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Sample records for major therapeutic challenge

  1. 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 There is a need to reflect on the reason for many new drugs being withdrawn during post marketing surveillance.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.

  2. 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 There is a need to reflect on the reason for many new drugs being withdrawn during post marketing surveillance.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.

  3. Therapeutic ultrasound - Exciting applications and future challenges

    Saffari, Nader

    2018-04-01

    This paper presents an overview of the applications of ultrasound for the treatment of an ever-growing range of medical conditions. After presenting a brief history of the development of therapeutic ultrasound, the different mechanisms by which beneficial bio-effects are triggered will be discussed. This will be followed by a discussion of some of the more promising applications, some of which have already been licensed and introduced into the clinic. The case of liver tumour ablation will be discussed to demonstrate some of the engineering challenges that still need to be overcome before this technology finds wider uptake in the medical world.

  4. [Cardiac sarcoidosis: Diagnosis and therapeutic challenges].

    Cohen Aubart, F; Nunes, H; Mathian, A; Haroche, J; Hié, M; Le-Thi Huong Boutin, D; Cluzel, P; Soussan, M; Waintraub, X; Fouret, P; Valeyre, D; Amoura, Z

    2017-01-01

    Sarcoidosis is a granulomatous disorder of unknown cause characterized by non-caseating granuloma in young adults. Cardiac involvement is rare and range from 2 to 75% depending on diagnostic criteria. Cardiac involvement in sarcoidosis may be asymptomatic or may manifest as rhythm/conduction troubles or congestive heart failure. The diagnosis and treatment of cardiac sarcoidosis may be challenging. However, advances have come in recent years from the use of cardiac MRI and 18 FDG-TEP scanner, as well as from the stratification of the risk of ventricular tachycardia/fibrillation. Due to the rarity of the disease, there is no reliable prospective large study to guide therapeutic strategy for cardiac sarcoidosis. Corticosteroids are probably efficacious, in particular in case of atrio-ventricular block or moderate heart failure. Immunosuppressive drugs have not been largely studied but methotrexate could be helpful. In refractory forms, TNF-α antagonists have been used with success. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges

    Vugmeyster, Yulia; Xu, Xin; Theil, Frank-Peter; Khawli, Leslie A; Leach, Michael W

    2012-01-01

    Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins. PMID:22558487

  6. [Gap junctions: A new therapeutic target in major depressive disorder?].

    Sarrouilhe, D; Dejean, C

    2015-11-01

    Major depressive disorder is a multifactorial chronic and debilitating mood disease with high lifetime prevalence and is associated with excess mortality, especially from cardiovascular diseases and through suicide. The treatments of this disease with tricyclic antidepressants and monoamine oxidase inhibitors are poorly tolerated and those that selectively target serotonin and norepinephrine re-uptake are not effective in all patients, showing the need to find new therapeutic targets. Post-mortem studies of brains from patients with major depressive disorders described a reduced expression of the gap junction-forming membrane proteins connexin 30 and connexin 43 in the prefrontal cortex and the locus coeruleus. The use of chronic unpredictable stress, a rodent model of depression, suggests that astrocytic gap junction dysfunction contributes to the pathophysiology of major depressive disorder. Chronic treatments of rats with fluoxetine and of rat cultured cortical astrocytes with amitriptyline support the hypothesis that the upregulation of gap junctional intercellular communication between brain astrocytes could be a novel mechanism for the therapeutic effect of antidepressants. In conclusion, astrocytic gap junctions are emerging as a new potential therapeutic target for the treatment of patients with major depressive disorder. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Therapeutic strategies to fight HIV-1 latency: progress and challenges

    Manoto, Sello L

    2017-10-01

    Full Text Available —1112, 2017 Therapeutic strategies to fight HIV-1 latency: progress and challenges Sello Lebohang Manoto, Lebogang Thobakgale, Rudzani Malabi, Charles Maphanga, Saturnin Ombinda-Lemboumba, Patience Mthunzi-Kufa Abstract: The life...

  8. Old and new challenges in Parkinson's disease therapeutics.

    Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

    2017-09-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Cell differentiation: therapeutical challenges in diabetes.

    Roche, Enrique; Vicente-Salar, Nestor; Arribas, Maribel; Paredes, Beatriz

    2012-01-01

    Stem cells, derived from either embryonic or adult tissues, are considered to be potential sources of insulin-secreting cells to be transplanted into type 1 and advanced stages of type 2 diabetic patients. Many laboratories have considered this possibility, resulting in a large amount of published protocols, with a wide degree of complexity among them. Our group was the first to report that it was possible to obtain insulin-secreting cells from mouse embryonic stem cells, proving the feasibility of this new challenge. The same observation was immediately reported using human embryonic stem cells. However, the resulting cell product was not properly characterised, affecting the reproducibility of the protocol by other groups. A more elaborated protocol was developed by Lumelsky and co-workers, demonstrating that neuroectodermal cells could be an alternative source for insulin-producing cells. However, the resulting cells of this protocol produced low amounts of the hormone. This aimed other groups to perform key changes in order to improve the insulin content of the resulting cells. Recently, Baetge's group has published a new protocol based on the knowledge accumulated in pancreatic development. In this protocol, human embryonic stem cells were differentiated into islet-like structures through a five step protocol, emulating the key steps during embryonic development of the endocrine pancreas. The final cell product, however, seemed to be in an immature state, thus further improvement is required. Despite this drawback, the protocol represents the culmination of work performed by different groups and offers new research challenges for the investigators in this exciting field. Concerning adult stem cells, the possibility of identifying pancreatic precursors or of reprogramming extrapancreatic derived cells are key possibilities that may circumvent the problems that appear when using embryonic stem cells, such as immune rejection and tumour formation.

  10. Postpartum Tuberculosis: A Diagnostic and Therapeutic Challenge

    Vijay Kodadhala

    2016-01-01

    Full Text Available Tuberculosis (TB infection in pregnant women and newborn babies is always challenging. Appropriate treatment is pivotal to curtail morbidity and mortality. TB diagnosis or exposure to active TB can be emotionally distressing to the mother. Circumstances can become more challenging for the physician if the mother’s TB status is unclear. Effective management of TB during pregnancy and the postpartum period requires a multidisciplinary approach including pulmonologist, obstetrician, neonatologist, infectious disease specialist, and TB public health department. Current guidelines recommend primary Isoniazid prophylaxis in TB exposed pregnant women who are immune-suppressed and have chronic medical conditions or obstetric risk factors and close and sustained contact with a patient with infectious TB. Treatment during pregnancy is the same as for the general adult population. Infants born to mothers with active TB at delivery should undergo a complete diagnostic evaluation. Primary Isoniazid prophylaxis for at least twelve weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. This case highlights important aspects for management of TB during the postpartum period which has a higher morbidity. We present a case of a young mother migrating from a developing nation to the USA, who was found to have a positive quantiFERON test associated with multiple cavitary lung lesions and gave birth to a healthy baby.

  11. Protein based therapeutic delivery agents: Contemporary developments and challenges.

    Yin, Liming; Yuvienco, Carlo; Montclare, Jin Kim

    2017-07-01

    As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Affordances and Alignments: Continuing Challenges in Advising Undergraduate Psychology Majors

    Landrum, R. Eric

    2018-01-01

    Challenges abound in providing accurate and useful information to prospective and declared psychology majors about their career options and how to make decisions that will lead to satisfying and rewarding postgraduate lives. One component of this challenge is that by majoring in psychology, career affordances (i.e., the opportunities and…

  13. Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

    Goyenvalle Aurélie

    2011-02-01

    Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

  14. Challenges in the development of therapeutics for narcolepsy.

    Black, Sarah Wurts; Yamanaka, Akihiro; Kilduff, Thomas S

    2017-05-01

    Narcolepsy is a neurological disorder that afflicts 1 in 2000 individuals and is characterized by excessive daytime sleepiness and cataplexy-a sudden loss of muscle tone triggered by positive emotions. Features of narcolepsy include dysregulation of arousal state boundaries as well as autonomic and metabolic disturbances. Disruption of neurotransmission through the hypocretin/orexin (Hcrt) system, usually by degeneration of the HCRT-producing neurons in the posterior hypothalamus, results in narcolepsy. The cause of Hcrt neurodegeneration is unknown but thought to be related to autoimmune processes. Current treatments for narcolepsy are symptomatic, including wake-promoting therapeutics that increase presynaptic dopamine release and anticataplectic agents that activate monoaminergic neurotransmission. Sodium oxybate is the only medication approved by the US Food and Drug Administration that alleviates both sleep/wake disturbances and cataplexy. Development of therapeutics for narcolepsy has been challenged by historical misunderstanding of the disease, its many disparate symptoms and, until recently, its unknown etiology. Animal models have been essential to elucidating the neuropathology underlying narcolepsy. These models have also aided understanding the neurobiology of the Hcrt system, mechanisms of cataplexy, and the pharmacology of narcolepsy medications. Transgenic rodent models will be critical in the development of novel therapeutics for the treatment of narcolepsy, particularly efforts directed to overcome challenges in the development of hypocretin replacement therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Major Management Challenges and Program Risks. Department of Labor

    2001-01-01

    This report addresses the major performance and accountability challenges facing the Department of Labor as it seeks to promote the welfare and economic security of the nations work force and ensure...

  16. Major Management Challenges and Program Risks: Small Business Administration

    2001-01-01

    2001 Major Management Challenges and Program Risks Small Business AdministrationGAO-01-260 Form SF298 Citation Data Report Date ("DD MON YYYY...34) 00JAN2001 Report Type N/A Dates Covered (from... to) ("DD MON YYYY") Title and Subtitle Major Management Challenges and Program Risks Small Business ...Administration (SBA) as it seeks to aid, counsel, assist, and protect the interests of the nations small businesses and help businesses and families

  17. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential

    Vij, Neeraj

    2011-01-01

    The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions is airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hyper secretion in these diseases, that is further induc...

  18. Polycystic Ovarian Syndrome: A Diagnostic and Therapeutic Challenge

    Manmohan K Kamboj

    2010-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is the commonest endocrinopathy in women with a multi-factorial etiology, and presents not just a diagnostic dilemma but also a therapeutic challenge as well. The clinical features of the syndrome in adolescents result from hyperandrogenemia and oligo/anovulation. Most women presenting with non-pregnancy related secondary amenorrhea, oligomenorrhoea, acne, hirsutism, and infertility have PCOS. Consensus diagnostic criteria have been developed by the United States National Institutes of Health (NIH, and the European Society of Human Reproduction and Embryology and American Society of Reproduction (Rotterdam criteria. PCOS needs to be suspected, recognized, and treated to prevent some long term complications. Treatment modalities need to be individualized to address the specific concerns of each female presenting with this entity. This article reviews the diagnosis and principles of management of PCOS.

  19. Challenges in searching for therapeutics against Botulinum Neurotoxins.

    Pirazzini, Marco; Rossetto, Ornella

    2017-05-01

    Botulinum neurotoxins (BoNTs) are the most potent toxins known. BoNTs are responsible for botulism, a deadly neuroparalytic syndrome caused by the inactivation of neurotransmitter release at peripheral nerve terminals. Thanks to their specificity and potency, BoNTs are both considered potential bio-weapons and therapeutics of choice for a variety of medical syndromes. Several variants of BoNTs have been identified with individual biological properties and little antigenic relation. This expands greatly the potential of BoNTs as therapeutics but poses a major safety problem, increasing the need for finding appropriate antidotes. Areas covered: The authors describe the multi-step molecular mechanism through which BoNTs enter nerve terminals and discuss the many levels at which the toxins can be inhibited. They review the outcomes of the different strategies adopted to limit neurotoxicity and counter intoxication. Potential new targets arising from the last discoveries of the mechanism of action and the approaches to promote neuromuscular junction recovery are also discussed. Expert opinion: Current drug discovery efforts have mainly focused on BoNT type A and addressed primarily light chain proteolytic activity. Development of pan-BoNT inhibitors acting independently of BoNT immunological properties and targeting a common step of the intoxication process should be encouraged.

  20. Mesenteric ischemia: Pathogenesis and challenging diagnostic and therapeutic modalities.

    Mastoraki, Aikaterini; Mastoraki, Sotiria; Tziava, Evgenia; Touloumi, Stavroula; Krinos, Nikolaos; Danias, Nikolaos; Lazaris, Andreas; Arkadopoulos, Nikolaos

    2016-02-15

    Mesenteric ischemia (MI) is an uncommon medical condition with high mortality rates. ΜΙ includes inadequate blood supply, inflammatory injury and eventually necrosis of the bowel wall. The disease can be divided into acute and chronic MI (CMI), with the first being subdivided into four categories. Therefore, acute MI (AMI) can occur as a result of arterial embolism, arterial thrombosis, mesenteric venous thrombosis and non-occlusive causes. Bowel damage is in proportion to the mesenteric blood flow decrease and may vary from minimum lesions, due to reversible ischemia, to transmural injury, with subsequent necrosis and perforation. CMI is associated to diffuse atherosclerotic disease in more than 95% of cases, with all major mesenteric arteries presenting stenosis or occlusion. Because of a lack of specific signs or due to its sometime quiet presentation, this condition is frequently diagnosed only at an advanced stage. Computed tomography (CT) imaging and CT angiography contribute to differential diagnosis and management of AMI. Angiography is also the criterion standard for CMI, with mesenteric duplex ultrasonography and magnetic resonance angiography also being of great importance. Therapeutic approach of MI includes both medical and surgical treatment. Surgical procedures include restoration of the blood flow with arteriotomy, endarterectomy or anterograde bypass, while resection of necrotic bowel is always implemented. The aim of this review was to evaluate the results of surgical treatment for MI and to present the recent literature in order to provide an update on the current concepts of surgical management of the disease. Mesh words selected include MI, diagnostic approach and therapeutic management.

  1. Conservation biology in Asia: the major policy challenges.

    McNeely, Jeffrey A; Kapoor-Vijay, Promila; Zhi, Lu; Olsvig-Whittaker, Linda; Sheikh, Kashif M; Smith, Andrew T

    2009-08-01

    With about half the world's human population and booming economies, Asia faces numerous challenges to its biodiversity. The Asia Section of the Society for Conservation Biology has identified some key policy issues in which significant progress can be made. These include developing new sources of funding for forest conservation; identifying potential impacts of energy alternatives on the conservation of biodiversity; curbing the trade in endangered species of plants and animals; a special focus on the conservation of mountain biodiversity; enhancing relevant research; ensuring that conservation biology contributes to major international conventions and funding mechanisms; using conservation biology to build a better understanding of zoonotic diseases; more effectively addressing human-animal conflicts; enhancing community-based conservation; and using conservation biology to help address the pervasive water-deficit problems in much of Asia. These challenges can be met through improved regional cooperation among the relevant stakeholders.

  2. The intercultural and interracial therapeutic relationship: challenges and recommendations.

    Qureshi, Adil; Collazos, Francisco

    2011-01-01

    Although research has demonstrated that mental health services function with patients from different cultural backgrounds, a variety of culture- and race-related factors can result in services being of lower quality than that which occurs when the clinician and patient are from the same culture. The provision of culturally competent care requires many institutional and organizational adaptations that lie beyond the control of most mental health professionals. The therapeutic relationship, however, remains a key factor of mental healthcare that can be attended to by individual therapists. The therapeutic relationship plays an important role in almost every therapeutic approach, and has been increasingly recognized as representing a means to the provision of quality intercultural and interracial treatment. At the same time, a host of cultural and racial factors relating to both the patient and clinician can compromise the development of the therapeutic relationship. This paper will explore some of the key issues that complicate therapeutic contact and communication, and will outline means by which to strengthen key components of the therapeutic relationship.

  3. Challenges in the development of magnetic particles for therapeutic applications.

    Barry, Stephen E

    2008-09-01

    Certain iron-based particle formulations have useful magnetic properties that, when combined with low toxicity and desirable pharmacokinetics, encourage their development for therapeutic applications. This mini-review begins with background information on magnetic particle use as MRI contrast agents and the influence of material size on pharmacokinetics and tissue penetration. Therapeutic investigations, including (1) the loading of bioactive materials, (2) the use of stationary, high-gradient (HG) magnetic fields to concentrate magnetic particles in tissues or to separate material bound to the particles from the body, and (3) the application of high power alternating magnetic fields (AMF) to generate heat in magnetic particles for hyperthermic therapeutic applications are then surveyed. Attention is directed mainly to cancer treatment, as selective distribution to tumors is well-suited to particulate approaches and has been a focus of most development efforts. While magnetic particles have been explored for several decades, their use in therapeutic products remains minimal; a discussion of future directions and potential ways to better leverage magnetic properties and to integrate their use into therapeutic regimens is discussed.

  4. Hypertension in Developing Countries: A Major Challenge for the Future.

    Mohsen Ibrahim, M

    2018-05-01

    Outline recent epidemiologic data regarding hypertension in developing countries, distinguish differences from developed countries, and identify challenges in management and future perspectives. Increased sugar intake, air and noise pollution, and low birth weight are emerging hypertension risk factors. The major challenges in management are difficulties in accurate diagnosis of hypertension and adequate blood pressure control. In contrast to developed countries, hypertension prevalence rates are on the rise in developing countries with no improvement in awareness or control rates. The increasing burden of hypertension is largely attributable to behavioral factors, urbanization, unhealthy diet, obesity, social stress, and inactivity. Health authorities, medical societies, and drug industry can collaborate to improve hypertension control through education programs, public awareness campaigns, legislation to limit salt intake, encourage generic drugs, development and dissemination of national guidelines, and involving nurses and pharmacists in hypertension management. More epidemiologic data are needed in the future to identify reasons behind increased prevalence and poor blood pressure control and examine trends in prevalence, awareness, treatment, and control. National programs for better hypertension control based on local culture, economic characteristics, and available resources in the population are needed. The role of new tools for hypertension management should be tested in developing world.

  5. Nano-based theranostics for chronic obstructive lung diseases: challenges and therapeutic potential.

    Vij, Neeraj

    2011-09-01

    The major challenges in the delivery and therapeutic efficacy of nano-delivery systems in chronic obstructive airway conditions are airway defense, severe inflammation and mucous hypersecretion. Chronic airway inflammation and mucous hypersecretion are hallmarks of chronic obstructive airway diseases, including asthma, COPD (chronic obstructive pulmonary disease) and CF (cystic fibrosis). Distinct etiologies drive inflammation and mucous hypersecretion in these diseases, which are further induced by infection or components of cigarette smoke. Controlling chronic inflammation is at the root of treatments such as corticosteroids, antibiotics or other available drugs, which pose the challenge of sustained delivery of drugs to target cells or tissues. In spite of the wide application of nano-based drug delivery systems, very few are tested to date. Targeted nanoparticle-mediated sustained drug delivery is required to control inflammatory cell chemotaxis, fibrosis, protease-mediated chronic emphysema and/or chronic lung obstruction in COPD. Moreover, targeted epithelial delivery is indispensable for correcting the underlying defects in CF and targeted inflammatory cell delivery for controlling other chronic inflammatory lung diseases. We propose that the design and development of nano-based targeted theranostic vehicles with therapeutic, imaging and airway-defense penetrating capability, will be invaluable for treating chronic obstructive lung diseases. This paper discusses a novel nano-theranostic strategy that we are currently evaluating to treat the underlying cause of CF and COPD lung disease.

  6. DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

    Atsushi eKamiya

    2012-03-01

    Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

  7. Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

    Grant, Igor; Cahn, B. Rael

    2008-01-01

    The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control. PMID:18806886

  8. Diagnostic and therapeutic challenges in superficial CNS siderosis

    Kondziella, Daniel; Lindelof, M.; Haziri, Donika

    2015-01-01

    the challenges related to the diagnosis and treatment of superficial siderosis. RESULTS: A potential bleeding aetiology was identified in all patients, but removal of the offending bleeding source was achieved only in three (33%). Symptom progression was halted in just one patient (11%), which suggests...... neurotoxicity due to accumulating iron toxicity. FUNDING: not relevant. TRIAL REGISTRATION: not relevant....

  9. Sustainable Digital Environments: What Major Challenges Is Humankind Facing?

    Roland W. Scholz

    2016-07-01

    Full Text Available This paper identifies and discusses the benefits, threats, and vulnerabilities related to the digital revolution. It aims to motivate research and its funding regarding digital threats and vulnerabilities related, in particular, to anticipating unintended, undesirable rebound effects, tipping points, critically fast evolutionary change rates, trade-offs, etc. A brief analysis of the history of the mind and technology reveals slow technological development over tens of thousands of years (including the invention of a place-value digital number system. Then, a small series of groundbreaking ideas (e.g., binary logic, Shannon’s symbolic analysis of relay and switching circuits, architectures of computing enabled the industry-driven invention of programmable computing machines. Ultimately, the mastery of electron and semiconductor physics allowed for economical and seemingly unlimited storage capacity that made digital tools available to all domains of society. Based on the historical analysis, a coupled human-environment systems perspective (that includes a hierarchy assumption ranging from the human cell to the human species enables the identification of several potential challenges to society and science. First, digital nano-engineering promotes genetic modifications (i.e., directed evolution, and synthetic biology enables a new level of the appropriation of nature. The understanding of cell-based biocomputers may call for new forms of logic. These and other challenges require thorough sustainability research in order to anticipate major changes on all levels of human systems. Second, the human individual is exposed to new forms of vulnerability. In particular, the potential epigenetic effects resulting from the excessive use of digital information of historically unknown speed, density, and contents and the loss of (the Western common-law right to privacy resulting from big data (whose ownership is often unknown should become subjects of

  10. Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

    Laforêt, Pascal; Vianey-Saban, Christine

    2010-11-01

    Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. Copyright © 2010 Elsevier B.V. All rights reserved.

  11. Therapeutic challenge in brain metastases: chemotherapy, surgery or radiotherapy

    Mena, Ivan; Contreras, Manuel; Ceballos Francisco

    1998-01-01

    Metastases to the brain occur in 25 to 35% of patients with systemic cancer. Cerebral metastatic is the most common intracranial tumor in adults and occur up to 10 times more frequently than primary tumors in the central nervous system. Significant advances have occurred in the diagnosis and treatment of metastases to the brain, and the therapeutic nihilism of the past is now no longer warranted for most patients. With the currently available treatments, most patients do not die of their brain metastases and usually experience effective palliation of neurologic symptoms and meaning full extension of life. As a trial to limit the cerebral metastatic disease, many and diverse therapy options have been developed such as: chemotherapy, surgery plus whole-brain radiotherapy, only radiation therapy, therapy with neutron, intersticial brachytherapy and stereotactic radiosurgery. In selected cases, surgery plus whole-brain radiotherapy is the conventional treatment for single metastases. However, recurrence usually limits the quality of life and greatly decrease the patients time life, and the therapy options are scarce. This piece of writing also includes a review of the available therapy forms to manage this kind of lesions. (The author)

  12. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

    Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

    2017-01-01

    Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  13. Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach

    Mario Stampanoni Bassi

    2017-12-01

    Full Text Available Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS, structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the “clinico-radiological paradox.” The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

  14. Dyslipidemia and its therapeutic challenges in renal transplantation.

    Riella, L V; Gabardi, S; Chandraker, A

    2012-08-01

    Cardiovascular disease is the leading cause of mortality in kidney transplant recipients. Dyslipidemia is a common finding after renal transplantation and a significant risk factor in the development of coronary heart disease. Although a causal relationship with cardiovascular mortality has not been proven in the transplant population, it is reasonable to extrapolate data from the general population and aggressively treat posttransplant dyslipidemia. Statins are considered the agents of choice, though their use may be complicated by drug misadventures. Pravastatin, fluvastatin and pitavastatin are considered to be the safest statins to use in this population; however, given their low-potency, a high-potency statin, such as atorvastatin, may be necessary in patients with significant dyslipidemia. In this article, we discuss the etiology of and treatment strategies for dyslipidemia in renal transplant recipients based on a literature review of potential therapeutic adverse effects and benefits in this population. We will also evaluate the reasons for and consequences of the latest Food and Drug Administration (FDA) warnings regarding the use of simvastatin. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Amiodarone-Induced Thyrotoxic Thyroiditis: A Diagnostic and Therapeutic Challenge

    Umang Barvalia

    2014-01-01

    Full Text Available Amiodarone is an iodine-based, potent antiarrhythmic drug bearing a structural resemblance to thyroxine (T4. It is known to produce thyroid abnormalities ranging from abnormal thyroid function testing to overt hypothyroidism or hyperthyroidism. These adverse effects may occur in patients with or without preexisting thyroid disease. Amiodarone-induced thyrotoxicosis (AIT is a clinically recognized condition commonly due to iodine-induced excessive synthesis of thyroid, also known as type 1 AIT. In rare instances, AIT is caused by amiodarone-induced inflammation of thyroid tissue, resulting in release of preformed thyroid hormones and a hyperthyroid state, known as type 2 AIT. Distinguishing between the two states is important, as both conditions have different treatment implications; however, a mixed presentation is not uncommon, posing diagnostic and treatment challenges. We describe a case of a patient with amiodarone-induced type 2 hyperthyroidism and review the current literature on the best practices for diagnostic and treatment approaches.

  16. Psychopathy: clinical features, developmental basis and therapeutic challenges.

    Thompson, D F; Ramos, C L; Willett, J K

    2014-10-01

    amygdala and prefrontal cortex. There also appear to be physiological derangements in psychopathy, including alterations/dysregulation in neurotransmitter homeostasis (dopamine and serotonin), altered endocrine responses (testosterone and cortisol) and altered autonomic responses to emotional stimuli and stressors. Although both genetic and environmental factors likely contribute to the developmental basis of psychopathy, these factors are poorly understood at present. To date, limited studies with pharmacologic interventions in psychopathy are available and there are insufficient trials to determine efficacy. Psychopathy is a serious personality disorder with profound negative effects on individuals and society. To design rational therapeutic strategies for this disorder, additional research is needed to discover the specific pathological and pathophysiological basis of psychopathy and to further elucidate the genetic and environmental factors responsible for psychopathic development. There is emerging evidence of phenotypic variants in psychopathy, including successful and unsuccessful types. It is important for clinicians to be cognizant of the psychopathic personality. © 2014 John Wiley & Sons Ltd.

  17. Therapeutic Application of Pluripotent Stem Cells: Challenges and Risks

    Ulrich Martin

    2017-12-01

    Full Text Available Stem-cell-based therapies are considered to be promising and innovative but complex approaches. Induced pluripotent stem cells (iPSCs combine the advantages of adult stem cells with the hitherto unique characteristics of embryonic stem cells (ESCs. Major progress has already been achieved with regard to reprogramming technology, but also regarding targeted genome editing and scalable expansion and differentiation of iPSCs and ESCs, in some cases yielding highly enriched preparations of well-defined cell lineages at clinically required dimensions. It is noteworthy, however, that for many applications critical requirements such as the targeted specification into distinct cellular subpopulations and a proper cell maturation remain to be achieved. Moreover, current hurdles such as low survival rates and insufficient functional integration of cellular transplants remain to be overcome. Nevertheless, PSC technologies obviously have come of age and matured to a stage where various clinical applications of PSC-based cellular therapies have been initiated and are conducted.

  18. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    Fabliha Ahmed Chowdhury

    2018-01-01

    Full Text Available Glioblastoma multiforme (GBM is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ, the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM.

  19. Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges.

    Köhler, Stephan; Guhn, Anne; Betzler, Felix; Stiglmayr, Christian; Brakemeier, Eva-Lotta; Sterzer, Philipp

    2017-01-01

    In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT) by so-called "third-wave" strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to "classical CBT," some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a) acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT), (b) the concept of "limited reparenting" as used in Schema Therapy (ST), and (c) disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

  20. [Improving treatment adherence in kidney transplantation: a major challenge].

    Kessler, Michèle

    2014-06-01

    The kidney transplant recipient is faced not only with the perspective of taking immunosuppressive drugs lifelong, but also the possibility of other long-term treatments prescribed for preexisting conditions, complications, or side effects. Proper management, and most importantly patient adherence, can become a complex challenge. Here we recall current definitions and describe methods for measuring treatment adherence, followed by a discussion on the prevalence of non-adherence in kidney transplant recipients, its effect on graft survival, and factors predictive of non-adherence. Ways of improving adherence are examined, leading to the conviction that helping patients take their medications regularly would probably have a greater impact on graft survival than marketing a new immunosuppressive agent. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  1. Self trust, a major challenge for nuclear regulators

    Eibenschutz, J. [National Nuclear Safety and Safeguards Commission (CNSN), Mexico City (Mexico)

    2014-07-01

    Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

  2. Self trust, a major challenge for nuclear regulators

    Eibenschutz, J.

    2014-01-01

    Self trust. The nuclear community and particularly nuclear regulators overreact to accidents, this has been the case with the three NPP major accidents. Lowering admissible radiation levels, for example, conveys the wrong message to politicians and the general public, and contributes to enhance mistrust towards nuclear. Industry as well as regulators should mature and act with self respect, since the scientific bases of regulation are very solid and should be trusted. Lessons learned should be seriously pursued in spite of the 'uneven playing field'. Obviously safety continues as the main priority, but paranoid reactions from the nuclear professionals could destroy the future of nuclear power. (author)

  3. Neuroimaging Mechanisms of Therapeutic Transcranial Magnetic Stimulation for Major Depressive Disorder.

    Philip, Noah S; Barredo, Jennifer; Aiken, Emily; Carpenter, Linda L

    2018-03-01

    Research into therapeutic transcranial magnetic stimulation (TMS) for major depression has dramatically increased in the last decade. Understanding the mechanism of action of TMS is crucial to improve efficacy and develop the next generation of therapeutic stimulation. Early imaging research provided initial data supportive of widely held assumptions about hypothesized inhibitory or excitatory consequences of stimulation. Early work also indicated that while TMS modulated brain activity under the stimulation site, effects at deeper regions, in particular, the subgenual anterior cingulate cortex, were associated with clinical improvement. Concordant with earlier findings, functional connectivity studies also demonstrated that clinical improvements were related to changes distal, rather than proximal, to the site of stimulation. Moreover, recent work suggests that TMS modulates and potentially normalizes functional relationships between neural networks. An important observation that emerged from this review is that similar patterns of connectivity changes are observed across studies regardless of TMS parameters. Though promising, we stress that these imaging findings must be evaluated cautiously given the widespread reliance on modest sample sizes and little implementation of statistical validation. Additional limitations included use of imaging before and after a course of TMS, which provided little insight into changes that might occur during the weeks of stimulation. Furthermore, as studies to date have focused on depression, it is unclear whether our observations were related to mechanisms of action of TMS for depression or represented broader patterns of functional brain changes associated with clinical improvement. Published by Elsevier Inc.

  4. Major ecosystems in China: dynamics and challenges for sustainable management.

    Lü, Yihe; Fu, Bojie; Wei, Wei; Yu, Xiubo; Sun, Ranhao

    2011-07-01

    Ecosystems, though impacted by global environmental change, can also contribute to the adaptation and mitigation of such large scale changes. Therefore, sustainable ecosystem management is crucial in reaching a sustainable future for the biosphere. Based on the published literature and publicly accessible data, this paper discussed the status and trends of forest, grassland, and wetland ecosystems in China that play important roles in the ecological integrity and human welfare of the nation. Ecological degradation has been observed in these ecosystems at various levels and geographic locations. Biophysical (e.g., climate change) and socioeconomic factors (e.g., intensive human use) are the main reasons for ecosystem degradation with the latter factors serving as the dominant driving forces. The three broad categories of ecosystems in China have partially recovered from degradation thanks to large scale ecological restoration projects implemented in the last few decades. China, as the largest and most populated developing nation, still faces huge challenges regarding ecosystem management in a changing and globalizing world. To further improve ecosystem management in China, four recommendations were proposed, including: (1) advance ecosystem management towards an application-oriented, multidisciplinary science; (2) establish a well-functioning national ecological monitoring and data sharing mechanism; (3) develop impact and effectiveness assessment approaches for policies, plans, and ecological restoration projects; and (4) promote legal and institutional innovations to balance the intrinsic needs of ecological and socioeconomic systems. Any change in China's ecosystem management approach towards a more sustainable one will benefit the whole world. Therefore, international collaborations on ecological and environmental issues need to be expanded.

  5. 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.

  6. Relationships among alexithymia, therapeutic alliance, and psychotherapy outcome in major depressive disorder.

    Quilty, Lena C; Taylor, Graeme J; McBride, Carolina; Bagby, R Michael

    2017-08-01

    Previous studies have found that alexithymia predicts process and outcome of psychodynamic psychotherapy across a range of psychiatric disorders. There is preliminary evidence that alexithymia may exert its effects on outcome through the therapist. Other studies have found that alexithymia does not influence outcome of cognitive-behavioral therapy (CBT). The aim of the current study was to investigate the capacity of alexithymia to predict therapist- and patient-rated therapeutic alliance and response to CBT and interpersonal psychotherapy (IPT) for major depressive disorder. A total of 75 adults with major depressive disorder were randomized to receive weekly sessions of manualized individual CBT or IPT for a period of 16 weeks. Pre-treatment alexithymia exhibited a positive direct effect on depression change, and a negative indirect effect on depression change via patient-rated alliance at week 13. There was no mediating role of therapist-rated alliance. Although these findings are preliminary, they suggest that pre-treatment alexithymia has meaningful links to psychotherapy process and outcome, and that nuanced analyses incorporating intervening variables are necessary to elucidate the nature of these links. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  7. Argos at NRPA - added value and major challenges

    Thorshaug, S.; Holo, E.N.

    2003-01-01

    Full text: The national emergency response organization with the Crisis Committee for Nuclear Accidents, their advisors and their information group will gather at NRPA in case of a nuclear or radiological accident. Prognoses and actual measurements presented through a decision support system are regarded being of major importance as a basis for the decision making. ARGOS presents predictions of several quantities that are likely to be of interest to decision makers during and alter an accident, such as air concentration, deposition, effective dose and foodstuff activity. It is expected that ARGOS will be an important tool for the decision makers in case of an accident at a foreign nuclear power plant, at one of the two research reactors in Norway or in case of a nuclear accident in a nuclear powered vessel. Information from meteorological forecasts and atmospheric dispersion models will be of key importance in case of such an accident. Therefore, the main emphasis in the implementation process so far has been on the integration between ARGOS and the long-range dispersion model, SNAP, used at the Norwegian Meteorological Institute. A new technical solution represents an improvement of the existing arrangement within the Norwegian emergency preparedness organization, and facilitates presentation of dose calculations based on numerical weather prediction data in a clear and intuitive manner. ARGOS also represents an improved and more centralized approach to data handling and data processing within the Norwegian nuclear emergency response organization. This is due mainly to its quality as a central repository for different types of measurement data. The data of interest are produced for example by mobile ground- or air-based measuring teams (civilian or military), by measuring stations within the automatic monitoring network or by laboratory analysis of air samples or environmental- and food samples. The ability to graphically present such measuring data together with

  8. Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges

    Stephan Köhler

    2017-11-01

    Full Text Available In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT by so-called “third-wave” strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to “classical CBT,” some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT, (b the concept of “limited reparenting” as used in Schema Therapy (ST, and (c disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP. On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

  9. Dental implants modified with drug releasing titania nanotubes: therapeutic potential and developmental challenges.

    Gulati, Karan; Ivanovski, Sašo

    2017-08-01

    The transmucosal nature of dental implants presents a unique therapeutic challenge, requiring not only rapid establishment and subsequent maintenance of osseointegration, but also the formation of resilient soft tissue integration. Key challenges in achieving long-term success are sub-optimal bone integration in compromised bone conditions and impaired trans-mucosal tissue integration in the presence of a persistent oral microbial biofilm. These challenges can be targeted by employing a drug-releasing implant modification such as TiO 2 nanotubes (TNTs), engineered on titanium surfaces via electrochemical anodization. Areas covered: This review focuses on applications of TNT-based dental implants towards achieving optimal therapeutic efficacy. Firstly, the functions of TNT implants will be explored in terms of their influence on osseointegration, soft tissue integration and immunomodulation. Secondly, the developmental challenges associated with such implants are reviewed including sterilization, stability and toxicity. Expert opinion: The potential of TNTs is yet to be fully explored in the context of the complex oral environment, including appropriate modulation of alveolar bone healing, immune-inflammatory processes, and soft tissue responses. Besides long-term in vivo assessment under masticatory loading conditions, investigating drug-release profiles in vivo and addressing various technical challenges are required to bridge the gap between research and clinical dentistry.

  10. CCR 20th Anniversary Commentary: Prospects and Challenges of Therapeutic Nanoparticles in Cancer.

    Rahman, Mohammad Aminur; Shin, Dong M

    2015-10-15

    In their review article published in the March 1, 2008, issue of Clinical Cancer Research, Cho and colleagues presented the strong potential of nanotechnology in cancer. This commentary discusses the latest advances in nanotechnology, which provide novel approaches for cancer diagnosis, imaging, drug delivery, and personalized therapy; highlights the perspectives for therapeutic nanoparticles; and describes the advantages and challenges of their multifunctionalities. ©2015 American Association for Cancer Research.

  11. Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

    Putcha, Lakshmi

    2011-01-01

    An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

  12. Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach.

    Taylor, Sophie; Spugnini, Enrico Pierluigi; Assaraf, Yehuda G; Azzarito, Tommaso; Rauch, Cyril; Fais, Stefano

    2015-11-01

    Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the extracellular microenvironment and the acidic organelles of tumor cells. It is therefore essential to develop new strategies to overcome the entrapment and neutralization of weak base drugs. One such strategy is the use of proton pump inhibitors which can enhance tumor chemosensitivity by increasing the pH of the tumor microenvironment. Recent clinical trials in animals with spontaneous tumors have indicated that patient alkalization is capable of reversing acquired chemoresistance in a large percentage of tumors that are refractory to chemotherapy. Of particular interest was the benefit of alkalization for patients undergoing metronomic regimens which are becoming more widely used in veterinary medicine. Overall, these results provide

  13. [Beat therapeutic inertia in dyslipidemic patient management: A challenge in daily clinical practice] [corrected].

    Morales, Clotilde; Mauri, Marta; Vila, Lluís

    2014-01-01

    Beat therapeutic inertia in dyslipidemic patient management: a challenge in daily clinical practice. In patients with dyslipidemia, there is the need to reach the therapeutic goals in order to get the maximum benefit in the cardiovascular events risk reduction, especially myocardial infarction. Even having guidelines and some powerful hypolipidemic drugs, the goals of low-density lipoprotein-cholesterol (LDL-c) are often not reached, being of special in patients with a high cardiovascular risk. One of the causes is the therapeutic inertia. There are tools to plan the treatment and make the decisions easier. One of the challenges in everyday clinical practice is to know the needed percentage of reduction in LDL-c. Moreover: it is hard to know which one is the treatment we should use in the beginning of the treatment but also when the desired objective is not reached. This article proposes a practical method that can help solving these questions. Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  14. Component-resolved evaluation of the content of major allergens in therapeutic extracts for specific immunotherapy of honeybee venom allergy

    Blank, Simon; Etzold, Stefanie; Darsow, Ulf

    2017-01-01

    Allergen-specific immunotherapy is the only curative treatment of honeybee venom (HBV) allergy, which is able to protect against further anaphylactic sting reactions. Recent analyses on a molecular level have demonstrated that HBV represents a complex allergen source that contains more relevant...... major allergens than formerly anticipated. Moreover, allergic patients show very diverse sensitization profiles with the different allergens. HBV-specific immunotherapy is conducted with HBV extracts which are derived from pure venom. The allergen content of these therapeutic extracts might differ due...... to natural variations of the source material or different down-stream processing strategies of the manufacturers. Since variations of the allergen content of therapeutic HBV extracts might be associated with therapeutic failure, we adressed the component-resolved allergen composition of different therapeutic...

  15. Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

    Dounay, Amy B; Tuttle, Jamison B; Verhoest, Patrick R

    2015-11-25

    The kynurenine pathway is responsible for the metabolism of more than 95% of dietary tryptophan (TRP) and produces numerous bioactive metabolites. Recent studies have focused on three enzymes in this pathway: indoleamine dioxygenase (IDO1), kynurenine monooxygenase (KMO), and kynurenine aminotransferase II (KAT II). IDO1 inhibitors are currently in clinical trials for the treatment of cancer, and these agents may also have therapeutic utility in neurological disorders, including multiple sclerosis. KMO inhibitors are being investigated as potential treatments for neurodegenerative diseases, such as Huntington's and Alzheimer's diseases. KAT II inhibitors have been proposed in new therapeutic approaches toward psychiatric and cognitive disorders, including cognitive impairment associated with schizophrenia. Numerous medicinal chemistry studies are currently aimed at the design of novel, potent, and selective inhibitors for each of these enzymes. The emerging opportunities and significant challenges associated with pharmacological modulation of these enzymes will be explored in this review.

  16. Development of therapeutic antibodies to G protein-coupled receptors and ion channels: Opportunities, challenges and their therapeutic potential in respiratory diseases.

    Douthwaite, Julie A; Finch, Donna K; Mustelin, Tomas; Wilkinson, Trevor C I

    2017-01-01

    The development of recombinant antibody therapeutics continues to be a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Therapeutic drug targets such as soluble cytokines, growth factors and single transmembrane spanning receptors have been successfully targeted by recombinant monoclonal antibodies and the development of new product candidates continues. Despite this growth, however, certain classes of important disease targets have remained intractable to therapeutic antibodies due to the complexity of the target molecules. These complex target molecules include G protein-coupled receptors and ion channels which represent a large target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these important regulators of cell function. Given this opportunity, a significant effort has been applied to address the challenges of targeting these complex molecules and a number of targets are linked to the pathophysiology of respiratory diseases. In this review, we provide a summary of the importance of GPCRs and ion channels involved in respiratory disease and discuss advantages offered by antibodies as therapeutics at these targets. We highlight some recent GPCRs and ion channels linked to respiratory disease mechanisms and describe in detail recent progress made in the strategies for discovery of functional antibodies against challenging membrane protein targets such as GPCRs and ion channels. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures

    Huang Xuan

    2012-07-01

    Full Text Available Abstract Men with metastatic castration-resistant prostate cancer (mCRPC carry poor prognosis despite the use of docetaxel-based regimens which has modest survival benefit shown by randomized clinical trials. Significant progress in the discovery of novel therapeutic agents has been made in the past few years. While sipuleucel-T, cabazitaxel, and abiraterone gained regulatory approval in 2010 and 2011, several highly promising candidates/regimens have failed in large scale clinical trials. Challenges remain to optimize the design and interpretation of clinical trial results and develop more effective strategies for mCRPC. In this review, we examined the positive and negative clinical trials in mCRPC in the past and discussed the various aspects of clinical trial design including selection of targets and appropriate outcome measures, biomarker development and implementation, and strategies for combination therapy.

  18. Frontal fibrosing alopecia and lichen planus pigmentosus: diagnosis and therapeutic challenge.

    Mulinari-Brenner, Fabiane Andrade; Guilherme, Marina Riedi; Peretti, Murilo Calvo; Werner, Betina

    2017-01-01

    Frontal fibrosing alopecia is a variant of lichen planopilaris with marginal progressive hair loss on the scalp, eyebrows and axillae. We report a case of frontal fibrosing alopecia and lichen planus pigmentosus in a postmenopausal woman, that started with alopecia on the eyebrows and then on the frontoparietal region, with periocular and cervical hyperpigmentation of difficult management. The condition was controlled with systemic corticosteroid therapy and finasteride. Lichen planus pigmentosus is an uncommon variant of lichen planus frequently associated with frontal fibrosing alopecia in darker phototipes. It should be considered in patients affected by scarring alopecia with a pattern of lichen planopilaris and areas of skin hyperpigmentation revealing perifollicular hyperpigmentation refractory to multiple treatments. This case illustrates diagnostic and therapeutic challenge in face of scarring alopecia and perifollicular hyperpigmentation.

  19. Therapeutic potential and challenges of Natural killer cells in treatment of solid tumors

    Andrea eGras Navarro

    2015-04-01

    Full Text Available Natural killer (NK cells are innate lymphoid cells that hold tremendous potential for effective immunotherapy for a broad range of cancers. Due to the mode of NK cell killing requiring one–to-one target engagement and site directed release of cytolytic granules, the therapeutic potential of NK cells has been most extensively explored in hematological malignancies. However, their ability to precisely kill antibody coated cells, cancer stem cells (CSCs and genotoxically altered cells, while maintaining tolerance to healthy cells makes them appealing therapeutic effectors for all cancer forms, including metastases. Due to their release of pro-inflammatory cytokines, NK cells may potently reverse the anti-inflammatory tumor microenvironment (TME and augment adaptive immune responses by promoting differentiation, activation and/ or recruitment of accessory immune cells to sites of malignancy. Nevertheless, integrated and coordinated mechanisms of subversion of NK cell activity against the tumor and its microenvironment exist. Although our understanding of the receptor ligand interactions that regulate NK cell functionality has evolved remarkably, the diversity of ligands and receptors is complex, as is their mechanistic foundations in regulating NK cell function. In this article, we review the literature and highlight how the TME manipulates the NK cell phenotypes, genotypes and tropism to evade tumor recognition and elimination. We discuss counter strategies that may be adopted to augment the efficacy of NK cell anti-tumor surveillance, the clinical trials that have been undertaken so far in solid malignancies, critically weighing the challenges and opportunities with this approach.

  20. Galantamine is a novel post-exposure therapeutic against lethal VX challenge

    Hilmas, Corey J.; Poole, Melissa J.; Finneran, Kathryn; Clark, Matthew G.; Williams, Patrick T.

    2009-01-01

    The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 μg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

  1. Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges.

    McKenna, Dennis J

    2004-05-01

    Ayahuasca is a hallucinogenic beverage that is prominent in the ethnomedicine and shamanism of indigenous Amazonian tribes. Its unique pharmacology depends on the oral activity of the hallucinogen, N,N-dimethyltryptamine (DMT), which results from inhibition of monoamine oxidase (MAO) by beta-carboline alkaloids. MAO is the enzyme that normally degrades DMT in the liver and gut. Ayahuasca has long been integrated into mestizo folk medicine in the northwest Amazon. In Brazil, it is used as a sacrament by several syncretic churches. Some of these organizations have incorporated in the United States. The recreational and religious use of ayahuasca in the United States, as well as "ayahuasca tourism" in the Amazon, is increasing. The current legal status of ayahuasca or its source plants in the United States is unclear, although DMT is a Schedule I controlled substance. One ayahuasca church has received favorable rulings in 2 federal courts in response to its petition to the Department of Justice for the right to use ayahuasca under the Religious Freedom Restoration Act. A biomedical study of one of the churches, the Uñiao do Vegetal (UDV), indicated that ayahuasca may have therapeutic applications for the treatment of alcoholism, substance abuse, and possibly other disorders. Clinical studies conducted in Spain have demonstrated that ayahuasca can be used safely in normal healthy adults, but have done little to clarify its potential therapeutic uses. Because of ayahuasca's ill-defined legal status and variable botanical and chemical composition, clinical investigations in the United States, ideally under an approved Investigational New Drug (IND) protocol, are complicated by both regulatory and methodological issues. This article provides an overview of ayahuasca and discusses some of the challenges that must be overcome before it can be clinically investigated in the United States.

  2. Turning Weaknesses into Strengths: Nordic Tourism, Potentials for Growth and Major Challenges

    Ruhet Genc

    2010-03-01

    Full Text Available Nordic region is a geographical area which is characterized by a combination of nature, culture, history and technology and regarded as a common entity in political, economical and historical sense. Although rich in its resources, Nordic tourism has not actualized its potential in full. The present paper aims to identify weaknesses of the region, to outline a new set of directions for improving Nordic tourism and to delineate major challenges. Its geographical and natural beauties, cultural characteristics, technological advancement and policy development are identified as assets for tourism advancement in the region. Winter tourism, adventure tourism, nature-based tourism and cultural tourism are demonstrated as potential routes of growth. Marketing strategies and changing trends are discussed as major challenges, with suggestions for implementation.

  3. The importance of fungi and mycology for addressing major global challenges*

    Lange, Lene

    2014-01-01

    In the new bioeconomy, fungi play a very important role in addressing major global challenges, being instrumental for improved resource efficiency, making renewable substitutes for products from fossil resources, upgrading waste streams to valuable food and feed ingredients, counteracting life-style diseases and antibiotic resistance through strengthening the gut biota, making crop plants more robust to survive climate change conditions, and functioning as host organisms for production of new...

  4. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  5. An Aggressive Form of Langerhan Cell Histiocytosis in an Adult: Therapeutic Challenges

    Karan Seegobin

    2017-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is rare in adults. Regular follow-up is mandatory due to reoccurrence. A 35-year-old male with an incidental left iliac bone lesion was diagnosed with LCH. He later became symptomatic with hip pain and spread of the disease. Despite excision of the symptomatic iliac lesion, he had progression while on cytarabine and nivolumab, evidenced by increased bone pain and involvement of other bones on imaging. He underwent excision of the jaw lesion followed by vinblastine; he was pain free and had stable disease on PET imaging after 3 months. LCH is an uncommon neoplasia. Treatment is reserved for symptomatic patients while asymptomatic patients are observed. Follow-up is imperative due to the risk of reoccurrence. Despite surgical treatment together with one of the front-line agents for refractory disease, in this case cytarabine, he still had progression of the disease. Furthermore, the trial of nivolumab was of no benefit. This case highlights good response to vinblastine which is previously reported to have good success. No trials are published, and the optimal strategy has yet to be defined. LCH with multiple bony involvement can be aggressive and therapeutically challenging.

  6. ESBL Escherichia coli Ventriculitis after Aneurysm Clipping: A Rare and Difficult Therapeutic Challenge

    F. A. Zeiler

    2015-01-01

    Full Text Available Background. Extended spectrum beta-lactamase (ESBL produced Escherichia coli (E. coli ventriculitis is a rare infection of the central nervous system, with increasing rarity in the adult population. The therapeutic strategy to achieve cure may need to involve a combination of intraventricular and intravenous (IV therapy. Objective. To describe a case of ESBL E. coli meningitis/ventriculitis in an adult and outline the antimicrobial therapy that leads to cure. Methods. We retrospectively reviewed the records of a patient admitted to the neurosurgical department for aneurysmal subarachnoid hemorrhage, who developed ESBL E. coli ventriculitis. Results. A 55-year-old female, admitted for a Fisher grade 3, World Federation of Neurological Surgeons grade 1, subarachnoid hemorrhage, developed ESBL E. coli ventriculitis requiring a combination of intraventricular gentamicin and high dose intravenous meropenem for clearance. Cerebrospinal fluid clearance occurred at 7 days after initiation of combined therapy. The patient remained shunt dependent. Conclusions. Meningitis and ventriculitis caused by ESBL E. coli species are rare and pose significant challenges to the treating physician. Early consideration for combined intraventricular and IV therapy should be made.

  7. Therapeutic Potential, Challenges and Future Perspective of Cancer Stem Cells in Translational Oncology: A Critical Review.

    Shukla, Gaurav; Khera, Harvinder Kour; Srivastava, Amit Kumar; Khare, Piush; Patidar, Rahul; Saxena, Rajiv

    2017-01-01

    Stem cell research is a rapidly developing field that offers effective treatment for a variety of malignant and non-malignant diseases. Stem cell is a regenerative medicine associated with the replacement, repair, and restoration of injured tissue. Stem cell research is a promising field having maximum therapeutic potential. Cancer stem cells (CSCs) are the cells within the tumor that posses capacity of selfrenewal and have a root cause for the failure of traditional therapies leading to re-occurrence of cancer. CSCs have been identified in blood, breast, brain, and colon cancer. Traditional therapies target only fast growing tumor mass, but not slow-dividing cancer stem cells. It has been shown that embryonic pathways such as Wnt, Hedgehog and Notch, control self-renewal capacity and involved in cancer stem cell maintenance. Targeting of these pathways may be effective in eradicating cancer stem cells and preventing chemotherapy and radiotherapy resistance. Targeting CSCs has become one of the most effective approaches to improve the cancer survival by eradicating the main root cause of cancer. The present review will address, in brief, the importance of cancer stem cells in targeting cancer as better and effective treatment along with a concluding outlook on the scope and challenges in the implication of cancer stem cells in translational oncology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Postoperative Treatment in a Patient After Hemithyroidectomy: the Therapeutic Challenges of a Hidden Thyrotropinoma

    Sabine Vermeersch

    2015-07-01

    Full Text Available Objectives: We report the unusual case of a patient with a thyrotropinoma, discovered after a hemithyroidectomy for a suspicious thyroid nodule, and its therapeutic challenges. Materials and methods: In a patient who underwent hemithyroidectomy for cold thyroid nodule, hyperthyroid symptoms persisted, despite stopping levothyroxine treatment. Further investigation was carried out through the following laboratory tests: thyroid-stimulating hormone (TSH test; free thyroxine (fT4 test; and the thyrotropin releasing hormone (TRH test. A pituitary magnetic resonance imaging (MRI scan and genetic analysis was also carried out. The test results confirmed the diagnosis of a thyrotropinoma. Results: Treatment with long-acting somatostatin analogues normalised thyroid hormones and symptoms of hyperthyroidism. Conclusion: The diagnostic approach to the thyroid nodule should include a detailed clinical and biochemical examination. Initial biochemical evaluation by TSH alone does not allow detecting inappropriate TSH secretion that may increase the risk of thyroid malignancy. In case of a thyrotropinoma, the ideal treatment consists of combined care of central and peripheral thyroid disease.

  9. Developing a therapeutic relationship with a blind client with a severe intellectual disability and persistent challenging behaviour

    Sterkenburg, P.S.; Janssen, C.G.C.; Schuengel, C.

    2008-01-01

    Purpose. A blind, severely intellectually impaired boy aged 17 with Down syndrome and persistent serious challenging behavior received attachment-based behavior modification treatment. The aim was to study the effect of the treatment and the development of the therapeutic attachment relationship.

  10. A qualitative exploration of the major challenges facing pharmacovigilance in Saudi Arabia.

    Aljadhey, Hisham; Mahmoud, Mansour A; Alshammari, Thamir M; Al-Dhaeefi, Mohammed; Le Louet, Herve; Perez-Gutthann, Susana; Pitts, Peter J

    2015-09-01

    To explore the challenges facing pharmacovigilance in Saudi Arabia and formulate recommendations to improve it from the perspective of healthcare professionals in Saudi Arabia. This was a qualitative study of 4 focus group discussions with pharmacists, physicians, and academicians held under the auspices of the King Saud University School of Pharmacy and the Center for Medicine in the Public Interest, Riyadh, Saudi Arabia. A total of 29 eligible healthcare professionals were invited to participate in the discussion. The predefined themes of the study were the current practice and major challenges facing pharmacovigilance in regulatory bodies, hospitals, the community, and academia, as well as recommendations to improve pharmacovigilance practice.  Of the 29 participants invited, 27 attended the discussion. Challenges facing regulatory bodies included complicated adverse drug reactions (ADR) reporting forms, lack of feedback on ADRs submitted to the Saudi Food and Drug Authority, lack of decisions from the local authority to withdraw medications, and lack of data on pharmacovigilance. The challenges to pharmacovigilance in hospitals included the lack of knowledge of the significance of ADR reporting, workload, blaming culture, and lack of collaboration between regulatory bodies and hospitals. However, challenges facing pharmaceutical industries included the lack of drug manufacturers in Saudi Arabia and lack of interest in pharmacovigilance. Recommendations to improve pharmacovigilance included the need for communication, stronger regulatory requirements, the need for research, the need for unified ADRs reporting, and continuous education and training.  The study has identified the challenges facing pharmacovigilance in Saudi Arabia and made certain recommendations to overcome them. These recommendations might be helpful for regulatory bodies to enhance spontaneous reporting and promote pharmacovigilance.

  11. Morbidly obese patient with obstructive sleep apnoea for major spine surgery: An anaesthetic challenge

    Shruti Redhu

    2016-01-01

    Full Text Available Morbidly obese patients with clinical features of obstructive sleep apnoea can present a myriad of challenges to the anaesthesiologists which must be addressed to minimise the perioperative risks. Initiation of continuous positive airway pressure (CPAP therapy early in the pre- and post-operative period along with appropriate anaesthetic planning is of paramount importance in such patients. This case report emphasises the usefulness of CPAP therapy, even for a short duration, to minimise morbidity, improve recovery and hasten early discharge from the hospital after major surgery.

  12. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α in Major Depressive Disorder: A Systematic Review

    Ke Ma

    2016-05-01

    Full Text Available Major depressive disorder (MDD is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α, play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies.

  13. Abnormal function of monoamine oxidase-A in comorbid major depressive disorder and cardiovascular disease: pathophysiological and therapeutic implications (review).

    Machado-Vieira, Rodrigo; Mallinger, Alan G

    2012-11-01

    The association between major depressive disorder (MDD) and cardiovascular disease (CVD) is among the best described medical comorbidities. The presence of MDD increases the risk of cardiac admissions and mortality and increases healthcare costs in patients with CVD, and similarly, CVD affects the course and outcome of MDD. The potential shared biological mechanisms involved in these comorbid conditions are not well known. However, the enzyme monoamine oxidase-A (MAO-A), which has a key role in the degradation of catecholamines, has been associated with the pathophysiology and therapeutics of both MDD and CVD. Increased MAO-A activity results in the dysregulation of downstream targets of this enzyme and thus affects the pathophysiology of the two diseases. These deleterious effects include altered noradrenaline turnover, with a direct elevation in oxidative stress parameters, as well as increased platelet activity and cytokine levels. These effects were shown to be reversed by MAO inhibitors. Here, a model describing a key role for the MAO-A in comorbid MDD and CVD is proposed, with focus on the shared pathophysiological mechanisms and the potential therapeutic relevance of agents targeting this enzyme.

  14. Pathogenetic and Therapeutic Applications of Tumor Necrosis Factor-α (TNF-α) in Major Depressive Disorder: A Systematic Review

    Ma, Ke; Zhang, Hongxiu; Baloch, Zulqarnain

    2016-01-01

    Major depressive disorder (MDD) is characterized by mood, vegetative, cognitive, and even psychotic symptoms and signs that can cause substantial impairments in quality of life and functioning. Up to now, the exact pathogenesis of MDD remains poorly understood. Recent research has begun to reveal that the pro-inflammatory cytokines, particularly, tumor necrosis factor-α (TNF-α), play an integral role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. On the base of several observations: it is found that subsets of MDD patients have enhanced plasma levels TNF-α; antidepressant treatments had linked with the decline of TNF-α; central administration of TNF-α gives rise to sickness behavior which shares features with depression; and a blockade of it can ameliorate depressive symptomatology in animal models and clinical trials. In this review article, we focus on recent evidence linking TNF-α and MDD looking at data from animal and clinical studies, illustrating the pathophysiological role, susceptibility and its therapeutic application in depression. We conclude by discussing future directions for research, in particular the opportunities for the development of novel therapeutics that target TNF-α. This will be very important for designing preventative strategies and for the identification of new drug targets and preventative strategies. PMID:27187381

  15. Babesia major: protection of intact calves against homologous challenge by the injection of irradiated piroplasms

    Purnell, R.E.; Lewis, D.; Brocklesby, D.W.

    1979-01-01

    Blood from a splenectomized calf infected with Babesia major was divided into 20 ml aliquots which were γ-irradiated at doses of 0, 23.3, 27.3, 31.4, 35.4 and 39.5 krad and then inoculated into groups of three intact calves. Animals receiving non-irradiated blood had typical mild B. major reactions, but those receiving blood irradiated at 23.3, 27.3 and 31.4 krad and 2 of 3 receiving blood irradiated at 35.4 krad had minimal reactions. The remaining 4 animals had no detectable parasitaemic reactions. When the calves were challenged with a similar number (6.0 x 10 9 ) of homologous parasites, they were all immune with the exception of the 4 animals which had not reacted initially. The immune status of individual cattle was reflected accurately in the results of the micro-ELISA test, which detected a significant rise in serum antibody titre of the 4 susceptible animals 7 days after challenge. (author)

  16. Babesia major: protection of intact calves against homologous challenge by the injection of irradiated piroplasms

    Purnell, R E; Lewis, D; Brocklesby, D W [Agricultural Research Council, Compton (UK). Inst. for Research on Animal Diseases

    1979-02-01

    Blood from a splenectomized calf infected with Babesia major was divided into 20 ml aliquots which were ..gamma..-irradiated at doses of 0, 23.3, 27.3, 31.4, 35.4 and 39.5 krad and then inoculated into groups of three intact calves. Animals receiving non-irradiated blood had typical mild B. major reactions, but those receiving blood irradiated at 23.3, 27.3 and 31.4 krad and 2 of 3 receiving blood irradiated at 35.4 krad had minimal reactions. The remaining 4 animals had no detectable parasitaemic reactions. When the calves were challenged with a similar number (6.0 x 10/sup 9/) of homologous parasites, they were all immune with the exception of the 4 animals which had not reacted initially. The immune status of individual cattle was reflected accurately in the results of the micro-ELISA test, which detected a significant rise in serum antibody titre of the 4 susceptible animals 7 days after challenge.

  17. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Tilahun Alelign

    2018-01-01

    Full Text Available Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy.

  18. Kidney Transplantation: The Challenge of Human Leukocyte Antigen and Its Therapeutic Strategies

    Ahmed, Momina M.; Bobosha, Kidist; Tadesse, Yewondwossen; Howe, Rawleigh; Petros, Beyene

    2018-01-01

    Kidney transplantation remains the treatment of choice for end-stage renal failure. When the immune system of the recipient recognizes the transplanted kidney as a foreign object, graft rejection occurs. As part of the host immune defense mechanism, human leukocyte antigen (HLA) is a major challenge for graft rejection in transplantation therapy. The impact of HLA mismatches between the donor and the potential recipient prolongs the time for renal transplantation therapy, tethered to dialysis, latter reduces graft survival, and increases mortality. The formation of pretransplant alloantibodies against HLA class I and II molecules can be sensitized through exposures to blood transfusions, prior transplants, and pregnancy. These preformed HLA antibodies are associated with rejection in kidney transplantation. On the other hand, the development of de novo antibodies may increase the risk for acute and chronic rejections. Allograft rejection results from a complex interplay involving both the innate and the adaptive immune systems. Thus, further insights into the mechanisms of tissue rejection and the risk of HLA sensitization is crucial in developing new therapies that may blunt the immune system against transplanted organs. Therefore, the purpose of this review is to highlight facts about HLA and its sensitization, various mechanisms of allograft rejection, the current immunosuppressive approaches, and the directions for future therapy. PMID:29693023

  19. Challenges of therapeutic substitution of drugs for economic reasons: focus on CVD prevention.

    Johnston, Atholl

    2010-04-01

    Healthcare systems throughout the world are under increasing pressure to control and minimise costs. The substitution of initially-prescribed drugs with cheaper equivalents is an obvious option which presents a rapid and visible means to reduce these costs. Whether the substitution improves patient and/or population outcomes must be appraised and this paper highlights the conditions under which therapeutic substitution may require additional thought and consideration. In this paper, some of the medical evidence and the regulatory environment for and against the three types of therapeutic substitution - generic, within-class and between-class - are discussed. This article is not an exhaustive review of the literature, but captures some of the key clinical, pharmacological, economic, policy and ethical issues regarding generic and therapeutic substitution. Search criteria of the most commonly used terms, i.e. therapeutic substitution, switching, interchange, and bioequivalence, were applied to Embase, PubMed and Google Scholar to identify relevant publications. Although population studies support therapeutic substitution in principle, there is evidence that substitution may not always result in therapeutic equivalence in individual patients, with the consequent potential for greater risks of decreased efficacy and/or increased safety concerns. Factors such as patient choice and therapeutic equivalence also play an important role in the effectiveness of the treatment and overall management of the patient. The pan-European regulatory environment provides another contradiction, encouraging widespread cost containment through reduction in drug acquisition costs, while simultaneously promoting an increased role for patients in defining and managing their own treatment. There is a strong rationale for careful management in some patients with cardiovascular disease. Treatment decisions should be transparent and based on strong clinical evidence. If not, drug substitution on

  20. Plasmodium falciparum Resistance to Artemisinin Derivatives and Piperaquine: A Major Challenge for Malaria Elimination in Cambodia

    Duru, Valentine; Witkowski, Benoit; Ménard, Didier

    2016-01-01

    Artemisinin-based combination therapies (ACTs) are the cornerstone of current strategies for fighting malaria. Over the last decade, ACTs have played a major role in decreasing malaria burden. However, this progress is being jeopardized by the emergence of artemisinin-resistant Plasmodium falciparum parasites. Artemisinin resistance was first detected in western Cambodia in 2008 and has since been observed in neighboring countries in southeast Asia. The problem of antimalarial drug resistance has recently worsened in Cambodia, with reports of parasites resistant to piperaquine, the latest generation of partner drug used in combination with dihydroartemisinin, leading to worrying rates of clinical treatment failure. The monitoring and the comprehension of both types of resistance are crucial to prevent the spread of multidrug-resistant parasites outside southeast Asia, and particularly to Africa, where the public health consequences would be catastrophic. To this end, new tools are required for studying the biological and molecular mechanisms underlying resistance to antimalarial drugs and for monitoring the geographic distribution of the resistant parasites. In this review, we detail the major advances in our understanding of resistance to artemisinin and piperaquine and define the challenges that the malaria community will have to face in the coming years. PMID:27928074

  1. Major health service transformation and the public voice: conflict, challenge or complicity?

    Martin, Graham P; Carter, Pam; Dent, Mike

    2018-01-01

    Objectives Calls for major reconfigurations of health services have been accompanied by recommendations that wide ranging stakeholders be involved. In particular, patients and the wider public are seen as critical contributors as both funders and beneficiaries of public health care. But public involvement is fraught with challenges, and little research has focused on involvement in the health service transformation initiatives. This paper examines the design and function of public involvement in reconfiguration of health services within the English NHS. Methods Qualitative data including interviews, observation and documents were collected in two health service 'transformation' programmes; interviews include involved public and professional participants. Data were analysed using parallel deductive and inductive approaches. Results Public involvement in the programmes was extensive but its terms of reference, and the individuals involved, were restricted by policy pressures and programme objectives. The degree to which participants descriptively or substantively represented the wider public was limited; participants sought to 'speak for' this public but their views on what was 'acceptable' and likely to influence decision-making led them to constrain their contributions. Conclusions Public involvement in two major service reconfiguration programmes in England was seen as important and functional, and could not be characterized as tokenistic. Yet involvement in these programmes fell short of normative ideals, and could inadvertently reduce, rather than enlarge, public influence on health service reconfiguration decisions.

  2. Linezolid in the treatment of drug-resistant tuberculosis: the challenge of its narrow therapeutic index.

    Wasserman, Sean; Meintjes, Graeme; Maartens, Gary

    2016-10-01

    Linezolid is an oxazolidinone with potent activity against M tuberculosis, and improves culture conversion and cure rates when added to treatment regimens for drug resistant tuberculosis. However, linezolid has a narrow therapeutic window, and the optimal dosing strategy that minimizes the substantial toxicity associated with linezolid's prolonged use in tuberculosis treatment has not been determined, limiting the potential impact of this anti-mycobacterial agent. This paper aims to review and summarize the current knowledge on linezolid for the treatment of drug-resistant tuberculosis. The focus is on the pharmacokinetic-pharmacodynamic determinants of linezolid's efficacy and toxicity in tuberculosis, and how this relates to defining an optimal dose. Mechanisms of linezolid toxicity and resistance, and the potential role of therapeutic drug monitoring are also covered. Expert commentary: Prospective pharmacokinetic-pharmacodynamic studies are required to define optimal therapeutic targets and to inform improved linezolid dosing strategies for drug-resistant tuberculosis.

  3. The Relationship Between Brain Oscillatory Activity and Therapeutic Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder

    Andrew Francis Leuchter

    2013-02-01

    Full Text Available Major Depressive Disorder (MDD is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive Transcranial Magnetic Stimulation (rTMS is a robust treatment for MDD, but the mechanism of action (MOA of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this mechanism of action and achieve better antidepressant effectiveness. We propose that rTMS can be administered: 1 synchronized to a patient’s individual alpha rhythm (IAF, or synchronized rTMS (sTMS; 2 as a low magnetic field strength sinusoidal wave form; and, 3 broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

  4. The CRC 20 years: An overview of some of the major achievements and remaining challenges.

    Doek, Jaap E

    2009-11-01

    On 20 November 1989, the General Assembly of the United Nations adopted the Convention on the Rights of the Child (CRC). It entered into force on 2 September 1990 and has by now been ratified by 193 States, making the most universally ratified human rights treaty. This overview will present and discuss the impact of this treaty both at the international and the national level, an overview which necessarily has to be limited to some of the developments as a result of the implementation of the CRC. The first part of this paper will be devoted to the impact the CRC had and still has on the setting and development of the international agenda for the promotion and protection of the rights and welfare of children. Special attention will given to developments, achievements, and remaining challenges at the international level with regard to protection of children in armed conflict; prevention and the protection of children from sexual exploitation; and from all forms of violence. This will include some information on the impact of these international developments and actions at the national level, for example, in the area of legislation. The second part will focus on the impact at the national level. Given the wide scope of the CRC this part will be limited to some of the General Measures of Implementation (law reform, national programmes, and independent monitoring) and the General Principles (non-discrimination, best interest, right to be heard) of the CRC. This will be based on reports of States on the implementation of the CRC submitted to the CRC Committee and the Concluding Observations of this Committee and on a number of studies. The conclusion will provide remarks on poverty as one of the major remaining challenges for the implementation of children's rights.

  5. Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia

    Abuajela Sreh

    2017-11-01

    Full Text Available This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia. After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH. The same management plan was followed until the platelet count exceeded 50×10sup>9/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count.

  6. Investigating Challenges Facing Self-Management Empowerment Education in Adolescents and Youths with Major Thalassemia

    Razzazan

    2014-10-01

    Full Text Available Background Thalassemia is considered an important public health problem worldwide, especially in developing and poor countries. Although several advanced techniques have been developed for prevention of thalassemia in the recent years, many adolescents and youths are still living with this disease. Independence from parents, decisions about high-risk behaviors, uncovering the identity, and adapting to mental and physical effects of the disease occur together in adolescents. Objectives This study was conducted to explore challenges of self-management empowerment in adolescents and youths with major thalassemia. Materials and Methods This was a descriptive-exploratory study. The study population consisted of adolescents and youths with major thalassemia who had medical records in the Bushehr Thalassemia Center, affiliated with Bushehr University of Medical Sciences. The study samples were purposively selected. Demographic information questionnaire and empowerment questionnaire were used to collect data from the semistructured interview. We analyzed qualitative data by content analysis method and quantitative data by descriptive (mean, standard deviation and analytical (Student's t-test, ANOVA and Pearson’s correlation coefficient statistical methods, using the statistical software SPSS 18. Results In qualitative part of the study, data from semistructured in-depth interviews with 15 participants were coded and summarized in five themes including: 1 awareness of personal changes; 2 need for adaptation; 3 maintaining independence and self-management; 4 uncovering the identity and role playing; and 5 sense of control and satisfaction. Results of the quantitative part showed that the overall score of participants on empowerment was 92.46 of 149 scores, which showed a moderate situation in the empowerment of these individuals. In addition, the empowerment score showed no statistically significant correlation with demographic characteristics

  7. Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

    Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

    2015-01-01

    Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

  8. The emergence of precision therapeutics: New challenges and opportunities for Canada's health leaders.

    Slater, Jim; Shields, Laura; Racette, Ray J; Juzwishin, Donald; Coppes, Max

    2015-11-01

    In the era of personalized and precision medicine, the approach to healthcare is quickly changing. Genetic and other molecular information are being increasingly demanded by clinicians and expected by patients for prevention, screening, diagnosis, prognosis, health promotion, and treatment of an increasing number of conditions. As a result of these developments, Canadian health leaders must understand and be prepared to lead the necessary changes associated with these disruptive technologies. This article focuses on precision therapeutics but also provides background on the concepts and terminology related to personalized and precision medicine and explores Canadian health leadership and system issues that may pose barriers to their implementation. The article is intended to inspire, educate, and mobilize Canadian health leaders to initiate dialogue around the transformative changes necessary to ready the healthcare system to realize the benefits of precision therapeutics. © 2015 Collège canadien des leaders en santé

  9. Grave’s Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge

    Bhuyan, Ashok Krishna; Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

    2014-01-01

    Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was...

  10. Pregnancy-related hemophagocytic lymphohistiocytosis associated with cytomegalovirus infection: A diagnostic and therapeutic challenge

    Nor Rafeah Tumian

    2015-08-01

    Conclusion: This case highlights the challenges and difficulties involved in the diagnosis and management of pregnancy-related HLH. Immunosuppressive treatment for HLH can precipitate life-threatening opportunistic infections, which need to be promptly diagnosed and treated.

  11. Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease - Spinocerebellar Ataxia - Opportunities and Challenges

    Satya Prakash

    2008-01-01

    Full Text Available Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic disorder that is caused by the formation of an abnormal protein. There have been several reports on ataxic drug development but actual clinical treatment is yet to be achieved. Oligonucleotide therapy called sequence specific siRNA mediated gene silencing has evolved with promising results. This approach emphasizes on suppressing the expression of the diseased gene at mRNA level. However, there is a limitation in delivery of siRNA to the target site. Several methods have been developed over the last decade to enhance the target specific delivery of DNA, siRNA, protein and small drug molecules for therapeutic purpose with less or no side effects. This review discusses the latest upcoming technologies in the field that focus on a number of nonviral nanocarriers for targeted delivery. In this review, we explore the promise and potential of novel therapeutics with interest on ataxia therapy.

  12. The importance of fungi and mycology for addressing major global challenges*.

    Lange, Lene

    2014-12-01

    In the new bioeconomy, fungi play a very important role in addressing major global challenges, being instrumental for improved resource efficiency, making renewable substitutes for products from fossil resources, upgrading waste streams to valuable food and feed ingredients, counteracting life-style diseases and antibiotic resistance through strengthening the gut biota, making crop plants more robust to survive climate change conditions, and functioning as host organisms for production of new biological drugs. This range of new uses of fungi all stand on the shoulders of the efforts of mycologists over generations: the scientific discipline mycology has built comprehensive understanding within fungal biodiversity, classification, evolution, genetics, physiology, ecology, pathogenesis, and nutrition. Applied mycology could not make progress without this platform. To unfold the full potentials of what fungi can do for both environment and man we need to strengthen the field of mycology on a global scale. The current mission statement gives an overview of where we are, what needs to be done, what obstacles to overcome, and which potentials are within reach. It further provides a vision for how mycology can be strengthened: The time is right to make the world aware of the immense importance of fungi and mycology for sustainable global development, where land, water and biological materials are used in a more efficient and more sustainable manner. This is an opportunity for profiling mycology by narrating the role played by fungi in the bioeconomy. Greater awareness and appreciation of the role of fungi can be used to build support for mycology around the world. Support will attract more talent to our field of study, empower mycologists around the world to generate more funds for necessary basic research, and strengthen the global mycology network. The use of fungi for unlocking the full potentials of the bioeconomy relies on such progress. The fungal kingdom can be an

  13. Having Confidence in Therapeutic Work with Young People: Constraints and Challenges to Confidentiality

    Jenkins, Peter

    2010-01-01

    Confidentiality presents particular challenges to practitioners working with young people, on account of the latter's vulnerability and emotional immaturity. Ethical codes place a key importance on confidentiality, from deontological and teleological perspectives. However, young clients may rely on a more pragmatic approach in deciding whether to…

  14. Giant Colonic Diverticulum: a Rare Diagnostic and Therapeutic Challenge of Diverticular Disease.

    Macht, Ryan; Sheldon, Holly K; Fisichella, P Marco

    2015-08-01

    A giant colonic diverticulum is a diverticulum of the colon greater than 4 cm in diameter that can present, albeit rarely, as a complication of diverticular disease. We discuss the three different histologic subtypes that have been described and the challenges in the diagnosis and treatment.

  15. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  16. What's your opinion? The experience of therapeutic climate in a treatment facility for adults with mild intellectual disability and severe challenging behavior

    Helmond, P.; Vermaes, I.P.R.; Helm, G.H.P. van der

    2014-01-01

    Aim: A therapeutic climate is important so that clients can optimally develop themselves. In a treatment facility for adults with mild intellectual disability and severe challenging behavior we assessed clients’ experiences of therapeutic climate in relation to their internalizing and externalizing

  17. HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

    Hillman, Richard

    2002-01-01

    .... The leadership provided by this subcommittee and the Senate Committee on Governmental Affairs has been especially important in focusing attention on the federal government s human capital challenges.

  18. Recent Perspectives on Genome, Transmission, Clinical Manifestation, Diagnosis, Therapeutic Strategies, Vaccine Developments, and Challenges of Zika Virus Research

    Apoorva Shankar

    2017-09-01

    Full Text Available One of the potential threats to public health microbiology in 21st century is the increased mortality rate caused by Zika virus (ZIKV, a mosquito-borne flavivirus. The severity of ZIKV infection urged World Health Organization (WHO to declare this virus as a global concern. The limited knowledge on the structure, virulent factors, and replication mechanism of the virus posed as hindrance for vaccine development. Several vector and non-vector-borne mode of transmission are observed for spreading the disease. The similarities of the virus with other flaviviruses such as dengue and West Nile virus are worrisome; hence, there is high scope to undertake ZIKV research that probably provide insight for novel therapeutic intervention. Thus, this review focuses on the recent aspect of ZIKV research which includes the outbreak, genome structure, multiplication and propagation of the virus, current animal models, clinical manifestations, available treatment options (probable vaccines and therapeutics, and the recent advancements in computational drug discovery pipelines, challenges and limitation to undertake ZIKV research. The review suggests that the infection due to ZIKV became one of the universal concerns and an interdisciplinary environment of in vitro cellular assays, genomics, proteomics, and computational biology approaches probably contribute insights for screening of novel molecular targets for drug design. The review tried to provide cutting edge knowledge in ZIKV research with future insights required for the development of novel therapeutic remedies to curtail ZIKV infection.

  19. Regulatory T cells, maternal-foetal immune tolerance and recurrent miscarriage: new therapeutic challenging opportunities.

    Alijotas-Reig, Jaume; Melnychuk, Taisiia; Gris, Josep Maria

    2015-03-15

    Because maternal alloreactive lymphocytes are not depleted during pregnancy, local and/or systemic mechanisms have to play a key role in altering the maternal immune response. Peripheral T regulatory cells (pTregs) at the maternal-foetal interface are necessary in situ to prevent early abortion, but only those pTregs that have been previously exposed to paternal alloantigens. It has been showed that pregnancy selectively stimulates the accumulation of maternal Foxp3(+)CD4(+)CD25(+) (Foxp3Tregs) cells with foetal specificity. Interestingly, after delivery, foetal-specific pTregs persist at elevated levels, maintain tolerance to pre-existing foetal antigen, and rapidly re-accumulate during subsequent pregnancy. pTreg up-regulation could be hypothesized as a possible future therapeutic strategy in humans. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  20. Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

    Dobrovolskaia, Marina A; McNeil, Scott E

    2015-07-01

    Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation. This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents. NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.

  1. Dealing with completeness, structural hierarchy, and seismic coupling issues: three major challenges for #Fault2SHA

    Valensise, Gianluca; Barba, Salvatore; Basili, Roberto; Bonini, Lorenzo; Burrato, Pierfrancesco; Carafa, Michele; Kastelic, Vanja; Fracassi, Umberto; Maesano, Francesco Emanuele; Tarabusi, Gabriele; Tiberti, Mara Monica; Vannoli, Paola

    2016-04-01

    The vast majority of active faulting studies are performed at the scale of individual, presumably seismogenic faults or fault strands. Most SHA approaches and models, however, require homogeneus information on potential earthquake sources over the entire tectonic domain encompassing the site(s) of interest. Although it is out of question that accurate SHA must rely on robust investigations of individual potential earthquake sources, it is only by gathering this information in regionally extensive databases that one can address some of the most outstanding issues in the use of #Fault2SHA. We will briefly recall three issues that are particularly relevant in the investigation of seismogenic faulting in southern Europe. A fundamental challenge is the completeness of the geologic record of active faulting. In most tectonic environments many potential seismogenic faults are blind or hidden, or deform the lower crust without leaving a discernible signal at the surface, or occur offshore, or slip so slowly that nontectonic erosional-depositional processes easily outpace their surface effects. Investigating only well-expressed faults is scientifically rewarding but also potentially misleading as it draws attention on the least insidious faults, leading to a potential underestimation of the regional earthquake potential. A further issue concerns the hierarchy of fault systems. Most active faults do not comprise seismogenic sources per se but are part of larger systems, and slip only in conjunction with the master fault of each system. In the most insidious cases, only secondary faults are expressed at the surface while the master fault lies hidden beneath them. This may result in an overestimation of the true number of seismogenic sources that occur in each region and in a biased identification of the characteristics of the main player in each system. Recent investigations of geologic and geodetic vs earthquake release budgets have shown that the "seismic coupling", which

  2. Sleep-Disordered Breathing in Neuromuscular Disease: Diagnostic and Therapeutic Challenges.

    Aboussouan, Loutfi S; Mireles-Cabodevila, Eduardo

    2017-10-01

    Normal sleep-related rapid eye movement sleep atonia, reduced lung volumes, reduced chemosensitivity, and impaired airway dilator activity become significant vulnerabilities in the setting of neuromuscular disease. In that context, the compounding effects of respiratory muscle weakness and disease-specific features that promote upper airway collapse or cause dilated cardiomyopathy contribute to various sleep-disordered breathing events. The reduction in lung volumes with neuromuscular disease is further compromised by sleep and the supine position, exaggerating the tendency for upper airway collapse and desaturation with sleep-disordered breathing events. The most commonly identified events are diaphragmatic/pseudo-central, due to a decrease in the rib cage contribution to the tidal volume during phasic rapid eye movement sleep. Obstructive and central sleep apneas are also common. Noninvasive ventilation can improve survival and quality of sleep but should be used with caution in the context of dilated cardiomyopathy or significant bulbar symptoms. Noninvasive ventilation can also trigger sleep-disordered breathing events, including ineffective triggering, autotriggering, central sleep apnea, and glottic closure, which compromise the potential benefits of the intervention by increasing arousals, reducing adherence, and impairing sleep architecture. Polysomnography plays an important diagnostic and therapeutic role by correctly categorizing sleep-disordered events, identifying sleep-disordered breathing triggered by noninvasive ventilation, and improving noninvasive ventilation settings. Optimal management may require dedicated hypoventilation protocols and a technical staff well versed in the identification and troubleshooting of respiratory events. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  3. Grave’s Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge

    Ashok Krishna Bhuyan

    2014-01-01

    Full Text Available Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations.

  4. Grave's Disease with Severe Hepatic Dysfunction: A Diagnostic and Therapeutic Challenge.

    Bhuyan, Ashok Krishna; Sarma, Dipti; Kaimal Saikia, Uma; Choudhury, Bipul Kumar

    2014-01-01

    Hepatic dysfunction in a patient with thyrotoxicosis may result from hyperthyroidism per se, as a side effect of antithyroid drugs, and causes unrelated to hyperthyroidism which sometimes causes diagnostic and therapeutic difficulties. A young female patient was admitted to our hospital with symptoms of thyrotoxicosis, diffuse goiter and ophthalmopathy along with cholestatic pattern of jaundice, and proximal muscle weakness. She was treated with propylthiouracil with gradual recovery. She was continuing her antithyroid medication with regular follow-up. The patient was readmitted a few months later with worsening thyrotoxicosis, proximal muscle weakness, fever, and a hepatocellular pattern of jaundice with sepsis. Propylthiouracil was stopped and lithium along with steroid coverage was given to control her thyrotoxicosis which was later changed to methimazole. Broad spectrum antibiotic therapy was also started but without any response. During her hospital stay, the patient also developed a flaccid paraplegia resembling Guillain-Barre syndrome. IV steroid was started for the neuropathy but meanwhile the patient succumbed to her illness. So in centers where facility for radioiodine therapy is not readily available, some definite well-tested protocols should be formulated to address such common but complicated clinical situations.

  5. HUMAN CAPITAL: Major Human Capital Challenges at SEC and Key Trade Agencies

    Hillman, Richard

    2002-01-01

    We appreciate the opportunity to appear here today to discuss the human capital challenges facing the agencies that play key roles in monitoring publicly traded companies and enforcing our nation's trade laws...

  6. Major Challenges for the Modern Chemistry in Particular and Science in General.

    Uskokovíc, Vuk

    2010-11-01

    In the past few hundred years, science has exerted an enormous influence on the way the world appears to human observers. Despite phenomenal accomplishments of science, science nowadays faces numerous challenges that threaten its continued success. As scientific inventions become embedded within human societies, the challenges are further multiplied. In this critical review, some of the critical challenges for the field of modern chemistry are discussed, including: (a) interlinking theoretical knowledge and experimental approaches; (b) implementing the principles of sustainability at the roots of the chemical design; (c) defining science from a philosophical perspective that acknowledges both pragmatic and realistic aspects thereof; (d) instigating interdisciplinary research; (e) learning to recognize and appreciate the aesthetic aspects of scientific knowledge and methodology, and promote truly inspiring education in chemistry. In the conclusion, I recapitulate that the evolution of human knowledge inherently depends upon our ability to adopt creative problem-solving attitudes, and that challenges will always be present within the scope of scientific interests.

  7. Primary unclassified sarcoma of the parotid gland: a case of diagnostic and therapeutic challenge.

    Saravakos, Panagiotis; Hartwein, Joerg; Fayyazi, Afshin

    2017-05-01

    Malignant salivary gland sarcomas represent a clinically and histologically diagnostic challenge. Primary unclassified sarcomas of the parotid gland consist a rare salivary gland tumor. We report an unusual case of such a tumor, which occurred in the right parotid gland of a 54-year-old male and presented as an asymptomatic painless mass. The pathologoanatomical examination revealed a rhabdoid large-cell unclassified sarcoma. The patient was treated with superficial parotidectomy and adjuvant radiotherapy. No recurrence was noted in a 10-year follow-up period. Due to the rare occurrence of primary unclassified sarcomas, there is no evidence-based treatment of choice. An optimal approach is best planned in a multidisciplinary setting, taking into consideration the resectability of the tumor, individual patient characteristics, presence of local or distant metastatic activity, local infiltrative behavior and tumor stage. A close follow-up of the patient is strongly recommended.

  8. A global perspective on mechanical prosthetic heart valve thrombosis: Diagnostic and therapeutic challenges

    Gürsoy, Mustafa Ozan; Kalçık, Macit; Yesin, Mahmut; Karakoyun, Süleyman; Bayam, Emrah; Gündüz, Sabahattin; Özkan, Mehmet

    2016-01-01

    Prosthetic valve thrombosis is one of the major causes of primary valve failure, which can be life-threatening. Multimodality imaging is necessary for determination of leaflet immobilization, cause of underlying pathology (thrombus versus pannus or both), and whether thrombolytic therapy attempt in the patient would be successful or surgery is needed. Current guidelines for the management of prosthetic valve thrombosis lack definitive class I recommendations due to lack of randomized controlled trials, and usually leave the choice of treatment to the clinician’s experience. In this review, we aimed to summarize the pathogenesis, diagnosis, and management of mechanical prosthetic valve thrombosis. PMID:28005024

  9. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results

    Pastorello, Elide A; Vieths, Stefan; Pravettoni, Valerio

    2002-01-01

    The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients...

  10. Meaning and challenges in the practice of multiple therapeutic massage modalities: a combined methods study.

    Porcino, Antony J; Boon, Heather S; Page, Stacey A; Verhoef, Marja J

    2011-09-20

    Therapeutic massage and bodywork (TMB) practitioners are predominantly trained in programs that are not uniformly standardized, and in variable combinations of therapies. To date no studies have explored this variability in training and how this affects clinical practice. Combined methods, consisting of a quantitative, population-based survey and qualitative interviews with practitioners trained in multiple therapies, were used to explore the training and practice of TMB practitioners in Alberta, Canada. Of the 5242 distributed surveys, 791 were returned (15.1%). Practitioners were predominantly female (91.7%), worked in a range of environments, primarily private (44.4%) and home clinics (35.4%), and were not significantly different from other surveyed massage therapist populations. Seventy-seven distinct TMB therapies were identified. Most practitioners were trained in two or more therapies (94.4%), with a median of 8 and range of 40 therapies. Training programs varied widely in number and type of TMB components, training length, or both. Nineteen interviews were conducted. Participants described highly variable training backgrounds, resulting in practitioners learning unique combinations of therapy techniques. All practitioners reported providing individualized patient treatment based on a responsive feedback process throughout practice that they described as being critical to appropriately address the needs of patients. They also felt that research treatment protocols were different from clinical practice because researchers do not usually sufficiently acknowledge the individualized nature of TMB care provision. The training received, the number of therapies trained in, and the practice descriptors of TMB practitioners are all highly variable. In addition, clinical experience and continuing education may further alter or enhance treatment techniques. Practitioners individualize each patient's treatment through a highly adaptive process. Therefore, treatment

  11. Important hemoprotozoan diseases of livestock: Challenges in current diagnostics and therapeutics: An update

    Biswa Ranjan Maharana

    2016-05-01

    Full Text Available Hemoprotozoan parasites pose a serious threat to the livestock population in terms of mortality, reduced milk yield and lowered draft power. Diagnosis of these diseases often poses a challenging task. Needless to say that impact of disease in health and productivity is huge though a fair economic assessment on the quantum of economic loss associated is yet to be worked out from India. The diagnosis of hemoprotozoan infections largely depends on various laboratory-based diagnostic methods as the clinical manifestations are often inconspicuous and non-specific. Traditional diagnostic methods rely on microscopical demonstration of infective stages in blood or tissue fluids. However, it is laborious, lesser sensitive, and cannot differentiate between morphologically similar organisms. Recent development in the technologies has opened new avenues for improvement in the accurate diagnosis of parasitic infections. Serological tests are simple, fast but lack specificity. With advent of molecular techniques, as DNA hybridization assays, polymerase chain reaction and its modifications ensure the detection of infection in the latent phase of the disease. Nucleic acid-based assays are highly sensitive, free from immunocompetence and can differentiate between morphologically similar parasites. With the advent of newer diagnostics complemented with traditional ones will be of huge help for targeted selective treatment with better chemotherapeutic agents.

  12. Aggressive NK-cell leukemia: A rare entity with diagnostic and therapeutic challenge

    Alia Nazarullah

    2016-06-01

    Full Text Available Aggressive natural killer cell leukemia (ANKL is a rare neoplasm of mature natural killer cells, with an extremely poor overall survival, which is almost always EBV related, with majority of cases reported in East Asia. Here we report the case of an ANKL presenting in a young Hispanic male with secondary hemophagocytosis. Aggressive clinical course, high EBV DNA levels and leukemic presentation, often with associated hemophagocytosis, should raise suspicion of an NK/T-cell neoplasm like ANKL. Due to significant diagnostic overlap with extranodal NK/T-cell lymphoma, nasal type (ENKL, accurate diagnostic classification is crucial due to differing treatment and prognosis. L-asparaginase including chemotherapy followed by allogeneic stem cell transplantation appears to slightly prolong overall survival, but relapse is almost inevitable. Clinical monitoring of EBV DNA levels shows good correlation with disease activity.

  13. Ensuring energy security in ASEAN countries: Current trends and major challenges

    Senderov, Sergey; Vorobev, Sergey

    2018-01-01

    The paper discusses the issues of formation of future challenges to energy security of the ASEAN countries in the period up to 2035. The article gives examples of strategic threats to the energy security of Russia. The opportunities to meet future demand for primary energy for individual countries of ASEAN and the whole region are discussed.

  14. [Paraneoplastic Cushing's syndrome, a real diagnostic and therapeutic challenge: A case report and literature review].

    Meftah, A; Moumen, A; Massine El Hammoumi, M; Hajhouji, S; El Jadi, H; Anas Guerboub, A; Elmoussaoui, S; Mayaudon, H; Hassane Kabiri, E; Hakkou, K; Belmejdoub, G

    2015-12-01

    Paraneoplastic Cushing's syndrome is a rare cause of endogenous hypercortisolism attributable to ectopic ACTH secretion by non-pituitary tumors. Imaging and biochemical results are often inconclusive and differential diagnosis with Cushing's disease can then be challenging. Moreover, these tumors may be occult and difficult to find and thus the need of new imaging tools such as (18)FDG-PET scan and (18)DOPA-PET scan. We report a 50-year-old man who presented with very aggressive clinical features related to Cushing's syndrome. Biological work-up confirmed the hypercortisolism and was consistent with an ectopic ACTH secretion. Conventional localization techniques failed to show any tumor and bilateral adrenalectomy was performed because of life-threatening complications. Two years later, thoracic computed tomography reveals an 11 mm mass in the left lower pulmonary lobe, (18)FDG-PET scan found a non-specific mild hypermetabolism of the lung nodule, and the (18)DOPA-PET scan confirmed the high uptake of this nodule suggesting an endocrine carcinoma. Histology confirmed a typical carcinoid tumor. The tumor cells stained positive for ACTH, CD56, chromogranin and synaptophysin. This case illustrates the dilemma between the need for morphological diagnosis of the ectopic ACTH source and control of the life-threatening hypercortisolism. (18)FDG-PET scan and (18)DOPA-PET scan should be considered early as a secondary diagnostic tool when conventional imagery fails to show any tumor. Copyright © 2015 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  15. Technological progress and challenges towards cGMP manufacturing of human pluripotent stem cells based therapeutic products for allogeneic and autologous cell therapies.

    Abbasalizadeh, Saeed; Baharvand, Hossein

    2013-12-01

    Recent technological advances in the generation, characterization, and bioprocessing of human pluripotent stem cells (hPSCs) have created new hope for their use as a source for production of cell-based therapeutic products. To date, a few clinical trials that have used therapeutic cells derived from hESCs have been approved by the Food and Drug Administration (FDA), but numerous new hPSC-based cell therapy products are under various stages of development in cell therapy-specialized companies and their future market is estimated to be very promising. However, the multitude of critical challenges regarding different aspects of hPSC-based therapeutic product manufacturing and their therapies have made progress for the introduction of new products and clinical applications very slow. These challenges include scientific, technological, clinical, policy, and financial aspects. The technological aspects of manufacturing hPSC-based therapeutic products for allogeneic and autologous cell therapies according to good manufacturing practice (cGMP) quality requirements is one of the most important challenging and emerging topics in the development of new hPSCs for clinical use. In this review, we describe main critical challenges and highlight a series of technological advances in all aspects of hPSC-based therapeutic product manufacturing including clinical grade cell line development, large-scale banking, upstream processing, downstream processing, and quality assessment of final cell therapeutic products that have brought hPSCs closer to clinical application and commercial cGMP manufacturing. © 2013.

  16. Enterohemorrhagic Escherichia coli Hybrid Pathotype O80:H2 as a New Therapeutic Challenge

    Soysal, Nurcan; Mariani-Kurkdjian, Patricia; Smail, Yasmine; Liguori, Sandrine; Gouali, Malika; Loukiadis, Estelle; Fach, Patrick; Bruyand, Mathias; Blanco, Jorge; Bidet, Philippe

    2016-01-01

    We describe the epidemiology, clinical features, and molecular characterization of enterohemorrhagic Escherichia coli (EHEC) infections caused by the singular hybrid pathotype O80:H2, and we examine the influence of antibiotics on Shiga toxin production. In France, during 2005–2014, a total of 54 patients were infected with EHEC O80:H2; 91% had hemolytic uremic syndrome. Two patients had invasive infections, and 2 died. All strains carried stx2 (variants stx2a, 2c, or 2d); the rare intimin gene (eae-ξ); and at least 4 genes characteristic of pS88, a plasmid associated with extraintestinal virulence. Similar strains were found in Spain. All isolates belonged to the same clonal group. At subinhibitory concentrations, azithromycin decreased Shiga toxin production significantly, ciprofloxacin increased it substantially, and ceftriaxone had no major effect. Antibiotic combinations that included azithromycin also were tested. EHEC O80:H2, which can induce hemolytic uremic syndrome complicated by bacteremia, is emerging in France. However, azithromycin might effectively combat these infections. PMID:27533474

  17. The histamine H₃ receptor as a therapeutic drug target for metabolic disorders: status, challenges and opportunities.

    Plancher, Jean-Marc

    2011-01-01

    Since the histamine-3 receptor (H₃R) was cloned in 1999, huge efforts have been made by most of the key players in the pharmaceutical industry as well as in smaller biotech companies to increase the knowledge on this peculiar receptor, with the ultimate goal of bringing new drugs to the market. This review gives a survey on the most valuable chemical tools discovered so far and the significant pharmacological experiments on metabolic disease models published to date. Pharmacology of H₃R antagonists turns out to be very complex due to various functional activities, species selectivity, presence of H₃R isoforms and the poorly understood dichotomy in efficacy between CNS and metabolic disease models. Adding an extra layer of complexity, researchers have to cope with some recurrent safety concerns, some of them being tightly linked to the nature of the H₃R pharmacophore. Therefore this review also strives to summarize the major hurdles and some of the contradictions seen in the H₃R field, together with a brief overview of the clinical trials currently running.

  18. Next Generation Sequencing Identifies Five Major Classes of Potentially Therapeutic Enzymes Secreted by Lucilia sericata Medical Maggots.

    Franta, Zdeněk; Vogel, Heiko; Lehmann, Rüdiger; Rupp, Oliver; Goesmann, Alexander; Vilcinskas, Andreas

    2016-01-01

    Lucilia sericata larvae are used as an alternative treatment for recalcitrant and chronic wounds. Their excretions/secretions contain molecules that facilitate tissue debridement, disinfect, or accelerate wound healing and have therefore been recognized as a potential source of novel therapeutic compounds. Among the substances present in excretions/secretions various peptidase activities promoting the wound healing processes have been detected but the peptidases responsible for these activities remain mostly unidentified. To explore these enzymes we applied next generation sequencing to analyze the transcriptomes of different maggot tissues (salivary glands, gut, and crop) associated with the production of excretions/secretions and/or with digestion as well as the rest of the larval body. As a result we obtained more than 123.8 million paired-end reads, which were assembled de novo using Trinity and Oases assemblers, yielding 41,421 contigs with an N50 contig length of 2.22 kb and a total length of 67.79 Mb. BLASTp analysis against the MEROPS database identified 1729 contigs in 577 clusters encoding five peptidase classes (serine, cysteine, aspartic, threonine, and metallopeptidases), which were assigned to 26 clans, 48 families, and 185 peptidase species. The individual enzymes were differentially expressed among maggot tissues and included peptidase activities related to the therapeutic effects of maggot excretions/secretions.

  19. What Are the Lived Challenges Experienced by Black Females in a STEM Doctoral Program at a Majority White Institution?

    Cleare, Sharlane S.

    The purpose of this study is to explore the challenges experienced by Black female STEM doctoral students at a Majority White Institution. This study examined how, and to what extent did the Majority White Institution's STEM environment influenced such challenges. The qualitative phenomenological approach to this investigation utilized the lenses of Black Feminist Thought and Critical Race Feminism Theoretical Frameworks as interconnected lenses by which to conceptualize this phenomenon. This study answered the following question: What are the lived challenges experienced by Black female in a STEM doctoral program at a Majority White Institution? Purposeful and snowball sampling were employed to recruit participants for this investigation. Both sampling methods were selected because of their wide use in qualitative investigations, as well as their proven ability to precisely source quality participants (Biernacki, & Waldorf,1981; Palinkas, Horwitz, Green, Wisdom, Duan, & Hoagwood, (2015). Observations, in-depth semi-structured interviews, and focus groups were conducted with eleven (11) Black females STEM doctoral students currently studying at a large Majority White Institution in the Midwest. The findings from this study suggest that this is a phenomenon worthy of considerable attention. Research in the area of Black females in STEM doctoral programs at Majority White Institutions can be further expanded and updated. Therefore, this study will contribute and supplement existing literature on Black females in STEM doctoral programs at Majority White Institutions. Most importantly, the results obtained from this study can assist Majority White Institutions in the development and enhancement of programs and policies specifically geared towards addressing the needs of this underrepresented minority population segment.

  20. Courage under Fire: Duval County's School Board Chair Faces a Major Leadership Challenge

    Fossey, Richard; Jenkins, Lynn

    2011-01-01

    This case set in Jacksonville, Florida, covers the years 1998 to 2001. A new nontraditional superintendent, Major General John C. Fryer, focuses on student achievement, but financial needs and Florida law require him to bid contracts for student transportation, upsetting a 50-year pattern of contracting without competitive bidding with more than…

  1. The international gas markets. Of major changes and challenges for Europe

    Westphal, Kirsten

    2014-01-01

    Already in the 2010 edition of its World Energy Outlook the World Energy Agency noted an unprecedented degree of uncertainty surrounding the international energy markets. The rate of change in these markets is indeed stupendous, posing formidable tasks to business companies as well as the political leadership. The European gas markets face new challenges in protecting their security of supply which stem from the combined effects of the shift of LNG trade flows into the Pacific region, decreasing rates of home production and the ongoing transformation process within the EU.

  2. The utilisation of storytelling as a therapeutic intervention by educational psychologists to address behavioural challenges relating to grief of adolescent clients

    2014-01-01

    M.Ed. (Educational Psychology) Storytelling as a therapeutic intervention entails the narrating of events by externalising emotions, thoughts and responses to life-changing events such as loss and grief. This creates the opportunity for clients to engage with psychologists by projecting various beliefs and challenges, such as grief, through a range of therapeutic modalities. This study conducts an inquiry into the ways in which storytelling can be utilised by educational psychologists with...

  3. Novel Therapeutic and Prophylactic Modalities to Protect U.S. Armed Forces Against Major Biological Threat Agents

    2004-10-01

    56 A ppendices .................................................................................. . . 6 1 . INTRODUCTION In this report, we are...doses (Tanaka et al., 1997) and can cause different pathological conditions relevant to anthrax, such as acute respiratory distress syndrome (Matute...the pro-enzymes, however the major gelatinase enzymatic activity corresponds to the 55 kDa proteins in the BACS. Acute toxicity of B. anthracis

  4. Interoperability in healthcare: major challenges in the creation of the enterprise environment

    Lindsköld, L.; Wintell, M.; Lundberg, N.

    2009-02-01

    There is today a lack of interoperability in healthcare although the need for it is obvious. A new healthcare enterprise environment has been deployed for secure healthcare interoperability in the Western Region in Sweden (WRS). This paper is an empirical overview of the new enterprise environment supporting regional shared and transparent radiology domain information in the WRS. The enterprise environment compromises 17 radiology departments, 1,5 million inhabitants, using different RIS and PACS in a joint work-oriented network and additional cardiology, dentistry and clinical physiology departments. More than 160 terabytes of information are stored in the enterprise repository. Interoperability is developed according to the IHE mission, i.e. applying standards such as Digital Imaging and Communication in Medicine (DICOM) and Health Level 7 (HL7) to address specific clinical communication needs and support optimal patient care. The entire enterprise environment is implemented and used daily in WRS. The central prerequisites in the development of the enterprise environment in western region of Sweden were: 1) information harmonization, 2) reuse of standardized messages e.g. HL7 v2.x and v3.x, 3) development of a holistic information domain including both text and images, and 4) to create a continuous and dynamic update functionality. The central challenges in this project were: 1) the many different vendors acting in the region and the negotiations with them to apply communication roles/profiles such as HL7 (CDA, CCR), DICOM, and XML, 2) the question of whom owns the data, and 3) incomplete technical standards. This study concludes that to create a workflow that runs within an enterprise environment there are a number of central prerequisites and challenges that needs to be in place. This calls for negotiations on an international, national and regional level with standardization organizations, vendors, health management and health personnel.

  5. Medical mycology and fungal immunology: new research perspectives addressing a major world health challenge.

    Gow, Neil A R; Netea, Mihai G

    2016-12-05

    Fungi cause more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies and more than a million deaths each year. Global mortality owing to fungal infections is greater than for malaria and breast cancer and is equivalent to that owing to tuberculosis (TB) and HIV. These statistics evidence fungal infections as a major threat to human health and a major burden to healthcare budgets worldwide. Those patients who are at greatest risk of life-threatening fungal infections include those who have weakened immunity or have suffered trauma or other predisposing infections such as HIV. To address these global threats to human health, more research is urgently needed to understand the immunopathology of fungal disease and human disease susceptibility in order to augment the advances being made in fungal diagnostics and drug development. Here, we highlight some recent advances in basic research in medical mycology and fungal immunology that are beginning to inform clinical decisions and options for personalized medicine, vaccine development and adjunct immunotherapies.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'. © 2016 The Authors.

  6. Cardiorenal syndrome: therapeutical challenge

    Lopes, Sara Cristina Cerqueira

    2016-01-01

    Cardiorenal syndrome is described by the coexistence of cardiac and renal disease on the same individual, and it can affect both dogs and cats. The most consensual definition describes it as a “pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction of one of the organs causes acute or chronic dysfunction of the other”. The interest, recognition of the importance and prevailing of this syndrome in veterinary medicine has grown and, recently, a committee of ...

  7. The Network Model of Depression as a Basis for New Therapeutic Strategies for Treating Major Depressive Disorder in Parkinson’s Disease

    D’Ostilio, Kevin; Garraux, Gaëtan

    2016-01-01

    The high prevalence of major depressive disorder in people with Parkinson’s disease (PD), its negative impact on health-related quality of life and the low response rate to conventional pharmacological therapies call to seek innovative treatments. Here, we review the new approaches for treating major depressive disorder in patients with PD within the framework of the network model of depression. According to this model, major depressive disorder reflects maladaptive neuronal plasticity. Non-invasive brain stimulation (NIBS) using high frequency repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex has been proposed as a feasible and effective strategy with minimal risk. The neurobiological basis of its therapeutic effect may involve neuroplastic modifications in limbic and cognitive networks. However, the way this networks reorganize might be strongly influenced by the environment. To address this issue, we propose a combined strategy that includes NIBS together with cognitive and behavioral interventions. PMID:27148016

  8. Vaccine prevention of meningococcal disease in Africa: Major advances, remaining challenges.

    Mustapha, Mustapha M; Harrison, Lee H

    2017-12-06

    Africa historically has had the highest incidence of meningococcal disease with high endemic rates and periodic epidemics. The meningitis belt, a region of sub-Saharan Africa extending from Senegal to Ethiopia, has experienced large, devastating epidemics. However, dramatic shifts in the epidemiology of meningococcal disease have occurred recently. For instance, meningococcal capsular group A (NmA) epidemics in the meningitis belt have essentially been eliminated by use of conjugate vaccine. However, NmW epidemics have emerged and spread across the continent since 2000; NmX epidemics have occurred sporadically, and NmC recently emerged in Nigeria and Niger. Outside the meningitis belt, NmB predominates in North Africa, while NmW followed by NmB predominate in South Africa. Improved surveillance is necessary to address the challenges of this changing epidemiologic picture. A low-cost, multivalent conjugate vaccine covering NmA and the emergent and prevalent meningococcal capsular groups C, W, and X in the meningitis belt is a pressing need.

  9. Development of the German network for transporting electricity: A major challenge for managers

    Feix, Olivier

    2013-01-01

    The catastrophe at the Japanese nuclear power plant in Fukushima has deeply altered Germany's energy policy. The news from Japan forced the federal government to step up its efforts so as to expand more quickly the share of renewable sources in the German energy mix and, on short notice, put an end to nuclear power. This Energiewende, as the Germans call it, is a major policy priority for the government and an outstanding project that mobilizes all of German society. This turning point in energy policy has entailed rewriting several laws so as to provide a legal framework for the transition. Most stakeholders expect that important amendments will be made to the texts directly related to production facilities. What is noticeable and even surprising is the scope of the changes in laws about electricity grids, in particular about managing and developing the network for transporting electricity

  10. Challenges in Downscaling Surge and Flooding Predictions Associated with Major Coastal Storm Events

    Bowman, M. J.

    2015-12-01

    Coastal zone managers, elected officials and emergency planning personnel are continually seeking more reliable estimates of storm surge and inundation for better land use planning, the design, construction and operation of coastal defense systems, resilience evaluation and evacuation planning. Customers of modern regional weather and storm surge prediction models demand high resolution, speed, accuracy, with informative, interactive graphics and easy evaluation of potentially dangerous threats to life and property. These challenges continue to get more difficult as the demand for street-scale and even building-scale predictions increase. Fluctuations in sub-grid-scale wind and water velocities can lead to unsuspected, unanticipated and dangerous flooding in local communities. But how reliable and believable are these models given the inherent natural uncertainty and chaotic behavior in the underlying dynamics, which can lead to rapid and unexpected perturbations in the wind and pressure fields and hence coastal flooding? Traditionally this uncertainty has been quantified by the use of the ensemble method, where a suite of model runs are made with varying physics and initial conditions, presenting the mean and variance of the ensemble as the best metrics possible. But this assumes that each component is equally possible and is statistically independent of the others. But this is rarely true, although the "safety in numbers" approach is comforting to those faced with life and death decisions. An example of the ensemble method is presented for the trajectory of superstorm Sandy's storm center as it approached coastal New Jersey. If one were to ask the question "was Sandy a worst case scenario", the answer would be "no: small variations in the timing (vis-à-vis tide phase) and location of landfall could easily have led to an additional surge of +50 cm at The Battery NY with even more catastrophic consequences to those experienced".

  11. A major challenge. Entrepreneurship characterizes the work of the Soviet Family Health Association.

    Manuilova, I A

    1991-09-01

    The work of the Soviet Family Health Association (SFHA) is described. Created in January, 1989, the organization boasts 25 state-paid workers, and as of June 1991, membership of 15,000 corporate and individual members. Individual annual membership fee is 5 rubles, and entitles members to counseling and family planning (FP) services. The SFHA works in cooperation with the Commission on Family Planning Problems of the USSR's Academy of Sciences, and has been a member of the International Planned Parenthood Federation (IPPF) since 1990. Association activities include lectures for students, newly-weds, adolescents, and working women on modern contraceptive methods; research on attitude regarding sex, sex behaviors, and the perceived need for effective contraception; clinical trials of contraceptive suitability for women; and the training of doctors in FP and contraceptives. Problems central to the SFHA's operations include insufficient service and examination equipment, a shortage of hard currency, and the small number of FP specialists in the country. Solutions to these obstacles are sought through collaboration with the government, non-governmental organizations in the Soviet Union, and international groups. The SFHA has a series of activities planned for 1991 designed to foster wider acceptance of FP. Increased FP services at industrial enterprises, establishing more FP centers throughout the Soviet Union, and studying FP programs in other countries are among Association targets for the year. Research on and promotion of contraceptives has been virtually stagnant since abortion was declared illegal in 1936. Catching up on these lost decades and remaining self-reliant are challenges to the SPHA.

  12. Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

    Sedighi, Iraj; Karimi, Abdollah; Amanati, Ali

    2016-01-01

    Context Universal immunization against Bordetella pertussis has partially controlled the burden of the disease and its transmission. However, according to recent data, the epidemiology of this vaccine-preventable disease has changed. Now, younger infants, adolescents, and adults are at greater risk of infection. This article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention. Evidence Acquisition In this narrative review, the most recently published sources of information on pertussis control measures, consisting of textbooks and articles, have been reviewed. We focused on the more recent data about the changing epidemiology or pertussis in Scopus through the use of the MeSH-term words [pertussis] or [whooping cough] and [epidemiology] or [outbreak] or [resurgence], but our search was not restricted to this particular strategy; we also tried to find all of the most recent available data in the general field through other means. Results Primary and booster doses of the pertussis vaccine seem to partially control transmission of the disease, but despite the different preventive strategies available, pertussis continues to cause mortality and morbidity among high-risk groups. Conclusions Adding booster doses of acellular pertussis vaccine to the current national immunization practices with whole-cell vaccines for young adults and pregnant women seems to be a good option for controlling mortality and morbidity among high-risk groups such as very young infants. PMID:27729960

  13. Inequalities in non-communicable diseases between the major population groups in Israel: achievements and challenges.

    Muhsen, Khitam; Green, Manfred S; Soskolne, Varda; Neumark, Yehuda

    2017-06-24

    Israel is a high-income country with an advanced health system and universal health-care insurance. Overall, the health status has improved steadily over recent decades. We examined differences in morbidity, mortality, and risk factors for selected non-communicable diseases (NCDs) between subpopulation groups. Between 1975 and 2014, life expectancy in Israel steadily increased and is currently above the average life expectancy for the Organisation for Economic Co-operation and Development countries. Nevertheless, life expectancy has remained lower among Israeli Arabs than Israeli Jews, and this gap has recently widened. Age-adjusted mortality as a result of heart disease, stroke, or diabetes remains higher in Arabs, whereas age-adjusted incidence and mortality of cancer were higher among Jews. The prevalence of obesity and low physical activity in Israel is considerably higher among Arabs than Jews. Smoking prevalence is highest for Arab men and lowest for Arab women. Health inequalities are also evident by the indicators of socioeconomic position and in subpopulations, such as immigrants from the former Soviet Union, ultra-Orthodox Jews, and Bedouin Arabs. Despite universal health coverage and substantial improvements in the overall health of the Israeli population, substantial inequalities in NCDs persist. These differences might be explained, at least in part, by gaps in social determinants of health. The Ministry of Health has developed comprehensive programmes to reduce these inequalities between the major population groups. Sustained coordinated multisectoral efforts are needed to achieve a greater impact and to address other social inequalities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Learning from the Experts: A Thematic Analysis of Parent's Experiences of Attending a Therapeutic Group for Parents of Children with Learning Disabilities and Challenging Behaviour

    Thompson-Janes, Emily; Brice, Samuel; McElroy, Rebecca; Abbott, Jennie; Ball, June

    2016-01-01

    The Confident Parenting group is a therapeutic group for parents of children with learning disabilities and challenging behaviour, which is informed by the principles of behavioural theory and acceptance and commitment therapy. Parent's experiences of the group were elicited through participation in a large focus group which followed a…

  15. Profiling Prostate Cancer Therapeutic Resistance

    Cameron A. Wade; Natasha Kyprianou

    2018-01-01

    The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival ...

  16. Triple antithrombotic therapy is the independent predictor for the occurrence of major bleeding complications: analysis of percent time in therapeutic range.

    Naruse, Yoshihisa; Sato, Akira; Hoshi, Tomoya; Takeyasu, Noriyuki; Kakefuda, Yuki; Ishibashi, Mayu; Misaki, Masako; Abe, Daisuke; Aonuma, Kazutaka

    2013-08-01

    Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention. However, it remains unclear whether good control of percent time in therapeutic range is associated with reduced occurrence of bleeding complications in patients undergoing triple antithrombotic therapy. This study included 2648 patients (70 ± 11 years; 2037 men) who underwent percutaneous coronary intervention with stent in the Ibaraki Cardiovascular Assessment Study registry and received dual antiplatelet therapy with or without warfarin. Clinical end points were defined as the occurrence of major bleeding complications (MBC), major adverse cardiac and cerebrovascular event, and all-cause death. Among these 2648 patients, 182 (7%) patients received warfarin. After a median follow-up period of 25 months (interquartile range, 15-35 months), MBC had occurred in 48 (2%) patients, major adverse cardiac and cerebrovascular event in 484 (18%) patients, and all-cause death in 206 (8%) patients. Multivariable Cox regression analysis revealed that triple antithrombotic therapy was the independent predictor for the occurrence of MBC (hazard ratio, 7.25; 95% confidence interval, 3.05-17.21; Prange value did not differ between the patients with and without MBC occurrence (83% [interquartile range, 50%-90%] versus 75% [interquartile range, 58%-87%]; P=0.7). However, the mean international normalized ratio of prothrombin time at the time of MBC occurrence was 3.3 ± 2.1. Triple antithrombotic therapy did not have a predictive value for the occurrence of all-cause death (P=0.1) and stroke (P=0.2). Triple antithrombotic therapy predisposes patients to an increased risk of MBC regardless of the time in therapeutic range.

  17. Heterogeneity among hospitals statewide in percentage shares of the annual growth of surgical caseloads of inpatient and outpatient major therapeutic procedures.

    Dexter, Franklin; Jarvie, Craig; Epstein, Richard H

    2018-04-18

    Suppose that it were a generalizable finding, in both densely populated and rural states, that there is marked heterogeneity among hospitals in the percentage change in surgical caseload and/or in the total change in caseload. Then, individual hospitals should not simply rely on federal and state forecasts to infer their expected growth. Likewise, individual hospitals and their anesthesiology groups would best not rely on national or US regional surgical trends as causal reasons for local trends in caseload. We examined the potential utility of using state data on surgical caseload to predict local growth by using 6 years of data for surgical cases performed at hospitals in the States of Florida and Iowa. Observational cohort study. 303 hospitals in Iowa and Florida. Cases with major therapeutic procedures in 2010 or 2011 were compared pairwise by hospital with such cases in 2015 and 2016. Changes in counts of cases were decreases or increases, while study of growth set decreases equal to zero. Hospitals in Iowa had slightly lesser percentage changes than did hospitals in Florida (Mann-Whitney P = 0.016). Hospitals in Iowa had greater variability among hospitals in the change in counts of cases with a major therapeutic procedure than did hospitals in Florida (P < 0.0001). The 10% of hospitals with the largest growths in counts of cases accounted for approximately half of the total growth in Iowa (70%) and Florida (54%). The large share of total growth attributable to the upper 10th percentile of hospitals was not caused solely by the hospitals having large percentage growths, based on there being weak correlation between growth and percentage growth, among the hospitals that grew (Iowa: Kendall's tau = 0.286 [SE 0.120]; Florida tau = 0.253 [SE 0.064]). Even if the data from states or federal agencies reported growth in surgical cases, there is too much concentration of growth at a few hospitals for statewide growth rates to be useful for

  18. An analysis of the major challenges and obstacles for international technical cooperation in health, Brazil-Mozambique.

    Pereira, Eduardo Mazzaroppi Barao

    2017-07-01

    Health has become a priority issue on the agenda in relation to Brazilian international technical cooperation in the last decade. This applies to Mozambique which is a strategic partner of Brazil's when one takes into consideration the volume of projects that have been undertaken between the two countries and the available resources on offer. There has been a shift in the foreign policy paradigm which has resulted in a new Brazilian foreign policy posture that promotes bilateral agreements and international cooperation. On conducting a retrospective and current analysis it is clear that there are, however, major obstacles and challenges for bilateral agreements and technical international cooperation that require in-depth study and which need to be dealt with in the area of health. This paper seeks to identify and analyze these obstacles with a view to providing proposals for ways forward. It takes the approach of using the methodology of reviewing specialized journals on this topic as well as using qualitative research from the main actors and institutions involved in bilateral cooperation.

  19. Perseverative thought: a robust predictor of response to emotional challenge in generalized anxiety disorder and major depressive disorder.

    Ruscio, Ayelet Meron; Seitchik, Allison E; Gentes, Emily L; Jones, Jason D; Hallion, Lauren S

    2011-12-01

    Generalized anxiety disorder (GAD) and major depressive disorder (MDD) frequently co-occur, yet the reasons for their comorbidity remain poorly understood. In the present experiment, we tested whether a tendency to engage in negative, repetitive thinking constitutes a common risk process for the two disorders. A mixed sample of adults with comorbid GAD-MDD (n=50), GAD only (n=35), MDD only (n=34), or no lifetime psychopathology (n=35) was administered noncontingent failure and success feedback on consecutive performance tasks. Perseverative thought (PT), measured by negative thought intrusions during a baseline period of focused breathing, emerged as a powerful prospective predictor of responses to this experimental challenge. Participants reporting more frequent negative thought intrusions at baseline, irrespective of thought content or diagnostic status, exhibited a stronger negative response to failure that persisted even after subsequent success. Higher PT over the course of the experiment was associated with later behavioral avoidance, with negative affect and other traits closely linked to anxiety and depression, and with the presence and severity of GAD and MDD. These findings provide evidence for a broadly-defined PT trait that is shared by GAD and MDD and contributes to adverse outcomes in these disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Functional Neurosurgery in the Treatment of Severe Obsessive Compulsive Disorder and Major Depression: Overview of Disease Circuits and Therapeutic Targeting for the Clinician

    Shah, Dhwani B.; Pesiridou, Angeliki; Baltuch, Gordon H.; Malone, Donald A.; O’Reardon, John P.

    2008-01-01

    Over the past 20 years, there has been a concerted effort to expand our understanding of the neural circuitry involved in the pathogenesis of psychiatric disorders. Distinct neuronal circuits and networks have been implicated in obsessive compulsive disorder (OCD) and major depressive disorder (MDD) involving feedback loops between the cortex, striatum, and thalamus. When neurosurgery is used as a therapeutic tool in severe OCD and MDD, the goal is to modulate specific targets or nodes within these networks in an effort to produce symptom relief. Currently, four lesioning neurosurgical procedures are utilized for treatment refractory OCD and MDD: cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Deep brain stimulation (DBS) is a novel neurosurgical approach that has some distinct advantages over lesioning procedures. With DBS, the desired clinical effect can be achieved by reversible, high frequency stimulation in a nucleus or at a node in the circuit without the need to produce an irreversible lesion. Recent trials of deep brain stimulation in both OCD and MDD at several neuroanatomical targets have reported promising early results in highly refractory patients and with a good safety profile. Future definitive trials in MDD and OCD are envisaged. PMID:19727257

  1. Recent Advancements in Targeted Delivery of Therapeutic Molecules in Neurodegenerative Disease–-Spinocerebellar Ataxia–-Opportunities and Challenges

    Satya Prakash

    2008-01-01

    Full Text Available Drug discovery and its methodologies have been very effective in terms of treating cancers and immunological disorders but have not been able to stop genetic diseases as most of the drugs target at the protein level. They merely mitigate the symptoms of the disease. Spinocerebellar ataxia is a neurological genetic disorder that is caused by the formation of an abnormal protein. There have been several reports on ataxic drug development but actual clinical treatment is yet to be achieved. Oligonucleotide therapy called sequence specific siRNA mediated gene silencing has evolved with promising results. This approach emphasizes on suppressing the expression of the diseased gene at mRNA level. However, there is a limitation in delivery of siRNA to the target site. Several methods have been developed over the last decade to enhance the target specific delivery of DNA, siRNA, protein and small drug molecules for therapeutic purpose with less or no side effects. This review discusses the latest upcoming technologies in the field that focus on a number of nonviral nanocarriers for targeted delivery. In this review, we explore the promise and potential of novel therapeutics with interest on ataxia therapy.

  2. Oesophageal Perforation: A diagnostic and therapeutic challenge in a resource limited setting. A report of three cases

    Mahalu William

    2011-09-01

    Full Text Available Abstract Background Oesophageal perforation is a condition associated with a high mortality. Its management is still controversial with operative treatment being favoured but a shift to conservative management is occurring. Very little exists in medical literature about its management in Sub-Saharan Africa, where the paucity of thoracic surgeons is compounded by limited diagnostic and therapeutic facilities. Case Presentation We report three cases of oesophageal perforation which were all treated conservatively with tube thoracostomy, nil by mouth with feeding gastrostomy, intravenous antibiotics and chest physiotherapy. Two patients achieved oesophageal healing but one died due to severe septicaemia. Conclusion In a resource restricted setting, conservative management which includes enteral nutrition by feeding gastrostomy, tube thoracostomy to drain inter pleural contaminants, intravenous antibiotics and chest physiotherapy is a safe and effective treatment for oesophageal perforations.

  3. Discovery of innovative therapeutics: today's realities and tomorrow's vision. 2. Pharma's challenges and their commitment to innovation.

    Abou-Gharbia, Magid; Childers, Wayne E

    2014-07-10

    The pharmaceutical industry is facing enormous challenges, including reduced efficiency, stagnant success rate, patent expirations for key drugs, fierce price competition from generics, high regulatory hurdles, and the industry's perceived tarnished image. Pharma has responded by embarking on a range of initiatives. Other sectors, including NIH, have also responded. Academic drug discovery groups have appeared to support the transition of innovative academic discoveries and ideas into attractive drug discovery opportunities. Part 1 of this two-part series discussed the criticisms that have been leveled at the pharmaceutical industry over the past 3 decades and summarized the supporting data for and against these criticisms. This second installment will focus on the current challenges facing the pharmaceutical industry and Pharma's responses, focusing on the industry's changing perspective and new business models for coping with the loss of talent and declining clinical pipelines as well as presenting some examples of recent drug discovery successes.

  4. Linguistic Knowledge Aspects in Academic Reading: Challenges and Deployed Strategies by English-Major Undergraduates at a Jordanian Institution of Higher Education

    Albashtawi, Abeer H.; Jaganathan, Paramaswari; Singh, Manjet

    2016-01-01

    This study aimed to investigate the linguistic knowledge aspect in academic reading, the challenges and the deployed strategies by English major undergraduates at a Jordanian institution of higher education. The importance of the study is attributed to the importance of the academic reading at university which is closely related to the academic…

  5. Challenges and opportunities in establishing scientific and regulatory standards for determining therapeutic equivalence of modified-release products: Workshop summary report.

    Chen, Mei-Ling; Shah, Vinod P; Ganes, Derek; Midha, Kamal K; Caro, James; Nambiar, Prabu; Rocci, Mario L; Thombre, Avinash G; Abrahamsson, Bertil; Conner, Dale; Davit, Barbara; Fackler, Paul; Farrell, Colm; Gupta, Suneel; Katz, Russell; Mehta, Mehul; Preskorn, Sheldon H; Sanderink, Gerard; Stavchansky, Salomon; Temple, Robert; Wang, Yaning; Winkle, Helen; Yu, Lawrence

    2010-09-01

    Modified-release (MR) products are complex dosage forms designed to release drug in a controlled manner to achieve the desired efficacy and safety profiles. Inappropriate control of drug release from such products may result in reduced efficacy or increased toxicity. This paper is a summary report of the American Association of Pharmaceutical Scientists, International Pharmaceutical Federation, and Product Quality Research Institute workshop titled "Challenges and Opportunities in Establishing Scientific and Regulatory Standards for Assuring Therapeutic Equivalence of Modified Release Products", held October 1-2, 2009, in Baltimore, Maryland. The workshop provided an opportunity for pharmaceutical scientists from academia, industry, and regulatory agencies to discuss current regulatory expectations and industry practices for evaluating the pharmaceutical equivalence and bioequivalence of oral MR products. In the case of conventional monophasic MR formulations, the current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and inter-changeability of drug products. Additional measures may occasionally be needed to determine the bioequivalence of multiphasic MR products. The metric of partial AUC proposed by the US Food and Drug Administration received broad support as an additional measure for evaluating bioequivalence of multiphasic MR products designed to have a rapid onset of drug action followed by sustained response. The cutoff for partial AUCs may be based on the pharmacokinetic/pharmacodynamic or pharmacokinetic/ response characteristics of the products under examination. If the new metric is highly variable, the bioequivalence limits may be set based on the known within-subject variability for the reference product. The current regulatory approaches and criteria for bioequivalence evaluation were considered adequate for the assessment of therapeutic equivalence and

  6. Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

    Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

    2017-11-01

    3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Differential responsiveness of Holstein and Angus dermal fibroblasts to LPS challenge occurs without major differences in the methylome.

    Benjamin, Aimee L; Green, Benjamin B; Crooker, Brian A; McKay, Stephanie D; Kerr, David E

    2016-03-24

    We have previously found substantial animal-to-animal and age-dependent variation in the response of Holstein fibroblast cultures challenged with LPS. To expand on this finding, fibroblast cultures were established from dairy (Holstein) and beef (Angus) cattle and challenged with LPS to examine breed-dependent differences in the innate immune response. Global gene expression was measured by RNA-Seq, while an epigenetic basis for expression differences was examined by methylated CpG island recovery assay sequencing (MIRA-Seq) analysis. The Holstein breed displayed a more robust response to LPS than the Angus breed based on RNA-Seq analysis of cultures challenged with LPS for 0, 2, and 8 h. Several immune-associated genes were expressed at greater levels (FDR Angus fibroblasts, and two of these regions fell within the promoter region (-2500 to +500 bp of the transcription start site) of the genes NTRK2 and ADAMTS5. Fibroblasts isolated from Holstein cattle display a more robust response to LPS in comparison to cultures from Angus cattle. Different selection strategies and management practices exist between these two breeds that likely give rise to genetic and epigenetic factors contributing to the different immune response phenotypes.

  8. ‘Moderate universalism’ in China and the Nordic countries: reviewing the major challenges in unemployment protection

    Kristian Kongshøj

    2015-02-01

    Full Text Available Rapid welfare expansion is taking place in China across a range of policy fields. In the Nordic countries, intra-Nordic diversity and significant policy changes are not difficult to identify despite the notion of universal Nordic welfare regimes. This article will bridge these very different worlds of welfare in an effort to classify the Chinese unemployment-protection system with a comparative framework aimed at furthering the emerging Sino-Nordic research dialogue. This research dialogue has gained relevance in recent years with the new official Chinese goal of building a more universal welfare system. Welfare research that includes China from a comparative perspective is still extremely rare. Despite the lofty Chinese goals, many Chinese policy challenges still loom large. These are the rural-urban divide exacerbated by the Chinese household registration system, coverage of unemployment insurance and social assistance, inadequate and declining benefit levels, and, finally, funding issues. As this article will also substantiate, Denmark and Finland are something approaching best cases for illustrating intra-Nordic diversity. As regards the Chinese challenges, it is explained how they can to some extent be understood as the teething troubles of a developmental welfare state, since the Nordic counterparts have faced similar issues during their eras of welfare expansion.

  9. Major challenges to scale up of visual inspection-based cervical cancer prevention programs: the experience of Guatemalan NGOs.

    Chary, Anita Nandkumar; Rohloff, Peter J

    2014-08-01

    Like many other low- and middle-income countries, Guatemala has adopted visual inspection with acetic acid (VIA) as a low-resource alternative to the Pap smear for cervical cancer screening. Nongovernmental organizations (NGOs) introduced VIA to Guatemala in 2004, and a growing number of NGOs, working both independently and in collaboration with the Guatemalan Ministry of Health, employ VIA in cervical cancer prevention programs today. While much research describes VIA efficacy and feasibility in Latin America, little is known about NGO involvement with VIA programming or experiences with VIA outside the context of clinical trials and pilot projects in the region. To explore challenges faced by NGOs implementing VIA programs in Guatemala, we conducted semi-structured interviews with 36 NGO staff members involved with 20 VIA programs as direct service providers, program administrators, and training course instructors. Additionally, we collected data through observation at 30 NGO-sponsored cervical cancer screening campaigns, 8 cervical cancer prevention conferences, and 1 week-long NGO-sponsored VIA training course. Frequently highlighted challenges included staff turnover, concerns over training quality, a need for opportunities for continued supervision, and problems with cryotherapy referrals when immediate treatment for VIA-positive women was unavailable. Reducing staff turnover, budgeting to train replacement providers, standardizing training curricula, and offering continued supervision are key strategies to improve VIA service quality and program sustainability. Alternative training methods, such as on-the-job mentoring and course prerequisites of online learning, could help increase training time available for clinical supervision. Efforts should be made to ensure that VIA testing is coupled with immediate cryotherapy, that providers trained in VIA are also trained in cryotherapy, and that cryotherapy supplies and equipment are maintained. Where this is not

  10. Challenges in devising economic spray thresholds for a major pest of Australian canola, the redlegged earth mite (Halotydeus destructor).

    Arthur, Aston L; Hoffmann, Ary A; Umina, Paul A

    2015-10-01

    A key component for spray decision-making in IPM programmes is the establishment of economic injury levels (EILs) and economic thresholds (ETs). We aimed to establish an EIL for the redlegged earth mite (Halotydeus destructor Tucker) on canola. Complex interactions between mite numbers, feeding damage and plant recovery were found, highlighting the challenges in linking H. destructor numbers to yield. A guide of 10 mites plant(-1) was established at the first-true-leaf stage; however, simple relationships were not evident at other crop development stages, making it difficult to establish reliable EILs based on mite number. Yield was, however, strongly associated with plant damage and plant densities, reflecting the impact of mite feeding damage and indicating a plant-based alternative for establishing thresholds for H. destructor. Drawing on data from multiple field trials, we show that plant densities below 30-40 plants m(-2) could be used as a proxy for mite damage when reliable estimates of mite densities are not possible. This plant-based threshold provides a practical tool that avoids the difficulties of accurately estimating mite densities. The approach may be applicable to other situations where production conditions are unpredictable and interactions between pests and plant hosts are complex. © 2015 Society of Chemical Industry.

  11. General discussion of data quality challenges in social media metrics: Extensive comparison of four major altmetric data aggregators

    2018-01-01

    The data collection and reporting approaches of four major altmetric data aggregators are studied. The main aim of this study is to understand how differences in social media tracking and data collection methodologies can have effects on the analytical use of altmetric data. For this purpose, discrepancies in the metrics across aggregators have been studied in order to understand how the methodological choices adopted by these aggregators can explain the discrepancies found. Our results show that different forms of accessing the data from diverse social media platforms, together with different approaches of collecting, processing, summarizing, and updating social media metrics cause substantial differences in the data and metrics offered by these aggregators. These results highlight the importance that methodological choices in the tracking, collecting, and reporting of altmetric data can have in the analytical value of the data. Some recommendations for altmetric users and data aggregators are proposed and discussed. PMID:29772003

  12. [Adenomyosis - diagnostic and therapeutic challenge].

    Seikkula, Jaana; Niinimäki, Maarit; Suvitie, Pia

    2016-01-01

    In adenomyosis, endometrial glandular and stromal cells grow inside the myometrium, and form localized or diffusely expanding islets. Smooth muscle cells of the uterus surrounding the adenomyosis colonies become hypertrophic, which may lead to abnormal contractions of the uterine wall. Adenomyosis is an estrogen-dependent disease with abnormal uterine bleeding and dysmenorrhea as typical symptoms. The disease may even be asymptomate. The diagnosis is made by histologically or ultrasonic or MRI imaging. Adenomyosis can be treated with hormonal medications. Fertility-sparing radiologic and surgical techniques are also available.

  13. Phenylketonuria: dietary and therapeutic challenges.

    Giovannini, M; Verduci, E; Salvatici, E; Fiori, L; Riva, E

    2007-04-01

    PKU subjects need special attention in the definition of optimal supplementation of nutrients, which may be insufficient in relation to the type of diet and may otherwise manifest symptoms of deficit. In particular, it is necessary to pay great attention to the long-chain polyunsaturated fatty acid (LC-PUFA) levels in relation to correct development of the central nervous system. On the basis of numerous beneficial effects currently known, a permanent supplementation with LC-PUFAs, in particular with docosahexaenoic acid, should be considered. Moreover, new formulas, Phe-free peptides, and 'modulated' amino acid preparations might help in preventing nutritional deficiencies and imbalances, with the ultimate aim of improving growth. New strategies--such as supply of tetrahydrobiopterin--need to be optimized in terms of targets, patients and expected outcomes.

  14. Metabolic Diseases Downregulate the Majority of Histone Modification Enzymes, Making a Few Upregulated Enzymes Novel Therapeutic Targets--"Sand Out and Gold Stays".

    Shao, Ying; Chernaya, Valeria; Johnson, Candice; Yang, William Y; Cueto, Ramon; Sha, Xiaojin; Zhang, Yi; Qin, Xuebin; Sun, Jianxin; Choi, Eric T; Wang, Hong; Yang, Xiao-feng

    2016-02-01

    To determine whether the expression of histone modification enzymes is regulated in physiological and pathological conditions, we took an experimental database mining approach pioneered in our labs to determine a panoramic expression profile of 164 enzymes in 19 human and 17 murine tissues. We have made the following significant findings: (1) Histone enzymes are differentially expressed in cardiovascular, immune, and other tissues; (2) our new pyramid model showed that heart and T cells are among a few tissues in which histone acetylation/deacetylation, and histone methylation/demethylation are in the highest varieties; and (3) histone enzymes are more downregulated than upregulated in metabolic diseases and regulatory T cell (Treg) polarization/ differentiation, but not in tumors. These results have demonstrated a new working model of "Sand out and Gold stays," where more downregulation than upregulation of histone enzymes in metabolic diseases makes a few upregulated enzymes the potential novel therapeutic targets in metabolic diseases and Treg activity.

  15. Metabolic Diseases Downregulate the Majority of Histone Modification Enzymes, Making a Few Upregulated Enzymes Novel Therapeutic Targets – “Sand out and Gold Stays”

    Shao, Ying; Chernaya, Valeria; Johnson, Candice; Yang, William Y.; Cueto, Ramon; Sha, Xiaojin; Zhang, Yi; Qin, Xuebin; Sun, Jianxin; Choi, Eric T.; Wang, Hong; Yang, Xiao-feng

    2016-01-01

    To determine whether the expression of histone modification enzymes is regulated in physiological and pathological conditions, we took an experimental database mining approach pioneered in our labs to determine a panoramic expression profile of 164 enzymes in 19 human and 17 murine tissues. We have made the following significant findings: 1) Histone enzymes are differentially expressed in cardiovascular, immune and other tissues; 2) Our new pyramid model showed that heart and T cells are among a few tissues in which histone acetylation/deacetylation, histone methylation/demethylation are in the highest varieties; and 3) Histone enzymes are more downregulated than upregulated in metabolic diseases and Treg polarization/differentiation, but not in tumors. These results have demonstrated a new working model of “sand out and gold stays,” where more downregulation than upregulation of histone enzymes in metabolic diseases makes a few upregulated enzymes the potential novel therapeutic targets in metabolic diseases and Treg activity. PMID:26746407

  16. Costs, Benefits and Challenges of Sustainable Livestock Intensification in a Major Deforestation Frontier in the Brazilian Amazon

    Edenise Garcia

    2017-01-01

    Full Text Available Extensive livestock production is a major deforestation driver in the Brazilian Amazon. This study presents an assessment of the economic and environmental feasibility of sustainable livestock intensification in São Félix do Xingu municipality, a deforestation frontier with an area of more than 8.5 million hectares, and home to the largest cattle herd in Brazil. Proposed intensification was limited to approximately three animal units per hectare to avoid negative environmental impacts. Transition costs to sustainable cattle intensification were estimated for thirteen pilot farms taking into account adoption of good agriculture practices, pasture maintenance/restoration, and restoration of environmental liabilities. To move to sustainable intensification practices, a mean total annual investment of US$1335/ha ± US$619/ha would be necessary, varying from US$750 to US$2595/ha. Internal rate of return and net present value estimates indicated that the sustainable livestock intensification approach proposed was profitable in farms with more than 400 hectares of pastureland, but not in those where the pasture areas were smaller than 150 hectares. Livestock sustainable intensification also had the potential to promote social and environmental benefits, including a 54% increase in the number of contract workers, improvement of landowners’ managerial skills, and workers’ training, in addition to avoiding emission of 1.9 Mt CO2eq and sequestration of 0.36 Mt CO2eq. We conclude that the sustainable intensification of pasture areas has the potential to prevent further deforestation in the Amazon while generating social and other environmental benefits.

  17. The success factors and the major challenges that Tal-Massar Winery in Gozo needs to address to develop the full potential of wine tourism

    Borg, Jesmond

    2017-01-01

    This study focuses on the concept of wine tourism as a growing niche on the island of Gozo. Over the last decade, Gozo has seen a synergy between wine and the tourism indus-try which has led to the development of what is commonly known as wine tourism. As in other countries, wine tourism on this small island is leaving an impact on the social and economic aspects. This research aims to portray the success factors and the major challenges that Gozo needs to address to develop the full pot...

  18. 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)

  19. BALB/c Mice Vaccinated with Leishmania major Ribosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

    Laura Ramírez

    2010-01-01

    Full Text Available Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity.

  20. Dendrimer Advances for the Central Nervous System Delivery of Therapeutics

    2013-01-01

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included. PMID:24274162

  1. Dendrimer advances for the central nervous system delivery of therapeutics.

    Xu, Leyuan; Zhang, Hao; Wu, Yue

    2014-01-15

    The effectiveness of noninvasive treatment for central nervous system (CNS) diseases is generally limited by the poor access of therapeutic agents into the CNS. Most CNS drugs cannot permeate into the brain parenchyma because of the blood-brain barrier (BBB), and overcoming this has become one of the most significant challenges in the development of CNS therapeutics. Rapid advances in nanotechnology have provided promising solutions to this challenge. This review discusses the latest applications of dendrimers in the treatment of CNS diseases with an emphasis on brain tumors. Dendrimer-mediated drug delivery, imaging, and diagnosis are also reviewed. The toxicity, biodistribution, and transport mechanisms in dendrimer-mediated delivery of CNS therapeutic agents bypassing or crossing the BBB are also discussed. Future directions and major challenges of dendrimer-mediated delivery of CNS therapeutic agents are included.

  2. The influence of 5-HTTLPR genotype on the association between the plasma concentration and therapeutic effect of paroxetine in patients with major depressive disorder.

    Tetsu Tomita

    Full Text Available The efficacy of treatment with selective serotonin reuptake inhibitors in patients with major depressive disorder (MDD can differ depending on the patient's serotonin transporter-linked polymorphic region (5-HTTLPR genotype, and the effects of varying plasma concentrations of drugs can also vary. We investigated the association between the paroxetine plasma concentration and clinical response in patients with different 5-HTTLPR genotypes.Fifty-one patients were enrolled in this study. The Montgomery-Asberg Depression Rating Scale (MADRS was used to evaluate patients at 0, 1, 2, 4, and 6 weeks. The patients' paroxetine plasma concentrations at week 6 were measured using high-performance liquid chromatography. Additionally, their 5-HTTLPR polymorphisms (alleles S and L were analyzed using a polymerase chain reaction with specific primers. We divided the participants into two groups based on their L haplotype: the SS group and the SL and LL group. We performed single and multiple regression analyses to investigate the associations between MADRS improvement and paroxetine plasma concentrations or other covariates for each group.There were no significant differences between the two groups with regard to demographic or clinical data. In the SS group, the paroxetine plasma concentration was significantly negatively correlated with improvement in MADRS at week 6. In the SL and LL group, the paroxetine plasma concentration was significantly positively correlated with improvement in MADRS at week 6 according to the results of the single regression analysis; however, it was not significantly correlated with improvement in MADRS at week 6 according to the results of the multiple regression analysis.Among patients with MDD who do not respond to paroxetine, a lower plasma concentration or a lower oral dose of paroxetine might be more effective in those with the SS genotype, and a higher plasma concentration might be more effective in those with the SL or LL

  3. Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

    Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2017-09-01

    Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process.

    Bousquet, Cedric; Dahamna, Badisse; Guillemin-Lanne, Sylvie; Darmoni, Stefan J; Faviez, Carole; Huot, Charles; Katsahian, Sandrine; Leroux, Vincent; Pereira, Suzanne; Richard, Christophe; Schück, Stéphane; Souvignet, Julien; Lillo-Le Louët, Agnès; Texier, Nathalie

    2017-09-21

    Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to guarantee data privacy of patients posting on Internet, (3) took into account pharmacovigilance expert requirements with use case diagrams and scenarios, (4) built domain-specific knowledge resources embeding a lexicon, morphological rules, context rules, semantic rules

  5. Present Status and Future Challenges of New Therapeutic Targets in Preclinical Models of Stroke in Aged Animals with/without Comorbidities

    Aurel Popa-Wagner

    2018-01-01

    Full Text Available The aging process, comorbidities, and age-associated diseases are closely dependent on each other. Cerebral ischemia impacts a wide range of systems in an age-dependent manner. However, the aging process has many facets which are influenced by the genetic background and epigenetic or environmental factors, which can explain why some people age differently than others. Therefore, there is an urgent need to identify age-related changes in body functions or structures that increase the risk for stroke and which are associated with a poor outcome. Multimodal imaging, electrophysiology, cell biology, proteomics, and transcriptomics, offer a useful approach to link structural and functional changes in the aging brain, with or without comorbidities, to post-stroke rehabilitation. This can help us to improve our knowledge about senescence firstly, and in this context, aids in elucidating the pathophysiology of age-related diseases that allows us to develop therapeutic strategies or prevent diseases. These processes, including potential therapeutical interventions, need to be studied first in relevant preclinical models using aged animals, with and without comorbidities. Therefore, preclinical research on ischemic stroke should consider age as the most important risk factor for cerebral ischemia. Furthermore, the identification of effective therapeutic strategies, corroborated with successful translational studies, will have a dramatic impact on the lives of millions of people with cerebrovascular diseases.

  6. Glycosylation profiles of therapeutic antibody pharmaceuticals.

    Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

    2011-11-01

    Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. The unknown on the doorstep: Hong Kong's fears concerning Daya Bay, China's first major nuclear power station and the public relations challenges

    Chan, Albert

    1995-01-01

    The Guangdong Nuclear Power Station at Daya Bay is located east of the Shenzhen Special Economic Zone in Southern China. It is a joint venture between Hong Kong and China. In terms of construction schedule, budget and performance, Daya Bay ranks amongst the best plants anywhere. This achievement is even more apparent when one takes into account the fact that Daya Bay is the first major nuclear power station in China and that a large amount of interface and co-ordination is required to bring together French and British technologies in a non-English speaking environment. This Paper addresses the various and challenging public relations issues faced by Daya Bay during the last 15 years (from feasibility study stage). The negotiation for the Daya Bay nuclear power station project coincided with the political negotiations between China and Britain over the future of Hong Kong - the 1997 issue. (The political negotiations commenced in September 1982 and concluded in late 1984). Concerns over the nuclear project were heard during this phase but were limited to local environmental groups rather than the general public. The focus was more on the environmental and radiological impact of a nuclear power station than specific technical and safety issues. As for the general public, the project wasn't much of an issue until April, 1986 (Chernobyl accident). Period from 1986-1993 was the period of construction of the Daya Bay nuclear power station. An antinuclear campaign was launched by a few local activists who claimed to have collected signatures from one million people in Hong Kong urging the Chinese Government to shelve the project. The Hong Kong public did not understand the difference between Chernobyl type and PWR-type nuclear reactors (Daya Bay is a PWR) nor were they aware that even in the case of Chernobyl, only residents within 30 km needed to be evacuated. These rational arguments and facts could not compete with the horror stories and news photos appearing in the

  8. The unknown on the doorstep: Hong Kong's fears concerning Daya Bay, China's first major nuclear power station and the public relations challenges

    Chan, Albert [Hong Kong Nuclear Investment Co Ltd., Hongkong (China)

    1995-07-01

    The Guangdong Nuclear Power Station at Daya Bay is located east of the Shenzhen Special Economic Zone in Southern China. It is a joint venture between Hong Kong and China. In terms of construction schedule, budget and performance, Daya Bay ranks amongst the best plants anywhere. This achievement is even more apparent when one takes into account the fact that Daya Bay is the first major nuclear power station in China and that a large amount of interface and co-ordination is required to bring together French and British technologies in a non-English speaking environment. This Paper addresses the various and challenging public relations issues faced by Daya Bay during the last 15 years (from feasibility study stage). The negotiation for the Daya Bay nuclear power station project coincided with the political negotiations between China and Britain over the future of Hong Kong - the 1997 issue. (The political negotiations commenced in September 1982 and concluded in late 1984). Concerns over the nuclear project were heard during this phase but were limited to local environmental groups rather than the general public. The focus was more on the environmental and radiological impact of a nuclear power station than specific technical and safety issues. As for the general public, the project wasn't much of an issue until April, 1986 (Chernobyl accident). Period from 1986-1993 was the period of construction of the Daya Bay nuclear power station. An antinuclear campaign was launched by a few local activists who claimed to have collected signatures from one million people in Hong Kong urging the Chinese Government to shelve the project. The Hong Kong public did not understand the difference between Chernobyl type and PWR-type nuclear reactors (Daya Bay is a PWR) nor were they aware that even in the case of Chernobyl, only residents within 30 km needed to be evacuated. These rational arguments and facts could not compete with the horror stories and news photos appearing in the

  9. 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"…

  10. FIGO IVB (Para-aortic lymph adenopathy) squamous cell carcinoma of uterine cervix associated with a left pelvic kidney: a therapeutic challenge

    Ali, N.; Karsan, F.; Abbasi, A.N.; Khan, Z.R.

    2012-01-01

    The standard of care for locally advanced carcinoma of uterine cervix is concurrent chemoradiation therapy followed by intracavitary brachytherapy, when there is para-aortic lymphadenopathy, radiation field needs to be extended to para-aortic region. In the latter case dose limiting organs are spinal cord, kidneys and small intestine. We present a challenging case of FIGO IVB squamous cell carcinoma of cervix and a pelvic kidney. This patient received chemoradiation to pelvis and para-aortic field, brachytherapy was not performed as patient already had undergone attempted hysterectomy. Treatment, outcome and challenges encountered in this case are presented and literature is reviewed. (author)

  11. A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma

    Tomofumi Yamamoto

    2018-03-01

    Full Text Available Multiple myeloma (MM is a malignancy of terminally differentiated plasma cells and is the second most common hematological cancer. MM frequently occurs in the elderly population with the median age as the middle sixties. Over the last 10 years, the prognosis of MM has been dramatically improved by new therapeutic drugs; however, MM is still incurable. The pathogenesis of MM is still unclear, thus greater understanding of the molecular mechanisms of MM malignancy is desirable. Recently, microRNAs (miRNAs were shown to modulate the expression of genes critical for MM pathogenesis. In addition, miRNAs are secreted via extracellular vesicles (EVs, which are released from various cell types including MM cells, and these miRNAs are involved in multiple types of cell-cell interactions, which lead to the malignancy of MM. In this review, we summarize the current knowledge regarding the role of miRNA secretion via EVs and of EVs themselves in MM development. We also discuss the potential clinical applications of EVs as promising biomarkers and new therapeutic targets for improving the outcome of MM, resulting in a brighter future for aging societies.

  12. Anti-N-methyl-D-aspartate receptor encephalitis after Herpes simplex virus-associated encephalitis: an emerging disease with diagnosis and therapeutic challenges.

    Schein, Flora; Gagneux-Brunon, Amandine; Antoine, Jean-Christophe; Lavernhe, Sylvie; Pillet, Sylvie; Paul, Stéphane; Frésard, Anne; Boutet, Claire; Grange, Rémi; Cazorla, Céline; Lucht, Frédéric; Botelho-Nevers, Elisabeth

    2017-08-01

    Morbidity and mortality of Herpes simplex virus encephalitis (HSE) remain high. Relapses of neurological signs may occur after initial clinical improvement under acyclovir treatment. We report here a case of post-HSE anti-N-methyl-d-aspartate receptor-mediated encephalitis in an adult and perform a systematic search on PubMed to identify other cases in adults. We identified 11 previously published cases, to discuss diagnostic and therapeutic management. Symptoms in adults are often inappropriate behaviors, confusion and agitation. Diagnosis of anti-NMDA-R encephalitis after HSE is often delayed. Treatment consists in steroids, plasma exchange, and rituximab. Prognosis is often favorable. Anti-NMDA-R antibodies should be searched in cerebrospinal fluid of patients with unexpected evolution of HSE. This emerging entity reopens the hot debate about steroids in HSE.

  13. Outcomes of antiretroviral treatment program in Ethiopia: Retention of patients in care is a major challenge and varies across health facilities

    Kloos Helmut

    2011-04-01

    major challenge and varies across health facilities with high, medium and low retention rates. We therefore recommend further studies to understand the organization of care in health facilities with high, medium and low retention rates. It is also imperative that early initiation of patients on ART is taken seriously as more than 79% of the patients had baseline CD4-cell counts less than 200 cells per micro-liter of blood. Finally, we recommend that the shift to second-line ART might be too low and warrants close monitoring.

  14. A 10-Year Experience of Therapeutic Drug Monitoring (TDM) of Linezolid in a Hospital-wide Population of Patients Receiving Conventional Dosing: Is there Enough Evidence for Suggesting TDM in the Majority of Patients?

    Pea, Federico; Cojutti, Pier Giorgio; Baraldo, Massimo

    2017-10-01

    A retrospective study was conducted to assess our 10-year experience of therapeutic drug monitoring (TDM) of linezolid in a large patient population to establish whether conventional dosing may result in adequate drug exposure in the majority of patients. Patients included in this study underwent TDM of linezolid trough concentration (C min ) during treatment with conventional doses of 600 mg every 12 hr in the period between January 2007 and June 2016. The desired range of C min was set between 2 and 7 mg/L (underexposure, C min   7 mg/L). Multivariate logistic regression analysis investigated variables potentially correlated with linezolid C min . One thousand and forty-nine patients had 2484 linezolid C min assessed during treatment with conventional doses. Median (IQR) linezolid C min was 5.08 mg/L (2.78-8.52 mg/L). Linezolid C min was within the desired range in 50.8% of cases (1262/2484). Overexposure (n = 821; 33%) occurred much more frequently than underexposure (n = 401; 16.2%) and was severe (>20 mg/L) in 3.9% of cases (98/2484). Linezolid overexposure was significantly associated with CrCL C -G estimates ≤40 mL/min. (OR 1.463; 95% CI 1.124-1.904, p = 0.005). Linezolid underexposure was significantly associated with CrCL C -G estimates >100 mL/min. (OR 3.046; 95% CI 2.234-4.152, p Linezolid C min was not correlated linearly with CrCL C -G (R 2  = 0.061). Variability in renal function explained only partially the very wide interindividual linezolid C min variability. Our study suggests that TDM could represent a valuable approach in optimizing linezolid exposure in the majority of patients. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  15. 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.

  16. Therapeutic cloning: The ethical limits

    Whittaker, Peter A.

    2005-01-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated

  17. A Computational Methodology to Overcome the Challenges Associated With the Search for Specific Enzyme Targets to Develop Drugs Against Leishmania major.

    Catharina, Larissa; Lima, Carlyle Ribeiro; Franca, Alexander; Guimarães, Ana Carolina Ramos; Alves-Ferreira, Marcelo; Tuffery, Pierre; Derreumaux, Philippe; Carels, Nicolas

    2017-01-01

    We present an approach for detecting enzymes that are specific of Leishmania major compared with Homo sapiens and provide targets that may assist research in drug development. This approach is based on traditional techniques of sequence homology comparison by similarity search and Markov modeling; it integrates the characterization of enzymatic functionality, secondary and tertiary protein structures, protein domain architecture, and metabolic environment. From 67 enzymes represented by 42 enzymatic activities classified by AnEnPi (Analogous Enzymes Pipeline) as specific for L major compared with H sapiens , only 40 (23 Enzyme Commission [EC] numbers) could actually be considered as strictly specific of L major and 27 enzymes (19 EC numbers) were disregarded for having ambiguous homologies or analogies with H sapiens . Among the 40 strictly specific enzymes, we identified sterol 24-C-methyltransferase, pyruvate phosphate dikinase, trypanothione synthetase, and RNA-editing ligase as 4 essential enzymes for L major that may serve as targets for drug development.

  18. 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.

  19. Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease

    Manoj Kumar Jaiswal

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenera-tive diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord.The clinical phenotype is characterized by loss of motor neurons (MNs), mus-cular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3–5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro"disease in dish"and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.

  20. Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease.

    Jaiswal, Manoj Kumar

    2017-05-01

    Amyotrophic lateral sclerosis (ALS) and motor neuron diseases (MNDs) are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons (UMNs/LMNs), brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons (MNs), muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3-5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro " disease in dish " and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.

  1. NATO Advanced Research Workshop on Emergency Management after a Major Terror Attack : the New Challenges for First Responders and Civil Protection

    Steinhäusler, Friedrich

    2007-01-01

    International terrorism remains a significant threat to the peace of the world. Weapons using various materials and delivery systems have been directed against cities and infrastructure, and other materials are postulated to be usable within the near future. Some of these materials are unusual or exotic, while some are modifications of materials used daily for other purposes: biological, chemical, radiological, nuclear and explosive. These materials pose a safety challenge for first responders, slowing the response and potentially killing scarce trained personnel. This book provides information about how leading agencies across the NATO membership are preparing to confront and respond to terrorists deploying Weapons of Mass Destruction (WMD), Weapons of Mass Killing (WMK) and Weapons of Mass Disruption (WMDi). Based on contributions by experts from NATO member states, Israel and the Russian Federation, this book offers information on fourth generation warfare as a new challenge to first responders. It also pr...

  2. To be, or not to be obese - that's the challenge: a hypothesis on the cortical inhibition of the hypothalamus and its therapeutical consequences.

    Kreier, Felix

    2010-08-01

    the subject will gain weight again. It is suggested that this is why diets do not work in the long term. In anorexic patients, the cortex is fully occupied to control the hypothalamus resulting in extreme weight loss. In obese subjects, the cortex is less disciplined and the hypothalamus will take control again to stimulate positive energy balance. From this viewpoint, the limbic-reward system interacts both with the hypothalamus and the cortex to achieve demands by emotional motivation. The last part of this paper describes a therapeutic strategy based on this hypothesis. We propose a dual approach to fight obesity. First, interventions should be implemented that remind the cortex to control the hypothalamus and second, to stimulate physiological feedback to the hypothalamus. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Family Life and the Impact of Previous and Present Residential and Day Care Support for Children with Major Cognitive and Behavioural Challenges: A Dilemma for Services and Policy

    Brown, R. I.; Geider, S.; Primrose, A.; Jokinen, N. S.

    2011-01-01

    Introduction: Since the development of inclusion and integration, parents have increasingly become the major, and sometimes the only, carers of their children with disabilities. Many families speak of stress and frustration with service and community support, and some have turned to residential and specialised day care services to overcome…

  4. The international gas markets. Of major changes and challenges for Europe; Die internationalen Gasmaerkte. Von grossen Veraenderungen und Herausforderungen fuer Europa

    Westphal, Kirsten [Deutsches Institut fuer Internationale Politik und Sicherheit, Berlin (Germany). Stiftung Wissenschaft und Politik (SWP), Forschungsgruppe Globale Fragen

    2014-01-15

    Already in the 2010 edition of its World Energy Outlook the World Energy Agency noted an unprecedented degree of uncertainty surrounding the international energy markets. The rate of change in these markets is indeed stupendous, posing formidable tasks to business companies as well as the political leadership. The European gas markets face new challenges in protecting their security of supply which stem from the combined effects of the shift of LNG trade flows into the Pacific region, decreasing rates of home production and the ongoing transformation process within the EU.

  5. The New World challenge: Performance trends in wine production in major wine-exporting countries in the 2000s and their implications for the Australian wine industry

    Euan Fleming

    2014-12-01

    Full Text Available Anderson, K., Nelgen, S., 2011. Global Wine Markets, 1961 to 2009: A Statistical Compendium. University of Adelaide Press, Adelaide publication of an index of revealed comparative advantage suggests that the Australian wine industry had come under increased competition from other “New World” producers in the first decade of this century. We examine this influence by comparing the transformation of winegrapes into wine volume and value in the 11 largest wine-exporting countries during the years, 2000–2009. Our focus is on the challenge issued by other New World producers from the Southern Hemisphere to Australian producers, and the continuing challenge to Old World global supremacy by New World producers and its response. Four performance measures are used this study. Two key trends are evident. First, all countries migrated to higher price points, albeit with differing degrees of success: slightly declining productivity in transforming winegrapes into wine output was overwhelmed by price/quality effects, leading to substantial gains in transforming winegrapes into wine value. Second, New World producers plus Portugal and Spain were much more successful in achieving gains in their export value proposition than they were in extracting value in their domestic markets. Results show that Australian wine producers had lost some of their competitive advantage during the 2000s as their pre-existing strategy dominated by the export of high-volume wines by large companies at low to medium price points, and their reliance on a reputation for reliable good quality for the price point was beginning to fail in the face of competition from both New World and Old World producers. Acknowledgement of this outcome has led to a good deal of introspection, and recognition of the need to promote the wine regions of Australia, based on higher-quality wines, and to select and promote quality indicators.

  6. Major depression

    Depression - major; Depression - clinical; Clinical depression; Unipolar depression; Major depressive disorder ... providers do not know the exact causes of depression. It is believed that chemical changes in the ...

  7. MIGRATION AND REFUGEE CRISIS: A MAJOR CHALLENGE FOR THE EUROPEAN UNION. MEASURES AND POSSIBLE SOLUTIONS IN THE CONTEXT OF YEAR 2016

    Dan VĂTĂMAN

    2016-06-01

    Full Text Available The rising number of people trying to get into Europe from the Middle East and Africa has highlighted some structural problems of EU migration policy, fact which revealed the need for setting out and adoption of immediate and long-term responses to the migration challenges that Europe faces. Taking into account the complexity of the migration phenomenon and possible impact of the refugee crisis on the proper functioning of the European Union, the aim of this study is to highlight the way in which the crisis is managed, a particular attention being paid to the initiatives of the European Commission for shaping an effective and balanced European migration policy. For a full understanding of the real situation, were analysed the implementation of EU asylum and migration law by Member States, especially because the crisis has been made worse by the failure to implement existing laws in this area. Also, a particular attention was given to Romania's involvement in finding solutions and resolving the crisis.

  8. Dysphagia in Parkinson's disease: a therapeutic challenge?

    Michou, Emilia; Hamdy, Shaheen

    2010-06-01

    This article focuses on the current status and research directions on swallowing disorders (dysphagia) in patients with Parkinson's disease (PD). Although epidemiological data are scarce, increased incidence of dysphagia in patients with PD leads to increased risk of mortality, secondary to aspiration pneumonia. Although studies show that aspiration pneumonia is a common cause of death in this group of patients, clinical practice lacks an evidence base and there is an increased need for randomized clinical trials. Importantly, the underlying mechanisms accounting for the progression of dysphagia in PD are still unclear. Furthermore, evidence shows that dopaminergic medication does not affect swallowing performance. Future research in the field is urgently needed and may result in improved management of dysphagia in patients with PD.

  9. [Beyond suffering, schizophrenic improvisation and therapeutic challenges].

    Bizot, Tatiana

    2016-01-01

    Led jointly by an actress and an occupational therapist, an 'improvisation' activity has been set up within the Sainte-Anne University Hospital SHU Sector 14 for hospitalised patients, on medical prescription. This containing environment provides psychological support and encourages patients with schizophrenia to explore their creativity and to 'let go' so as to discover new physical possibilities. The group thereby becomes a support for the relationship and the development of verbal and non-verbal communication. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Vulvodynia – still a challenging therapeutic problem

    Magdalena Pawlaczyk

    2017-04-01

    Full Text Available Introduction . Vulvodynia is a chronic condition characterized by pain and burning in the vulvar area without any abnormalities in clinical and laboratory examinations. The diagnosis is based on detailed assessment of medical history, physical examination and exclusion of other potential causes of vulvar pain. As yet, no definitive treatment algorithm has been universally accepted for vulvodynia. Objective . To present a case of successful treatment of generalized spontaneous vulvodynia with low doses of amitriptyline. Case report . A 42-year-old patient presented to a dermatology outpatient clinic with chronic generalized vulvar pain of 2 years’ duration. She was diagnosed with generalized spontaneous vulvodynia. Amitriptyline treatment was introduced and supported by topical application of lignocaine gel. After 13 months of amitriptyline therapy a complete remission was achieved. Conclusions . Vulvodynia is a complex disease with numerous presentations, the symptoms of which often overlap. Since the diagnosis of vulvodynia requires the exclusion of other abnormalities, it is fundamental to raise the awareness of the disease among clinicians, so as to enable early correct diagnosis and adequate treatment.

  11. Microbiological and therapeutic challenges in infectious spondylodiscitis

    Aagaard, Theis; Roed-Petersen, Casper; Dragsted, Casper

    2013-01-01

    The microbiological diagnosis of infectious spondylodiscitis is often difficult to establish and the disease requires prolonged antibiotic treatment. We analyzed the medical records of 100 patients admitted for infectious spondylodiscitis from 2006 to 2011 with an emphasis on (1) the diagnostic u...... utility of blood cultures and invasive biopsies in the microbiological diagnosis, (2) clinical features differentiating Staphylococcus aureus infections from those with other aetiologies, and (3) evaluation of the outcome of the antimicrobial therapy.......The microbiological diagnosis of infectious spondylodiscitis is often difficult to establish and the disease requires prolonged antibiotic treatment. We analyzed the medical records of 100 patients admitted for infectious spondylodiscitis from 2006 to 2011 with an emphasis on (1) the diagnostic...

  12. A Therapeutic Challenge: Management of Atrial Thrombus

    Serkan Burc Deser

    2016-09-01

    Full Text Available Introduction: Primary cause of atrial thrombi include atrial fibrillation, foreign bodies inside the atrium such as catheters and pacemaker leads, emboli of deep venous thrombus and primary or metastatic tumors of the heart. We review the clinical features, epidemiology, diagnosis and treatment of nine intriguing cases with atrial thrombus. Methods: This is a retrospective study of nine patients (seven female (78%, two male (33% who were diagnosed with atrial thrombi (average age of 50 ± 12 years and were treated at the Ondokuz Mayis University, Department of Cardiovascular Surgery from February 2014 to January 2015. Among them, six patients had atrial fibrillation (one male, five female, seven patients were suffering from dispne and orthopnoea, five patients were suffering from leg swelling, seven patients had a history of hypertension and three patients had a history of mitral valve replacement surgery. Results: All patients underwent surgery except one. Four patients recovered uneventfully and discharged with oral anticoagulation (warfarin therapy (adjusted to maintain an international normalized ratio of INR between two and three times. Five of nine patients (55% died after surgery. Conclusion: The response to the thrombolytic therapy is poor, mostly ineffective and unsafe so it is often recommended as a bridge to surgery. In patients diagnosed with mechanical mitral valve thrombosis, medical therapy has the possibility of end organ emboli and also fail to resolve the organised thrombus on the stuck valve. On the other hand surgery does not always give satisfactory results. J Clin Exp Invest 2016; 7(4: 278-282

  13. Challenges of Translating Basic Research Into Therapeutics

    Smoliga, James M.; Vang, Ole; Baur, Joseph A.

    2012-01-01

    motivates smaller nutraceutical companies to complicate the scientific problem even more—each creates its own proprietary blend, making it extremely difficult to compare their data with those of other companies, or of academic labs using pure compounds. But even beyond these problems lies a deeper one......; resveratrol, and almost every natural compound, is likely to have many clinically relevant targets with different dose–response profiles, tissue distributions, and modifiers. Tackling this type of problem efficiently, and even beginning to address the spectrum of other molecules with claimed benefits...

  14. Therapeutic Challenge in a Severely Atrophic Mandible

    Edvard Janev

    2018-03-01

    Full Text Available BACKGROUND: After tooth loss, however, severely atrophic residual alveolar ridges are fairly common, especially in patients who have been edentulous for a long period. Anterior area of the mandible is areas where clinicians have greater anatomical limitations. Reduced alveolar bone height very often represents a contraindication to implant therapy, unless a procedure such as a ridge augmentation is performed. CASE REPORT: This study aims to present two separate cases in highly selected edentulous anterior mandibular sites, where one stage, mini implants were used to support total prostheses. Small diameter implants have been used for retention of complete removable mandibular overdentures. This is an excellent option for those who suffer from the inconvenience and embarrassment of loose lower dentures and are tired of having to use sticky pastes and creams to make their dentures stay in place. CONCLUSION: Small diameter implants, when used multiples may offer adequate support for a removable prosthesis and overcome this problem.

  15. Therapeutic Challenge in a Severely Atrophic Mandible

    Janev, Edvard; Janeva, Nadica; Peeva–Petreska, Marija; Mitic, Kristina

    2018-01-01

    BACKGROUND: After tooth loss, however, severely atrophic residual alveolar ridges are fairly common, especially in patients who have been edentulous for a long period. Anterior area of the mandible is areas where clinicians have greater anatomical limitations. Reduced alveolar bone height very often represents a contraindication to implant therapy, unless a procedure such as a ridge augmentation is performed. CASE REPORT: This study aims to present two separate cases in highly selected edentulous anterior mandibular sites, where one stage, mini implants were used to support total prostheses. Small diameter implants have been used for retention of complete removable mandibular overdentures. This is an excellent option for those who suffer from the inconvenience and embarrassment of loose lower dentures and are tired of having to use sticky pastes and creams to make their dentures stay in place. CONCLUSION: Small diameter implants, when used multiples may offer adequate support for a removable prosthesis and overcome this problem. PMID:29610621

  16. Erosive lichen planus: a therapeutic challenge.

    Romero, Williams; Giesen, Laura; Navajas-Galimany, Lucas; Gonzalez, Sergio

    2016-01-01

    Erosive lichen planus is an uncommon variant of lichen planus. Chronic erosions of the soles, accompanied by intense and disabling pain, are some of its most characteristic manifestations. We present the case of a woman who developed oral and plantar erosive lichen planus associated with lichen planus pigmentosus and ungueal lichen planus that were diagnosed after several years. The patient failed to respond to multiple therapies requiring longstanding medication but remained refractory. Knowledge of the treatment options for erosive lichen planus is insufficient. Further research is required to clarify their effectiveness, ideally adopting an evidence-based methodology.

  17. Trace elements in bivalves from the Rio Cruces, Chile, trace watershed evolution after a major earthquake and challenge a postulated chemical spill from a pulp plant

    Risk, M.; Burchell, M.; Nairn, R.; Tubrett, M.; Forsterra, G.

    2009-05-01

    In May, 1960, the largest recorded earthquake in the history of the planet hit southern Chile, dropping part of the course of the Rio Cruces by 2m and creating an extensive wetland. The Brazilian Waterweed Egeria densa colonised the area, and became a primary food source for large populations of the Black-necked Swan, Cygnus melancoryphus. In 2004, a large pulp mill commenced operations upstream on the river. According to local reports, immediately after the opening of the plant, the weed died and the swans left. There was public outcry, and a search for a cause or a culprit. It was postulated that some sort of chemical spill from the plant caused the weed to die, resulting in departure of the swans. In 2008, we collected specimens of the bivalve Diplodon chilensis from several locations downstream from the Plant and towards the wetland to see if there was evidence of a chemical spill recorded in the shells. We prepared thin-sections of the shells to observe growth line development and patterns. Additionally, shell samples were analysed for stable oxygen isotopes and trace elements, using LA-ICP/MS. Based on annual growth lines, some of the bivalves were long-lived, with an age of more than 50 years. These individuals settled in the river shortly after the earthquake, and have lived there continuously ever since. Annual and sub-annual banding was clear, and the annual cyclicity of the major bands was verified with oxygen isotope analysis. There are no changes in growth corresponding to 2004. Trace element scans provided a wealth of information on the evolution of this earthquake-impacted wetland. Barium, Strontium and Manganese all showed strong annual cyclicity. From the analysis of older specimens, we interpret the high peaks of the Ba signal as reflecting soil erosion-Ba peaks are large immediately after the earthquake, then they diminish through time. Sr is likely a temperature signal, and Mn reflects runoff. Minor peaks in Cu, As and Pb probably reflect

  18. Prospects for therapeutic mitochondrial transplantation.

    Gollihue, Jenna L; Rabchevsky, Alexander G

    2017-07-01

    Mitochondrial dysfunction has been implicated in a multitude of diseases and pathological conditions- the organelles that are essential for life can also be major players in contributing to cell death and disease. Because mitochondria are so well established in our existence, being present in all cell types except for red blood cells and having the responsibility of providing most of our energy needs for survival, then dysfunctional mitochondria can elicit devastating cellular pathologies that can be widespread across the entire organism. As such, the field of "mitochondrial medicine" is emerging in which disease states are being targeted therapeutically at the level of the mitochondrion, including specific antioxidants, bioenergetic substrate additions, and membrane uncoupling agents. New and compelling research investigating novel techniques for mitochondrial transplantation to replace damaged or dysfunctional mitochondria with exogenous healthy mitochondria has shown promising results, including tissue sparing accompanied by increased energy production and decreased oxidative damage. Various experimental techniques have been attempted and each has been challenged to accomplish successful transplantation. The purpose of this review is to present the history of mitochondrial transplantation, the different techniques used for both in vitro and in vivo delivery, along with caveats and pitfalls that have been discovered along the way. Results from such pioneering studies are promising and could be the next big wave of "mitochondrial medicine" once technical hurdles are overcome. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  19. Deploying Missile Defense: Major Operational Challenges

    Bunn, M

    2004-01-01

    By October 2004, the United States will have begun initial deployment of a missile defense capability albeit a modest, limited, and not completely proven one to defend the homeland against a limited...

  20. Major achievements and challenges of fusion research

    Tendler, Michael

    2015-01-01

    The ITER project is truly at the frontier of knowledge, a collective effort to explore the tantalizing future of free, clean and inexhaustible energy offered by nuclear fusion. Where the Large Hadron Collider at CERN pushes the boundaries of physics to find the origins of matter, the ITER Project seeks to give humans an endless stream of power which could have potentially game-changing consequences for the entire planet. Seminal contributions to the general physics knowledge accomplished by the plasma physics research for the benefit of the ITER project will be brought to light. The legacy of Professor H Alfvén within the framework of the ITER project will be described. (invited comment)

  1. OR Challenges in Major Sport Events

    Barros, A.I.

    2012-01-01

    Although the origins of Operations Research are usually linked to the military, nowadays successful applications in different areas of the society (business, industrial, health sector and sports) can be found. In particular, applications in sports like sport tactics and strategy, scheduling and

  2. Benefits of and Barriers to Pharmacogenomics-Guided Treatment for Major Depressive Disorder.

    Ahmed, Ahmed T; Weinshilboum, Richard; Frye, Mark A

    2018-05-01

    Antidepressants have reduced the symptom burden for many Major Depressive Disorder (MDD) patients, but drug-related side effects and treatment resistance continue to present major challenges. Pharmacogenomics represents one approach to enhance antidepressant efficacy and avoid adverse reactions, but concerns remain with regard to the overall "value equation," and several barriers must be overcome to achieve the full potential of MDD pharmacogenomics. © 2018 American Society for Clinical Pharmacology and Therapeutics.

  3. Major Links.

    Henderson, Tona

    1995-01-01

    Provides electronic mail addresses for resources and discussion groups related to the following academic majors: art, biology, business, chemistry, computer science, economics, health sciences, history, literature, math, music, philosophy, political science, psychology, sociology, and theater. (AEF)

  4. Major Roads

    Minnesota Department of Natural Resources — This data set contains roadway centerlines for major roads (interstates and trunk highways) found on the USGS 1:24,000 mapping series. These roadways are current...

  5. Desafíos y esperanzas de un procedimiento científico terapéutico: hemodiálisis arteriovenosa continua Challenges and Hopes of a scientific therapeutic procedure: Continuous Hemodialisis

    Lourdes Elena Yera Loyola

    2003-08-01

    Full Text Available Se realiza un estudio sobre las interacciones entre el contexto sociocultural, la ciencia y la tecnología en el surgimiento y desarrollo de un novedoso procedimiento científico terapéutico: La Hemodiálisis Arteriovenosa continua, así como los posibles impactos sociales, económicos y científicos que traería consigo la aplicación de esta nueva tecnología, se concluye que el desarrollo científico tecnológico alcanzado alrededor de la segunda guerra mundial, así como la alta mortalidad en heridos con Insuficiencia renal aguda jugaron un importante papel en el surgimiento de la hemodiálisis. Las ventajas económicas que ofrece la aplicación de este proceder hace muy útil su aplicación en Cuba y otros países en vías de desarrollo que no tienen acceso a las caras tecnologías capitalistas. El modelo cubano de construcción del socialismo con una visión amplia en ciencia, tecnología y sociedad, ofrece respuestas efectivas al desafío científico tecnológico que hoy enfrentan los países subdesarrolladosA study on the interactions among the sociocultural context, science and technology in the emergence and development of a novel therapeutic scientific procedure: Continuous Arteriovenous Hemodyalisis is carried out, as well as the possible social, economic and scientific impacts of the application of this new technology. It is concluded that the technological-scientific development reached around the Second World War, as well as the high mortality among wounded soldiers with acute renal insufficiency played an important role in the emergence of hemodialysis. The economic advantages that the application of this procedure offers makes very useful its application in Cuba and other developing countries that don't have access to expensive capitalist technologies. The Cuban pattern for the construction of socialism, with its wide vision of science, technology and society, offers effective answers to the technological-scientific challenge

  6. Mechanisms of Plasma Therapeutics

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  7. Therapeutic Sleep for Traumatic Brain Injury

    2017-06-01

    AWARD NUMBER: W81XWH-16-1-0166 TITLE: Therapeutic Sleep for Traumatic Brain Injury PRINCIPAL INVESTIGATOR: Ravi Allada CONTRACTING...1. REPORT DATE June 2017 2. REPORT TYPE Annual 3. DATES COVERED 1June2016 - 31May2017 4. TITLE AND SUBTITLE Therapeutic Sleep for Traumatic Brain ...proposal will test the hypothesis that correcting sleep disorders can have a therapeutic effect onTraumatic Brain Injury (TBI) The majority of TBI

  8. Synthetic Immunology: Hacking Immune Cells to Expand Their Therapeutic Capabilities.

    Roybal, Kole T; Lim, Wendell A

    2017-04-26

    The ability of immune cells to survey tissues and sense pathologic insults and deviations makes them a unique platform for interfacing with the body and disease. With the rapid advancement of synthetic biology, we can now engineer and equip immune cells with new sensors and controllable therapeutic response programs to sense and treat diseases that our natural immune system cannot normally handle. Here we review the current state of engineered immune cell therapeutics and their unique capabilities compared to small molecules and biologics. We then discuss how engineered immune cells are being designed to combat cancer, focusing on how new synthetic biology tools are providing potential ways to overcome the major roadblocks for treatment. Finally, we give a long-term vision for the use of synthetic biology to engineer immune cells as a general sensor-response platform to precisely detect disease, to remodel disease microenvironments, and to treat a potentially wide range of challenging diseases.

  9. [Therapeutic touch and anorexia nervosa].

    Satori, Nadine

    2016-01-01

    An innovative practice, therapeutic touch has been used for around ten years in the treatment of eating disorders. Delivered by nurse clinicians having received specific training, this approach is based on nursing diagnoses which identify the major symptoms of this pathology. The support is built around the body and its perceptions. Through the helping relationship, it mobilises the patient's resources to favour a relationship of trust, a letting-go, physical, psychological and emotional relaxation, and improves the therapeutic alliance. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Some major challenges: Nuclear non-proliferation, nuclear arms control and nuclear terrorism. Vienna, 29 October 2001. Statement to the symposium on international safeguards: Verification and nuclear material security

    ElBaradei, M.

    2001-01-01

    The main topics dealt with the ensuring of an effective, universal and adequately financed system for the verification of nuclear non-proliferation, namely as follows: Effectiveness of the system; Participation in the system ; Financing of the system; Making Progress in Nuclear Arms Control; Protection Against Nuclear Terrorism. In the Safeguards Implementation Report (SIR) for 2000, the Agency was able to conclude that for all 140 states with safeguards agreements in place the nuclear material and other items placed under safeguards remained in peaceful nuclear activities or were otherwise adequately accounted for. The Agency currently safeguards over 900 facilities in 70 countries on a regular safeguards budget of approximately US $80 million per year. Turning to the major recent challenge, protection against nuclear terrorism, the IAEA has long been active in encouraging States to make security an integral part of the management of their nuclear programmes. The recent attacks in the United States were, however, a wake-up call to all that more can and must be done. In the week immediately following the tragedy, the IAEA General Conference adopted a resolution which requested a thorough review of Agency activities and programmes relevant to preventing acts of nuclear terrorism

  11. Major Channels Involved In Neuropsychiatric Disorders And Therapeutic Perspectives

    Paola eImbrici

    2013-05-01

    Full Text Available Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders or schizophrenia. Moreover, point mutations in calcium, sodium and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium and potassium channels in bipolar disorder, schizophrenia and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

  12. Nanoparticles for therapeutic and diagnostic applications

    Chiu, Yin To

    2014-01-01

    Nanomedicine focuses on the development and engineering of novel and unique therapeutic and diagnostic agents that can overcome the challenges associated with using traditional modalities. Nanoparticles (NPs) in the size range between 1 and 1000 nm have many advantages for use in these applications, such as, low polydispersity, established characterization methodologies, and the ability to be loaded with therapeutics for diseases, conjugated to targeting ligands to enhance specificity, and co...

  13. Bordetella pertussis pathogenesis: current and future challenges

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  14. Protein nanoparticles for therapeutic protein delivery.

    Herrera Estrada, L P; Champion, J A

    2015-06-01

    Therapeutic proteins can face substantial challenges to their activity, requiring protein modification or use of a delivery vehicle. Nanoparticles can significantly enhance delivery of encapsulated cargo, but traditional small molecule carriers have some limitations in their use for protein delivery. Nanoparticles made from protein have been proposed as alternative carriers and have benefits specific to therapeutic protein delivery. This review describes protein nanoparticles made by self-assembly, including protein cages, protein polymers, and charged or amphipathic peptides, and by desolvation. It presents particle fabrication and delivery characterization for a variety of therapeutic and model proteins, as well as comparison of the features of different protein nanoparticles.

  15. 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.

  16. Primary breast tuberculosis: diagnostic and therapeutic dilemmas.

    Hiremath, Bharati V; Subramaniam, Narayana

    2015-01-01

    To review the diagnostic and therapeutic challenges associated with treating isolated primary breast tuberculosis through discussion of our series of seven cases. Although breast is an uncommon site of occurrence of tuberculosis and isolated primary breast tuberculosis is an even rarer entity, its importance lies in distinguishing it from more common pathologies like abscesses or malignancy and avoiding unnecessary erroneous surgical intervention. The spectrum and presentation is wide and varied and we present our experience in managing seven such cases. A retrospective analysis of all the cases of histopathologically proven primary breast tuberculosis in the last three years at M.S. Ramaiah Hospital (2012-2014) was done. Analysis was in terms of mode of presentation, clinical features, diagnostic modalities used for evaluation and confirmation of the diagnosis, medical treatment and surgical intervention, if any. Special emphasis was placed on dilemmas in diagnosis and difficulties encountered during treatment. All cases were followed up till cure. Patients most commonly presented with a breast abscess, painful breast lumps and recurrent abscesses. Other foci of tuberculosis were ruled out in all of these patients. Majority were treated exclusively with anti-tubercular therapy (although regimens varied), but those with abscesses underwent incision and drainage. All cases were treated and followed up till cure. The challenges associated with primary breast tuberculosis are multiple, including which anti-tubercular therapy regimen to use, when to surgically intervene (as the breast is a cosmetically important area) and treating atypical mycobacteria. We provide a detailed discussion of the challenges we faced and review of literature.

  17. RNAi nanomedicines: challenges and opportunities within the immune system

    Weinstein, Shiri; Peer, Dan

    2010-01-01

    RNAi, as a novel therapeutic modality, has an enormous potential to bring the era of personalized medicine one step further from notion into reality. However, delivery of RNAi effector molecules into their target tissues and cells remain extremely challenging. Major attempts have been made in recent years to develop sophisticated nanocarriers that could overcome these hurdles. This review will present the recent progress with the challenges and opportunities in this emerging field, focusing mostly on the in vivo applications with special emphasis on the strategies for RNAi delivery into immune cells. (topical review)

  18. 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.

  19. Developing patient rapport, trust and therapeutic relationships.

    Price, Bob

    2017-08-09

    Rapport is established at the first meeting between the patient and nurse, and is developed throughout the therapeutic relationship. However, challenges can arise during this process. Initially, nurses can establish trust with the patient through the questions they ask, however, as care progresses, the nurse will be required to demonstrate a commitment to maintaining the patient's psychological well-being. When the therapeutic relationship ends, the nurse should assist the patient to assess progress and plan the next stage of recovery. This article provides three reflective exercises using case study examples to demonstrate how rapport is developed and sustained. Evidence is provided to identify why challenges arise in the therapeutic relationship and how the nurse can ensure they provide care that the patient regards as genuine.

  20. Reading Philemon as therapeutic narrative | Jordaan | HTS ...

    This article analysed the different narratives implied in Philemon by utilising the narrative therapeutic approach, as developed by Epston and White (1990). A dominant narrative (the harsh treatment of slaves in the early Christian environment) and a challenging narrative (a more humane conduct of slaves) were clearly ...

  1. The boomer challenge.

    Barr, Paul

    2014-01-01

    Hospitals and the rest of health care will have to make some major adjustments to meet the needs of the aging baby boom generation. The first article in our year-long series inventories the many challenges that lie ahead.

  2. Global challenges

    Blix, H.

    1990-01-01

    A major challenge now facing the world is the supply of energy needed for growth and development in a manner which is not only economically viable but also environmentally acceptable and sustainable in view of the demands of and risks to future generations. The internationally most significant pollutants from energy production through fossil fuels are SO 2 and NO x which cause acid rain, and CO 2 which is the most significant contributor to the greenhouse effect. Nuclear power, now providing about 17% of the world's electricity and 5% of the primary energy already is making a notable contribution to avoiding these emissions. While the industrialized countries will need more energy and especially electricity in the future, the needs of the developing countries are naturally much larger and present a tremendous challenge to the shaping of the world's future energy supply system. The advanced countries will have to accept special responsibilities, as they can most easily use advanced technologies and they have been and remain the main contributors to the environmental problems we now face. Energy conservation and resort to new renewable energy sources, though highly desirable, appear inadequate alone to meet the challenges. The world can hardly afford to do without an increased use of nuclear power, although it is strongly contested in many countries. The objections raised against the nuclear option focus on safety, waste management and disposal problems and the risk for proliferation of nuclear weapons. These issues are not without their problems. The risk of proliferation exists but will not appreciably diminish with lesser global reliance on nuclear power. The waste issue is more of a political than a technical problem. The use of nuclear power, or any other energy source, will never be at zero risk, but the risks are constantly reduced by new techniques and practices. The IAEA sees it as one of its priority tasks to promote such techniques. (author)

  3. Data Challenges

    McCubbin, N A

    Some two years ago we planned a series of Data Challenges starting at the end of 2001. At the time, that seemed to be comfortingly far in the future... Well, as the saying goes, doesn't time fly when you are having fun! ATLAS Computing is now deep in the throes of getting the first Data Challenge (DC0) up and running. One of the main aims of DC0 is to have a software 'release' in which we can generate full physics events, track all particles through the detector, simulate the detector response, reconstruct the event, and study it, with appropriate data storage en route. As all software is "always 95% ready" (!), we have been able to do most of this, more or less, for some time. But DC0 forces us to have everything working, together, at the same time: a reality check. DC0 should finish early next year, and it will be followed almost immediately afterwards by DC1 (DC0 was foreseen as the 'check' for DC1). DC1 will last into the middle of 2002, and has two major goals. The first is generation, simulation, and r...

  4. Advancing Stem Cell Biology toward Stem Cell Therapeutics

    Scadden, David; Srivastava, Alok

    2012-01-01

    Here, the International Society for Stem Cell Research (ISSCR) Clinical Translation Committee introduces a series of articles outlining the current status, opportunities, and challenges surrounding the clinical translation of stem cell therapeutics for specific medical conditions.

  5. Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

    Mario Gimona

    2017-06-01

    Full Text Available Extracellular vesicles (EVs derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

  6. Individualised cancer therapeutics: dream or reality? Therapeutics construction.

    Shen, Yuqiao; Senzer, Neil; Nemunaitis, John

    2005-11-01

    The analysis of DNA microarray and proteomic data, and the subsequent integration into functional expression sets, provides a circuit map of the hierarchical cellular networks responsible for sustaining the viability and environmental competitiveness of cancer cells, that is, their robust systematics. These technologies can be used to 'snapshot' the unique patterns of molecular derangements and modified interactions in cancer, and allow for strategic selection of therapeutics that best match the individual profile of the tumour. This review highlights technology that can be used to selectively disrupt critical molecular targets and describes possible vehicles to deliver the synthesised molecular therapeutics to the relevant cellular compartments of the malignant cells. RNA interference (RNAi) involves a group of evolutionarily conserved gene silencing mechanisms in which small sequences of double-stranded RNA or intrinsic antisense RNA trigger mRNA cleavage or translational repression, respectively. Although RNAi molecules can be synthesised to 'silence' virtually any gene, even if upregulated, a mechanism for selective delivery of RNAi effectors to sites of malignant disease remains challenging. The authors will discuss gene-modified conditionally replicating viruses as candidate vehicles for the delivery of RNAi.

  7. Cognitive Challenges

    ... Privacy Policy Sitemap Learn Engage Donate About TSC Cognitive Challenges Approximately 45% to 60% of individuals with TSC develop cognitive challenges (intellectual disabilities), although the degree of intellectual ...

  8. Exubera. Inhale therapeutic systems.

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  9. 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.

  10. 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...

  11. 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.

  12. 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…

  13. 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

  14. PAX6 aniridia syndrome: clinics, genetics, and therapeutics.

    Lim, Hyun Taek; Kim, Dae Hee; Kim, Hyuna

    2017-09-01

    Aniridia is a rare and panocular disorder affecting most of the ocular structures which may have significant impact on vision. The purpose of this review is to describe the clinical features, genetics, and therapeutic options for this disease and to provide an update of current knowledge and latest research findings. Aside from the ocular features, a variety of associated systemic abnormalities, including hormonal, metabolic, gastrointestinal, genitourinary, and neurologic pathologies have been reported in children with aniridia. Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia. Recent improvement in genetic testing technique will help more rapid and precise diagnosis for aniridia. A promising therapeutic approach called nonsense suppression therapy has been introduced and successfully used in an animal model. Aniridia is a challenging disease. The progressive nature of this condition and its potential complications require continuous and life-long ophthalmologic care. Genetic diagnosis for aniridia is important for establishing definitive molecular characterization as well as identifying individuals at high risk for Wilms tumor. Recent advancement in understanding the genetic pathogenesis of this disease offers promise for the approaches to treatment.

  15. MicroRNAs as Therapeutic Targets for Alzheimer's Disease.

    Di Meco, Antonio; Praticò, Domenico

    2016-05-07

    Alzheimer's disease (AD) is the most common cause of dementia in the elderly. With increasing longevity and the absence of a cure, AD has become not only a major health problem but also a heavy social and economic burden worldwide. Given this public health challenge, and that the current approved therapy for AD is limited to symptomatic treatment (i.e., cholinesterase inhibitors and NMDA receptor antagonists), exploration of new molecular pathways as novel therapeutic targets remains an attractive option for disease modifying drug development. microRNAs (miRNAs) are short non-coding RNA that control gene expression at the post-translational level by inhibiting translation of specific mRNAs or degrading them. Dysregulation of several miRNAs has been described in AD brains. Interestingly, their molecular targets are pathways that are well-established functional players in the onset and development of AD pathogenesis. Today several molecular tools have been developed to modulate miRNA levels in vitro and in vivo. These scientific advancements are affording us for the first time with the real possibility of targeting in vivo these dysregulated miRNAs as a novel therapeutic approach against AD.

  16. Skewed Epigenetics: An Alternative Therapeutic Option for Diabetes Complications

    Gabriele Togliatto

    2015-01-01

    Full Text Available Vascular complications are major causes of morbidity and mortality in type 2 diabetes patients. Mitochondrial reactive oxygen species (ROS generation and a lack of efficient antioxidant machinery, a result of hyperglycaemia, mainly contribute to this problem. Although advances in therapy have significantly reduced both morbidity and mortality in diabetic individuals, diabetes-associated vascular complications are still one of the most challenging health problems worldwide. New healing options are urgently needed as current therapeutics are failing to improve long-term outcomes. Particular effort has recently been devoted to understanding the functional relationship between chromatin structure regulation and the persistent change in gene expression which is driven by hyperglycaemia and which accounts for long-lasting diabetic complications. A detailed investigation into epigenetic chromatin modifications in type 2 diabetes is underway. This will be particularly useful in the design of mechanism-based therapeutics which interfere with long-lasting activating epigenetics and improve patient outcomes. We herein provide an overview of the most relevant mechanisms that account for hyperglycaemia-induced changes in chromatin structure; the most relevant mechanism is called “metabolic memory.”

  17. Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development.

    Krishnan, Navasona; Bonham, Christopher A; Rus, Ioana A; Shrestha, Om Kumar; Gauss, Carla M; Haque, Aftabul; Tocilj, Ante; Joshua-Tor, Leemor; Tonks, Nicholas K

    2018-01-18

    The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity.

  18. Illuminating the gateway of gene silencing: perspective of RNA interference technology in clinical therapeutics.

    Sindhu, Annu; Arora, Pooja; Chaudhury, Ashok

    2012-07-01

    A novel laboratory revolution for disease therapy, the RNA interference (RNAi) technology, has adopted a new era of molecular research as the next generation "Gene-targeted prophylaxis." In this review, we have focused on the chief technological challenges associated with the efforts to develop RNAi-based therapeutics that may guide the biomedical researchers. Many non-curable maladies, like neurodegenerative diseases and cancers have effectively been cured using this technology. Rapid advances are still in progress for the development of RNAi-based technologies that will be having a major impact on medical research. We have highlighted the recent discoveries associated with the phenomenon of RNAi, expression of silencing molecules in mammals along with the vector systems used for disease therapeutics.

  19. Challenges in comparing the acute cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) vs. electroconvulsive therapy (ECT) in major depression: A systematic review.

    Kedzior, Karina Karolina; Schuchinsky, Maria; Gerkensmeier, Imke; Loo, Colleen

    2017-08-01

    The present study aimed to systematically compare the cognitive outcomes of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) and electroconvulsive therapy (ECT) in head-to-head studies with major depression (MDD) patients. A systematic literature search identified six studies with 219 MDD patients that were too heterogeneous to reliably detect meaningful differences in acute cognitive outcomes after ECT vs. HF-rTMS. Cognitive effects of brain stimulation vary depending on the timeframe and methods of assessment, stimulation parameters, and maintenance treatment. Thus, acute and longer-term differences in cognitive outcomes both need to be investigated at precisely defined timeframes and with similar instruments assessing comparable functions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Glomar challenger

    Carroll, J P

    1969-01-01

    The Glomar Challenger has a length of 400 ft, a 65-ft beam, and a depth of 27 ft 6-in. She has a draft of 20 ft with a gross displacement of 10,500 long tons. The principal specifications of the vessel are tabulated. To achieve dynamic positioning, 4 fixed thrusters and the vessel's 2 propulsion screws are utilized. The ''fix'' is obtained by placing a sonar beacon, with self contained batteries, on the ocean floor at a selected site. The vessel is provided with 4 hydrophones installed in the hull at the 4 corners of a square. The sonar beacon radiates sound waves at a fixed pulse rate. If the vessel is directly over the beacon, the sound waves will arrive at all hydrophones simultaneously. A difference in time of arrival indicates the vessel is off location. The sound signals received by the hydrophones are fed into a computer. They are changed into coordinate information, which serves as the primary function of determining corrective action by the vessel's propulsion and thruster system. The computer feeds back information into a control system, which enables the propulsion and thrusters to automatically respond, in order to keep the vessel on the predetermined location. The major drilling components are listed. The deep-sea drilling project is described. A summary of the first leg is given in tabular form.

  1. Toxin-Based Therapeutic Approaches

    Itai Benhar

    2010-10-01

    Full Text Available Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin.

  2. Toxin-Based Therapeutic Approaches

    Shapira, Assaf; Benhar, Itai

    2010-01-01

    Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin. PMID:22069564

  3. Guidelines for Rational Cancer Therapeutics

    Byunghee Yoo

    2017-12-01

    Full Text Available Traditionally, cancer therapy has relied on surgery, radiation therapy, and chemotherapy. In recent years, these interventions have become increasingly replaced or complemented by more targeted approaches that are informed by a deeper understanding of the underlying biology. Still, the implementation of fully rational patient-specific drug design appears to be years away. Here, we present a vision of rational drug design for cancer that is defined by two major components: modularity and image guidance. We suggest that modularity can be achieved by combining a nanocarrier and an oligonucleotide component into the therapeutic. Image guidance can be incorporated into the nanocarrier component by labeling with a specific imaging reporter, such as a radionuclide or contrast agent for magnetic resonance imaging. While limited by the need for additional technological advancement in the areas of cancer biology, nanotechnology, and imaging, this vision for the future of cancer therapy can be used as a guide to future research endeavors.

  4. Overcoming challenges

    Full Text Available ... breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding ... myths Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding ...

  5. Overcoming challenges

    Full Text Available ... section Back to section menu It's Only Natural Planning ahead Breastfeeding and baby basics Making breastfeeding work ... It's Only Natural Overcoming challenges It's Only Natural Planning ahead Addressing breastfeeding myths Overcoming challenges Common questions ...

  6. Neurobiology of Major Depressive Disorder

    Rosa Villanueva

    2013-01-01

    Full Text Available We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed.

  7. 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

  8. Syphilis in the AIDS era: diagnostic dilemma and therapeutic challenge.

    Scythes, John B; Jones, Colman M

    2013-06-01

    This review argues that syphilis has been underdiagnosed and undertreated, a problem that goes back to the beginning of the Wassermann era, and indeed long before. Non-treponemal tests do not detect the larger pool of persons with latent syphilis, the immunological consequences of which have not been systematically investigated in the context of HIV infection and progression to AIDS. Recent efforts to confirm the prevalence of syphilis in high-risk patients by reverse sequence screening, i.e. using a treponemal test first, as the screening test, have revealed untreated syphilis at higher rates than expected. Further testing using PCR discovered even more previously undetected cases. We suggest that latent syphilis is a chronic active immunological condition that drives the AIDS process and cannot be managed with the older Wassermann-based algorithm, and that non-treponemal tests have failed to associate syphilis with immune suppression since this screening concept was developed in 1906. In light of the overwhelming association between a past history of syphilis and HIV seroconversion, more sensitive tools, including recombinant antigen-based immunological tests and direct detection (PCR) technology, are needed to adequately assess the role of latent syphilis in persons with HIV/AIDS. Repeating older syphilis reinoculation studies may help establish a successful animal model for AIDS, and resolve many paradoxes in HIV science.

  9. Emerging Therapeutic Strategies and Future Challenges in Clinical Periodontics.

    Shin, Daniel; Hamada, Yusuke; John, Vanchit

    2016-01-01

    Currently, the protocol for treating periodontitis follows a standardized and straightforward algorithm: 1) review and reinforce oral hygiene; 2) perform scaling and root planing; 3) proceed to periodontal surgery if the disease process has not been arrested; then 4) enroll the patient in a customized periodontal maintenance recall program to maintain the health of the reduced periodontium. Multiple longitudinal studies have demonstrated that the aforementioned treatment regimen can arrest the progression of periodontitis and can increase the likelihood of tooth retention and periodontal stability.

  10. Primary intestinal lymphangiectasia in adults - diagnostic and therapeutic challenge

    Jocić Tatiana

    2018-01-01

    Full Text Available Introduction. Primary intestinal lymphangiectasia is a rare disorder, characterized by abnormal dilation of intestinal lymphatic vessels and extensive enteric loss of lymph rich in plasma proteins, lymphocytes and chylomicrons. The main characteristics of the disease are hypoalbuminemia, hypogammaglobulinemia, lymphocytopenia, and more rarely, the deficit of liposoluble vitamins and anemia. Except for primary, there are secondary lymphangiectasia, associated with celiac disease, malignant, infective and inflammatory diseases of the small intestine, fibrosis, liver and cardiovascular diseases. Case report. A male, 33 years of age, presented for his medical examination suffering from diarrhea and edema. The diagnosis was established upon the histological examination of a small intestine biopsy during double balloon enteroscopy, which revealed changes only in one segment of the intestine examined. Such a finding was later confirmed by the video endoscopy capsule. Conclusion. The diagnosis of intestinal lymphangiectasia is usually established before the age of 3, but it can also be diagnosed in adults. The diagnosis is based on the histological analysis of the intestinal mucosa biopsy, obtained by endoscopic procedures. The diagnosis of primary intestinal lymphangiectasia is also made upon the exclusion of secondary causes.

  11. Type V hypertriglyceridemia in children, a therapeutic challenge in pediatrics

    Mărginean, Cristina Oana; Meliţ, Lorena Elena; Dobreanu, Minodora; Mărginean, Maria Oana

    2017-01-01

    Abstract Rationale: Hypertriglyceridemia is defined as a level of triglycerides above 150 mg/dL. The complex causes and classification of hypertriglyceridemia lead to difficulties in the diagnosis and management of this condition. Patient concerns: We present the case of a 15 years and 6 months old female teenager, admitted in our clinic for the following complaints: severe abdominal pain predominantly in the lateral left quadrant, nausea, vomiting, and the lack of stools for 2 days. The clinical exam showed: impaired general status, painful abdomen at superficial and deep palpation in the left and upper abdominal quadrants, the absence of stools for 2 days. Diagnoses: The laboratory parameters revealed leukocytosis with neutrophilia, thrombocytopenia, high level of serum amylase and triglycerides, and increased inflammatory biomarkers. The imagistic investigations showed ascites and paralytic ileus. Interventions: The management was burdened by the side-effects of hypolipidemic drugs impairing the liver function and leading to rhabdomyolysis, but eventually the patient's outcome was good. Outcomes: Type V hyperlipoproteinemia is a rare condition accounting for approximately 5% of the cases. The risk for acute pancreatitis is well-known to be associated with hypertriglyceridemia, even though in rare cases. Lessons: The prognosis of hypertriglyceridemia is pediatrics is burdened not only by the long-term risk factors associated to the diseases itself, but also by the negative effects of long-term hypolipidemic treatment. PMID:29390422

  12. Therapeutic effects of glutamic acid in piglets challenged with deoxynivalenol.

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Tan, Bie; Liu, Gang; Li, Lili; Nyachoti, Charles Martin; Xiong, Xia; Wu, Guoyao

    2014-01-01

    The mycotoxin deoxynivalenol (DON), one of the most common food contaminants, primarily targets the gastrointestinal tract to affect animal and human health. This study was conducted to examine the protective function of glutamic acid on intestinal injury and oxidative stress caused by DON in piglets. Twenty-eight piglets were assigned randomly into 4 dietary treatments (7 pigs/treatment): 1) uncontaminated control diet (NC), 2) NC+DON at 4 mg/kg (DON), 3) NC+2% glutamic acid (GLU), and 4) NC+2% glutamic acid + DON at 4 mg/kg (DG). At day 15, 30 and 37, blood samples were collected to determine serum concentrations of CAT (catalase), T-AOC (total antioxidant capacity), H2O2 (hydrogen peroxide), NO (nitric oxide), MDA (maleic dialdehyde), DAO (diamine oxidase) and D-lactate. Intestinal morphology, and the activation of Akt/mTOR/4EBP1 signal pathway, as well as the concentrations of H2O2, MDA, and DAO in kidney, liver and small intestine, were analyzed at day 37. Results showed that DON significantly (Pglutamic acid supplementation according to the change of oxidative parameters in blood and tissues. Meanwhile, DON caused obvious intestinal injury from microscopic observations and permeability indicators, which was alleviated by glutamic acid supplementation. Moreover, the inhibition of DON on Akt/mTOR/4EBP1 signal pathway was reduced by glutamic acid supplementation. Collectively, these data suggest that glutamic acid may be a useful nutritional regulator for DON-induced damage manifested as oxidative stress, intestinal injury and signaling inhibition.

  13. Background and treatment of metabolic syndrome: a therapeutic challenge

    van Zwieten, Pieter A.; Mancia, Giuseppe

    2006-01-01

    Metabolic syndrome is characterized by a clustering of cardiovascular and metabolic risk factors. This syndrome is now widely recognized as a distinct pathologic entity. It is receiving a great deal of attention in the medical literature and also in the lay press. People with metabolic syndrome have

  14. ACTH-secreting bronchial carcinoid: a diagnostic and therapeutic challenge.

    McDermott, J H

    2008-09-01

    We describe a case of Cushing\\'s syndrome due to ectopic ACTH secretion, where the only potential source on conventional imaging was a tiny benign-appearing lung nodule, which failed to take up radiolabelled octreotide.

  15. Challenges of Huntington's disease and quest for therapeutic biomarkers

    Kotrčová, Eva; Jarkovská, Karla; Valeková, Ivona; Žižková, Martina; Motlík, Jan; Gadher, S. J.; Kovářová, Hana

    2015-01-01

    Roč. 9, 1-2 (2015), s. 147-158 ISSN 1862-8346 R&D Projects: GA MŠk ED2.1.00/03.0124; GA TA ČR(CZ) TA01011466 Institutional support: RVO:67985904 Keywords : HD biomarkers * Huntington´s disease * Huntingtin neurotoxicity * Huntingtin pathogenesis Subject RIV: FH - Neurology Impact factor: 2.959, year: 2015

  16. Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

    Kahaly, George J; Grebe, Stefan K G; Lupo, Mark A; McDonald, Nicole; Sipos, Jennifer A

    2011-06-01

    Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Molecular, Phenotypic Aspects and Therapeutic Horizons of Rare Genetic Bone Disorders

    Taha Faruqi

    2014-01-01

    Full Text Available A rare disease afflicts less than 200,000 individuals, according to the National Organization for Rare Diseases (NORD of the United States. Over 6,000 rare disorders affect approximately 1 in 10 Americans. Rare genetic bone disorders remain the major causes of disability in US patients. These rare bone disorders also represent a therapeutic challenge for clinicians, due to lack of understanding of underlying mechanisms. This systematic review explored current literature on therapeutic directions for the following rare genetic bone disorders: fibrous dysplasia, Gorham-Stout syndrome, fibrodysplasia ossificans progressiva, melorheostosis, multiple hereditary exostosis, osteogenesis imperfecta, craniometaphyseal dysplasia, achondroplasia, and hypophosphatasia. The disease mechanisms of Gorham-Stout disease, melorheostosis, and multiple hereditary exostosis are not fully elucidated. Inhibitors of the ACVR1/ALK2 pathway may serve as possible therapeutic intervention for FOP. The use of bisphosphonates and IL-6 inhibitors has been explored to be useful in the treatment of fibrous dysplasia, but more research is warranted. Cell therapy, bisphosphonate polytherapy, and human growth hormone may avert the pathology in osteogenesis imperfecta, but further studies are needed. There are still no current effective treatments for these bone disorders; however, significant promising advances in therapeutic modalities were developed that will limit patient suffering and treat their skeletal disabilities.

  18. Evolving paradigms in clinical pharmacology and therapeutics for the treatment of Duchenne muscular dystrophy.

    Huard, J; Mu, X; Lu, A

    2016-08-01

    Progressive muscle weakness and degeneration due to the lack of dystrophin eventually leads to the loss of independent ambulation by the middle of the patient's second decade, and a fatal outcome due to cardiac or respiratory failure by the third decade. More specifically, loss of sarcolemmal dystrophin and the dystrophin-associated glycoprotein (DAG) complex promotes muscle fiber damage during muscle contraction. This process results in an efflux of creatine kinase (CK), an influx of calcium ions, and the recruitment of T cells, macrophages, and mast cells to the damaged muscle, causing progressive myofiber necrosis. For the last 20 years, the major goal in the development of therapeutic approaches to alleviate muscle weakness in DMD has been centered on the restoration of dystrophin or proteins that are analogous to dystrophin, such as utrophin, through a variety of modalities including cell therapy, gene therapy, gene correction, and the highly promising techniques utilizing CRISPR/Cas9 technology. Despite the development of new therapeutic options, there still exist numerous challenges that we must face with regard to these new strategies and, consequently, we still do not have any feasible options available to ultimately slow the progression of this devastating disease. The purpose of this article is to highlight the current knowledge and advancements in the evolving paradigms in clinical pharmacology and therapeutics for this devastating musculoskeletal disease. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  19. Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder.

    Zheng, Xiao; Zhang, Xueli; Wang, Guangji; Hao, Haiping

    2015-05-01

    The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhile, the identification of a host of targets outside the brain opens the way to treat MDD by targeting systemic signals. We examine these emerging findings and consider the implications for current thinking regarding MDD pathogenesis and treatment. We highlight the opportunities and challenges of a periphery-targeting strategy and propose its incorporation into a holistic approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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

  1. On Informatics Diagnostics and Informatics Therapeutics - Good Medical Informatics Research Is Needed Here.

    Haux, Reinhold

    2017-01-01

    In the era of digitization some new procedures play an increasing role for diagnosis as well as for therapy: informatics diagnostics and informatics therapeutics. Challenges for such procedures are described. It is discussed, when research on such diagnostics and therapeutics can be regarded as good research. Examples are mentioned for informatics diagnostics and informatics therapeutics, which are based on health-enabling technologies.

  2. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  3. Breast Cancer in Low- and Middle-Income Countries: An Emerging and Challenging Epidemic

    Arafat Tfayli

    2010-01-01

    Full Text Available Breast cancer is a major health care problem that affects more than one million women yearly. While it is traditionally thought of as a disease of the industrialized world, around 45% of breast cancer cases and 55% of breast cancer deaths occur in low and middle income countries. Managing breast cancer in low income countries poses a different set of challenges including access to screening, stage at presentation, adequacy of management and availability of therapeutic interventions. In this paper, we will review the challenges faced in the management of breast cancer in low and middle income countries.

  4. 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

  5. Personality, academic majors and performance

    Vedel, Anna; Thomsen, Dorthe Kirkegaard; Larsen, Lars

    2015-01-01

    Personality–performance research typically uses samples of psychology students without questioning their representativeness. The present article reports two studies challenging this practice. Study 1: group differences in the Big Five personality traits were explored between students (N = 1067......) in different academic majors (medicine, psychology, law, economics, political science, science, and arts/humanities), who were tested immediately after university enrolment. Study 2: six and a half years later the students’ academic records were obtained, and predictive validity of the Big Five personality...... traits and their subordinate facets was examined in the various academic majors in relation to Grade Point Average (GPA). Significant group differences in all Big Five personality traits were found between students in different academic majors. Also, variability in predictive validity of the Big Five...

  6. Pharmacogenetics approach to therapeutics.

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care.

  7. Therapeutic nuclear medicine

    Baum, Richard P.

    2014-01-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  8. Therapeutic nuclear medicine

    Baum, Richard P. (ed.) [ENETS Center of Excellence, Bad Berka (Germany). THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging

    2014-07-01

    Discusses all aspects of radionuclide therapy, including basic principles, newly available treatments, regulatory requirements, and future trends. Provides the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Explains the role of the therapeutic nuclear physician in effectively coordinating a diverse multidisciplinary team. Written by leading experts. The recent revolution in molecular biology offers exciting new opportunities for targeted radionuclide therapy. The selective irradiation of tumor cells through molecular biological mechanisms is now permitting the radiopharmaceutical control of tumors that are unresectable and unresponsive to either chemotherapy or conventional radiotherapy. In this up-to-date, comprehensive book, world-renowned experts discuss the basic principles of radionuclide therapy, explore in detail the available treatments, explain the regulatory requirements, and examine likely future developments. The full range of clinical applications is considered, including thyroid cancer, hematological malignancies, brain tumors, liver cancer, bone and joint disease, and neuroendocrine tumors. The combination of theoretical background and practical information will provide the reader with all the knowledge required to administer radionuclide therapy safely and effectively in the individual patient. Careful attention is also paid to the important role of the therapeutic nuclear physician in delivering the effective coordination of a diverse multidisciplinary team that is essential to the safe provision of treatment.

  9. Toxicological perspectives of inhaled therapeutics and nanoparticles.

    Hayes, Amanda J; Bakand, Shahnaz

    2014-07-01

    The human respiratory system is an important route for the entry of inhaled therapeutics into the body to treat diseases. Inhaled materials may consist of gases, vapours, aerosols and particulates. In all cases, assessing the toxicological effect of inhaled therapeutics has many challenges. This article provides an overview of in vivo and in vitro models for testing the toxicity of inhaled therapeutics and nanoparticles implemented in drug delivery. Traditionally, inhalation toxicity has been performed on test animals to identify the median lethal concentration of airborne materials. Later maximum tolerable concentration denoted by LC0 has been introduced as a more ethically acceptable end point. More recently, in vitro methods have been developed, allowing the direct exposure of airborne material to cultured human target cells on permeable porous membranes at the air-liquid interface. Modifications of current inhalation therapies, new pulmonary medications for respiratory diseases and implementation of the respiratory tract for systemic drug delivery are providing new challenges when conducting well-designed inhalation toxicology studies. In particular, the area of nanoparticles and nanocarriers is of critical toxicological concern. There is a need to develop toxicological test models, which characterise the toxic response and cellular interaction between inhaled particles and the respiratory system.

  10. Challenges in obesity research.

    Palou, Andreu; Bonet, M Luisa

    2013-09-01

    Obesity is the main nutritional problem and one of the most important health problems in developed societies. Central to the challenge of obesity prevention and management is a thoroughly understanding of its determinants. Multiple socio-cultural, socio-economic, behavioural and biological factors--often interrelated and many of them still unknown or poorly understood--can contribute to the establishment and perpetuation of obese phenotypes. Here, we address current research challenges regarding basic aspects of obesity and emerging science for its control, including brown adipose tissue thermogenesis and browning of white fat as possible therapeutic targets for obesity, the influence of the microbioma, and genetics, epigenetics, nutrigenomics and nutrigenetics of obesity. We also highlight hot topics in relation to food and lifestyle as determinants of obesity, including the brain mechanisms underlying environmental motivation to eat, the biological control of spontaneous physical activity, the possible role of concrete foods and food components, and the importance of early life nutrition and environment. Challenges regarding the connections of obesity with other alterations and pathologies are also briefly addressed, as well as social and economical challenges in relation to healthy food production and lifestyle for the prevention of obesity, and technological challenges in obesity research and management. The objective is to give a panoramic of advances accomplished and still ahead relevant to the different stakeholders engaged in understanding and combating obesity. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  11. Determinants of immunogenic response to protein therapeutics.

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. Copyright © 2012. Published by Elsevier Ltd.. All rights reserved.

  12. Therapeutics of postpartum depression.

    Thomson, Michael; Sharma, Verinder

    2017-05-01

    Postpartum depression is a prevalent disorder affecting many women of reproductive age. Despite increasing public awareness, it is frequently underdiagnosed and undertreated leading to significant maternal morbidity and adverse child outcomes. When identified, postpartum depression is usually treated as major depressive disorder. Many studies have identified the postpartum as a period of high risk for first presentations and relapses of bipolar disorder. Areas covered: This article reviews the acute and prophylactic treatment of postpartum major depressive disorder, bipolar depression and major depressive disorder with mixed features. The safety of antidepressant and mood stabilizing medications in pregnancy and breastfeeding will also be reviewed. Expert commentary: Differentiating postpartum major depressive disorder and postpartum bipolar depression can be difficult given their clinical similarities but accurate identification is vital for initiating proper treatment. Antidepressants are the mainstay of drug treatment for postpartum major depressive disorder, yet randomized controlled trials have shown conflicting results. A paucity of evidence exists for the effectiveness of antidepressant prophylaxis in the prevention of recurrences of major depressive disorder. Mood stabilizing medications reduce the risk of postpartum bipolar depression relapse but no randomized controlled trials have examined their use in the acute or prophylactic treatment of postpartum bipolar depression.

  13. Africa and electricity: To electrify Africa - necessary financial and human investments; The development of hydroelectricity in sub-Saharan Africa; A major challenge: to improve distribution efficiency; Smart grids in Africa?; Rural electrification in Africa; The development of renewable energies in Ethiopia - an example of empowerment of a local structure

    Horvilleur, Jacques; Favennec, Jean-Pierre; Cerdan, Jean-Pierre; Bauley, Jacky; Caumon, Pauline; Guerin, Andre-Jean; Beaussant, Henri; Louis, Frederic; Sall, Ousmane; Ledoux, Thierry; Boye, Henri; Bagayoko, Moussa

    2016-01-01

    This publication proposes a set of six articles which address various aspects related to the issue of Africa electrification. More precisely, the authors propose a general presentation of the present situation and an assessment of necessary financial, organisational, governance and training investments or needs (To electrify Africa: necessary financial and human investment), illustrate these issues in the case of hydroelectricity-rich Republic of Congo, discuss the issue of financing hydroelectricity development in Africa and of the need of operation and maintenance policies to meet needs associated with sustainable installations (The development of hydroelectricity in sub-Saharan Africa), address issues related to distribution through an improvement of existing distribution networks (A major challenge: to improve distribution efficiency) and through a possible development of smart grids (Smart grids in Africa?), comment issues related to rural electrification as a major challenge for these sometimes very poor areas with almost none financial resources, and evoke the possibilities associated with decentralised photovoltaic production (Rural electrification in Africa), and report interventions of an NGO in Ethiopia based on solar installations and actions of empowerment of local structures (The development of renewable energies in Ethiopia - an example of empowerment of a local structure)

  14. Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

    Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

    2016-02-01

    Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

  15. Antibody Engineering and Therapeutics

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  16. Therapeutic and diagnostic nanomaterials

    Devasena T

    2017-01-01

    This brief highlights nanoparticles used in the diagnosis and treatment of prominent diseases and toxic conditions. Ecofriendly methods which are ideal for the synthesis of medicinally valued nanoparticles are explained and the characteristic features of these particles projected. The role of these particles in the therapeutic field, and the induced biological changes in some diseases are discussed. The main focus is on inflammation, oxidative stress and cellular membrane integrity alterations. The effect of nanoparticles on these changes produced by various agents are highlighted using in vitro and in vivo models. The mechanism of nanoparticles in ameliorating the biological changes is supported by relevant images and data. Finally, the brief demonstrates recent developments on the use of nanoparticles in diagnosis or sensing of some biological materials and biologically hazardous environmental materials.

  17. [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.

  18. Challenges in sexual medicine

    Cellek, Selim; Giraldi, Annamaria

    2012-01-01

    The sexual medicine field has been in mode of revolution until recently. Like all other fields of biomedical research, the economic situation around the world has had a negative impact on the field's momentum-research funding bodies, regulatory bodies and pharmaceutical companies seem to have...... placed sexual medicine in their low-priority list. But this is not the only challenge the field is facing. The successful development of phosphodiesterase type 5 (PDE5) inhibitors for treatment of erectile dysfunction (ED) means that research in this area seems to have slowed. However, there remain...... several unmet medical needs within sexual medicine such as premature ejaculation, severe ED and hypoactive sexual desire disorder, which await novel therapeutic approaches. Despite these challenges, research into finding and developing such therapies is likely to continue in the sexual medicine field...

  19. Climatic changes: a major challenge; Changement climatique: un defi majeur

    NONE

    2001-07-01

    To sensitize the public opinion and change the energy consumption habits, the ADEME (french Agency for the environment and the energy mastership) published a document on the climatic change problem and its consequences. A state of the art of the situation, the international agreements and solutions are provided. (A.L.B.)

  20. Major challenges of beekeeping in Chiron Worde of West Harangue ...

    According to respondents the main sources of the foundation colony were catching swarm, gifting by family members and purchase of colonies. Respondents indicated that the three sources were unreliable because of different factors. The respondents kept their colonies both in and out door, but with no internal hive ...

  1. Major challenges in engineering and its role in society

    José Ismael Peña-Reyes

    2011-02-01

    Full Text Available Engineering has a long historical tradition; it began as a discipline in the sixteenth century and reached maturity during the twentieth century. However, the twenty-first century’s features strongly differentiate it from earlier times; when referring to this period, we speak of globalisation, knowledge society and national innovation systems. This is a period marked by contradictions. Technological developments and social and political changes have improved human beings’ quality of life. New technologies have provided the context for its opening decade: nanotechnology, microelectronics and nanoelectronics, photonics, materials science, biotechnology, information and communications technology, logistics, medical engineering and renewable and clean energy. Technologies feed each other and off each other, offering endless possibilities for development. This is a time where the doors of political democratisation, art and culture have opened; however, it is also a world facing political, financial and environmental crisis. Colombia, particularly, is a country encountering problems regarding its competitiveness, having crippling levels of corruption and impunity, problems related to education, health and infrastructure. Colombia needs more engineers who can contribute towards resolving complex problems. Such engineers must have had excellent technical and humanistic training; they must be creative, able to work as a team, have become leaders who can listen and communicate and help develop a world to ensure that humans and other living species on earth can flourish with a uniform, durable level regarding their quality of life. Work must thus be done on critical engineering education and the present work presents some characteristics concerning what these engineers training/education should be.

  2. Food Security In South Asia: Major Challenges And Solutions

    N. V. Galistcheva

    2018-01-01

    Full Text Available The subject of the study is analysis of the state of food security of the South Asian countries at the present time. The methodological basis of the study is such methods as induction and deduction, analysis and synthesis. The systematic approach to the overall study of the South Asian countries’ economy and the state of its food security in particular has become the base of this research. Historical and statistical method were used to solve the main task of the research to reveal the conditions of the region’s agricultural development and food availability and food accessibility in the region as well as to carry out an assessment of the ability of households to obtain nutritious food all year round. The author also used the comparative method to analyze the South Asian countries’ approaches to realization of food policy that has allowed to reveal the specific tools used by certain countries of the region and the common characteristics of all countries of South Asia. While selecting the research topics the author proceeded from the idea that the problem of the state of food security of the South Asian countries has not been studied for the last two decades. The research required to attract and summarize a large amount of statistical data that has been drawn from many sources including official-sites of international organizations and South Asian countries. The author also used Russian and Indian scientific journals and monographs. The article highlights the state of food security in the region in accordance with criteria offered by the FAO. The author examines the situation in the South Asian countries’ agriculture sector, its productivity, the volume of production, food waste as well as the countries’ dependency on food imports. The article also presents some information on food accessibility which is generally considered within the context of household income, food distribution systems and ability of the household to obtain food seasonally, as well as food consumption within the context of dietary energy consumption and dietary protein and fat consumption. The author examines all the seven South Asian countries’ national policies for food security aiming at struggle against undernourishment. The author draws the attention to the fact that despite the slight differences in tools they have common aims and tasks. The key directions of national policies for food security include measures to promote big agro-based industries financed by both private and public sector; increase agricultural productivity; enhance agricultural R&D; managing food security risks and vulnerabilities. The author also notes the steps to aiming the collective food security within the framework of the regional integration group – the SAARC. The article presents statistical data characterizing hunger and undernourishment trends in South Asia.

  3. Major Management Challenges and Program Risks Department of Defense

    1999-01-01

    .... The report also addresses corrective actions that DOD has taken or initiated on these issues- including DOD'S blueprint for a strategy-based, balanced, and affordable defense program as outlined...

  4. Major Sport Venues

    Department of Homeland Security — The Major Public Venues dataset is composed of facilities that host events for the National Association for Stock Car Auto Racing, Indy Racing League, Major League...

  5. Major Depression Among Adults

    ... Depressive Episode Among Adolescents Data Sources Share Major Depression Definitions Major depression is one of the most ... Bethesda, MD 20892-9663 Follow Us Facebook Twitter YouTube Google Plus NIMH Newsletter NIMH RSS Feed NIMH ...

  6. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  7. Hemodynamics and vasopressor support in therapeutic hypothermia after cardiac arrest

    Bro-Jeppesen, John; Kjaergaard, Jesper; Søholm, Helle

    2014-01-01

    AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level of vasopres......AIM: Inducing therapeutic hypothermia (TH) in Out-of-Hospital Cardiac Arrest (OHCA) can be challenging due to its impact on central hemodynamics and vasopressors are frequently used to maintain adequate organ perfusion. The aim of this study was to assess the association between level...

  8. Overcoming challenges

    Full Text Available ... Disease and Stroke HIV and AIDS Mental Health Pain Pregnancy Reproductive Health Sexual Health Sexually Transmitted Infections ... breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch ...

  9. Overcoming challenges

    Full Text Available ... menu It's Only Natural Planning ahead Breastfeeding and baby basics Making breastfeeding work for you Addressing breastfeeding ... in the African-American community Incredible facts about babies, breastmilk, and breastfeeding Overcoming challenges Common questions about ...

  10. Overcoming challenges

    Full Text Available ... facts about babies, breastmilk, and breastfeeding Overcoming challenges Common questions about breastfeeding and pain Breastfeeding checklist: How to get a good latch Finding support It takes a village: Building ...

  11. Cognitive Challenges

    ... Alliance Our Story Our Vision Our Team Our Leadership Our Results Our Corporate Policies FAQs Careers Contact Us Media Store Privacy Policy Sitemap Learn Engage Donate About TSC Cognitive Challenges Approximately 45% to 60% of individuals with TSC ...

  12. Overcoming challenges

    Full Text Available ... breastfeeding means to them. Subscribe To receive Breastfeeding email updates Enter email Submit Overcoming challenges Breastfeeding has a long list ... breastfeeding means to them. Subscribe To receive Breastfeeding email updates Enter email Submit All material contained on ...

  13. Overcoming challenges

    Full Text Available ... into your life Breastfeeding in daily life: At home and in public Laws that support breastfeeding 10 ... and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural ...

  14. Therapeutic Exercise and Hypertension

    Nekky Umera

    patients but may not reduce the BP of normotensive individual. Exercise function ... and mortality in all age groups; it also creates major social, personal and financial ... drug therapy by as symptomatic hypertensive and high cost of drugs particularly in a ..... Events in hypertensive patients randomized to doxagosin versus.

  15. [Organization of occupational therapeutic service, dynamics and structure of occupational morbidity in Krasnoyarsk area].

    Tereshchenko, Iu A; Zakharinskaia, O N

    2010-01-01

    The authors present organizational and functional structure of occupational therapeutic service in Krasnoyarsk area, major functional divisions of the territorial occupational therapeutic center and their activities. The article covers analysis of changes in levels and structure of occupational morbidity, defines main ways to optimize occupational therapeutic service for the territorial workers.

  16. [Nuclear transfer and therapeutic cloning].

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  17. 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)

  18. Rethinking Therapeutic Misconception in Biobanking

    Tupasela, Aaro; Snell, Karoliina; Cañada, Jose

    2017-01-01

    Some authors have noted that in biobank research participants may be guided by what is called therapeutic misconception, whereby participants attribute therapeutic intent to research procedures.This article argues that the notion of therapeutic misconception is increasingly less justified when...... underpinnings for the need to separate research and treatment, and thus the notion of therapeutic misconception in the fi rst place. We call this tension between research and treatment ambivalent research advancement to highlight the difficulties that various actors have in managing such shifts within...

  19. 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

  20. Antimicrobial Peptides: A Promising Therapeutic Strategy in Tackling Antimicrobial Resistance.

    Nuti, Ramya; Goud, Nerella S; Saraswati, A Prasanth; Alvala, Ravi; Alvala, Mallika

    2017-01-01

    Antimicrobial resistance (AMR) has posed a serious threat to global public health and it requires immediate action, preferably long term. Current drug therapies have failed to curb this menace due to the ability of microbes to circumvent the mechanisms through which the drugs act. From the drug discovery point of view, the majority of drugs currently employed for antimicrobial therapy are small molecules. Recent trends reveal a surge in the use of peptides as drug candidates as they offer remarkable advantages over small molecules. Newer synthetic strategies like organometalic complexes, Peptide-polymer conjugates, solid phase, liquid phase and recombinant DNA technology encouraging the use of peptides as therapeutic agents with a host of chemical functions, and tailored for specific applications. In the last decade, many peptide based drugs have been successfully approved by the Food and Drug Administration (FDA). This success can be attributed to their high specificity, selectivity and efficacy, high penetrability into the tissues, less immunogenicity and less tissue accumulation. Considering the enormity of AMR, the use of Antimicrobial Peptides (AMPs) can be a viable alternative to current therapeutics strategies. AMPs are naturally abundant allowing synthetic chemists to develop semi-synthetics peptide molecules. AMPs have a broad spectrum of activity towards microbes and they possess the ability to bypass the resistance induction mechanisms of microbes. The present review focuses on the potential applications of AMPs against various microbial disorders and their future prospects. Several resistance mechanisms and their strategies have also been discussed to highlight the importance in the current scenario. Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR. Copyright© Bentham Science Publishers; For any queries

  1. Technology in Parkinson disease: Challenges and Opportunities

    Espay, Alberto J.; Bonato, Paolo; Nahab, Fatta; Maetzler, Walter; Dean, John M.; Klucken, Jochen; Eskofier, Bjoern M.; Merola, Aristide; Horak, Fay; Lang, Anthony E.; Reilmann, Ralf; Giuffrida, Joe; Nieuwboer, Alice; Horne, Malcolm; Little, Max A.; Litvan, Irene; Simuni, Tanya; Dorsey, E. Ray; Burack, Michelle A.; Kubota, Ken; Kamondi, Anita; Godinho, Catarina; Daneault, Jean-Francois; Mitsi, Georgia; Krinke, Lothar; Hausdorff, Jeffery M.; Bloem, Bastiaan R.; Papapetropoulos, Spyros

    2016-01-01

    The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capturing of more and previously inaccessible phenomena in Parkinson disease (PD). However, more information has not translated into greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include non-compatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (in particular among vulnerable elderly patients), and the gap between the “big data” acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms enabling multi-channel data capture, sensitive to the broad range of motor and non-motor problems that characterize PD, and adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to: 1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones; 2) enhance tailoring of symptomatic therapy; 3) improve subgroup targeting of patients for future testing of disease modifying treatments; and 4) identify objective biomarkers to improve longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the Task Force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and quality of life of individuals with PD. PMID:27125836

  2. Targeting c-Met in Cancer by MicroRNAs: Potential Therapeutic Applications in Hepatocellular Carcinoma.

    Karagonlar, Zeynep F; Korhan, Peyda; Atabey, Neşe

    2015-11-01

    Preclinical Research Cancer is one of the world's deadliest diseases, with very low survival rates and increased occurrence in the future. Successfully developed target-based therapies have significantly changed cancer treatment. However, primary and/or acquired resistance in the tumor is a major challenge in current therapies and novel combinational therapies are required. RNA interference-mediated gene inactivation, alone or in combination with other current therapies, provides novel promising therapeutics that can improve cure rate and overcome resistance mechanisms to conventional therapeutics. Hepatocyte Growth Factor/c-Met signaling is one of the most frequently dysregulated pathways in human cancers and abnormal c-Met activation is correlated with poor clinical outcomes and drug resistance in hepatocellular carcinoma (HCC). In recent years, a growing number of studies have identified several inhibitors and microRNAs (miRNAs), specifically targeting c-Met in various cancers, including HCC. In this review, we discuss current knowledge regarding miRNAs, focusing on their involvement in cancer and their potential as research tools and therapeutics. Then, we focus on the potential use of c-Met targeting miRNAs for suppressing aberrant c-Met signaling in HCC treatment. © 2015 Wiley Periodicals, Inc.

  3. Therapeutic management of acute pulmonary embolism.

    Tromeur, Cécile; Van Der Pol, Liselotte M; Couturaud, Francis; Klok, Frederikus A; Huisman, Menno V

    2017-08-01

    Acute pulmonary embolism (PE) is a potentially fatal manifestation of venous thromboembolism. Prompt anticoagulant treatment is crucial for PE patients, which can decrease morbidity and mortality. Risk assessment is the cornerstone of the therapeutic management of PE. It guides physicians to the most appropriate treatment and selects patients for early discharge or home treatment. Areas covered: Here, we review the current treatments of acute PE according to contemporary risk stratification strategies, highlighting each step of PE therapeutic management. Expert commentary: Currently, direct oral anticoagulants (DOACs) represent the first-line therapy of patients presenting with non-high risk PE with a better risk-benefit ratios than vitamin K antagonists (VKAs) due to lower risk of major bleeding. Only high-risk patients with PE who present in shock should be treated with systematic thrombolysis, while surgical thrombectomy or catheter direct thrombolysis (CDT) should only be considered when thrombolysis is contraindicated because of too high bleeding risk.

  4. Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis

    Christoph Niemietz

    2015-09-01

    Full Text Available The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR, expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP. Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO and small interfering RNA (siRNA designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

  5. Genome Engineering for Personalized Arthritis Therapeutics.

    Adkar, Shaunak S; Brunger, Jonathan M; Willard, Vincent P; Wu, Chia-Lung; Gersbach, Charles A; Guilak, Farshid

    2017-10-01

    Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. 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

  8. Therapeutical aspect of trichomoniasis

    Vukićević Jelica

    2003-01-01

    Full Text Available Trichomoniasis is frequent, parasitic and sexually transmitted infection of genitourinary tract. It is treated by metronidazole (5-nitroimidazole according to protocol recommended by Center for Disease Control (CDC formerly called: Communicable Disease Center [19]. The resistance of Trichomonas vaginalis (TV strains to metronidazole (MND was described in USA in 1960, and later on in many European countries [8, 9, 10, 11, 12, 13]. In these cases, due to persistent trichomonas infection, it is necessary to repeat MND treatment with moderate modification of dose and/or length of its application. Nevertheless, oncogenic and toxic effects of MND have to be taken into consideration. OBJECT The aim of this study was to investigate and analyze the incidence of TV in STD and lower susceptibility of certain TV strains to MND were analyzed. MATERIAL AND METHODS In three-year period (1999-2001 612 patients (244 females and 368 males suspected of STD were examined clinically and microbiologically at the Institute of Dermatovenereology in Belgrade. The patients detected for TV were treated according to CDC protocol. The affected were considered cured if there was no manifest clinical infection, and no TV verified by microbiological test. Results TV was isolated in 216 patients (35.29 % of all subjects. Trichomonas infection was found in 90 (36.88 % out of 244 tested females and in 126 (32.34 % of 368 males. Clinically manifested infection, with extensive urethral and vaginal secretion, was recorded in 161 patients, while the asymptomatic form was found in 55 subjects. This result indicates the predominance of manifested trichomonas infections (75.54 % of cases. The difference of distribution of clinical forms of trichomoniasis, in relation to sex, was not statistically significant (c2=0.854; p>0.05. The patients with verified trichomonas infection were treated by metronidazole according to CDC protocol. The recommended therapeutical scheme consisted of three

  9. Report on the Technical Meeting on Therapeutic Radiopharmaceuticals

    2009-01-01

    The purpose of the TM was to provide an experts' platform to facilitate exploring the current status and future directions on therapeutic radiopharmaceuticals. The invited talks and presentations in the TM were in the following topics: - Radionuclide Production; - Production and availability of alpha emitters and their radiopharmaceuticals; - Therapeutic radiopharmaceutical chemistry; - Targets and biological evaluation; - Medical physics and dosimetry; - Clinical applications including radioimmunotherapy and clinical needs; - Peptide receptor mediated therapy Panel discussions: - Radionuclide therapy using alpha emitters; - Regulatory challenges with therapeutic radiopharmaceuticals; - International activities in radionuclide therapy. he technical meeting generated a large interest among scientists and physicians working in the field of targeted therapy using radiopharmaceuticals. Participants from both developed and developing MS reported on recent developments on the research work and clinical studies going on in the field and provided their views on the future developments in this field. The unexpected high number of participants and the high number of presentations with exceptional quality underlines the great interest of scientists and professionals in therapeutic applications using radiolabelled drugs / biomolecules. The intensive discussions including panels specified the challenges in the future on developing novel agents and to finally use them for the benefit of patients. The IAEA can play as vital role in streamlining developments and to provide tools to overcome scientific, professional and regulatory challenges in the field of therapeutic radiopharmaceuticals

  10. Report on the Technical Meeting on Therapeutic Radiopharmaceuticals

    NONE

    2009-07-01

    The purpose of the TM was to provide an experts' platform to facilitate exploring the current status and future directions on therapeutic radiopharmaceuticals. The invited talks and presentations in the TM were in the following topics: - Radionuclide Production; - Production and availability of alpha emitters and their radiopharmaceuticals; - Therapeutic radiopharmaceutical chemistry; - Targets and biological evaluation; - Medical physics and dosimetry; - Clinical applications including radioimmunotherapy and clinical needs; - Peptide receptor mediated therapy Panel discussions: - Radionuclide therapy using alpha emitters; - Regulatory challenges with therapeutic radiopharmaceuticals; - International activities in radionuclide therapy. he technical meeting generated a large interest among scientists and physicians working in the field of targeted therapy using radiopharmaceuticals. Participants from both developed and developing MS reported on recent developments on the research work and clinical studies going on in the field and provided their views on the future developments in this field. The unexpected high number of participants and the high number of presentations with exceptional quality underlines the great interest of scientists and professionals in therapeutic applications using radiolabelled drugs / biomolecules. The intensive discussions including panels specified the challenges in the future on developing novel agents and to finally use them for the benefit of patients. The IAEA can play as vital role in streamlining developments and to provide tools to overcome scientific, professional and regulatory challenges in the field of therapeutic radiopharmaceuticals

  11. Prospects after Major Trauma

    Holtslag, H.R.

    2007-01-01

    Introduction. After patients survived major trauma, their prospects, in terms of the consequences for functioning, are uncertain, which may impact severely on patient, family and society. The studies in this thesis describes the long-term outcomes of severe injured patients after major trauma. In

  12. Therapeutic Inertia and Treatment Intensification.

    Josiah Willock, Robina; Miller, Joseph B; Mohyi, Michelle; Abuzaanona, Ahmed; Muminovic, Meri; Levy, Phillip D

    2018-01-29

    This review aims to emphasize how therapeutic inertia, the failure of clinicians to intensify treatment when blood pressure rises or remains above therapeutic goals, contributes to suboptimal blood pressure control in hypertensive populations. Studies reveal that the therapeutic inertia is quite common and contributes to suboptimal blood pressure control. Quality improvement programs and standardized approaches to support antihypertensive treatment intensification are ways to combat therapeutic inertia. Furthermore, programs that utilize non-physician medical professionals such as pharmacists and nurses demonstrate promise in mitigating the effects of this important problem. Therapeutic inertia impedes antihypertensive management and requires a broad effort to reduce its effects. There is an ongoing need for renewed focus and research in this area to improve hypertension control.

  13. Environmental challenge

    Conable, B.; Warford, J.; Partow, Z.; Lutz, E.; Munasinghe, M.

    1991-09-01

    The contents include the following: Development and the Environment: A Global Balance; Evolution of the World Bank's Environmental Policy; Accounting for the Environment; Public Policy and the Environment; Managing Drylands; Environmental Action Plans in Africa; Agroforestry in Sub-Saharan Africa; Irrigation and the Environmental Challenge; Curbing Pollution in Developing Countries; Global Warming and the Developing World; and The Global Environment Facility

  14. Challenging Identities

    depends on the conceptual or ideological constellation in which it takes part. This volume on one hand demonstrates the role of notions of identity in a variety of European contexts, and on the other hand highlights how there may be reasons to challenge the use of the term and corresponding social...

  15. Overcoming challenges

    Full Text Available ... Contact Us Blog Popular topics Vision and mission Leadership Programs and activities In your community Funding opportunities Internships and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural Planning ahead Addressing breastfeeding myths ...

  16. Overcoming challenges

    Full Text Available ... we are What we do Programs and activities Work with us Contact Us Blog Popular topics Vision and mission Leadership Programs and activities In your community Funding opportunities Internships and jobs View all pages in this section Home It's Only Natural Overcoming challenges It's Only Natural ...

  17. Therapeutic value of adjustment practices and copining with grand ...

    Menopause is one of the stages of human development and is full of encounters, tasks and challenges; it could be different from the encounter of the preceding stages of life. This study examined the therapeutic value of adjustment practices toward menopause and evaluates the effectiveness of health education on coping ...

  18. Cooling the crisis: Therapeutic hypothermia after sickle cardiac arrest

    Metske, Hennie A.; Postema, Pieter G.; Biemond, Bart J.; Bouman, Catherine S. C.

    2012-01-01

    Objective: The management of patients with sickle-cell disease and cardiac arrest presents special challenges. Mild therapeutic hypothermia may improve survival and neurologic outcome after cardiac arrest, however, it may also precipitate sickling in patients with sickle-cell disease. Rigorous

  19. Molecular Strategies for Targeting Antioxidants to Mitochondria: Therapeutic Implications

    2015-01-01

    Abstract Mitochondrial function and specifically its implication in cellular redox/oxidative balance is fundamental in controlling the life and death of cells, and has been implicated in a wide range of human pathologies. In this context, mitochondrial therapeutics, particularly those involving mitochondria-targeted antioxidants, have attracted increasing interest as potentially effective therapies for several human diseases. For the past 10 years, great progress has been made in the development and functional testing of molecules that specifically target mitochondria, and there has been special focus on compounds with antioxidant properties. In this review, we will discuss several such strategies, including molecules conjugated with lipophilic cations (e.g., triphenylphosphonium) or rhodamine, conjugates of plant alkaloids, amino-acid- and peptide-based compounds, and liposomes. This area has several major challenges that need to be confronted. Apart from antioxidants and other redox active molecules, current research aims at developing compounds that are capable of modulating other mitochondria-controlled processes, such as apoptosis and autophagy. Multiple chemically different molecular strategies have been developed as delivery tools that offer broad opportunities for mitochondrial manipulation. Additional studies, and particularly in vivo approaches under physiologically relevant conditions, are necessary to confirm the clinical usefulness of these molecules. Antioxid. Redox Signal. 22, 686–729. PMID:25546574

  20. 188W/188Re Generator System and Its Therapeutic Applications

    A. Boschi

    2014-01-01

    Full Text Available The 188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV, which can efficiently be used for imaging and calculations of radiation dose. 188Re may be conveniently produced by 188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent 188W radionuclide indeed have been one of the major issues about the use of 188Re in nuclear medicine. Since the specific activity of 188W used in the generator is relatively low (<185 GBq/g, the eluted Re188O4- can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically useful Re188O4- solutions. This review summarizes the technologies developed for the preparation of 188W/188Re generators, postelution concentration of the 188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of 188Re radiopharmaceuticals.

  1. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

    2011-03-31

    Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

  2. Combined analgesics in (headache pain therapy: shotgun approach or precise multi-target therapeutics?

    Fiebich Bernd L

    2011-03-01

    Full Text Available Abstract Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix" are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA, paracetamol (acetaminophen and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden

  3. Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

    2011-01-01

    Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

  4. Medication adherence in schizophrenia: The role of insight, therapeutic alliance and perceived trauma associated with psychiatric care.

    Tessier, Arnaud; Boyer, Laurent; Husky, Mathilde; Baylé, Franck; Llorca, Pierre-Michel; Misdrahi, David

    2017-11-01

    Medication non adherence in schizophrenia is a major cause of relapse and hospitalization and remains for clinicians an important challenge. This study investigates the associations between insight, therapeutic alliance, perceived trauma related to psychiatric treatment and medication adherence in patients with schizophrenia. In this multicenter study, 72 patients were assessed regarding symptomatology, self-reported adherence with medication, insight, medication side-effects, therapeutic alliance and perceived trauma related to psychiatric treatment. Structural Equation Modeling (SEM) was used to test predicted paths among these variables. The data fit a model in which medication adherence was directly predicted by insight, therapeutic alliance and perceived trauma related to psychiatric treatment. Perceived trauma moderates the role of insight on medication adherence. The final model showed good fit, based on four reliable indices. Greater adherence was correlated with higher insight, higher therapeutic alliance and lower perceived trauma. These three variables appear to be important determinants of patient's medication adherence. Medication adherence could be enhanced by reducing perceived trauma and by increasing insight. The need for mental health providers to acknowledge patients' potentially traumatic experience with psychiatric treatment and the need to encourage greater involvement in care are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The challenge of global warming

    Bryner, G.C.

    1992-01-01

    The chapter outlines the science of global warming, the likely consequences of global warming and some of the major challenges in dealing with global climate change. Some of the major international organisations concerned with environmental issues are listed. International agreements might be used to limit emissions of greenhouse gases. 32 refs., 2 tabs

  6. Human Factor in Therapeutic Relationship

    Ramazan Akdogan

    2011-03-01

    Full Text Available herapeutic relationship is a professional relationship that has been structured based on theoretical props. This relationship is a complicated, wide and unique relationship which develops between two people, where both sides' personality and attitudes inevitably interfere. Therapist-client relationship experienced through transference and counter transference, especially in psychodynamic approaches, is accepted as the main aspect of therapeutic process. However, the approaches without dynamic/deterministic tendency also take therapist-client relationship into account seriously and stress uniqueness of interaction between two people. Being a person and a human naturally sometimes may negatively influence the relationship between the therapist and client and result in a relationship going out of the theoretical frame at times. As effective components of a therapeutic process, the factors that stem from being human include the unique personalities of the therapist and the client, their values and their attitude either made consciously or subconsciously. Literature has shown that the human-related factors are too effective to be denied in therapeutic relationship process. Ethical and theoretical knowledge can be inefficient to prevent the negative effects of these factors in therapeutic process at which point a deep insight and supervision would have a critical role in continuing an acceptable therapeutic relationship. This review is focused on the reflection of some therapeutic factors resulting from being human and development of counter transference onto the therapeutic process.

  7. NEW DATA ON THE CLINICAL AND THERAPEUTIC MANAGEMENT OF OCCLUSAL CARIES (III

    Sorin ANDRIAN

    2017-06-01

    Full Text Available In the control of occlusal caries, the major challenges are related not only to the detection of non-cavitary lesions, but also to the establishment of the treatment strategies to be subsequently applied. Considering the objective of each treatment, that of helping the patient, it is essential to control the progression of carious lesions by means of nonsurgical, preventive/therapeutical methods, whenever necessary. The new strategies applied in caries management are based on the evaluation and predictibility of possible risks, a major aspect in the daily taking of therapeutical decisions. The management plan should include: (I patient’s level of risk, (II patient’s activity level and (III severity of the lesion. Various strategies for a most efficient management of patient’s problems, as well as of the carious lesions, have been elaborated by specialized medical organisms, such as: strategies established within ICDAS, CAMBRA, strategies of the caries management system (SMC and protocols indicated by the system of caries classification according to ADA (American Dental Association. The mission of any new model of caries management is first of all to preserve the dental tissues, and to restore them when only recommended – an idea to guide the decisions of practitioners, starting with the moment of anamnesis, clinical examination and estabishment of diagnosis, until the end of the treatment

  8. Therapeutic activity of a Saccharomyces cerevisiae-based probiotic and inactivated whole yeast on vaginal candidiasis.

    Pericolini, Eva; Gabrielli, Elena; Ballet, Nathalie; Sabbatini, Samuele; Roselletti, Elena; Cayzeele Decherf, Amélie; Pélerin, Fanny; Luciano, Eugenio; Perito, Stefano; Jüsten, Peter; Vecchiarelli, Anna

    2017-01-02

    Vulvovaginal candidiasis is the most prevalent vaginal infection worldwide and Candida albicans is its major agent. Vulvovaginal candidiasis is characterized by disruption of the vaginal microbiota composition, as happens following large spectrum antibiotic usage. Recent studies support the effectiveness of oral and local probiotic treatment for prevention of recurrent vulvovaginal candidiasis. Saccharomyces cerevisiae is a safe yeast used as, or for, the production of ingredients for human nutrition and health. Here, we demonstrate that vaginal administration of probiotic Saccharomyces cerevisiae live yeast (GI) and, in part, inactivated whole yeast Saccharomyces cerevisiae (IY), used as post-challenge therapeutics, was able to positively influence the course of vaginal candidiasis by accelerating the clearance of the fungus. This effect was likely due to multiple interactions of Saccharomyces cerevisiae with Candida albicans. Both live and inactivated yeasts induced coaggregation of Candida and consequently inhibited its adherence to epithelial cells. However, only the probiotic yeast was able to suppress some major virulence factors of Candida albicans such as the ability to switch from yeast to mycelial form and the capacity to express several aspartyl proteases. The effectiveness of live yeast was higher than that of inactivated whole yeast suggesting that the synergy between mechanical effects and biological effects were dominant over purely mechanical effects. The protection of epithelial cells to Candida-induced damage was also observed. Overall, our data show for the first time that Saccharomyces cerevisiae-based ingredients, particularly the living cells, can exert beneficial therapeutic effects on a widespread vaginal mucosal infection.

  9. Major operations and activities

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  10. A major safety overhaul

    2003-01-01

    A redefined policy, a revamped safety course, an environmental project... the TIS (Technical Inspection and Safety) Division has begun a major safety overhaul. Its new head, Wolfgang Weingarten, explains to the Bulletin why and how this is happening.

  11. Allegheny County Major Rivers

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — This dataset contains locations of major rivers that flow through Allegheny County. These shapes have been taken from the Hydrology dataset. The Ohio River,...

  12. Major operations and activities

    Black, D.G.

    1995-01-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development

  13. Mobility Challenges

    Jensen, Ole B.; Lassen, Claus

    2011-01-01

    This article takes point of departure in the challenges to understand the importance of contemporary mobility. The approach advocated is a cross-disciplinary one drawing on sociology, geography, urban planning and design, and cultural studies. As such the perspective is to be seen as a part...... of the so-called ‘mobility turn’ within social science. The perspective is illustrative for the research efforts at the Centre for Mobility and Urban Studies (C-MUS), Aalborg University. The article presents the contours of a theoretical perspective meeting the challenges to research into contemporary urban...... mobilities. In particular the article discusses 1) the physical city, its infrastructures and technological hardware/software, 2) policies and planning strategies for urban mobility and 3) the lived everyday life in the city and the region....

  14. [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.

  15. Frontiers in nano-therapeutics

    Tasnim, Nishat; Sai Krishna, Katla; Kalagara, Sudhakar; Narayan, Mahesh; Noveron, Juan C; Joddar, Binata

    2017-01-01

    This brief highlights recent research advances in the area of nano-therapeutics. Nanotechnology holds immense potential for application in a wide range of biological and engineering applications such as molecular sensors for disease diagnosis, therapeutic agents for the treatment of diseases, a vehicle for delivering therapeutics and imaging agents for theranostic applications, both in-vitro and in-vivo. The brief is grouped into the following sections namely, A) Discrete Nanosystems ; B) Anisotropic Nanoparticles; C) Nano-films/coated/layered and D) Nano-composites.

  16. Therapeutic hypothermia for acute stroke

    Olsen, Tom Skyhøj; Weber, Uno Jakob; Kammersgaard, Lars Peter

    2003-01-01

    Experimental evidence and clinical experience show that hypothermia protects the brain from damage during ischaemia. There is a growing hope that the prevention of fever in stroke will improve outcome and that hypothermia may be a therapeutic option for the treatment of stroke. Body temperature...... obvious therapeutic potential, hypothermia as a form of neuroprotection for stroke has been investigated in only a few very small studies. Therapeutic hypothermia is feasible in acute stroke but owing to serious side-effects--such as hypotension, cardiac arrhythmia, and pneumonia--it is still thought...

  17. Addressing challenges of heterogeneous tumor treatment through bispecific protein-mediated pretargeted drug delivery.

    Yang, Qi; Parker, Christina L; McCallen, Justin D; Lai, Samuel K

    2015-12-28

    Tumors are frequently characterized by genomically and phenotypically distinct cancer cell subpopulations within the same tumor or between tumor lesions, a phenomenon termed tumor heterogeneity. These diverse cancer cell populations pose a major challenge to targeted delivery of diagnostic and/or therapeutic agents, as the conventional approach of conjugating individual ligands to nanoparticles is often unable to facilitate intracellular delivery to the full spectrum of cancer cells present in a given tumor lesion or patient. As a result, many cancers are only partially suppressed, leading to eventual tumor regrowth and/or the development of drug-resistant tumors. Pretargeting (multistep targeting) approaches involving the administration of 1) a cocktail of bispecific proteins that can collectively bind to the entirety of a mixed tumor population followed by 2) nanoparticles containing therapeutic and/or diagnostic agents that can bind to the bispecific proteins accumulated on the surface of target cells offer the potential to overcome many of the challenges associated with drug delivery to heterogeneous tumors. Despite its considerable success in improving the efficacy of radioimmunotherapy, the pretargeting strategy remains underexplored for a majority of nanoparticle therapeutic applications, especially for targeted delivery to heterogeneous tumors. In this review, we will present concepts in tumor heterogeneity, the shortcomings of conventional targeted systems, lessons learned from pretargeted radioimmunotherapy, and important considerations for harnessing the pretargeting strategy to improve nanoparticle delivery to heterogeneous tumors. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Design Considerations in Therapeutic Exergaming

    Doyle, Julie; Kelly, Daniel; Caulfield, B.

    2011-01-01

    In this paper we discuss the importance of feedback in therapeutic exergaming. It is widely believed that exergaming benefits the patient in terms of encouraging adherence and boosting the patient’s confidence of correct execution and feedback is essential in achieving these. However, feedback and in particular visual feedback, may also have potential negative effects on the quality of the exercise. We describe in this paper a prototype single-sensor therapeutic exergame that we have develope...

  19. Evaluation of therapeutic patient education

    D'Ivernois , Jean-François; Gagnayre , Rémi; Assal , Jean-Philippe; Golay , Alain; Libion , France; Deccache , Alain

    2006-01-01

    9 pages; These guidelines mainly focus on the principles of evaluating Therapeutic Patient Education; Over the past thirty years, therapeutic patient education (TPE) has become an essential part of the treatment of long-term diseases. Evaluations of this new practice are expected, and are sometimes imposed according to protocols and criteria that do not always reflect the complexity of changes taking place within patients and healthcare providers. Sometimes, expected results are not achieved ...

  20. Review of Therapeutic Education: Working Alongside Troubled and Troublesome Children (Book Review)

    Bigger, Stephen

    2008-01-01

    Therapeutic education requires a move from “a punitive, blame-based, unfairly competitive and deviant-defined culture” to “one that celebrates diversity and cultural differences” (p.11), from a deficit model of SEN and deviant model of challenging behaviour to “a more humane and therapeutic approach to education and learning generally (p.12). Therapeutic education is holistic and encourages agency and responsibility. How adults relate to learners is viewed as more important than what is taugh...

  1. Factors associated with therapeutic strategies in patients with splanchnic vein thrombosis: Results of an international registry

    Riva, N.; Ageno, W.; Schulman, S.; Bang, S.M.; Sartori, M.T.; Grandone, E.; Beyer, J.; Barillari, G.; Di Minno, D.; Duce, R.; Malato, A.; Santoro, R.; Poli, D.; Verhamme, P.; Martinelli, I.; Kamphuisen, P.; Alatri, A.; Becattini, C.; Bucherini, E.; Piana, A.; De Stefano, V.; Dentali, F.

    2012-01-01

    Background Treatment of splanchnic vein thrombosis (SVT) is challenging due to the heterogeneous clinical presentation and the increased bleeding risk. We aimed to describe current treatment strategies and factors associated with therapeutic decisions. Materials and Methods Between May 2008 and

  2. Metabolomic Analysis in Brain Research: Opportunities & Challenges

    Catherine G Vasilopoulou

    2016-05-01

    Full Text Available Metabolism being a fundamental part of molecular physiology, elucidating the structure and regulation of metabolic pathways is crucial for obtaining a comprehensive perspective of cellular function and understanding the underlying mechanisms of its dysfunction(s. Therefore, quantifying an accurate metabolic network activity map under various physiological conditions is among the major objectives of systems biology in the context of many biological applications. Especially for CNS, metabolic network activity analysis can substantially enhance our knowledge about the complex structure of the mammalian brain and the mechanisms of neurological disorders, leading to the design of effective therapeutic treatments. Metabolomics has emerged as the high-throughput quantitative analysis of the concentration profile of small molecular weight metabolites, which act as reactants and products in metabolic reactions and as regulatory molecules of proteins participating in many biological processes. Thus, the metabolic profile provides a metabolic activity fingerprint, through the simultaneous analysis of tens to hundreds of molecules of pathophysiological and pharmacological interest. The application of metabolomics is at its standardization phase in general, and the challenges for paving a standardized procedure are even more pronounced in brain studies. In this review, we support the value of metabolomics in brain research. Moreover, we demonstrate the challenges of designing and setting up a reliable brain metabolomic study, which, among other parameters, has to take into consideration the sex differentiation and the complexity of brain physiology manifested in its regional variation. We finally propose ways to overcome these challenges and design a study that produces reproducible and consistent results.

  3. Major international sport profiles.

    Patel, Dilip R; Stier, Bernhard; Luckstead, Eugene F

    2002-08-01

    Sports are part of the sociocultural fabric of all countries. Although different sports have their origins in different countries, many sports are now played worldwide. International sporting events bring athletes of many cultures together and provide the opportunity not only for athletic competition but also for sociocultural exchange and understanding among people. This article reviews five major sports with international appeal and participation: cricket, martial arts, field hockey, soccer, and tennis. For each sport, the major aspects of physiological and biomechanical demands, injuries, and prevention strategies are reviewed.

  4. Sub therapeutic drug levels among HIV/TB co-infected patients ...

    Daniel W. Gunda

    2016-11-01

    Nov 1, 2016 ... NVP based regimen was associated with sub-therapeutic drug levels on uni- ... a number of important challenges including induction of sub- therapeutic levels of .... ARV plasma levels in the univariate model with p-values less than 0.05 .... clearance of ARVs.56 This may be one of the explanations that.

  5. An oncofetal glycosaminoglycan modification provides therapeutic access to Cisplatin-resistant bladder cancer

    Seiler, Roland; Oo, Htoo Zarni; Tortora, Davide

    2017-01-01

    the malaria parasite Plasmodium falciparum, we can target these sugar chains, and our results showed a significant antitumor effect in cisplatin-resistant bladder cancer. This novel treatment paradigm provides therapeutic access to bladder cancers not responding to cisplatin.......BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical...... significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2...

  6. Hemorrhagic Cardioembolic Stroke Secondary to a Left Ventricular Thrombus: a Therapeutic Dilemma

    Khalil Al-Farsi

    2013-01-01

    Full Text Available Cardiogenic embolism is a major cause of stroke and often leads to significant morbidity and mortality. Despite the recent advances in our understanding of the pathophysiology of stroke and its risk factors, diagnosis and therapy; some case scenarios still present a real challenge for the treating physicians. We report a case of a 50 year old male patient presenting with multi-territory cerebral infarctions due to a left ventricular mobile thrombus complicated with hemorrhagic transformation at the time of presentation. Gradual introduction of anticoagulation coupled with a multidisciplinary team approach advocating careful daily clinical assessment of the patient and regular echocardiographic and neuroimaging studies have resulted in a better management and achievement of therapeutic goals.

  7. Inhibiting DNA Polymerases as a Therapeutic Intervention against Cancer

    Anthony J. Berdis

    2017-11-01

    Full Text Available Inhibiting DNA synthesis is an important therapeutic strategy that is widely used to treat a number of hyperproliferative diseases including viral infections, autoimmune disorders, and cancer. This chapter describes two major categories of therapeutic agents used to inhibit DNA synthesis. The first category includes purine and pyrmidine nucleoside analogs that directly inhibit DNA polymerase activity. The second category includes DNA damaging agents including cisplatin and chlorambucil that modify the composition and structure of the nucleic acid substrate to indirectly inhibit DNA synthesis. Special emphasis is placed on describing the molecular mechanisms of these inhibitory effects against chromosomal and mitochondrial DNA polymerases. Discussions are also provided on the mechanisms associated with resistance to these therapeutic agents. A primary focus is toward understanding the roles of specialized DNA polymerases that by-pass DNA lesions produced by DNA damaging agents. Finally, a section is provided that describes emerging areas in developing new therapeutic strategies targeting specialized DNA polymerases.

  8. Major New Initiatives

    First page Back Continue Last page Overview Graphics. Major New Initiatives. Multi-party multi-rate video conferencing OOPS. Live Lecture OOPS. Rural ATM Machine Vortex. Finger print detection HP-IITM. Medical Diagnostic kit NeuroSynaptic. LCD projection system TeNeT. Web Terminal MeTeL Midas. Entertainment ...

  9. Major planning enquiries

    Shore, P

    1978-11-01

    This is a speech delivered by the U.K. Secretary of State for the Environment in Manchester (UK) on September 13th 1978. It outlines the Minister's views on the role and significance of major planning inquiries - such as that proposed to be held on the Commercial Demonstration Fast Reactor. (CDFR) (author).

  10. Major Biomass Conference

    Top Scientists, Industry and Government Leaders to Gather for Major Biomass Conference America, South America and Europe will focus on building a sustainable, profitable biomass business at the Third Biomass Conference of the Americas in Montreal. Scheduled presentations will cover all biomass

  11. Unity in Major Themes

    Booss-Bavnbek, Bernhelm; Davis, Philip J.

    We describe and explain the desire, common among mathematicians, both for unity and independence in its major themes. In the dialogue that follows, we express our spontaneous and considered judgment and reservations; by contrasting the development of mathematics as a goal-driven process as opposed...

  12. Allogenic banking of dental pulp stem cells for innovative therapeutics.

    Collart-Dutilleul, Pierre-Yves; Chaubron, Franck; De Vos, John; Cuisinier, Frédéric J

    2015-08-26

    Medical research in regenerative medicine and cell-based therapy has brought encouraging perspectives for the use of stem cells in clinical trials. Multiple types of stem cells, from progenitors to pluripotent stem cells, have been investigated. Among these, dental pulp stem cells (DPSCs) are mesenchymal multipotent cells coming from the dental pulp, which is the soft tissue within teeth. They represent an interesting adult stem cell source because they are recovered in large amount in dental pulps with non-invasive techniques compared to other adult stem cell sources. DPSCs can be obtained from discarded teeth, especially wisdom teeth extracted for orthodontic reasons. To shift from promising preclinical results to therapeutic applications to human, DPSCs must be prepared in clinical grade lots and transformed into advanced therapy medicinal products (ATMP). As the production of patient-specific stem cells is costly and time-consuming, allogenic biobanking of clinical grade human leukocyte antigen (HLA)-typed DPSC lines provides efficient innovative therapeutic products. DPSC biobanks represent industrial and therapeutic innovations by using discarded biological tissues (dental pulps) as a source of mesenchymal stem cells to produce and store, in good manufacturing practice (GMP) conditions, DPSC therapeutic batches. In this review, we discuss about the challenges to transfer biological samples from a donor to HLA-typed DPSC therapeutic lots, following regulations, GMP guidelines and ethical principles. We also present some clinical applications, for which there is no efficient therapeutics so far, but that DPSCs-based ATMP could potentially treat.

  13. Challenging makerspaces

    Sandvik, Kjetil; Thestrup, Klaus

    This paper takes its departure in the EU-project MakEY - Makerspaces in the early years – enhancing digital literacy and creativity that is part of a H2020 RISE-program and is running January 2017 - June 2019. Here digital literacy and creative skills of young children between the age of 3......-8 will be developed through participation in creative activities in specially-designed spaces termed ‘makerspaces’. This paper discusses, develops and challenges this term in relation to Danish pedagogical traditions, to expanding makerspaces onto the internet and on how to combine narratives and construction....... The Danish part of the project will be undertaken by a small network of partners: DOKK1, a public library and open urban space in Aarhus, that is experimenting with different kind of makerspaces, spaces and encounters between people, The LEGO-LAB situated at Computer Science, Aarhus University, that has...

  14. Recent progress in the therapeutic applications of nanotechnology.

    Solomon, Melani; D'Souza, Gerard G M

    2011-04-01

    The field of pharmaceutical and medical nanotechnology has grown rapidly in recent decades and offers much promise for therapeutic advances. This review is intended to serve as a quick summary of the major areas in the therapeutic application of nanotechnology. Nanotechnology for therapeutic application falls into two broad categories of particulate systems and nanoengineered devices. Recent studies appear to focus on the development of multifunctional particles for drug delivery and imaging and the development of nanotechnology-based biosensors for diagnostic applications. Cancer treatment and diagnosis appears to be the principal focus of many of these applications, but nanotechnology is also finding application in tissue engineering and surface engineering of medical implants. Particulate drug delivery systems in general appear to be poised for increased use in the clinic, whereas nanoengineered implants and diagnostic sensors might well be the next major wave in the medical use of nanotechnology.

  15. Educational Leadership: Key Challenges and Ethical Tensions

    Duignan, Patrick

    2007-01-01

    "Educational Leadership" is a major research book on contemporary leadership challenges for educational leaders. In this groundbreaking new work, educational leaders in schools, including teachers, are provided with ways of analysing and resolving common but complex leadership challenges. Ethical tensions inherent in these challenges are…

  16. Curcumin Nanomedicine: A Road to Cancer Therapeutics

    Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.

    2013-01-01

    Cancer is the second leading cause of death in the United States. Conventional therapies cause widespread systemic toxicity and lead to serious side effects which prohibit their long term use. Additionally, in many circumstances tumor resistance and recurrence is commonly observed. Therefore, there is an urgent need to identify suitable anticancer therapies that are highly precise with minimal side effects. Curcumin is a natural polyphenol molecule derived from the Curcuma longa plant which exhibits anticancer, chemo-preventive, chemo- and radio-sensitization properties. Curcumin’s widespread availability, safety, low cost and multiple cancer fighting functions justify its development as a drug for cancer treatment. However, various basic and clinical studies elucidate curcumin’s limited efficacy due to its low solubility, high rate of metabolism, poor bioavailability and pharmacokinetics. A growing list of nanomedicine(s) using first line therapeutic drugs have been approved or are under consideration by the Food and Drug Administration (FDA) to improve human health. These nanotechnology strategies may help to overcome challenges and ease the translation of curcumin from bench to clinical application. Prominent research is reviewed which shows that advanced drug delivery of curcumin (curcumin nanoformulations or curcumin nanomedicine) is able to leverage therapeutic benefits by improving bioavailability and pharmacokinetics which in turn improves binding, internalization and targeting of tumor(s). Outcomes using these novel drug delivery systems have been discussed in detail. This review also describes the tumor-specific drug delivery system(s) that can be highly effective in destroying tumors. Such new approaches are expected to lead to clinical trials and to improve cancer therapeutics. PMID:23116309

  17. Colorectal cancer: diagnostic and therapeutic strategies

    Vaillant, J.C.

    1996-01-01

    Technical advances that has been achieved during the past two decades have not dramatically improved the 35 % five-year rate observed in patients with colorectal cancer. These tumours remain one of the most challenging problems in public health policies in western countries. Screening applies to some subgroups of high-risk individuals and the general population aged over 50. In order to improve their efficacy, such screening programs imply large-scale information campaigns and a strong cooperation with the general physicians. The diagnosis is strongly suggested by any recent modification of bowel habits ad by rectal bleeding. It has to be confirmed by rectal examination and by colonoscopy which allows sampling to the tumour. Loco-regional and distant metastatic tumour spread must be assessed precisely before any therapeutic strategy is decided. Surgery, which resects the tumour en bloc with the corresponding lymphatic territories, is the only treatment that can achieve long term cure. In localized tumours, surgery alone can provide patients with 5-years survival rates close to 95 %. On the other hand, surgery alone is not sufficient to cure patients with advances cancers. In recent years, several adjuvant therapeutic modalities have been shown to improve the results of surgery in these cases (rectal cancer: pre-operative radiotherapy or post-operative radio-chemotherapy, colon cancer with nodal metastases: post-operative chemotherapy). There is a hope that a better use of our diagnostic and therapeutic armementarium would be able to avoid or to cure up to 75 % of the colorectal cancers we are dealing with. (author)

  18. Long-term delivery of protein therapeutics.

    Vaishya, Ravi; Khurana, Varun; Patel, Sulabh; Mitra, Ashim K

    2015-03-01

    Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

  19. Therapeutic conflicts in emergency department patients with multimorbidity: a cross-sectional study.

    Stefan Markun

    Full Text Available Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations.The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity.We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance.166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4. We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred.Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

  20. Therapeutic conflicts in emergency department patients with multimorbidity: a cross-sectional study.

    Markun, Stefan; Holzer, Barbara M; Rodak, Roksana; Kaplan, Vladimir; Wagner, Claudia C; Battegay, Edouard; Zimmerli, Lukas

    2014-01-01

    Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations. The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity. We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance. 166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4). We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred. Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

  1. The diesel challenge

    Tobin, Geoff

    1997-01-01

    This article is focused on the challenges being faced by the diesel producer and these include a number of interesting developments which illustrate the highly competitive world of the European refiner. These include: The tightening quality requirements being legislated coupled with the availability of the ''city diesel'' from Scandinavia and elsewhere which is already being sold into the market. For a time there will be a clear means of product differentiation. One of the key questions is whether the consumer will value the quality difference; a growing demand for diesel which is outstripping the growth in gasoline demand and causing refiners headaches when it comes to balancing their supply/demand barrels; the emergence of alternative fuels which are challenging the traditional markets of the refiner and in particular, the niche markets for the higher quality diesel fuels. All of this at a time of poor margins and over-capacity in the industry with further major challenges ahead such as fuel oil disposal, tighter environmental standards and the likelihood of heavier, higher sulphur crude oils in the future. Clearly, in such a difficult and highly-competitive business environment it will be important to find low-cost solutions to the challenges of the diesel quality changes. An innovative approach will be required to identify the cheapest and best route to enable the manufacture of the new quality diesel. (Author)

  2. Alzheimer Disease: Scientific Breakthroughs and Translational Challenges.

    Caselli, Richard J; Beach, Thomas G; Knopman, David S; Graff-Radford, Neill R

    2017-06-01

    Alzheimer disease (AD) was originally conceived as a rare disease that caused presenile dementia but has come to be understood as the most prevalent cause of dementia at any age worldwide. It has an extended preclinical phase characterized by sequential changes in imaging and cerebrospinal fluid biomarkers with subtle memory decline beginning more than a decade before the emergence of symptomatic memory loss heralding the beginning of the mild cognitive impairment stage. The apolipoprotein E ε4 allele is a prevalent and potent risk factor for AD that has facilitated research into its preclinical phase. Cerebral Aβ levels build from preclinical through early dementia stages followed by hyperphosphorylated tau-related pathology, the latter driving cognitive deficits and dementia severity. Structural and molecular imaging can now recapitulate the neuropathology of AD antemortem. Autosomal dominant forms of early-onset familial AD gave rise to the amyloid hypothesis of AD, which, in turn, has led to therapeutic trials of immunotherapy designed to clear cerebral amyloid, but to date results have been disappointing. Genome-wide association studies have identified multiple additional risk factors, but to date none have yielded an effective alternate therapeutic target. Current and future trials aimed at presymptomatic individuals either harboring cerebral amyloid or at genetically high risk offer the hope that earlier intervention might yet succeed where trials in patients with established dementia have failed. A major looming challenge will be that of expensive, incompletely effective disease-modifying therapy: who and when to treat, and how to pay for it. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  3. Intra Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

    2016-10-01

    size distribution therapeutic timepoints EPIC-µCT Articular cartilage Subchondral bone Osteophytes Proteoglycans 3. OVERALL PROJECT SUMMARY: In...joint degeneration induced by MMT. Previously documented in Year 1 annual report: Changes in articular cartilage and subchondral bone morphology...and resulted in increased cartilage thickness at 3 weeks. The majority of alterations to subchondral bone (density, thickness) were detected at 3

  4. 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.

  5. 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.

  6. Conflicts in the therapeutic field

    Antonino Aprea

    2012-06-01

    Full Text Available How the analytical knowledge that compare human consciousness with that, even more disturbing, moving behind his fifth can be said to be “for peace”? It can be - and this will be the contribution of the proposal - the same tortuous and enigmatic of therapeutic practice, with its hesitations and his impulses, to outline a path crossing and overcoming the conflict? May, finally, peace, in the sense of feasibility of intra-and interpersonal dialectic instead of tearing and hostileconfrontation with oneself and with the other, to be a reference in some crucial pivot of ethical therapeutic work? To these questions the intervention seeks to answer retracing some of the highlights of almost three years of therapeutic work with a young woman and her family.

  7. Engaging therapeutic citizenship and clientship: Untangling the reasons for therapeutic pacifism among people living with HIV in urban Zambia.

    Patterson, Amy S

    2016-10-01

    This article explores the reasons for therapeutic pacifism among people living with HIV (PLHIVs) in urban Zambia. It contributes to a growing ethnography on global health, biosociality, and patient-provider dynamics. Therapeutic citizenship is a biopolitical citizenship that includes claims and ethical projects that emerge from techniques to control and manage bodies. In some contexts, therapeutic citizenship has included activism and claims-making against local, national, and international power brokers. This article investigates therapeutic citizenship in the specific context of impoverished urban Zambian compounds, sites of food insecurity, unemployment, and political exclusion, as well as targets for donor, NGO, and faith-based organisation projects and PLHIV support group proliferation. The article utilises data from participant observations at two Lusaka AIDS clinics, interviews, and focused discussions with support groups of PLHIVs. It argues that PLHIVs continuously negotiate subjectivities related to kinship, clientship, religious belief, and political citizenship in processes that complicate therapeutic citizenship. Rather than fostering participation in PLHIV support groups or challenging 'politics as usual' through activist claims-making to institutions of biopower, these processes lead to therapeutic pacifism.

  8. Reactor-produced therapeutic radioisotopes

    Knapp, F.F. Jr.

    2002-01-01

    The significant worldwide increase in therapeutic radioisotope applications in nuclear medicine, oncology and interventional cardiology requires the dependable production of sufficient levels of radioisotopes for these applications (Reba, 2000; J. Nucl. Med., 1998; Nuclear News, 1999; Adelstein and Manning, 1994). The issues associated with both accelerator- and reactor-production of therapeutic radioisotopes is important. Clinical applications of therapeutic radioisotopes include the use of both sealed sources and unsealed radiopharmaceutical sources. Targeted radiopharmaceutical agents include those for cancer therapy and palliation of bone pain from metastatic disease, ablation of bone marrow prior to stem cell transplantation, treatment modalities for mono and oligo- and polyarthritis, for cancer therapy (including brachytherapy) and for the inhibition of the hyperplastic response following coronary angioplasty and other interventional procedures (For example, see Volkert and Hoffman, 1999). Sealed sources involve the use of radiolabeled devices for cancer therapy (brachytherapy) and also for the inhibition of the hyperplasia which is often encountered after angioplasty, especially with the exponential increase in the use of coronary stents and stents for the peripheral vasculature and other anatomical applications. Since neutron-rich radioisotopes often decay by beta decay or decay to beta-emitting daughter radioisotopes which serve as the basis for radionuclide generator systems, reactors are expected to play an increasingly important role for the production of a large variety of therapeutic radioisotopes required for these and other developing therapeutic applications. Because of the importance of the availability of reactor-produced radioisotopes for these applications, an understanding of the contribution of neutron spectra for radioisotope production and determination of those cross sections which have not yet been established is important. This

  9. Systems Challenges for Hypersonic Vehicles

    Hunt, James L.; Laruelle, Gerard; Wagner, Alain

    1997-01-01

    This paper examines the system challenges posed by fully reusable hypersonic cruise airplanes and access to space vehicles. Hydrocarbon and hydrogen fueled airplanes are considered with cruise speeds of Mach 5 and 10, respectively. The access to space matrix is examined. Airbreathing and rocket powered, single- and two-stage vehicles are considered. Reference vehicle architectures are presented. Major systems/subsystems challenges are described. Advanced, enhancing systems concepts as well as common system technologies are discussed.

  10. Starting an Actuarial Science Major at a Liberal Arts College

    Mills, Mark A.

    2014-01-01

    The article provides details of the process of starting an actuarial science major at a small, liberal arts college. Some critique of the major is included, as well as some challenges that may be faced by others wanting to start such a major at their institution.

  11. Scrapheap Challenge

    2004-01-01

    Three British guys at CERN recently took a break from work to try their hand at Scrapheap Challenge. Shown on Channel 4 in the UK, it is a show where two teams must construct a machine for a specific task using only the junk they can scavenge from the scrap yard around them. And they have just 10 hours to build their contraption before it is put to the test. The first round, aired 19 September, pitted a team of three women, from the British Army's Royal Electrical and Mechanical Engineers, against the CERN guys - the Up 'n Atoms: Ali Day, David McFarlane and James Ridewood. Each team, with the help of an appointed expert, had the task of making a giant, 3-metre self-propelled "bowling ball", to roll down a 50 metre bowling alley at skittles 4 metres high. The Up 'n Atoms' contraption featured a small car with a huge wheel on its back. Once up to speed, slamming on the brakes caused the wheel to roll over and take the car with it. On their very last run they managed to take out seven pins. Luckily, though, ...

  12. Advances and Challenges of Liposome Assisted Drug Delivery

    Lisa eSercombe

    2015-12-01

    Full Text Available The application of liposomes to assist drug delivery has already had a major impact on many biomedical areas. They have been shown to be beneficial for stabilizing therapeutic compounds, overcoming obstacles to cellular and tissue uptake, and improving biodistribution of compounds to target sites in vivo. This enables effective delivery of encapsulated compounds to target sites while minimizing systemic toxicity. Liposomes present as an attractive delivery system due to their flexible physicochemical and biophysical properties, which allow easy manipulation to address different delivery considerations. Despite considerable research in the last 50 years and the plethora of positive results in preclinical studies, the clinical translation of liposome assisted drug delivery platforms has progressed incrementally. In this review, we will discuss the advances in liposome assisted drug delivery, biological challenges that still remain, and current clinical and experimental use of liposomes for biomedical applications. The translational obstacles of liposomal technology will also be presented.

  13. Cold Plasmas for Biofilm Control: Opportunities and Challenges.

    Gilmore, Brendan F; Flynn, Padrig B; O'Brien, Séamus; Hickok, Noreen; Freeman, Theresa; Bourke, Paula

    2018-06-01

    Bacterial biofilm infections account for a major proportion of chronic and medical device associated infections in humans, yet our ability to control them is compromised by their inherent tolerance to antimicrobial agents. Cold atmospheric plasma (CAP) represents a promising therapeutic option. CAP treatment of microbial biofilms represents the convergence of two complex phenomena: the production of a chemically diverse mixture of reactive species and intermediates, and their interaction with a heterogeneous 3D interface created by the biofilm extracellular polymeric matrix. Therefore, understanding these interactions and physiological responses to CAP exposure are central to effective management of infectious biofilms. We review the unique opportunities and challenges for translating CAP to the management of biofilms. Copyright © 2018. Published by Elsevier Ltd.

  14. The Ursa Major supercluster

    Schuch, N.J.

    1983-01-01

    An optical and a radio survey have been carried out. The optical observations consist of a spectroscopic survey in which redshift data for cluster galaxies and optical identifications of radio sources were obtained with the 98-inch Isaac Newton telescope at the Royal Greenwich Observatory, and the 200-inch Hale telescope; the photographic survey in B, V and R colors was made with the 48-inch Schmidt telescope at Palomar. Some results on the galaxy distribution in the Ursa Major supercluster are briefly discussed. (Auth.)

  15. Japan's patent issues relating to life science therapeutic inventions.

    Tessensohn, John A

    2014-09-01

    Japan has made 'innovation in science and technology' as one of its central pillars to ensure high growth in its next stage of economic development and its life sciences market which hosts regenerative medicine was proclaimed to be 'the best market in the world right now.' Although life science therapeutic inventions are patentable subject matter under Japanese patent law, there are nuanced obviousness and enablement challenges under Japanese patent law that can be surmounted in view of some encouraging Japanese court developments in fostering a pro-patent applicant environment in the life sciences therapeutic patent field. Nevertheless, great care must be taken when drafting and prosecuting such patent applications in the world's second most important life sciences therapeutic market.

  16. Securing Major Events

    Loeoef, Susanna

    2013-01-01

    When asked why the IAEA should provide nuclear security support to countries that organize large public events, Nuclear Security Officer Sophia Miaw answers quickly and without hesitation. ''Imagine any major public event such as the Olympics, a football championship, or an Expo. If a dirty bomb were to be exploded at a site where tens of thousands of people congregate, the radioactive contamination would worsen the effects of the bomb, increase the number of casualties, impede a rapid emergency response, and cause long term disruption in the vicinity,'' she said. Avoiding such nightmarish scenarios is the driving purpose behind the assistance the IAEA offers States that host major sporting or other public events. The support can range from a single training course to a comprehensive programme that includes threat assessment, training, loaned equipment and exercises. The type and scope of assistance depends on the host country's needs. ''We incorporate nuclear security measures into their security plan. We don't create anything new,'' Miaw said

  17. Therapy Talk: Analyzing Therapeutic Discourse

    Leahy, Margaret M.

    2004-01-01

    Therapeutic discourse is the talk-in-interaction that represents the social practice between clinician and client. This article invites speech-language pathologists to apply their knowledge of language to analyzing therapy talk and to learn how talking practices shape clinical roles and identities. A range of qualitative research approaches,…

  18. Therapeutic approaches to genetic disorders

    salah

    Although prevention is the ideal goal for genetic disorders, various types of therapeutic ... The patient being ... pirical or aimed at controlling or mediating signs and symptoms without care. ... plications and gene therapy approaches .... genes family, have opened a wide and .... cancer where nanoparticles are used to.

  19. Medical therapeutic effect of hyperthyroidism

    Lee, K.B.

    1980-01-01

    In order to compare the therapeutic effect as well as side effects between antithyroid therapy and radioiodine therapy in hyperthyroidism, the author evaluated 111 cases of hyperthyroidism which were composed of 57 patients with antithyroid treatment, 23 patients with combined treatment comprising of antithyroid and radioactive iodine ( 131 I) and 31 patients with treatment of 131 I alone. (author)

  20. Regulatory challenges

    Austvik, Ole Gunnar

    2003-01-01

    The problem for policy makers wanting to liberalize natural gas markets is that its concentrated structure may also be the socially most efficient one. Because of scale economies, more firms operating in the market may incur higher transportation costs unless the market grows sufficiently in each geographic segment. This argument goes for product extension through vertical (or horizontal) integration and the exploitation of economies of scope as well. Thus, the challenge for governments is to intervene in a way that preserves a market structure that has the potential to minimize cost, and at the same lime change its behavior in order to avoid possible lax cost control and exploitation of market power. The existence of scope advantages indicates that liberalization of the market should open for the possibility to bundle services in competition with provision of unbundled services. If operations are unbundled and there exist economies of scope, the gain from increased competition should be weighed against the losses of less efficient operations of each firm. Thus, with the growth in the European market, gradually more arguments support the idea of unbundling. The significant scale economy in trunk pipelines, sunk investments and capital immobility, possible economies of scope in vertical integration and companies' bundling of services influences vertical and horizontal ownership relations and contractual terms in the European gas market. In specific segments of the markets, these relationships may promote efficient investments and pricing without public interference, but the strong concentration of market power indicates that this is rather the exception than the rule. In order to design an efficient and welfare maximizing way of regulating the market one needs a closer identification of the actual goal of the regulation. Microeconomic theory is often used for this purpose. The author discusses the alternatives of laissez-faire, nationalization or regulation for the

  1. Seven challenges for neuroscience.

    Markram, Henry

    2013-01-01

    Although twenty-first century neuroscience is a major scientific enterprise, advances in basic research have not yet translated into benefits for society. In this paper, I outline seven fundamental challenges that need to be overcome. First, neuroscience has to become "big science" - we need big teams with the resources and competences to tackle the big problems. Second, we need to create interlinked sets of data providing a complete picture of single areas of the brain at their different levels of organization with "rungs" linking the descriptions for humans and other species. Such "data ladders" will help us to meet the third challenge - the development of efficient predictive tools, enabling us to drastically increase the information we can extract from expensive experiments. The fourth challenge goes one step further: we have to develop novel hardware and software sufficiently powerful to simulate the brain. In the future, supercomputer-based brain simulation will enable us to make in silico manipulations and recordings, which are currently completely impossible in the lab. The fifth and sixth challenges are translational. On the one hand we need to develop new ways of classifying and simulating brain disease, leading to better diagnosis and more effective drug discovery. On the other, we have to exploit our knowledge to build new brain-inspired technologies, with potentially huge benefits for industry and for society. This leads to the seventh challenge. Neuroscience can indeed deliver huge benefits but we have to be aware of widespread social concern about our work. We need to recognize the fears that exist, lay them to rest, and actively build public support for neuroscience research. We have to set goals for ourselves that the public can recognize and share. And then we have to deliver on our promises. Only in this way, will we receive the support and funding we need.

  2. Therapeutic γ-globin inducers reduce transcriptional repression in hemoglobinopathy erythroid progenitors through distinct mechanisms

    Dai, Yan; Sangerman, Jose; Hong, Yuan Luo; Fuchareon, Suthat; Chui, David H.K.; Faller, Douglas V.; Perrine, Susan P.

    2015-01-01

    Pharmacologic augmentation of γ-globin expression sufficient to reduce anemia and clinical severity in patients with diverse hemoglobinopathies has been challenging. In studies here, representative molecules from four chemical classes, representing several distinct primary mechanisms of action, were investigated for effects on γ-globin transcriptional repressors, including components of the NuRD complex (LSD1 and HDACs 2-3), and the downstream repressor BCL11A, in erythroid progenitors from hemoglobinopathy patients. Two HDAC inhibitors (MS-275 and SB939), a short-chain fatty acid derivative (sodium dimethylbutyrate [SDMB]), and an agent identified in high-throughput screening, Benserazide, were studied. These therapeutics induced γ globin mRNA in progenitors above same subject controls up to 20-fold, and increased F-reticulocytes up to 20%. Cellular protein levels of BCL11A, LSD-1, and KLF1 were suppressed by the compounds. Chromatin immunoprecipitation assays demonstrated a 3.6-fold reduction in LSD1 and HDAC3 occupancy in the γ-globin gene promoter with Benserazide exposure, 3-fold reduction in LSD-1 and HDAC2 occupancy in the γ-globin gene promoter with SDMB exposure, while markers of gene activation (histone H3K9 acetylation and H3K4 demethylation), were enriched 5.7-fold. These findings identify clinical-stage oral therapeutics which inhibit or displace major co-repressors of γ-globin gene transcription and may suggest a rationale for combination therapy to produce enhanced efficacy. PMID:26603726

  3. Transport of nanoparticles through the blood-brain barrier for imaging and therapeutic applications

    Shilo, Malka; Motiei, Menachem; Hana, Panet; Popovtzer, Rachela

    2014-01-01

    A critical problem in the treatment of neurodegenerative disorders and diseases, such as Alzheimer's and Parkinson's, is the incapability to overcome the restrictive mechanism of the blood-brain barrier (BBB) and to deliver important therapeutic agents to the brain. During the last decade, nanoparticles have gained attention as promising drug delivery agents that can transport across the BBB and increase the uptake of appropriate drugs in the brain. In this study we have developed insulin-targeted gold nanoparticles (INS-GNPs) and investigated quantitatively the amount of INS-GNPs that cross the BBB by the receptor-mediated endocytosis process. For this purpose, INS-GNPs and control GNPs were injected into the tail vein of male BALB/c mice. Major organs were then extracted and a blood sample was taken from the mice, and thereafter analyzed for gold content by flame atomic absorption spectroscopy. Results show that two hours post-intravenous injection, the amount of INS-GNPs found in mouse brains is over 5 times greater than that of the control, untargeted GNPs. Results of further experimentation on a rat model show that INS-GNPs can also serve as CT contrast agents to highlight specific brain regions in which they accumulate. Due to the fact that they can overcome the restrictive mechanism of the BBB, this approach could be a potentially valuable tool, helping to confront the great challenge of delivering important imaging and therapeutic agents to the brain for detection and treatment of neurodegenerative disorders and diseases.

  4. Graphene- gold based nanocomposites applications in cancer diseases; Efficient detection and therapeutic tools.

    Al-Ani, Lina A; AlSaadi, Mohammed A; Kadir, Farkaad A; Hashim, Najihah M; Julkapli, Nurhidayatullaili M; Yehye, Wageeh A

    2017-10-20

    Early detection and efficient treatment of cancer disease remains a drastic challenge in 21st century. Throughout the bulk of funds, studies, and current therapeutics, cancer seems to aggressively advance with drug resistance strains and recurrence rates. Nevertheless, nanotechnologies have indeed given hope to be the next generation for oncology applications. According to US National cancer institute, it is anticipated to revolutionize the perspectives of cancer diagnosis and therapy. With such success, nano-hybrid strategy creates a marvelous preference. Herein, graphene-gold based composites are being increasingly studied in the field of oncology, for their outstanding performance as robust vehicle of therapeutic agents, built-in optical diagnostic features, and functionality as theranostic system. Additional modes of treatments are also applicable including photothermal, photodynamic, as well as combined therapy. This review aims to demonstrate the various cancer-related applications of graphene-gold based hybrids in terms of detection and therapy, highlighting the major attributes that led to designate such system as a promising ally in the war against cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies.

    Andrews, Jordan; Puri, Rishi; Kataoka, Yu; Nicholls, Stephen J; Psaltis, Peter J

    2016-08-01

    Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.

  6. Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy?

    Nickl-Jockschat, Thomas; Palomero Gallagher, Nicola; Kumar, Vinod; Hoffstaedter, Felix; Brügmann, Elisabeth; Habel, Ute; Eickhoff, Simon B; Grözinger, Michael

    2016-04-01

    The neurotrophic hypothesis has become the favorite model to explain the antidepressant properties of electroconvulsive therapy (ECT). It is based on the assumption that a restoration of previously defective neural networks drives therapeutic effects. Recent data in rather young patients suggest that neurotrophic effects of ECT might be detectable by diffusion tensor imaging. We here aimed to investigate whether the therapeutic response to ECT necessarily goes along with mesoscopic effects in gray matter (GM) or white matter (WM) in our patients in advanced age. Patients (n = 21, 15 males and 7 females) suffering from major depressive disorder were treated with ECT. Before the start of treatment and after the completion of the index series, they underwent magnetic resonance imaging, including a diffusion-weighed sequence. We used voxel-based morphometry to assess GM changes and tract-based spatial statistics and an SPM-based whole-brain analysis to detect WM changes in the course of treatment. Patients significantly improved clinically during the course of ECT. This was, however, not accompanied by GM or WM changes. This result challenges the notion that mesoscopic brain structure changes are an obligatory prerequisite for the antidepressant effects of ECT.

  7. Are therapeutic vaccines an answer to the global problem of drug and alcohol abuse?

    Brashier, Dick B S; Sharma, Ashok Kumar; Akhoon, Neha

    2016-01-01

    Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol. Research in field of nicotine abuse has gone a way ahead with number of vaccines being tried clinically followed by cocaine, opioids, methamphetamine, phencyclidine and alcohol. All of them have a common mechanism of action by antibody production whereas alcohol acts by genetic intervention. None have being approved yet due to poor results in phase II trials, possibly due to not able to trigger an adequate immunological response. But still quest is on for cracking the ice by developing first successful vaccine against drug of abuse, that would follow for other drugs too. It would be great step in field of therapeutic vaccines for drug abuse after similar successful vaccines being approved for other diseases like cancer.

  8. Robotic Seals as Therapeutic Tools in an Aged Care Facility: A Qualitative Study

    Melanie Birks

    2016-01-01

    Full Text Available Robots, including robotic seals, have been used as an alternative to therapies such as animal assisted therapy in the promotion of health and social wellbeing of older people in aged care facilities. There is limited research available that evaluates the effectiveness of robot therapies in these settings. The aim of this study was to identify, explore, and describe the impact of the use of Paro robotic seals in an aged care facility in a regional Australian city. A qualitative, descriptive, exploratory design was employed. Data were gathered through interviews with the three recreational therapists employed at the facility who were also asked to maintain logs of their interactions with the Paro and residents. Data were transcribed and thematically analysed. Three major themes were identified from the analyses of these data: “a therapeutic tool that’s not for everybody,” “every interaction is powerful,” and “keeping the momentum.” Findings support the use of Paro as a therapeutic tool, revealing improvement in emotional state, reduction of challenging behaviours, and improvement in social interactions of residents. The potential benefits justify the investment in Paro, with clear evidence that these tools can have a positive impact that warrants further exploration.

  9. MicroRNA-targeted therapeutics for lung cancer treatment.

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  10. [Blood transfusion: the challenges for tomorrow?].

    Folléa, Gilles; Garraud, Olivier; Tiberghien, Pierre

    2015-02-01

    As any therapeutic means, blood transfusion requires regular evaluation, particularly for its indications, effectiveness and risks. The availability of randomized clinical trials, the evolution of the quality of blood components, and the economic constraints shared by all countries, all lead to rethink both transfusion therapy as a whole and the organization of the transfusion chain from donor to recipient. The main tools available to improve transfusion and the transfusion chain management are the following: programs of patient blood management (PBM) to optimize the use of blood products with a patient centred approach, blood supply management tools to improve the effectiveness and efficiency of the transfusion chain, donor management tools to adapt donor collections to the patients' needs in compliance with safety requirements for patients and donors, and coordination of these activities. A better understanding of these tools and their implementation will certainly be major challenges for transfusion medicine in the near future. Integrating these evolutions in regulations through the revision of the European Directives on blood and blood components (the review process is expected to be launched in 2015) should enroll them in the long term, for the benefit of patients, donors and all other stakeholders involved in the transfusion chain. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  11. Pharmacogenetics of warfarin: challenges and opportunities

    Ta Michael Lee, Ming; Klein, Teri E

    2014-01-01

    Since the introduction in the 1950s, warfarin has become the commonly used oral anticoagulant for the prevention of thromboembolism in patients with deep vein thrombosis, atrial fibrillation or prosthetic heart valve replacement. Warfarin is highly efficacious; however, achieving the desired anticoagulation is difficult because of its narrow therapeutic window and highly variable dose response among individuals. Bleeding is often associated with overdose of warfarin. There is overwhelming evidence that an individual's warfarin maintenance is associated with clinical factors and genetic variations, most notably polymorphisms in cytochrome P450 2C9 and vitamin K epoxide reductase subunit 1. Numerous dose-prediction algorithms incorporating both genetic and clinical factors have been developed and tested clinically. However, results from major clinical trials are not available yet. This review aims to provide an overview of the field of warfarin which includes information about the drug, genetics of warfarin dose requirements, dosing algorithms developed and the challenges for the clinical implementation of warfarin pharmacogenetics. PMID:23657428

  12. Pregnancy with bilateral tubercular pleural effusion: challenges.

    Ahuja, Vanita; Gombar, Satinder; Kumar, Navneet; Goyal, Nitika; Gupta, Kanika

    2014-04-01

    Pulmonary tuberculosis (TB) during pregnancy mimics some of the physiological changes that occur during pregnancy. Diagnosis is challenging, especially when the patient presents with acute respiratory distress. The incidence of pleural effusion in TB is 3-25% and in the majority of patients, is unilateral. We describe the intensive care management of a 27-year-old pregnant woman admitted to our hospital with life threatening respiratory distress and circulatory shock. She continued to have severe metabolic and respiratory acidosis with shock in spite of the resuscitative measures undertaken. At that point, a bedside lung ultrasonography showed bilateral pleural effusion which was followed with therapeutic thoracocentesis of the right side. This resulted in the stabilization of the respiratory mechanics and haemodynamics of the patient. The pleural fluid culture tested positive for acid fast bacilli after 4 weeks in the intensive care unit. Anti-TB therapy was started and she made a rapid recovery with liberation from mechanical ventilation. The early use of bedside lung ultrasonography was instrumental in the successful management of this patient.

  13. Progress and challenges of the bioartificial pancreas

    Hwang, Patrick T. J.; Shah, Dishant K.; Garcia, Jacob A.; Bae, Chae Yun; Lim, Dong-Jin; Huiszoon, Ryan C.; Alexander, Grant C.; Jun, Ho-Wook

    2016-11-01

    Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.

  14. Major Depressive Disorder

    G Grobler

    2013-08-01

    Full Text Available The treatment guideline draws on several international guidelines: (iPractice Guidelines of the American Psychiatric Association (APAfor the Treatment of Patients with Major Depressive Disorder, SecondEdition;[1](ii Clinical Guidelines for the Treatment of DepressiveDisorders by the Canadian Psychiatric Association and the CanadianNetwork for Mood and Anxiety Treatments (CANMAT;[2](iiiNational Institute for Clinical Excellence (NICE guidelines;[3](iv RoyalAustralian and New Zealand College of Psychiatrists Clinical PracticeGuidelines Team for Depression (RANZCAP;[4](v Texas MedicationAlgorithm Project (TMAP Guidelines;[5](vi World Federation ofSocieties of Biological Psychiatry (WFSBP Treatment Guideline forUnipolar Depressive Disorder;[6]and (vii British Association forPsychopharmacology Guidelines.[7

  15. 'Take my hand, help me out': mental health service recipients' experience of the therapeutic relationship.

    Shattell, Mona M; Starr, Sharon S; Thomas, Sandra P

    2007-08-01

    The purpose of this study was to describe mental health service recipients' experience of the therapeutic relationship. The research question was 'what is therapeutic about the therapeutic relationship?' This study was a secondary analysis of qualitative interviews conducted with persons with mental illness as part of a study of the experience of being understood. This secondary analysis used data from 20 interviews with community-dwelling adults with mental illness, who were asked to talk about the experience of being understood by a health-care provider. Data were analysed using an existential phenomenological approach. Individuals experienced therapeutic relationships against a backdrop of challenges, including mental illness, domestic violence, substance abuse, and homelessness. They had therapeutic relationships with nurses (psychiatric/mental health nurses and dialysis nurses), physicians (psychiatrists and general practitioners), psychologists, social workers, and counsellors. Experiences of the therapeutic relationship were expressed in three figural themes, titled using participants' own words: 'relate to me', 'know me as a person', and 'get to the solution'. The ways in which these participants described therapeutic relationships challenge some long-held beliefs, such as the use of touch, self-disclosure, and blunt feedback. A therapeutic relationship for persons with mental illness requires in-depth personal knowledge, which is acquired only with time, understanding, and skill. Knowing the whole person, rather than knowing the person only as a service recipient, is key for practising nurses and nurse educators interested in enhancing the therapeutic potential of relationships.

  16. A modular platform for targeted RNAi therapeutics.

    Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

    2018-03-01

    Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs 1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting 4-8 , their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

  17. Therapeutic benefits of Nanoparticles in Stroke

    Stavros ePanagiotou

    2015-05-01

    Full Text Available Stroke represents one of the major causes of death and disability worldwide, for which no effective treatments are available. The thrombolytic drug alteplase (tissue plasminogen activator or tPA is the only treatment for acute ischemic stroke but its use is limited by several factors including short therapeutic window, selective efficacy and subsequent haemorrhagic complications. Numerous preclinical studies have reported very promising results using neuroprotective agents but they have failed at clinical trials because of either safety issues or lack of efficacy. The delivery of many potentially therapeutic neuroprotectants and diagnostic compounds to the brain is restricted by the blood-brain barrier (BBB. Nanoparticles (NPs, which can readily cross the BBB without compromising its integrity, have immense applications in the treatment of ischemic stroke. In this review, potential uses of NPs will be summarized for the treatment of ischemic stroke. Additionally, an overview of targeted NPs will be provided, which could be used in the diagnosis of stroke. Finally, the potential limitations of using NPs in medical applications will be mentioned. Since the use of NPs in stroke therapy is now emerging and is still in development, this review is far from comprehensive or conclusive. Instead, examples of NPs and their current use will be provided, as well as the potentials of NPs in an effort to meet the high demand of new therapies in stroke.

  18. Therapeutic application of lasers in ophthalmology

    Misiuk-Hojlo, M.; Krzyzanowska-Berkowska, P.; Hill-Bator, A.

    2007-01-01

    Lasers have found application in diverse branches of medicine. In ophthalmology, laser technology has various therapeutic and diagnostic applications. The purpose of this article is to review the major therapeutic applications of lasers in different eye disorders. The effects of lasers on biological tissues and different laser techniques as well as the indications for laser therapy in various parts of the eye are discussed. Lasers are used to treat glaucoma and many vascular disorders of the retina. Laser treatment may be useful in preventing the development of neovascularization in diabetic retinopathy, BRVO, or CRVO. Laser techniques are also available for the treatment of the exudative form of age-related macular degeneration (AMD) and some malignant and benign intraocular tumors and in retina abnormalities which predispose to rhegmatogenous retinal detachment. Corneal laser surgery is the most frequently applied laser procedure in ophthalmology. PRK, LASIK, and LASEK are used to correct errors in vision such as myopia, hyperopia, and astigmatism. Laser photocoagulation is also helpful in cataract surgery. Nowadays, lasers have become so universal that it is difficult to imagine ophthalmology without them. We are still witnessing rapid advances in the development of laser techniques, especially in plastic surgery, cataract extraction, and ocular imaging. (authors)

  19. A modular platform for targeted RNAi therapeutics

    Kedmi, Ranit; Veiga, Nuphar; Ramishetti, Srinivas; Goldsmith, Meir; Rosenblum, Daniel; Dammes, Niels; Hazan-Halevy, Inbal; Nahary, Limor; Leviatan-Ben-Arye, Shani; Harlev, Michael; Behlke, Mark; Benhar, Itai; Lieberman, Judy; Peer, Dan

    2018-01-01

    Previous studies have identified relevant genes and signalling pathways that are hampered in human disorders as potential candidates for therapeutics. Developing nucleic acid-based tools to manipulate gene expression, such as short interfering RNAs1-3 (siRNAs), opens up opportunities for personalized medicine. Yet, although major progress has been made in developing siRNA targeted delivery carriers, mainly by utilizing monoclonal antibodies (mAbs) for targeting4-8, their clinical translation has not occurred. This is in part because of the massive development and production requirements and the high batch-to-batch variability of current technologies, which rely on chemical conjugation. Here we present a self-assembled modular platform that enables the construction of a theoretically unlimited repertoire of siRNA targeted carriers. The self-assembly of the platform is based on a membrane-anchored lipoprotein that is incorporated into siRNA-loaded lipid nanoparticles that interact with the antibody crystallizable fragment (Fc) domain. We show that a simple switch of eight different mAbs redirects the specific uptake of siRNAs by diverse leukocyte subsets in vivo. The therapeutic potential of the platform is demonstrated in an inflammatory bowel disease model by targeting colon macrophages to reduce inflammatory symptoms, and in a Mantle Cell Lymphoma xenograft model by targeting cancer cells to induce cell death and improve survival. This modular delivery platform represents a milestone in the development of precision medicine.

  20. Recent Advances in Stem Cell-Based Therapeutics for Stroke

    Napoli, Eleonora; Borlongan, Cesar V.

    2016-01-01

    Regenerative medicine for central nervous system disorders, including stroke, has challenged the non-regenerative capacity of the brain. Among the many treatment strategies tailored towards repairing the injured brain, stem cell-based therapeutics have been demonstrated as safe and effective in animal models of stroke, and are being tested in limited clinical trials. We address here key lab-to-clinic translational research that relate to efficacy, safety, and mechanism of action underlying st...

  1. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies⋆

    Chen, Yunching; Gao, Dong-Yu; Huang, Leaf

    2016-01-01

    MicroRNAs (miRNAs), small non-coding RNAs, can regulate post-transcriptional gene expressions and silence a broad set of target genes. miRNAs, aberrantly expressed in cancer cells, play an important role in modulating gene expressions, thereby regulating downstream signaling pathways and affecting cancer formation and progression. Oncogenes or tumor suppressor genes regulated by miRNAs mediate cell cycle progression, metabolism, cell death, angiogenesis, metastasis and immunosuppression in cancer. Recently, miRNAs have emerged as therapeutic targets or tools and biomarkers for diagnosis and therapy monitoring in cancer. Since miRNAs can regulate multiple cancer-related genes simultaneously, using miRNAs as a therapeutic approach plays an important role in cancer therapy. However, one of the major challenges of miRNA-based cancer therapy is to achieve specific, efficient and safe systemic delivery of therapeutic miRNAs In vivo. This review discusses the key challenges to the development of the carriers for miRNA-based therapy and explores current strategies to systemically deliver miRNAs to cancer without induction of toxicity. PMID:24859533

  2. Cyclic peptide therapeutics: past, present and future.

    Zorzi, Alessandro; Deyle, Kaycie; Heinis, Christian

    2017-06-01

    Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use and around one new cyclic peptide drug enters the market every year on average. The vast majority of clinically approved cyclic peptides are derived from natural products, such as antimicrobials or human peptide hormones. New powerful techniques based on rational design and in vitro evolution have enabled the de novo development of cyclic peptide ligands to targets for which nature does not offer solutions. A look at the cyclic peptides currently under clinical evaluation shows that several have been developed using such techniques. This new source for cyclic peptide ligands introduces a freshness to the field, and it is likely that de novo developed cyclic peptides will be in clinical use in the near future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Harnessing the Helminth Secretome for Therapeutic Immunomodulators

    Dana Ditgen

    2014-01-01

    Full Text Available Helminths are the largest and most complex pathogens to invade and live within the human body. Since they are not able to outpace the immune system by rapid antigen variation or faster cell division or retreat into protective niches not accessible to immune effector mechanisms, their long-term survival depends on influencing and regulating the immune responses away from the mode of action most damaging to them. Immunologists have focused on the excretory and secretory products that are released by the helminths, since they can change the host environment by modulating the immune system. Here we give a brief overview of the helminth-associated immune response and the currently available helminth secretome data. We introduce some major secretome-derived immunomodulatory molecules and describe their potential mode of action. Finally, the applicability of helminth-derived therapeutic proteins in the treatment of allergic and autoimmune inflammatory disease is discussed.

  4. Therapeutic approaches to preventing cell death in Huntington disease.

    Kaplan, Anna; Stockwell, Brent R

    2012-12-01

    Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors-fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

    Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

    2018-03-20

    Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

  6. Dual-color bioluminescent sensor proteins for therapeutic drug monitoring of antitumor antibodies

    van Rosmalen, M.; Ni, Y.; Vervoort, D.F.M.; Arts, R.; Ludwig, S.K.J.; Merkx, M.

    2018-01-01

    Monitoring the levels of therapeutic antibodies in individual patients would allow patient-specific dose optimization, with the potential for major therapeutic and financial benefits. Our group recently developed a new platform of bioluminescent sensor proteins (LUMABS; LUMinescent AntiBody Sensor)

  7. "Clicking" Gene Therapeutics: A Successful Union of Chemistry and Biomedicine for New Solutions

    Astakhova, Kira; Ray, Roslyn; Taskova, Maria

    2018-01-01

    The use of nucleic acid, DNA and RNA, based strategies to disrupt gene expression as a therapeutic is quickly emerging. Indeed, synthetic oligonucleotides represent a major component of modern gene therapeutics. However, the efficiency and specificity of intracellular uptake for nonmodified oligo...

  8. 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

  9. Ectromelia Virus Infections of Mice as a Model to Support the Licensure of Anti-Orthopoxvirus Therapeutics

    R. Mark Buller

    2010-09-01

    Full Text Available The absence of herd immunity to orthopoxviruses and the concern that variola or monkeypox viruses could be used for bioterroristic activities has stimulated the development of therapeutics and safer prophylactics. One major limitation in this process is the lack of accessible human orthopoxvirus infections for clinical efficacy trials; however, drug licensure can be based on orthopoxvirus animal challenge models as described in the “Animal Efficacy Rule”. One such challenge model uses ectromelia virus, an orthopoxvirus, whose natural host is the mouse and is the etiological agent of mousepox. The genetic similarity of ectromelia virus to variola and monkeypox viruses, the common features of the resulting disease, and the convenience of the mouse as a laboratory animal underscores its utility in the study of orthopoxvirus pathogenesis and in the development of therapeutics and prophylactics. In this review we outline how mousepox has been used as a model for smallpox. We also discuss mousepox in the context of mouse strain, route of infection, infectious dose, disease progression, and recovery from infection.

  10. Conversational evidence in therapeutic dialogue.

    Strong, Tom; Busch, Robbie; Couture, Shari

    2008-07-01

    Family therapists' participation in therapeutic dialogue with clients is typically informed by evidence of how such dialogue is developing. In this article, we propose that conversational evidence, the kind that can be empirically analyzed using discourse analyses, be considered a contribution to widening psychotherapy's evidence base. After some preliminaries about what we mean by conversational evidence, we provide a genealogy of evaluative practice in psychotherapy, and examine qualitative evaluation methods for their theoretical compatibilities with social constructionist approaches to family therapy. We then move on to examine the notion of accomplishment in therapeutic dialogue given how such accomplishments can be evaluated using conversation analysis. We conclude by considering a number of research and pedagogical implications we associate with conversational evidence.

  11. [Therapeutic use of cannabis derivatives].

    Benyamina, Amine; Reynaud, Michel

    2014-02-01

    The therapeutic use of cannabis has generated a lot of interest in the past years, leading to a better understanding of its mechanisms of action. Countries like the United States and Canada have modified their laws in order to make cannabinoid use legal in the medical context. It's also the case in France now, where a recent decree was issued, authorizing the prescription of medication containing "therapeutic cannabis" (decree no. 2013-473, June 5, 2013). Cannabinoids such as dronabinol, Sativex and nabilone have been tested for the treatment of acute and chronic pain. These agents are most promising to relieve chronic pain associated with cancer, with human immunodeficiency virus infection and with multiple sclerosis. However, longer-term studies are required to determine potential long-term adverse effects and risks of misuse and addiction.

  12. Therapeutic Dancing for Parkinson's Disease

    Lorenna Pryscia Carvalho Aguiar

    2016-06-01

    Full Text Available Therapeutic dancing has been advocated as an effective adjunct to conventional physical therapies for people living with Parkinson's disease (PD. This systematic review evaluates studies on the outcomes of different dance genres on mobility and quality of life in PD. We searched databases including CINHAL (1982–2015, Medline (1922–2015, Scopus (1996–2015, Web of Science (2002–2015, Embase (2007–2015, PEDro (1999–2015 and the Cochrane Library (1996–2015. The key words were: Parkinson's disease, Parkinson*, Parkinsonism, dance, dance therapy, dance genres, safety, feasibility, and quality of life. Two independent investigators reviewed the texts. Only randomized controlled trials, quasirandomized controlled trials, and case series studies were included. There was emerging evidence that therapeutic dance can be safe and feasible for people with mild to moderately severe PD, with beneficial effects on walking, freezing of gait, and health related quality of life.

  13. 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

  14. 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.

  15. Potential Therapeutic Effects of Psilocybin.

    Johnson, Matthew W; Griffiths, Roland R

    2017-07-01

    Psilocybin and other 5-hydroxytryptamine 2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. However, in the twenty-first century, scientific interest in classic psychedelics has returned and grown as a result of several promising studies, validating earlier research. Here, we review therapeutic research on psilocybin, the classic psychedelic that has been the focus of most recent research. For mood and anxiety disorders, three controlled trials have suggested that psilocybin may decrease symptoms of depression and anxiety in the context of cancer-related psychiatric distress for at least 6 months following a single acute administration. A small, open-label study in patients with treatment-resistant depression showed reductions in depression and anxiety symptoms 3 months after two acute doses. For addiction, small, open-label pilot studies have shown promising success rates for both tobacco and alcohol addiction. Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.

  16. Yessotoxin, a Promising Therapeutic Tool

    Amparo Alfonso

    2016-01-01

    Full Text Available Yessotoxin (YTX is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

  17. Cell kinetics and therapeutic efficiency

    Andreeff, M.; Abenhardt, W.; Gruner, B.; Stoffner, D.; Mainz Univ.

    1976-01-01

    The study shows that cell kinetics effects correlate with the effects of cytostatic drugs in the tumour model investigated here. It should, however, be noted that even genetically related tumour cell types may react differently to the same cytostatic drug, and that the cell kinetics effects, due to the changes in the cell cycle, cannot be predicted but should be followed with a very fast method, e.g. sequential flan fluorescence cytophotometry, for optimal therapeutic results. (orig./GSE) [de

  18. Plain language and organisational challenges

    Pedersen, Karsten

    2014-01-01

    Changing the language in an organization is a major organizational change. In this article, I discuss some of the organizational challenges for one specific language change implementation, taking the stance that language change must be treated as any other organizational change for it to have an ...

  19. 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.

  20. 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.

  1. Avian Diagnostic and Therapeutic Antibodies

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  2. 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.

  3. [Limitation of the therapeutic effort].

    Herreros, B; Palacios, G; Pacho, E

    2012-03-01

    The limitation of the therapeutic effort (LTE) consists in not applying extraordinary or disproportionate measures for therapeutic purposes that are proposed for a patient with poor life prognosis and/or poor quality of life. There are two types. The first is to not initiate certain measures or to withdraw them when they are established. A decision of the LTE should be based on some rigorous criteria, so that we make the following proposal. First, it is necessary to know the most relevant details of the case to make a decision: the preferences of the patient, the preferences of the family when pertinent, the prognosis (severity), the quality of life and distribution of the limited resources. After, the decision should be made. In this phase, participatory deliberation should be established to clarify the end of the intervention. Finally, if it is decided to perform an LTE, it should be decided how to do it. Special procedures, disproportionate measures, that are useless and vain should not be initiated for the therapeutic objective designed (withdraw them if they have been established). When it has been decided to treat a condition (interim measures), the treatment should be maintained. This complex phase may need stratification of he measures. Finally, the necessary palliative measures should be established. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  4. Energy challenges in Asia

    Niquet, V.

    2007-01-01

    Energy challenges represent one of the most important security paradigms in the Asia Pacific region where you have a mixture of growing energy dependency, fuelled by high economic growth, the emergence of new major players like China and India, and a quasi-complete absence of regional regulatory mechanisms to tackle the challenges in a multilateral way. These challenges mostly concern Japan and China, where crucial energy issues are aggravated by power rivalry, historical and ideological issues, and a lack of both economic and political harmony between them. Neither countries are self sufficient in terms of energy needs. This can lead to a shared analysis and common approaches regarding Japan and China concerning this issue. Their cases are. however very different and the solutions applied are related to different world views that are not easily reconcilable. Both countries share common objectives: both want security and stable supply. But there are also big divergences and these divergences could be new sources of conflict and misunderstanding between Tokyo and Beijing. One of the main differences is history related. Both China and Japan are uneasy regarding outside energy dependency. In Japan, memories of the pre-war oil embargo have not disappeared. The oil shocks of the 70's renewed this uneasiness. However, Japan's outside dependency is not new. Tokyo has learned to live with it, finding a system to alleviate this vulnerability in cooperation with its partners, multilateral institutions like the International Energy Agency (IEA). China's outside dependency is new. The country's dependency on oil, which began in 1993, is particularly challenging since the principles of independence, non interference and military autonomy, principles at the core of Maoist foreign strategy, did not completely disappear in spite of China's new policy of reform and opening up. China's leadership, even the fourth generation, did not forget its isolation during the 60's and 70's

  5. Severe hypertriglyceridemia. Clinical characteristics and therapeutic management.

    Masson, Walter; Rossi, Emiliano; Siniawski, Daniel; Damonte, Juan; Halsband, Ana; Barolo, Ramiro; Scaramal, Miguel

    2018-05-19

    The therapeutic management of severe hypertriglyceridaemia represents a clinical challenge. The objectives of this study were 1) to identify the clinical characteristics of patients with severe hypertriglyceridaemia, and 2) to analyse the treatment established by the physicians in each case. A cross-sectional study was carried out using the computerised medical records of all patients>18 years of age with a blood triglyceride level≥1,000mg/dL between 1 January 2011 and 31 December 2016. Clinical and laboratory variables were collected. The behaviour of the physicians in the 6 months after the lipid finding was analysed. A total of 420 patients were included (mean age 49.1±11.4 years, males 78.8%). The median of triglycerides was 1,329mg/dL (interquartile range 1,174-1,658). No secondary causes were found in 34.1% of the patients. The most frequent secondary causes were obesity (38.6%) and diabetes (28.1%). Physical activity was recommended and a nutritionist was referred to in 49.1% and 44.2% of the patients, respectively. Secondary causes were identified and attempts were made to correct them in 40.7% of cases. The most indicated pharmacological treatments were fenofibrate 200mg/day (26.5%) and gemfibrozil 900mg/day (19.3%). Few patients received the indication of omega 3 fatty acids or niacin. This study showed, for the first time in our country, the characteristics of a population with severe hypertriglyceridaemia. The therapeutic measures instituted by the physicians were insufficient. Knowing the characteristics in this particular clinical scenario could improve the current approach of these patients. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Osteomyelitis: a current challenge

    Luciana Souza Jorge

    Full Text Available Over the last 30 years, the pathogenesis of osteomyelitis has almost been totally elucidated, and many factors responsible for the persistence of this infection have been identified. Numerous antimicrobial agents with distinct spectrums of action, pharmacokinetics, and pharmacodynamics have been used in its treatment. Surgical techniques, including muscle grafts, the Ilizarov technique, and antibiotic bone cements, have been applied. However, bone infections are still a challenge. Despite the importance of isolation and identification of microorganisms to determine the antimicrobial treatment of bone infections, there are few systematic national studies about the etiological profile of these diseases. This article describes the current knowledge of osteomyelitis and summarizes published national data based on the experience of different Orthopedic and Traumatology Services. In general, S. aureus was described as an important etiological agent; however, the difference in design of national studies makes a comparison between the prevalence of bone infection, the associated risk factors, and the different therapeutic approaches difficult. In conclusion, effort is necessary in order to stimulate systematic national studies in different Orthopedics and Traumatology Services to obtain a better consensus on preventive measures and therapies of bone infections.

  7. Trans-species Engineering of Glycosylated Therapeutic Proteins

    Yang, Zhang

    important to address. Whenever glycosylation has been found to be an important PTM for function or bioactivity, human therapeutics have generally been produced in mammalian Chinese hamster ovary (CHO) cell line. Oglycosylation is one of the most complex regulated PTMs of proteins but also one of the least...... understood. Currently, mammalian cells are required for human O-glycosylation. Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower......Recombinant expression of therapeutic proteins is one of the major tasks in modern biomedicine. One of the most important factors with respect to therapeutic use in human is posttranslational modifications (PTMs) of the recombinant proteins, of which protein glycosylation is by far the most...

  8. Manufacturing of recombinant therapeutic proteins in microbial systems.

    Graumann, Klaus; Premstaller, Andreas

    2006-02-01

    Recombinant therapeutic proteins have gained enormous importance for clinical applications. The first recombinant products have been produced in E. coli more than 20 years ago. Although with the advent of antibody-based therapeutics mammalian expression systems have experienced a major boost, microbial expression systems continue to be widely used in industry. Their intrinsic advantages, such as rapid growth, high yields and ease of manipulation, make them the premier choice for expression of non-glycosylated peptides and proteins. Innovative product classes such as antibody fragments or alternative binding molecules will further expand the use of microbial systems. Even more, novel, engineered production hosts and integrated technology platforms hold enormous potential for future applications. This review summarizes current applications and trends for development, production and analytical characterization of recombinant therapeutic proteins in microbial systems.

  9. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    Kampa, I.S.

    1985-01-01

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  10. 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

  11. Major therapeutic effect of pentoxifylline-tocopherol association in the superficial radioinduced fibrosis: phase II test

    Delanian, S.; Balla-Mekias, S.; Maylin, C.; Lefaix, J.L.

    1997-01-01

    The association of pentoxifylline-tocopherol seems efficient in the reduction of the superficial human radioinduced fibrosis. This phase II invites to realize a randomized test and to a comparison with the results got with the dismutase superoxide. (N.C.)

  12. Challenges in Designing Mechatronic Systems

    Torry-Smith, Jonas; Qamar, Ahsan; Achiche, Sofiane

    2013-01-01

    Development of mechatronic products is traditionally carried out by several design experts from different design domains. Performing development of mechatronic products is thus greatly challenging. In order to tackle this, the critical challenges in mechatronics have to be well understood and well...... supported through applicable methods and tools. This paper aims at identifying the major challenges, by conducting a systematic and thorough survey of the most relevant research work in mechatronic design. Solutions proposed in literature are assessed and illustrated through a case study in order...... to investigate if the challenges can be handled appropriately by the methods, tools, and mindsets suggested by the mechatronic community. Using a real world mechatronics case, the paper identifies the areas where further research is required, by showing a clear connection between the actual problems faced during...

  13. Transistor challenges - A DRAM perspective

    Faul, Juergen W.; Henke, Dietmar

    2005-01-01

    Key challenges of the transistor scaling from a DRAM perspective will be reviewed. Both, array transistors as well as DRAM support devices face challenges that differ essentially from high performance logic device scaling. As a major difference, retention time and standby current requirements characterize special boundary conditions in the DRAM device design. Array device scaling is determined by a chip size driven aggressive node scaling. To continue scaling, major innovations need to be introduced into state-of-the-art planar array transistors. Alternatively, non planar device concepts will have to be evaluated. Support device design for DRAMs is driven by today's market demand for increased chip performances at little to no extra cost. Major innovations are required to continue that path. Besides this strive for performance increase, special limitations for 'on pitch' circuits at the array edge will come up due to the aggressive cell size scaling

  14. Paradoxical Roles of Nanoparticles in Cancer Therapeutics and Carcinogenesis

    Despeaux, Emily

    Nanoparticles (NPs) are becoming increasingly common in consumer goods and are under investigation for a variety of industrial and biomedical applications. However, challenges in determining NP toxicity may prevent them from reaching their full potential. NPs cannot be treated as single class for toxicity evaluations. Even among particles made from the same material, particle-specific physical properties, including size, shape, surface charge, agglomeration state, and surface modifications have a strong effect on the toxicity. Even so, the obstacles to conclusively and reproducibly evaluating toxicity span all NP classes. NP literature is riddled with confusing and often contradictory reports regarding the biocompatibility of both engineered NPs, designed with biocompatibility as a priority, and NPs from occupational or environmental exposures. Incomplete NP characterization and sample inhomogeneity represent major confounding factors in disparate results from seemingly comparable study setups. Additionally, NPs can interfere with many conventional toxicity screening methods. Inappropriate doses, exposure routes, and toxicity endpoints further diminish the utility of many published studies. Given the burgeoning interest in NP-based therapeutic agents, consistent, reliable standards are needed to ensure the biocompatibility of new formulations. To those ends, the synthesis, characterization, and in vitro toxicity of a multi-functional NP therapeutic were investigated (Chapter 2). Specifically, superparamagnetic iron oxide nanoparticles (SPIONs) were coated with amphiphilic polymer and functionalized with antisense oligonucleotides targeting survivin, an anti-apoptotic protein that is highly overexpressed in cancer. SPION physical properties, including particle size and composition, were characterized at each step of synthesis. Our results showed that the SPION platform is biocompatible and capable of delivering functional antisense oligonucleotides to regulate

  15. Diagnostic and therapeutic management of hepatocellular carcinoma

    Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

    2015-01-01

    Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

  16. Therapeutic touch: influence on vital signs of newborns

    Ramada, Nadia Christina Oliveira; Almeida, Fabiane de Amorim; Cunha, Mariana Lucas da Rocha

    2013-01-01

    ABSTRACT Objective>: To compare vital signs before and after the therapeutic touch observed in hospitalized newborns in neonatal intensive care unit. Methods: This was a quasi-experimental study performed at a neonatal intensive care unit of a municipal hospital, in the city of São Paulo (SP), Brazil. The sample included 40 newborns submitted to the therapeutic touch after a painful procedure. We evaluated the vital signs, such as heart and respiratory rates, temperature and pain intensity, before and after the therapeutic touch. Results: The majority of newborns were male (n=28; 70%), pre-term (n=19; 52%) and born from vaginal delivery (n=27; 67%). Respiratory distress was the main reason for hospital admission (n=16; 40%). There was a drop in all vital signs after therapeutic touch, particularly in pain score, which had a considerable reduction in the mean values, from 3.37 (SD=1.31) to 0 (SD=0.0). All differences found were statistically significant by the Wilcoxon test (p<0.05). Conclusion: The results showed that therapeutic touch promotes relaxation of the baby, favoring reduction in vital signs and, consequently in the basal metabolism rate. PMID:24488378

  17. ROCK as a therapeutic target for ischemic stroke.

    Sladojevic, Nikola; Yu, Brian; Liao, James K

    2017-12-01

    Stroke is a major cause of disability and the fifth leading cause of death. Currently, the only approved acute medical treatment of ischemic stroke is tissue plasminogen activator (tPA), but its effectiveness is greatly predicated upon early administration of the drug. There is, therefore, an urgent need to find new therapeutic options for acute stroke. Areas covered: In this review, we summarize the role of Rho-associated coiled-coil containing kinase (ROCK) and its potential as a therapeutic target in stroke pathophysiology. ROCK is a major regulator of cell contractility, motility, and proliferation. Many of these ROCK-mediated processes in endothelial cells, vascular smooth muscle cells, pericytes, astrocytes, glia, neurons, leukocytes, and platelets are important in stroke pathophysiology, and the inhibition of such processes could improve stroke outcome. Expert commentary: ROCK is a potential therapeutic target for cardiovascular disease and ROCK inhibitors have already been approved for human use in Japan and China for the treatment of acute stroke. Further studies are needed to determine the role of ROCK isoforms in the pathophysiology of cerebral ischemia and whether there are further therapeutic benefits with selective ROCK inhibitors.

  18. Therapeutic irradiation and brain injury

    Sheline, G.E.; Wara, W.M.; Smith, V.

    1980-01-01

    This is a review and reanalysis of the literature on adverse effects of therapeutic irradiation on the brain. Reactions have been grouped and considered according to time of appearance. The emphasis of the analysis is on delayed reactions, especially those that occur from a few months to several years after irradiation. All dose specifications were converted into equivalent megavoltage rads. The data were analyzed in terms of total dose, overall treatment time and number of treatment fractions. Also discussed were acute radiation reactions, early delayed radiation reactions, somnolence and leukoencephalopathy post-irradiation/chemotherapy and combined effects of radiation and chemotherapy

  19. 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.

  20. Diabetes mellitus: Exploring the challenges in the drug development process

    Julius A Vaz

    2012-01-01

    Full Text Available Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  1. Diabetes mellitus: Exploring the challenges in the drug development process.

    Vaz, Julius A; Patnaik, Ashis

    2012-07-01

    Diabetes mellitus has reached epidemic proportions and continues to be a major burden on society globally. The International Diabetes Federation (IDF) estimated the global burden of diabetes to be 366 million in 2011 and predicted that by 2030 this will have risen to 552 million. In spite of newer and effective treatment options, newer delivery and diagnostic devices, stricter glycaemic targets, better treatment guidelines and increased awareness of the disease, baseline glycosylated hemoglobin remains relatively high in subjects diagnosed and treated with type 2 diabetes. The search continues for an ideal anti diabetic drug that will not only normalize blood glucose but also provide beta cell rest and possibly restoration of beta cell function. The development of anti diabetic drugs is riddled with fundamental challenges. The concept of beta cell rest and restoration is yet to be completely understood and proven on a long term. The ideal therapeutic approach to treating type 2 diabetes is not yet determined. Our understanding of drug safety in early clinical development is primarily limited to "Type A" reactions. Until marketing authorization most drugs are approved based on the principle of confirming non-inferiority with an existing gold standard or determining superiority to a placebo. The need to obtain robust pharmaco-economic data prior to marketing authorization in order to determine appropriate pricing of a new drug remains a major challenge. The present review outlines some of the challenges in drug development of anti-diabetic drugs citing examples of pulmonary insulin, insulin analogues, thiazolidinediones and the GLP1 analogues.

  2. Therapeutic spaces of care farming: Transformative or ameliorating?

    Kaley, Alexandra; Hatton, Chris; Milligan, Christine

    2018-05-04

    Since Wil Gesler's earliest articulation (Gesler, 1992; Gesler, 1996) key thinkers in the field of therapeutic landscapes have sought to emphasise the embodied, contextual and wholly relational nature of the relationship that exists between people and place. However, the extant research has tended to focus on the relational healing experience as this occurs 'in the moment' and with reference to a specific location or site of healing, with less attention being paid to what happens to people when they return to their ordinary or everyday places. In this paper, we reflect on findings from visual ethnographic work (including photography and film) that explored the therapeutic landscape experiences of people with intellectual disabilities engaged in care farming interventions for health and wellbeing. The study also recruited farm staff and family members or carers to take part, and comprised 20 participants in total. Having identified a gap in our understanding, consideration is given to wider impact that engaging in these sorts of activities had on the everyday lives of the participants in this study. We argue that this study has identified two types of therapeutic journey that broadly fit the experiences of study participants. The first type of journey denotes landscape experiences that are transformative. Here the therapeutic power of the care farm landscape resides in the ability of activities conducted on care farms to influence other aspects of participants' lives in ways that promote wellbeing. By contrast, there is another type of journey where the therapeutic power of the care farm resides in its ability to ameliorate challenging or harmful life situations, thus offering people a temporary site of respite or refuge. We conclude that these findings denote an important development for this sub-field of health geography, not only because they draw attention to the transformative power of the therapeutic encounter, but also the broader socio-spatial environments

  3. Challenges and opportunities in multichannel customer management

    Neslin, Scott A.; Grewal, Dhruv; Leghorn, Robert; Shankar, Venkatesh; Teerling, Marije L.; Thomas, Jacquelyn S.; Verhoef, Peter C.

    2006-01-01

    Multichannel customer management is the design, deployment, coordination, and evaluation of channels through which firms and customers interact, with the goal of enhancing customer value through effective customer acquisition, retention, and development. The authors identify five major challenges

  4. Challenges and opportunities in multichannel customer management

    Neslin, Scott A.; Grewal, Dhruv; Leghorn, Robert; Shankar, Venkatesh; Teerling, Marije L.; Thomas, Jacquelyn S.; Verhoef, Peter C.

    Multichannel customer management is the design, deployment, coordination, and evaluation of channels through which firms and customers interact, with the goal of enhancing customer value through effective customer acquisition, retention, and development. The authors identify five major challenges

  5. Positivists, Postmodernists, Aristotelians, and the Challenger Disaster.

    Walzer, Arthur E.; Gross, Alan

    1994-01-01

    Examines the deliberations prior to the Challenger disaster from the perspective of three major approaches in recent scholarship in rhetoric as applied to technical communications: positivism, postmodernistic social constructionism, and classical Aristotelianism. Champions an approach based on Aristotle's "Rhetoric." (HB)

  6. Next-generation sequencing for endocrine cancers: Recent advances and challenges.

    Suresh, Padmanaban S; Venkatesh, Thejaswini; Tsutsumi, Rie; Shetty, Abhishek

    2017-05-01

    Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives.

  7. 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.

  8. [Therapeutic Aggressiveness and Liquid Oncology].

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  9. Therapeutic drug monitoring in pregnancy.

    Matsui, Doreen M

    2012-10-01

    Therapeutic drug monitoring (TDM) is commonly recommended to optimize drug dosing regimens of various medications. It has been proposed to guide therapy in pregnant women, in whom physiological changes may lead to altered pharmacokinetics resulting in difficulty in predicting the appropriate drug dosage. Ideally, TDM may play a role in enhancing the effectiveness of treatment while minimizing toxicity of both the mother and fetus. Monitoring of drug levels may also be helpful in assessing adherence to prescribed therapy in selected cases. Limitations exist as therapeutic ranges have only been defined for a limited number of drugs and are based on data obtained in nonpregnant patients. TDM has been suggested for anticonvulsants, antidepressants, and antiretroviral drugs, based on pharmacokinetic studies that have shown reduced drug concentrations. However, there is only relatively limited (and sometimes inconsistent) information regarding the clinical impact of these pharmacokinetic changes during pregnancy and the effect of subsequent dose adjustments. Further studies are required to determine whether implementation of TDM during pregnancy improves outcome and is associated with any benefit beyond that achieved by clinical judgment alone. The cost effectiveness of TDM programs during pregnancy also remains to be examined.

  10. Multicore Programming Challenges

    Perrone, Michael

    The computer industry is facing fundamental challenges that are driving a major change in the design of computer processors. Due to restrictions imposed by quantum physics, one historical path to higher computer processor performance - by increased clock frequency - has come to an end. Increasing clock frequency now leads to power consumption costs that are too high to justify. As a result, we have seen in recent years that the processor frequencies have peaked and are receding from their high point. At the same time, competitive market conditions are giving business advantage to those companies that can field new streaming applications, handle larger data sets, and update their models to market conditions faster. The desire for newer, faster and larger is driving continued demand for higher computer performance.

  11. Investigating the Molecular Basis of Major Depressive Disorder Etiology

    Jabbi, Mbemba; Korf, Jaalp; Ormel, Johan; Kema, Ido P.; den Boer, Johan A.; Kvetnansky, R; Aguilera, G; Goldstein, D; Jezova, D; Krizanova, O; Sabban, EL; Pacak, K

    2008-01-01

    Genes play a major role in behavioral adaptation to challenging environmental stimuli, but the complexity of their contribution remains unclear. There is growing evidence linking disease phenotypes with genes on the one hand, and the genesis of stress-related disorders like major depression, as a

  12. Personal Investigator: A Therapeutic 3D Game for Adolescent Psychotherapy

    Coyle, David; Matthews, Mark; Sharry, John; Nisbet, Andy; Doherty, Gavin

    2005-01-01

    Although mental health problems increase markedly during adolescent years, therapists often find it difficult to engage withadolescents. The majority of disturbed adolescents do not receive professional mental health care and of those who do fewerstill will fully engage with the therapeutic process (Offer et al. 1991; US Surgeon General 1999). Personal Investigator (PI) is a3D computer game specifically designed to help adolescents overcome mental health problems such as depression and helpth...

  13. New Advances in Nanotechnology-Based Diagnosis and Therapeutics for Breast Cancer: An Assessment of Active-Targeting Inorganic Nanoplatforms.

    Falagan-Lotsch, Priscila; Grzincic, Elissa M; Murphy, Catherine J

    2017-01-18

    Breast cancer is a major cause of suffering and mortality among women. Limitations in the current diagnostic methods and treatment approaches have led to new strategies to positively impact the survival rates and quality of life of breast cancer patients. Nanotechnology offers a real possibility of mitigating breast cancer mortality by early-stage cancer detection and more precise diagnosis as well as more effective treatments with minimal side effects. The current nanoplatforms approved for breast cancer therapeutics are based on passive tumor targeting using organic nanoparticles and have not provided the expected significant improvements in the clinic. In this review, we present the emerging approaches in breast cancer nanomedicine based on active targeting using versatile inorganic nanoplatforms with biomedical relevance, such as gold, silica, and iron oxide nanoparticles, as well as their efficacy in breast cancer imaging, drug and gene delivery, thermal therapy, combinational therapy, and theranostics in preclinical studies. The main challenges for clinical translation and perspectives are discussed.

  14. Radiation caries: a therapeutical option

    Biazolla, E.R.; Miziara, T.C.

    1988-01-01

    It is showed a clinical report about radiation caries. As the tooth destruction was, mainly, of the majority of the teeth, was made a therapy where, besides avoiding the osteoradiomielite, also is possible to reability the patient. (author)

  15. New Therapeutic Targets in Soft Tissue Sarcoma

    Demicco, Elizabeth G; Maki, Robert G; Lev, Dina C.; Lazar, Alexander J

    2012-01-01

    Soft tissue sarcomas are an uncommon and diverse group of more than 50 mesenchymal malignancies. The pathogenesis of many of these is poorly understood, but others have begun to reveal the secrets of their inner workings. With considerable effort over recent years, soft tissue sarcomas have increasingly been classified on the basis of underlying molecular alterations. In turn, this has allowed the development and application of targeted agents in several specific, molecularly defined, sarcoma subtypes. This review will focus the rationale for targeted therapy in sarcoma, with emphasis on the relevance of specific molecular factors and pathways in both translocation-associated sarcomas and in genetically complex tumors. In addition, we will address some of the early successes in sarcoma targeted therapy as well as a few challenges and disappointments in this field. Finally we will discuss several possible opportunities represented by poorly understood, but potentially promising new therapeutic targets, as well as several novel biologic agents currently in preclinical and early phase I/II trials. This will provide the reader with context for understanding the current state this field and a sense of where it may be headed in the coming years. PMID:22498582

  16. Therapeutic modalities for cow's milk allergy.

    Seidman, Ernest G; Singer, Sanford

    2003-06-01

    To discuss current therapeutic modalities for cow's milk allergy and its prevention. The sources of data include original clinical studies carried out at Ste. Justine Hospital, as well as a systematic search of the published English and French language scientific literature restricted to human subjects using computerized searches (National Public Library of Medicine, Cochrane Database Systems Review) from 1997 to 2002. Search terms for article retrieval included food allergy, milk allergy, therapy, and prevention. The therapy of food allergies depends upon an accurate diagnosis, which remains a challenge in non--IgE-mediated cases. Dietary exclusion remains the mainstay of therapy, with medications reserved for exceptional patients. Preliminary evidence suggests that pancreatic enzyme supplementation may be of benefit for cases with multiple food allergies and severe eczema. Hydrolysate formula use is currently recommended for dietary allergy prevention in infants at an increased risk when maternal milk is insufficient or unavailable. The use of partially hydrolyzed formulas to prevent allergic disorders, including atopic dermatitis, is supported by clinical studies, but cannot be used in the already sensitized, milk-allergic child. Probiotics show enormous potential in preventing food allergic disorders as well.

  17. Site-Specific PEGylation of Therapeutic Proteins

    Jonathan K. Dozier

    2015-10-01

    Full Text Available The use of proteins as therapeutics has a long history and is becoming ever more common in modern medicine. While the number of protein-based drugs is growing every year, significant problems still remain with their use. Among these problems are rapid degradation and excretion from patients, thus requiring frequent dosing, which in turn increases the chances for an immunological response as well as increasing the cost of therapy. One of the main strategies to alleviate these problems is to link a polyethylene glycol (PEG group to the protein of interest. This process, called PEGylation, has grown dramatically in recent years resulting in several approved drugs. Installing a single PEG chain at a defined site in a protein is challenging. Recently, there is has been considerable research into various methods for the site-specific PEGylation of proteins. This review seeks to summarize that work and provide background and context for how site-specific PEGylation is performed. After introducing the topic of site-specific PEGylation, recent developments using chemical methods are described. That is followed by a more extensive discussion of bioorthogonal reactions and enzymatic labeling.

  18. Generation of “LYmph Node Derived Antibody Libraries” (LYNDAL) for selecting fully human antibody fragments with therapeutic potential.

    Diebolder, Philipp; Keller, Armin; Haase, Stephanie; Schlegelmilch, Anne; Kiefer, Jonathan D; Karimi, Tamana; Weber, Tobias; Moldenhauer, Gerhard; Kehm, Roland; Eis-Hübinger, Anna M; Jäger, Dirk; Federspil, Philippe A; Herold-Mende, Christel; Dyckhoff, Gerhard; Kontermann, Roland E; Arndt, Michaela A E; Krauss, Jürgen

    2014-01-01

    The development of efficient strategies for generating fully human monoclonal antibodies with unique functional properties that are exploitable for tailored therapeutic interventions remains a major challenge in the antibody technology field. Here, we present a methodology for recovering such antibodies from antigen-encountered human B cell repertoires. As the source for variable antibody genes, we cloned immunoglobulin G (IgG)-derived B cell repertoires from lymph nodes of 20 individuals undergoing surgery for head and neck cancer. Sequence analysis of unselected “LYmph Node Derived Antibody Libraries” (LYNDAL) revealed a naturally occurring distribution pattern of rearranged antibody sequences, representing all known variable gene families and most functional germline sequences. To demonstrate the feasibility for selecting antibodies with therapeutic potential from these repertoires, seven LYNDAL from donors with high serum titers against herpes simplex virus (HSV) were panned on recombinant glycoprotein B of HSV-1. Screening for specific binders delivered 34 single-chain variable fragments (scFvs) with unique sequences. Sequence analysis revealed extensive somatic hypermutation of enriched clones as a result of affinity maturation. Binding of scFvs to common glycoprotein B variants from HSV-1 and HSV-2 strains was highly specific, and the majority of analyzed antibody fragments bound to the target antigen with nanomolar affinity. From eight scFvs with HSV-neutralizing capacity in vitro,the most potent antibody neutralized 50% HSV-2 at 4.5 nM as a dimeric (scFv)2. We anticipate our approach to be useful for recovering fully human antibodies with therapeutic potential.

  19. ATLAS Data Challenge 1

    Poulard, G

    2003-01-01

    In 2002 the ATLAS experiment started a series of Data Challenges (DC) of which the goals are the validation of the Computing Model, of the complete software suite, of the data model, and to ensure the correctness of the technical choices to be made. A major feature of the first Data Challenge (DC1) was the preparation and the deployment of the software required for the production of large event samples for the High Level Trigger (HLT) and physics communities, and the production of those samples as a world-wide distributed activity. The first phase of DC1 was run during summer 2002, and involved 39 institutes in 18 countries. More than 10 million physics events and 30 million single particle events were fully simulated. Over a period of about 40 calendar days 71000 CPU-days were used producing 30 Tbytes of data in about 35000 partitions. In the second phase the next processing step was performed with the participation of 56 institutes in 21 countries (~ 4000 processors used in parallel). The basic elements of ...

  20. 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.

  1. The Marihuana Dilemma: Challenge to Commanders.

    The marihuana dilemma poses a major challenge to commanders in the US Army today. The problem was analyzed as to the characteristics of the drug...available to commanders to meet the challenge. The essay concludes that marihuana should not be legalized; drug users or former drug users should not be

  2. Challenges and Prospects of Traditional Food Processing ...

    This paper focuses on challenges and prospects of traditional food processing technologies and their products in Nigeria. The major objective of the paper is to identify the challenges confronting traditional food processing technologies as well as the potentials the traditional food processing technologies has in boosting the ...

  3. The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

    Hudson, Brian D; Ulven, Trond; Milligan, Graeme

    2013-01-01

    G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

  4. Preexisting Antibodies to an F(ab′)2 Antibody Therapeutic and Novel Method for Immunogenicity Assessment

    Ruppel, Jane; Brady, Ann; Elliott, Rebecca; Leddy, Cecilia; Palencia, Marco; Coleman, Daniel; Couch, Jessica A.; Wakshull, Eric

    2016-01-01

    Anti-therapeutic antibodies (ATAs) may impact drug exposure and activity and induce immune complex mediated toxicity; therefore the accurate measurement of ATA is important for the analysis of drug safety and efficacy. Preexisting ATAs to the hinge region of anti-Delta like ligand 4 (anti-DLL4) F(ab′)2, a potential antitumor therapeutic, were detected in cynomolgus monkey serum, which presented a challenge in developing assays for detecting treatment induced ATA. A total ATA assay was develop...

  5. Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

    Gareth R. Willis

    2017-10-01

    Full Text Available Exosomes are defined as submicron (30–150 nm, lipid bilayer-enclosed extracellular vesicles (EVs, specifically generated by the late endosomal compartment through fusion of multivesicular bodies with the plasma membrane. Produced by almost all cells, exosomes were originally considered to represent just a mechanism for jettisoning unwanted cellular moieties. Although this may be a major function in most cells, evolution has recruited the endosomal membrane-sorting pathway to duties beyond mere garbage disposal, one of the most notable examples being its cooption by retroviruses for the generation of Trojan virions. It is, therefore, tempting to speculate that certain cell types have evolved an exosome subclass active in intracellular communication. We term this EV subclass “signalosomes” and define them as exosomes that are produced by the “signaling” cells upon specific physiological or environmental cues and harbor cargo capable of modulating the programming of recipient cells. Our recent studies have established that signalosomes released by mesenchymal stem/stromal cells (MSCs represent the main vector of MSC immunomodulation and therapeutic action in animal models of lung disease. The efficacy of MSC-exosome treatments in a number of preclinical models of cardiovascular and pulmonary disease supports the promise of application of exosome-based therapeutics across a wide range of pathologies within the near future. However, the full realization of exosome therapeutic potential has been hampered by the absence of standardization in EV isolation, and procedures for purification of signalosomes from the main exosome population. This is mainly due to immature methodologies for exosome isolation and characterization and our incomplete understanding of the specific characteristics and molecular composition of signalosomes. In addition, difficulties in defining metrics for potency of exosome preparations and the challenges of industrial

  6. Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

    Alsharif, Naser Z.; And Others

    1997-01-01

    Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

  7. The therapeutic relationship after psychiatric admission.

    Roche, Eric

    2014-03-01

    The therapeutic relationship is one of the most central and important factors in the treatment of mental health disorders. A better therapeutic relationship is associated with service engagement, medication adherence, and satisfaction with services. This study aimed to compare the demographic and clinical factors associated with the therapeutic relationship in voluntarily and involuntarily admitted psychiatric service users. We found that individuals who had been admitted involuntarily, who had a diagnosis of a psychotic disorder, and who reported higher levels of perceived pressures on admission were more likely to have a poorer therapeutic relationship with their consultant psychiatrist. Greater levels of insight and treatment satisfaction, together with higher levels of procedural justice experienced on admission, were associated with a better therapeutic relationship. We found that the level of perceived coercion on admission was not related to the therapeutic relationship. Targeted interventions to improve the therapeutic relationship, particularly for involuntarily admitted service users, are discussed.

  8. The Major Histocompatibility Complex in Transplantation

    Marco Antonio Ayala García

    2012-01-01

    Full Text Available The transplant of organs is one of the greatest therapeutic achievements of the twentieth century. In organ transplantation, the adaptive immunity is considered the main response exerted to the transplanted tissue, since the principal target of the immune response is the MHC (major histocompatibility complex molecules expressed on the surface of donor cells. However, we should not forget that the innate and adaptive immunities are closely interrelated and should be viewed as complementary and cooperating. When a human transplant is performed, HLA (human leukocyte antigens molecules from a donor are recognized by the recipient's immune system triggering an alloimmune response Matching of donor and recipient for MHC antigens has been shown to have a significant positive effect on graft acceptance. This paper will present MHC, the innate and adaptive immunities, and clinical HLA testing.

  9. Sugar-based amphiphilic polymers for biomedical applications: from nanocarriers to therapeutics.

    Gu, Li; Faig, Allison; Abdelhamid, Dalia; Uhrich, Kathryn

    2014-10-21

    Various therapeutics exhibit unfavorable physicochemical properties or stability issues that reduce their in vivo efficacy. Therefore, carriers able to overcome such challenges and deliver therapeutics to specific in vivo target sites are critically needed. For instance, anticancer drugs are hydrophobic and require carriers to solubilize them in aqueous environments, and gene-based therapies (e.g., siRNA or pDNA) require carriers to protect the anionic genes from enzymatic degradation during systemic circulation. Polymeric micelles, which are self-assemblies of amphiphilic polymers (APs), constitute one delivery vehicle class that has been investigated for many biomedical applications. Having a hydrophobic core and a hydrophilic shell, polymeric micelles have been used as drug carriers. While traditional APs are typically comprised of nondegradable block copolymers, sugar-based amphiphilic polymers (SBAPs) synthesized by us are comprised of branched, sugar-based hydrophobic segments and a hydrophilic poly(ethylene glycol) chain. Similar to many amphiphilic polymers, SBAPs self-assemble into polymeric micelles. These nanoscale micelles have extremely low critical micelle concentrations offering stability against dilution, which occurs with systemic administration. In this Account, we illustrate applications of SBAPs for anticancer drug delivery via physical encapsulation within SBAP micelles and chemical conjugation to form SBAP prodrugs capable of micellization. Additionally, we show that SBAPs are excellent at stabilizing liposomal delivery systems. These SBAP-lipid complexes were developed to deliver hydrophobic anticancer therapeutics, achieving preferential uptake in cancer cells over normal cells. Furthermore, these complexes can be designed to electrostatically complex with gene therapies capable of transfection. Aside from serving as a nanocarrier, SBAPs have also demonstrated unique bioactivity in managing atherosclerosis, a major cause of cardiovascular

  10. Therapeutic Inertia in the New Landscape of Multiple Sclerosis Care

    Gustavo Saposnik

    2018-03-01

    Full Text Available The landscape of multiple sclerosis (MS treatment is constantly changing. Significant heterogeneity exists in the efficacy and risks associated with these therapies. Therefore, clinicians have the challenge to tailor treatment based on several factors (disease activity level, risk of progression, individual patient preferences and characteristics, personal expertise, etc., to identify the optimal balance between safety and efficacy. However, most clinicians have limited education in decision-making and formal training in risk management. Together, these factors may lead to therapeutic inertia (TI; defined as the absence of treatment initiation or intensification when therapeutic goals are unmet. TI may lead to suboptimal treatments choices, worse clinical outcomes, and more disability. This article provides a succinct overview on factors influencing TI in MS care.

  11. Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics.

    Sparrow, Janet R

    2016-04-26

    Although currently available treatment options for age-related macular degeneration (AMD) are limited, particularly for atrophic AMD, the identification of predisposing genetic variations has informed clinical studies addressing therapeutic options such as complement inhibitors and anti-inflammatory agents. To lower risk of early AMD, recommended lifestyle interventions such as the avoidance of smoking and the intake of low glycemic antioxidant-rich diets have largely followed from the identification of nongenetic modifiable factors. On the other hand, the challenge of understanding the complex relationship between aging and cumulative damage leading to AMD has fueled investigations of the visual cycle adducts that accumulate in retinal pigment epithelial (RPE) cells and are a hallmark of aging retina. These studies have revealed properties of these compounds that provide insights into processes that may compromise RPE and could contribute to disease mechanisms in AMD. This work has also led to the design of targeted therapeutics that are currently under investigation.

  12. A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

    Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

    2017-07-01

    There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Biological and therapeutic activities, and anticancer properties of curcumin.

    Perrone, Donatella; Ardito, Fatima; Giannatempo, Giovanni; Dioguardi, Mario; Troiano, Giuseppe; Lo Russo, Lucio; DE Lillo, Alfredo; Laino, Luigi; Lo Muzio, Lorenzo

    2015-11-01

    Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Curcumin has been used extensively in Ayurvedic medicine, as it is nontoxic and exhibits a variety of therapeutic properties, including antioxidant, analgesic, anti-inflammatory and antiseptic activities. Recently, certain studies have indicated that curcumin may exert anticancer effects in a variety of biological pathways involved in mutagenesis, apoptosis, tumorigenesis, cell cycle regulation and metastasis. The present study reviewed previous studies in the literature, which support the therapeutic activity of curcumin in cancer. In addition, the present study elucidated a number of the challenges concerning the use of curcumin as an adjuvant chemotherapeutic agent. All the studies reviewed herein suggest that curcumin is able to exert anti-inflammatory, antiplatelet, antioxidative, hepatoprotective and antitumor activities, particularly against cancers of the liver, skin, pancreas, prostate, ovary, lung and head neck, as well as having a positive effect in the treatment of arthritis.

  14. Angiogenesis and Its Therapeutic Opportunities

    So Young Yoo

    2013-01-01

    Full Text Available Angiogenesis plays critical roles in human physiology that range from reproduction and fetal growth to wound healing and tissue repair. The sophisticated multistep process is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells. Uncontrolled angiogenesis may lead to several angiogenic disorders, including vascular insufficiency (myocardial or critical limb ischemia and vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies. Thus, numerous therapeutic opportunities can be envisaged through the successful understanding and subsequent manipulation of angiogenesis. Here, we review the clinical implications of angiogenesis and discuss pro- and antiangiogenic agents that offer potential therapy for cancer and other angiogenic diseases.

  15. Therapeutic target for protozoal diseases

    Rathore, Dharmendar [Blacksburg, VA; Jani, Dewal [Blacksburg, VA; Nagarkatti, Rana [Blacksburg, VA

    2008-10-21

    A novel Fasciclin Related Adhesive Protein (FRAP) from Plasmodium and related parasites is provided as a target for therapeutic intervention in diseases caused by the parasites. FRAP has been shown to play a critical role in adhesion to, or invasion into, host cells by the parasite. Furthermore, FRAP catalyzes the neutralization of heme by the parasite, by promoting its polymerization into hemozoin. This invention provides methods and compositions for therapies based on the administration of protein, DNA or cell-based vaccines and/or antibodies based on FRAP, or antigenic epitopes of FRAP, either alone or in combination with other parasite antigens. Methods for the development of compounds that inhibit the catalytic activity of FRAP, and diagnostic and laboratory methods utilizing FRAP are also provided.

  16. Therapeutic Plasmapheresis in Kidney Transplantation

    Zeynep Kendi Celebi

    2013-02-01

    Full Text Available In 1960's, with succesfully renal transplantations, acute rejection became to be a serious problem for graft survival. From 1965 to 2010, with the introduction of new immunosuppressant agents such as cyclosporine, mycophenolate mofetile and tacrolimus, the acute rejection rates declined from 80% to 10% . There is an ongoing gradual improvement in allograft survival. Use of Therapeutic plasma exchange (TPE is not evidence based treatment, but TPE is necessary for pre- and also post transplantation in patients with DSA. TPE is also a main treatment for antibody mediated rejection (AMR , but in clinical practice the duration and frequency of TPE and individual difference of antibody production is unclear. There is a requirement for more specific antibody elimination. Further randomised controlled studies are needed to elucidate TPE use before and after kidney transplantation. [Dis Mol Med 2013; 1(1.000: 8-10

  17. Therapeutical uses of 131I

    Lago, Graciela.

    1994-01-01

    Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

  18. Therapeutic interventions in cerebral palsy.

    Patel, Dilip R

    2005-11-01

    Various therapeutic interventions have been used in the management of children with cerebral palsy. Traditional physiotherapy and occupational therapy are widely used interventions and have been shown to be of benefit in the treatment of cerebral palsy. Evidence in support of the effectiveness of the neurodevelopmental treatment is equivocal at best. There is evidence to support the use and effectiveness of neuromuscular electrical stimulation in children with cerebral palsy. The effectiveness of many other interventions used in the treatment of cerebral palsy has not been clearly established based on well-controlled trials. These include: sensory integration, body-weight support treadmill training, conductive education, constraint-induced therapy, hyperbaric oxygen therapy, and the Vojta method. This article provides an overview of salient aspects of popular interventions used in the management of children with cerebral palsy.

  19. Therapeutic options for lip augmentation.

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  20. Therapeutic Drug Monitoring of Lithium

    Mose, Tina; Damkier, Per; Petersen, Magnus

    2015-01-01

    BACKGROUND: Serum lithium is monitored to ensure levels within the narrow therapeutic window. This study examines the interlaboratory variation and inaccuracy of lithium monitoring in Denmark. METHODS: In 16 samples consisting of (1) control materials (n = 4), (2) pooled patient serum (n = 5......), and (3) serum from individual patients (n = 7), lithium was measured in 19 laboratories using 20 different instruments. The lithium concentrations were targeted by a reference laboratory. Ion-selective electrode (n = 5), reflective spectrophotometric (RSM, n = 5), and spectrophotometric (n = 10) methods...... of >12%. Seven of these instruments had a systematic positive or negative bias and more so at lower lithium concentrations. Three poorly calibrated instruments were found in the ion-selective electrode group, 3 in the spectrophotometric group, and 2 in the RSM group. The instruments using reflectance...

  1. Challenges in Piaget's legacy.

    Bibace, Roger

    2013-03-01

    The publication of After Piaget (Martí and Rodríguez 2012) hopefully triggers a new effort to understand the richness of the efforts of that major psychologist of the 20th century. Piaget was consistently concerned with part/whole relationships throughout his life. He addressed this issue philosophically, epistemologically, and psychologically. Conceptually Piaget struggled with the issue of continuity/discontinuity in development and changed his mind about how to reconcile the discontinuities of stages with his concept of development. I also attribute his variability to the implications of his important work on perception, and to his willingness to get involved in widespread concrete applications of his approach to education including the education of children with special needs; his center for genetic epistemology, and his interest in psychoanalysis. Benefiting from all the authors of After Piaget, I want to point out that Piaget has identified many major issues that will continue to constitute challenges to psychology in this century. These include specifying terms such as 'development;' methodological issues such as sampling both quantitatively in one culture and across cultures; comprehensive inclusion of the psychological processes covered by introductory textbooks in psychology; and conceptual issues such as the relationships among all these parts within a whole. I make a distinction between an 'issue' and a 'problem'--problems have solutions; while issues refer to controversies in science generally as well as in psychology that have persisted for centuries.

  2. Weaving History through the Major

    Mayfield, Betty

    2014-01-01

    The benefits of including the study of the history of mathematics in the education of mathematics majors have been discussed at length elsewhere. Many colleges and universities now offer a History of Mathematics course for mathematics majors, for mathematics education majors, or for general credit. At Hood College, we emphasize our commitment to…

  3. Therapeutic communication and relationships in chronic and complex care.

    Brownie, Sharon; Scott, Robin; Rossiter, Rachel

    2016-10-05

    As the population ages and the incidence of chronic diseases and lifestyle-related conditions rises, nurses are increasingly required to provide care for people with a range of chronic (long-term) conditions. The healthcare needs of patients are often complicated by comorbid conditions. Nurses deliver healthcare in the context of the patient's medical conditions, treatment regimens, the healthcare system, and the individual's socioeconomic, personal and family factors, which may include the challenges of social isolation and geographic distance. In such complex circumstances, patients may be perceived as 'difficult' or 'challenging', however, the challenge is not the patient themselves, but the relationship between the nurse and the patient. Communication difficulties can occur between nurses and patients, which may affect the therapeutic relationship and the quality of care provided. This article discusses the communication skills that nurses require to interact effectively with patients who have complex and chronic comorbid conditions. It focuses on therapeutic communication strategies and the nurse-patient relationship, while emphasising the need for nurses to be self-aware when caring for patients with complex healthcare needs.

  4. Do Biology Majors Really Differ from Non–STEM Majors?

    Cotner, Sehoya; Thompson, Seth; Wright, Robin

    2017-01-01

    Recent calls to action urge sweeping reform in science education, advocating for improved learning for all students—including those majoring in fields beyond the sciences. However, little work has been done to characterize the differences—if any exist—between students planning a career in science and those studying other disciplines. We describe an attempt to clarify, in broad terms, how non–STEM (science, technology, engineering, and mathematics) majors differ from life sciences majors, and how they are similar. Using survey responses and institutional data, we find that non–STEM majors are not unilaterally science averse; non–STEM majors are more likely than biology majors to hold misconceptions about the nature of science, yet they are not completely ignorant of how science works; non–STEM majors are less likely than biology majors to see science as personally relevant; and non–STEM majors populations are likely to be more diverse—with respect to incoming knowledge, perceptions, backgrounds, and skills—than a biology majors population. We encourage science educators to consider these characteristics when designing curricula for future scientists or simply for a well-informed citizenry. PMID:28798210

  5. The medical leadership challenge in healthcare is an identity challenge.

    Andersson, Thomas

    2015-01-01

    The purpose of this article is to describe and analyse the identity challenges that physicians with medical leadership positions face. Four qualitative case studies were performed to address the fact that identity is processual, relational and situational. Physicians with managerial roles were interviewed, as well as their peers, supervisors and subordinates. Furthermore, observations were made to understand how different identities are displayed in action. This study illustrates that medical leadership implies identity struggles when physicians have manager positions, because of the different characteristics of the social identities of managers and physicians. Major differences are related between physicians as autonomous individuals in a system and managers as subordinates to the organizational system. There are psychological mechanisms that evoke the physician identity more often than the managerial identity among physicians who are managers, which explains why physicians who are managers tend to remain foremost physicians. The implications of the findings, that there are major identity challenges by being both a physician and manager, suggest that managerial physicians might not be the best prerequisite for medical leadership, but instead, cooperative relationships between physicians and non-physician managers might be a less difficult way to support medical leadership. Acknowledging and addressing identity challenges can be important both in creating structures in organizations and designing the training for managers in healthcare (both physicians and non-physicians) to support medical leadership. Medical leadership is most often related to organizational structure and/or leadership skills, but this paper discusses identity requirements and challenges related to medical leadership.

  6. Therapeutic patient education in heart failure: do studies provide sufficient information about the educational programme?

    Albano, Maria Grazia; Jourdain, Patrick; De Andrade, Vincent; Domenke, Aukse; Desnos, Michel; d'Ivernois, Jean-François

    2014-05-01

    Therapeutic patient education programmes on heart failure have been widely proposed for many years for heart failure patients, but their efficiency remains questionable, partly because most articles lack a precise programme description, which makes comparative analysis of the studies difficult. To analyse the degree of precision in describing therapeutic patient education programmes in recent randomized controlled trials. Three major recent recommendations on therapeutic patient education in heart failure inspired us to compile a list of 23 relevant items that an 'ideal' description of a therapeutic patient education programme should contain. To discover the extent to which recent studies into therapeutic patient education in heart failure included these items, we analysed 19 randomized controlled trials among 448 articles published in this field from 2005 to 2012. The major elements required to describe a therapeutic patient education programme were present, but some other very important pieces of information were missing in most of the studies we analysed: the patient's educational needs, health literacy, projects, expectations regarding therapeutic patient education and psychosocial status; the educational methodology used; outcomes evaluation; and follow-up strategies. Research into how therapeutic patient education can help heart failure patients will be improved if more precise descriptions of patients, educational methodology and evaluation protocols are given by authors, ideally in a standardized format. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  7. Embracing the challenge of competition

    MacDonald, C.

    1998-01-01

    The new and creative solutions that Edmonton Power is using to meet the challenges of deregulation, competition and demand for customer choice in the electric power industry are discussed. Among these creative initiatives, in 1997 Edmonton Power extended account management services to 850 accounts to deliver commercial and operational analysis of energy consumption and management. Another major focus of effort has been the introduction of time of use (TOU) pricing options to commercial and industrial customers above 150 kWh. This required the installation of the latest hourly metering technology and the establishment of new price plans and contracts. Two major challenges were highlighted: (1) the mismatch between the prices utilities pay at the power pool and what the customer pays at the meter, and (2) the increased volatility of hour to hour price changes are just some of the risks that will have to be resolved under the new market structure

  8. Women's decision to major in STEM fields

    Conklin, Stephanie

    This paper explores the lived experiences of high school female students who choose to enter into STEM fields, and describes the influencing factors which steered these women towards majors in computer science, engineering and biology. Utilizing phenomenological methodology, this study seeks to understand the essence of women's decisions to enter into STEM fields and further describe how the decision-making process varies for women in high female enrollment fields, like biology, as compared with low enrollment fields like, computer science and engineering. Using Bloom's 3-Stage Theory, this study analyzes how relationships, experiences and barriers influenced women towards, and possibly away, from STEM fields. An analysis of women's experiences highlight that support of family, sustained experience in a STEM program during high school as well as the presence of an influential teacher were all salient factors in steering women towards STEM fields. Participants explained that influential teacher worked individually with them, modified and extended assignments and also steered participants towards coursework and experiences. This study also identifies factors, like guidance counselors as well as personal challenges, which inhibited participant's path to STEM fields. Further, through analyzing all six participants' experiences, it is clear that a linear model, like Bloom's 3-Stage Model, with limited ability to include potential barriers inhibited the ability to capture the essence of each participant's decision-making process. Therefore, a revised model with no linear progression which allows for emerging factors, like personal challenges, has been proposed; this model focuses on how interest in STEM fields begins to develop and is honed and then mastered. This study also sought to identify key differences in the paths of female students pursuing different majors. The findings of this study suggest that the path to computer science and engineering is limited. Computer

  9. Therapeutic Approaches to Target Cancer Stem Cells

    Diaz, Arlhee; Leon, Kalet

    2011-01-01

    The clinical relevance of cancer stem cells (CSC) remains a major challenge for current cancer therapies, but preliminary findings indicate that specific targeting may be possible. Recent studies have shown that these tumor subpopulations promote tumor angiogenesis through the increased production of VEGF, whereas the VEGF neutralizing antibody bevacizumab specifically inhibits CSC growth. Moreover, nimotuzumab, a monoclonal antibody against the epidermal growth factor receptor (EGFR) with a potent antiangiogenic activity, has been shown by our group to reduce the frequency of CSC-like subpopulations in mouse models of brain tumors when combined with ionizing radiation. These studies and subsequent reports from other groups support the relevance of approaches based on molecular-targeted therapies to selectively attack CSC. This review discusses the relevance of targeting both the EGFR and angiogenic pathways as valid approaches to this aim. We discuss the relevance of identifying better molecular markers to develop drug screening strategies that selectively target CSC

  10. Therapeutic Basis of Clinical Pain Modulation

    Kirkpatrick, Daniel R.; McEntire, Dan M.; Hambsch, Zakary J.; Kerfeld, Mitchell J.; Smith, Tyler A.; Reisbig, Mark D.; Youngblood, Charles F.

    2015-01-01

    Abstract Pain is a hallmark of almost all bodily ailments and can be modulated by agents, including analgesics and anesthetics that suppress pain signals in the central nervous system. Defects in the modulatory systems, including the endogenous pain‐inhibitory pathways, are a major factor in the initiation and chronicity of pain. Thus, pain modulation is particularly applicable to the practice of medicine. This review summarizes the existing literature on pain modulation. Here, we critically reviewed the literature from PubMed on pain modulation published primarily within the past 5 years in high impact journals. Specifically, we have discussed important anatomical landmarks of pain modulation and outlined the endogenous networks and underlying mechanisms of clinically relevant pain modulatory methods. The Gate Control Theory is briefly presented with discussion on the capacity of pain modulation to cause both hyper‐ and hypoalgesia. An emphasis has been given to highlight key areas in pain research that, because of unanswered questions or therapeutic potential, merit additional scientific scrutiny. The information presented in this paper would be helpful in developing novel therapies, metrics, and interventions for improved patient management. PMID:25962969

  11. Transendothelial Transport and Its Role in Therapeutics

    Upadhyay, Ravi Kant

    2014-01-01

    Present review paper highlights role of BBB in endothelial transport of various substances into the brain. More specifically, permeability functions of BBB in transendothelial transport of various substances such as metabolic fuels, ethanol, amino acids, proteins, peptides, lipids, vitamins, neurotransmitters, monocarbxylic acids, gases, water, and minerals in the peripheral circulation and into the brain have been widely explained. In addition, roles of various receptors, ATP powered pumps, channels, and transporters in transport of vital molecules in maintenance of homeostasis and normal body functions have been described in detail. Major role of integral membrane proteins, carriers, or transporters in drug transport is highlighted. Both diffusion and carrier mediated transport mechanisms which facilitate molecular trafficking through transcellular route to maintain influx and outflux of important nutrients and metabolic substances are elucidated. Present review paper aims to emphasize role of important transport systems with their recent advancements in CNS protection mainly for providing a rapid clinical aid to patients. This review also suggests requirement of new well-designed therapeutic strategies mainly potential techniques, appropriate drug formulations, and new transport systems for quick, easy, and safe delivery of drugs across blood brain barrier to save the life of tumor and virus infected patients. PMID:27355037

  12. [Therapeutic management of tics in Tourette's syndrome].

    Diallo, R; Welter, M L; Mallet, L

    2007-03-01

    Tourette's syndrome is a neuropsychiatric disorder characterised by both involuntary movements, tics, and psychiatric symptoms, attentional deficit disorder, hyperactivity, obsessive compulsive symptoms..., and can be the cause of major disability. Over the past 30 years, several types of treatment have been proposed for the treatment of tics in Tourette's Syndrome, ranging from psychotherapeutic approaches to neurosurgery. The education of the patient and his entourage is fundamental and must be offered to all patients. Psychotherapy does not directly improve the tics but contributes to a better adjustment of both patient and carers to his disability. The decision to start a course of drug therapy depends largely on the impact of the patient's tics on his personal life. Drug treatment relies on neuromodulators acting on a variety of neural systems and whose efficacy has been rarely demonstrated. The literature shows that the latest generation of dopaminergic antagonists have the highest benefit/risk ratio. Recently, deep brain stimulation, by modulating neuronal activity in structures involved in the pathophysiology of the disease, has become a promising therapeutical approach, producing a marked decrease in the severity of tics over that obtained with other treatments.

  13. Therapeutic touch: influence on vital signs of newborns.

    Ramada, Nadia Christina Oliveira; Almeida, Fabiane de Amorim; Cunha, Mariana Lucas da Rocha

    2013-12-01

    To compare vital signs before and after the therapeutic touch observed in hospitalized newborns in neonatal intensive care unit. This was a quasi-experimental study performed at a neonatal intensive care unit of a municipal hospital, in the city of São Paulo (SP), Brazil. The sample included 40 newborns submitted to the therapeutic touch after a painful procedure. We evaluated the vital signs, such as heart and respiratory rates, temperature and pain intensity, before and after the therapeutic touch. The majority of newborns were male (n=28; 70%), pre-term (n=19; 52%) and born from vaginal delivery (n=27; 67%). Respiratory distress was the main reason for hospital admission (n=16; 40%). There was a drop in all vital signs after therapeutic touch, particularly in pain score, which had a considerable reduction in the mean values, from 3.37 (SD=1.31) to 0 (SD=0.0). All differences found were statistically significant by the Wilcoxon test (ptouch promotes relaxation of the baby, favoring reduction in vital signs and, consequently in the basal metabolism rate.

  14. The therapeutic relationship in e-therapy for mental health: a systematic review.

    Sucala, Madalina; Schnur, Julie B; Constantino, Michael J; Miller, Sarah J; Brackman, Emily H; Montgomery, Guy H

    2012-08-02

    E-therapy is defined as a licensed mental health care professional providing mental health services via e-mail, video conferencing, virtual reality technology, chat technology, or any combination of these. The use of e-therapy has been rapidly expanding in the last two decades, with growing evidence suggesting that the provision of mental health services over the Internet is both clinically efficacious and cost effective. Yet there are still unanswered concerns about e-therapy, including whether it is possible to develop a successful therapeutic relationship over the Internet in the absence of nonverbal cues. Our objective in this study was to systematically review the therapeutic relationship in e-therapy. We searched PubMed, PsycINFO, and CINAHL through August 2011. Information on study methods and results was abstracted independently by the authors using a standardized form. From the 840 reviewed studies, only 11 (1.3%) investigated the therapeutic relationship. The majority of the reviewed studies were focused on the therapeutic alliance-a central element of the therapeutic relationship. Although the results do not allow firm conclusions, they indicate that e-therapy seems to be at least equivalent to face-to-face therapy in terms of therapeutic alliance, and that there is a relationship between the therapeutic alliance and e-therapy outcome. Overall, the current literature on the role of therapeutic relationship in e-therapy is scant, and much more research is needed to understand the therapeutic relationship in online environments.

  15. Translational nanomedicine--through the therapeutic window.

    Pierce, Robin L

    2015-01-01

    Translational nanomedicine occurs only through the successful integration of multiple inputs and iterative modifications. The therapeutic window plays a pivotal role in the trajectory of translational nanomedicine. Often defined in terms of the range of dosage for safe and effective therapeutic effect, a second definition of the therapeutic window refers to the often narrow temporal window in which a therapeutic effect can be obtained. Expanding the second definition to explicitly include the spatial dimension, this article explores aspects of the therapeutic spaces created by nanomedicine that shift the traditional dimensions of symptom, sign and pathology. This article analyzes three aspects of the therapeutic window in nanomedicine - temporal, spatial and manner of construction and their impact on the dimensions of modern medicine.

  16. Oral food challenge outcomes in a pediatric tertiary care center

    Abrams, Elissa M.; Becker, Allan B.

    2017-01-01

    Background Oral food challenges are the clinical standard for diagnosis of food allergy. Little data exist on predictors of oral challenge failure and reaction severity. Methods A retrospective chart review was done on all pediatric patients who had oral food challenges in a tertiary care pediatric allergy clinic from 2008 to 2010. Results 313 oral challenges were performed, of which the majority were to peanut (105), egg (71), milk (41) and tree nuts (29). There were 104 (33%) oral challenge...

  17. Interdisciplinary Project Experiences: Collaboration between Majors and Non-Majors

    Smarkusky, Debra L.; Toman, Sharon A.

    2014-01-01

    Students in computer science and information technology should be engaged in solving real-world problems received from government and industry as well as those that expose them to various areas of application. In this paper, we discuss interdisciplinary project experiences between majors and non-majors that offered a creative and innovative…

  18. Therapeutic cloning in individual parkinsonian mice

    Tabar, Viviane; Tomishima, Mark; Panagiotakos, Georgia; Wakayama, Sayaka; Menon, Jayanthi; Chan, Bill; Mizutani, Eiji; Al-Shamy, George; Ohta, Hiroshi; Wakayama, Teruhiko; Studer, Lorenz

    2009-01-01

    Cell transplantation with embryonic stem (ES) cell progeny requires immunological compatibility with host tissue. ‘Therapeutic cloning’ is a strategy to overcome this limitation by generating nuclear transfer (nt)ES cells that are genetically matched to an individual. Here we establish the feasibility of treating individual mice via therapeutic cloning. Derivation of 187 ntES cell lines from 24 parkinsonian mice, dopaminergic differentiation, and transplantation into individually matched host mice showed therapeutic efficacy and lack of immunological response. PMID:18376409

  19. Therapeutic potential of curcumin in gastrointestinal diseases

    Rajasekaran, Sigrid A

    2011-01-01

    Curcumin, also known as diferuloylmethane, is derived from the plant Curcuma longa and is the active ingredient of the spice turmeric. The therapeutic activities of curcumin for a wide variety of diseases such as diabetes, allergies, arthritis and other chronic and inflammatory diseases have been known for a long time. More recently, curcumin’s therapeutic potential for preventing and treating various cancers is being recognized. As curcumin’s therapeutic promise is being explored more system...

  20. 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.