. Transcranial Direct Current Stimulation Targeting Primary Motor Versus Dorsolateral Prefrontal Cortices: Proof-of-Concept Study Investigating Functional Connectivity of Thalamocortical Networks Specific to Sensory-Affective Information Processing.

    Sankarasubramanian, Vishwanath; Cunningham, David A; Potter-Baker, Kelsey A; Beall, Erik B; Roelle, Sarah M; Varnerin, Nicole M; Machado, Andre G; Jones, Stephen E; Lowe, Mark J; Plow, Ela B

    2017-04-01

    The pain matrix is comprised of an extensive network of brain structures involved in sensory and/or affective information processing. The thalamus is a key structure constituting the pain matrix. The thalamus serves as a relay center receiving information from multiple ascending pathways and relating information to and from multiple cortical areas. However, it is unknown how thalamocortical networks specific to sensory-affective information processing are functionally integrated. Here, in a proof-of-concept study in healthy humans, we aimed to understand this connectivity using transcranial direct current stimulation (tDCS) targeting primary motor (M1) or dorsolateral prefrontal cortices (DLPFC). We compared changes in functional connectivity (FC) with DLPFC tDCS to changes in FC with M1 tDCS. FC changes were also compared to further investigate its relation with individual's baseline experience of pain. We hypothesized that resting-state FC would change based on tDCS location and would represent known thalamocortical networks. Ten right-handed individuals received a single application of anodal tDCS (1 mA, 20 min) to right M1 and DLPFC in a single-blind, sham-controlled crossover study. FC changes were studied between ventroposterolateral (VPL), the sensory nucleus of thalamus, and cortical areas involved in sensory information processing and between medial dorsal (MD), the affective nucleus, and cortical areas involved in affective information processing. Individual's perception of pain at baseline was assessed using cutaneous heat pain stimuli. We found that anodal M1 tDCS and anodal DLPFC tDCS both increased FC between VPL and sensorimotor cortices, although FC effects were greater with M1 tDCS. Similarly, anodal M1 tDCS and anodal DLPFC tDCS both increased FC between MD and motor cortices, but only DLPFC tDCS modulated FC between MD and affective cortices, like DLPFC. Our findings suggest that M1 stimulation primarily modulates FC of sensory networks

  20. Diagnostic and therapeutic radiation exposure

    Russell, W J [Radiation Effects Research Foundation, Hiroshima (Japan)

    1975-09-01

    Diagnostic and therapeutic radiology were studied as possible contaminants in the evaluations of A-bomb survivors in the ABCC-JNIH Adult Health Study for radiation effects. Hiroshima and Nagasaki subjects received X-ray examinations elsewhere within three months of their ABCC visits at rates of 23 and 12%, respectively. Medical X-ray examinations were more frequent among survivors than comparison subjects. Hiroshima and Nagasaki radiologic practice steadily increased since 1948, and differed markedly by city. From 1946-70 the Hiroshima and Nagasaki X-ray bone marrow doses were 2,300 and 1,000 g-rads, respectively. By 1970, cumulated medical X-ray doses approximated A-bomb doses at distances from the hypocenters of 2,000 m in Hiroshima and 2,800 m in Nagasaki. ABCC X-ray examination doses per subject are routinely updated for comparison with A-bomb doses. Each subject's reported fluoroscopy, photofluorography and radiation therapy exposure elsewhere are for future reference. Dental radiography, though increasing, was not currently an important contributor to survivors' overall exposure. Radiation therapy exposures of 137 subjects were confirmed, and doses estimated for most. Two-thirds the treatments were for malignancies; therapy differed markedly by city; and five cancers possibly arose from earlier radiation therapy. This underscores the importance of considering diagnostic and therapeutic radiology when attributing diseases to the atomic bombs.

  1. Novel therapeutic approaches in chondrosarcoma.

    Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

    2017-03-01

    Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

  2. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Danbo Yang

    2010-12-01

    Full Text Available The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(L-g-glutamylglutamine-paclitaxel nano-conjugate (PGG-PTX. PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  3. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Yang, Danbo; Yu, Lei; Van, Sang

    2010-01-01

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic

  4. Clinically Relevant Anticancer Polymer Paclitaxel Therapeutics

    Yang, Danbo [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Yu, Lei, E-mail: yu-lei@gg.nitto.co.jp [Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062 (China); Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States); Van, Sang [Biomedical Group, Nitto Denko Technical Corporation, 501 Via Del Monte, Oceanside, CA 92058 (United States)

    2010-12-23

    The concept of utilizing polymers in drug delivery has been extensively explored for improving the therapeutic index of small molecule drugs. In general, polymers can be used as polymer-drug conjugates or polymeric micelles. Each unique application mandates its own chemistry and controlled release of active drugs. Each polymer exhibits its own intrinsic issues providing the advantage of flexibility. However, none have as yet been approved by the U.S. Food and Drug Administration. General aspects of polymer and nano-particle therapeutics have been reviewed. Here we focus this review on specific clinically relevant anticancer polymer paclitaxel therapeutics. We emphasize their chemistry and formulation, in vitro activity on some human cancer cell lines, plasma pharmacokinetics and tumor accumulation, in vivo efficacy, and clinical outcomes. Furthermore, we include a short review of our recent developments of a novel poly(l-γ-glutamylglutamine)-paclitaxel nano-conjugate (PGG-PTX). PGG-PTX has its own unique property of forming nano-particles. It has also been shown to possess a favorable profile of pharmacokinetics and to exhibit efficacious potency. This review might shed light on designing new and better polymer paclitaxel therapeutics for potential anticancer applications in the clinic.

  5. Therapeutic experiences of community gardens: putting flow in its place.

    Pitt, Hannah

    2014-05-01

    This paper develops the concept of therapeutic place experiences by considering the role of activity. Research of community gardening finds that particular tasks are therapeutic and exhibit the characteristics of flow, but those who lack influence over their community gardening are less likely to benefit from flow as their sense of control is reduced. The notion of emplaced flow is proposed to locate individual experiences amongst socio-spatial factors which limit self-determinacy and therefore affect wellbeing. Emplacing flow prompts critical reflection on who is excluded from therapeutic place experiences, and whether sites offering momentary escape have an enduring impact on wellbeing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Mathematical concepts

    Jost, Jürgen

    2015-01-01

    The main intention of this book is to describe and develop the conceptual, structural and abstract thinking of mathematics. Specific mathematical structures are used to illustrate the conceptual approach; providing a deeper insight into mutual relationships and abstract common features. These ideas are carefully motivated, explained and illustrated by examples so that many of the more technical proofs can be omitted. The book can therefore be used: ·         simply as an overview of the panorama of mathematical structures and the relations between them, to be supplemented by more detailed texts whenever you want to acquire a working knowledge of some structure ·         by itself as a first introduction to abstract mathematics ·         together with existing textbooks, to put their results into a more general perspective ·         to gain a new and hopefully deeper perspective after having studied such textbooks Mathematical Concepts has a broader scope and is less detaile...

  7. Membrane Currents in Airway Smooth Muscle: Mechanisms and Therapeutic Implications

    Luke J Janssen

    1997-01-01

    Full Text Available Electrophysiological and pharmacological techniques were used to characterize the membrane conductance changes underlying spasmogen-evoked depolarization in airway smooth muscle (ASM. Changes included a transient activation of chloride ion channels and prolonged suppression of potassium ion channels; both changes are triggered by release of internally sequestered calcium ion and in turn cause opening of voltage-dependent calcium channels. The resultant influx of calcium ions contributes to contraction as well as to refilling of the internal calcium ion pool. Bronchodilators, on the other hand, act in part through activation of potassium channels, with consequent closure of calcium channels. The tools used to study ion channels in ASM are described, and the investigations of the roles of ion channels in ASM physiology (autacoid-evoked depolarization and hyperpolarization and pathophysiology (airway hyperresponsiveness are summarized. Finally, how the relationship between ion channels and ASM function/dysfunction may relate to the treatment of asthma and related breathing disorders is discussed.

  8. Angioid streaks, clinical course, complications, and current therapeutic management

    Ilias Georgalas

    2008-12-01

    Full Text Available Ilias Georgalas1, Dimitris Papaconstantinou2, Chrysanthi Koutsandrea2, George Kalantzis2, Dimitris Karagiannis2, Gerasimos Georgopoulos2, Ioannis Ladas21Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, NHS, Athens, Greece; 2Department of Ophthalmology, “G. Gennimatas” Hospital of Athens, University of Athens, Athens, GreeceAbstract: Angioid streaks are visible irregular crack-like dehiscences in Bruch’s membrane that are associated with atrophic degeneration of the overlying retinal pigmented epithelium. Angioid streaks may be associated with pseudoxanthoma elasticum, Paget’s disease, sickle-cell anemia, acromegaly, Ehlers–Danlos syndrome, and diabetes mellitus, but also appear in patients without any systemic disease. Patients with angioid streaks are generally asymptomatic, unless the lesions extend towards the foveola or develop complications such as traumatic Bruch’s membrane rupture or macular choroidal neovascularization (CNV. The visual prognosis in patients with CNV secondary to angioid streaks if untreated, is poor and most treatment modalities, until recently, have failed to limit the devastating impact of CNV in central vision. However, it is likely that treatment with antivascular endothelial growth factor, especially in treatment-naive eyes to yield favorable results in the future and this has to be investigated in future studies.Keywords: angioid streaks, pseudoxanthoma elasticum, choroidal neovascularization

  9. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues.

    Ethan Budd Russo

    2016-09-01

    Full Text Available This overview covers a wide range of cannabis topics, initially examining issue in dispensaries and self-administration, plus regulatory requirement for production of cannabis-based medicines, particularly the Food and Drug Administration Botanical Guidance. The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety and public health issues remain.

  10. Therapeutic potential of snake venom in cancer therapy: current perspectives

    Vyas, Vivek Kumar; Brahmbhatt, Keyur; Bhatt, Hardik; Parmar, Utsav

    2013-01-01

    Many active secretions produced by animals have been employed in the development of new drugs to treat diseases such as hypertension and cancer. Snake venom toxins contributed significantly to the treatment of many medical conditions. There are many published studies describing and elucidating the anti-cancer potential of snake venom. Cancer therapy is one of the main areas for the use of protein peptides and enzymes originating from animals of different species. Some of these proteins or peptides and enzymes from snake venom when isolated and evaluated may bind specifically to cancer cell membranes, affecting the migration and proliferation of these cells. Some of substances found in the snake venom present a great potential as anti-tumor agent. In this review, we presented the main results of recent years of research involving the active compounds of snake venom that have anticancer activity. PMID:23593597

  11. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

    Russo, Ethan B.

    2016-01-01

    This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanical cannabis displays herbal synergy of its components, pharmacokinetics of cannabis and dose titration, whether cannabis medicines produce cyclo-oxygenase inhibition, cannabis-drug interactions, and cytochrome P450 issues, whether cannabis randomized clinical trials are properly blinded, combatting the placebo effect in those trials via new approaches, the drug abuse liability (DAL) of cannabis-based medicines and their regulatory scheduling, their effects on cognitive function and psychiatric sequelae, immunological effects, cannabis and driving safety, youth usage, issues related to cannabis smoking and vaporization, cannabis concentrates and vape-pens, and laboratory analysis for contamination with bacteria and heavy metals. Finally, the issue of pesticide usage on cannabis crops is addressed. New and disturbing data on pesticide residues in legal cannabis products in Washington State are presented with the observation of an 84.6% contamination rate including potentially neurotoxic and carcinogenic agents. With ongoing developments in legalization of cannabis in medical and recreational settings, numerous scientific, safety, and public health issues remain. PMID:27683558

  12. What are the current therapeutic options for haemorrhagic strokes

    Khan, M.; Kamal, A.K.

    2010-01-01

    The Factor Seven for Acute Haemorrhagic Stroke Trial (FAST) and Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage trial (INTERACT). Intracerebral haemorrhage (ICH) is the most devastating form of stroke carrying a mortality of up to 40% at one month. In our part of the world the levels of uncontrolled hypertension pose a greater risk of ICH for our population where ICH is about 30% of all strokes compared to 14% in developed countries. There is evidence to suggest that haematoma expansion occurs in as many as 70% of patients. This expansion translates into increased disability and death. Most of this expansion is within the initial three hours. Also early elevation of blood pressure (BP) is very common after ICH and many studies have highlighted an association between elevated BP post ICH and poor outcomes. The reason for this is postulated to be an increase in both the size of the haematoma and perilesional oedema. (author)

  13. Current Therapeutic Cannabis Controversies and Clinical Trial Design Issues

    Russo, Ethan B.

    2016-01-01

    This overview covers a wide range of cannabis topics, initially examining issues in dispensaries and self-administration, plus regulatory requirements for production of cannabis-based medicines, particularly the Food and Drug Administration “Botanical Guidance.” The remainder pertains to various cannabis controversies that certainly require closer examination if the scientific, consumer, and governmental stakeholders are ever to reach consensus on safety issues, specifically: whether botanica...

  14. Liquid fuel concept benefits

    Hron, M.

    1996-01-01

    There are principle drawbacks of any kind of solid nuclear fuel listed and analyzed in the first part of the paper. One of the primary results of the analyses performed shows that the solid fuel concept, which was to certain degree advantageous in the first periods of a nuclear reactor development and operation, has guided this branch of a utilization of atomic nucleus energy to a death end. On the background of this, the liquid fuel concept and its benefits are introduced and briefly described in the first part of the paper, too. As one of the first realistic attempts to utilize the advantages of liquid fuels, the reactor/blanket system with molten fluoride salts in the role of fuel and coolant simultaneously, as incorporated in the accelerator-driven transmutation technology (ADTT) being proposed and currently having been under development in the Los Alamos National Laboratory, will be studied both theoretically and experimentally. There is a preliminary design concept of an experimental assembly LA-O briefly introduced in the paper which is under preparation in the Czech Republic for such a project. Finally, there will be another very promising concept of a small low power ADTT system introduced which is characterized by a high level of safety and economical efficiency. In the conclusion, the overall survey of principal benefits which may be expected by introducing liquid nuclear fuel in nuclear power and research reactor systems is given and critically analyzed. 7 refs, 4 figs

  15. Stroke and Therapeutic Hypothermia

    Ozlem Ozkan Kuscu

    2016-09-01

    Full Text Available Stroke is significant cause of morbidity and mortality caused by disruption of blood flow. Neural injury occurs with two stage; while primary neural injury occurs with disruption of blood flow, after days and hours with metabolic processes secondary injury develops in tissues which is non injured in the first stage. Therefore it is important to prevent and treat the secondary injury as much as preventing and treating the primary neural injury. In this article developing pathophysiological changes after stroke, mechanisms of therapeutic hypothermia, application methods, the factors that determine the effectiveness, side effects and complications were reviewed. [Archives Medical Review Journal 2016; 25(3.000: 351-368

  16. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

    Schepetkin, Igor A; Quinn, Mark T

    2006-03-01

    Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

  17. Observational therapeutics: Scope, challenges, and organization.

    Vaidya, Rama

    2011-10-01

    The importance of Observational Therapeutics in the progress of medicine has been neglected in the current era of the hierarchal position imparted to Randomized Controlled Trials (RCTs) for new drug discovery and practice of evidence-based medicine. There is a need to reflect on the reason for many new drugs being withdrawn during post marketing surveillance. There are several examples in literature where drug-discovery has originated initially from keen clinical and / or laboratory observations. The roots of these discoveries have often been from observations made by practitioners of traditional medicine including Ayurveda. The present article draws attention to the scope and challenges for observational therapeutics. There is an urgent need for the meticulous planning for a systematic organization of developing observational therapeutics, with a full understanding of its strengths and limitations.

  18. Observational therapeutics: Scope, challenges, and organization

    Rama Vaidya

    2011-01-01

    Full Text Available The importance of Observational Therapeutics in the progress of medicine has been neglected in the current era of the hierarchal position imparted to Randomized Controlled Trials (RCTs for new drug discovery and practice of evidence-based medicine. There is a need to reflect on the reason for many new drugs being withdrawn during post marketing surveillance. There are several examples in literature where drug-discovery has originated initially from keen clinical and / or laboratory observations. The roots of these discoveries have often been from observations made by practitioners of traditional medicine including Ayurveda. The present article draws attention to the scope and challenges for observational therapeutics. There is an urgent need for the meticulous planning for a systematic organization of developing observational therapeutics, with a full understanding of its strengths and limitations.

  19. Perspectives for Preventive and Therapeutic HPV Vaccines

    Lin, Ken; Doolan, Kimberley; Hung, Chien-Fu; Wu, T-C

    2010-01-01

    Cervical cancer is the second most common cause of female cancer death worldwide. Persistent infection with `high risk' HPV genotypes is the major etiological factor in cervical cancer and thus effective vaccination against HPV provides an opportunity to reduce the morbidity and mortality associated with HPV. The FDA has approved two preventive vaccines to limit the spread of HPV. However, these are unlikely to impact upon HPV prevalence and cervical cancer rates for many years. Furthermore, preventive vaccines do not exert therapeutic effects on pre-existing HPV infections and HPV-associated lesions. In order to further impact upon the burden of HPV infections worldwide, therapeutic vaccines are being developed. These vaccines aim to generate a cell-mediated immune response to infected cells. This review discusses current preventive and therapeutic HPV vaccines and their future directions. PMID:20123582

  20. Instant standard concept for data standards development

    Folmer, Erwin Johan Albert; Kulcsor, Istvan Zsolt; Roes, Jasper

    2013-01-01

    This paper presents the current results of an ongoing research about a new data standards development concept. The concept is called Instant Standard referring to the pressure that is generated by shrinking the length of the standardization process. Based on this concept it is estimated that the