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Sample records for future treatment strategies

  1. Future treatment strategies in phenylketonuria.

    PubMed

    van Spronsen, Francjan J; Enns, Gregory M

    2010-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which treatment was found to prevent clinical features of the disorder; dietary management was established almost 60 years ago. The institution of a low-phenylalanine (Phe) diet in the first few weeks of life was made possible by Guthrie neonatal screening, which further increased effectiveness of therapy. Indeed, neonatal diagnosis of PKU followed by institution of a low-Phe diet has been a remarkable success in preventing the devastating brain damage associated with untreated PKU. Nevertheless, significant difficulties exist in caring for PKU patients, including problems with adhering to the prescribed dietary regimen and the presence of neurocognitive deficits despite therapy. During the past few years, several ideas for new treatment strategies have emerged. This review aims to address these treatment strategies based on theoretical considerations of the biochemistry and pathogenesis of PKU. Recent times have seen the introduction of a wide array of novel treatments currently in clinical use, including more palatable medical foods, glycomacropeptide, large neutral amino acids, and tetrahydrobiopterin. Human trials are underway using an enzymatic therapeutic approach, while preclinical work continues in the fields of gene and cellular therapy. These therapeutic strategies propose to treat PKU at various levels, including nutritional intake, gut, liver, and blood-brain barrier, and have the potential to further improve outcome in PKU. PMID:20123478

  2. Liver transplantation for malignancy: Current treatment strategies and future perspectives

    PubMed Central

    Hackl, Christina; Schlitt, Hans J; Kirchner, Gabriele I; Knoppke, Birgit; Loss, Martin

    2014-01-01

    In 1967, Starzl et al performed the first successful liver transplantation for a patient diagnosed with hepatoblastoma. In the following, liver transplantation was considered ideal for complete tumor resection and potential cure from primary hepatic malignancies. Several reports of liver transplantation for primary and metastatic liver cancer however showed disappointing results and the strategy was soon dismissed. In 1996, Mazzaferro et al introduced the Milan criteria, offering liver transplantation to patients diagnosed with limited hepatocellular carcinoma. Since then, liver transplantation for malignant disease is an ongoing subject of preclinical and clinical research. In this context, several aspects must be considered: (1) Given the shortage of deceased-donor organs, long-term overall and disease free survival should be comparable with results obtained in patients transplanted for non-malignant disease; (2) In this regard, living-donor liver transplantation may in selected patients help to solve the ethical dilemma of optimal individual patient treatment vs organ allocation justice; and (3) Ongoing research focusing on perioperative therapy and anti-proliferative immunosuppressive regimens may further reduce tumor recurrence in patients transplanted for malignant disease and thus improve overall survival. The present review gives an overview of current indications and future perspectives of liver transplantation for malignant disease. PMID:24833863

  3. Treatment strategies for inherited optic neuropathies: past, present and future

    PubMed Central

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-01-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations. PMID:24603424

  4. Intramedullary spinal cord tumors: a review of current and future treatment strategies.

    PubMed

    Tobin, Matthew K; Geraghty, Joseph R; Engelhard, Herbert H; Linninger, Andreas A; Mehta, Ankit I

    2015-08-01

    Intramedullary spinal cord tumors have low incidence rates but are associated with difficult treatment options. The majority of patients with these tumors can be initially treated with an attempted resection. Unfortunately, those patients who cannot undergo gross-total resection or have subtotal resection are left with few treatment options, such as radiotherapy and chemotherapy. These adjuvant treatments, however, are associated with the potential for significant adverse side effects and still leave patients with a poor prognosis. To successfully manage these patients and improve both their quality of life and prognosis, novel treatment options must be developed to supplement subtotal resection. New research is underway investigating alternative therapeutic approaches for these patients, including directed, localized drug delivery and nanomedicine techniques. These and other future investigations will hopefully lead to promising new therapies for these devastating diseases. PMID:26235012

  5. Hereditary motor and sensory neuropathies: Understanding molecular pathogenesis could lead to future treatment strategies.

    PubMed

    Jerath, Nivedita U; Shy, Michael E

    2015-04-01

    Inherited peripheral neuropathies, like many other degenerative disorders, have been challenging to treat. At this point, there is little specific therapy for the inherited neuropathies other than genetic counseling as well as symptomatic treatment and rehabilitation. In the past, ascorbic acid, progesterone antagonists, and subcutaneous neurotrophin-3 (NT3) injections have demonstrated improvement in animal models of CMT 1A, the most common inherited neuropathy, but have failed to translate any effect in humans. Given the difficulty in treatment, it is important to understand the molecular pathogenesis of hereditary neuropathies in order to strategize potential future therapies. The hereditary neuropathies are in an era of molecular insight and over the past 20 years, more than 78 subtypes of Charcot Marie Tooth disease (CMT) have been identified and extensively studied to understand the biological pathways in greater detail. Next generation molecular sequencing has also improved the diagnosis as well as the understanding of CMT. A greater understanding of the molecular pathways will help pave the way to future therapeutics of CMT. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. PMID:25108281

  6. Any Future for Fecal Microbiota Transplantation as Treatment Strategy for Inflammatory Bowel Diseases?

    PubMed

    Kump, Patrizia; Högenauer, Christoph

    2016-01-01

    Fecal microbiota transplantation (FMT) is a novel therapeutic procedure aiming at restoring a normal intestinal microbiota by application of fecal microorganisms from a healthy subject into the gastrointestinal tract of a patient. FMT is the most effective treatment for recurrent Clostridium difficile infections (CDI). These infections also occur in patients with inflammatory bowel diseases (IBDs), where case series demonstrated a successful treatment of CDI by FMT in 83-92% of patients. The effect of FMT on the activity of IBD has mainly been investigated in ulcerative colitis (UC) patients, including 3 randomized controlled trials. So far, 2 randomized controlled trials showed a superiority of FMT compared to placebo in inducing remission in UC, while 1 study found no significant difference to placebo. The variation in response to FMT between these studies as well as in the uncontrolled trials might be explained by many differences in the way of FMT application, patient pretreatment and patient and donor selection. The data for the use of FMT in Crohn's disease and pouchitis are sparse; currently, no conclusion can be drawn regarding the effectiveness of FMT in these indications. It needs to be noted that cases of IBD activation after FMT have been reported. So far, FMT can only be recommended to be used for the treatment of concomitant CDI in IBD in clinical practice. For treating IBD irrespective of CDI, FMT should be only used in clinical trials. Current forms of FMT, especially protocols using repeated application, are very time and personnel consuming. Future trends are the use of defined stable microbiota preparations, in particular oral preparations, which will enable better and larger controlled trails for investigating FMT in IBD. PMID:27548724

  7. Progression of mild Alzheimer’s disease: knowledge and prediction models required for future treatment strategies

    PubMed Central

    2013-01-01

    Introduction Knowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting. Methods This was a prospective, open-label, non-randomized, multicenter study of ChEI treatment (donepezil, rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at baseline and then semi-annually over three years. Outcome measures included the MMSE, Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change (CIBIC) and Instrumental Activities of Daily Living (IADL) scale. Results After three years of ChEI therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged cognitive ability, 33% showed improved/unchanged global performance and 14% showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower educational level were both predictors of more positive longitudinal cognitive and functional outcomes. Older participants and those with a better IADL score at baseline exhibited a slower rate of cognitive decline, whereas younger participants and those with higher cognitive status showed more preserved IADL ability over time. Gender and apolipoprotein E (APOE) genotype showed inconsistent results. Prediction models using the abovementioned scales are presented. Conclusions In naturalistic mild AD patients, a marked deterioration in IADL compared with cognitive and global long-term outcomes was observed, indicating the importance of functional assessments during the early stages of the disease. The participants’ time on ChEI treatment before inclusion in studies of new therapies might affect their rate of decline and thus the comparisons of changes in scores between various studies. An

  8. Future Workforce Strategy

    ERIC Educational Resources Information Center

    US Department of Energy, 2007

    2007-01-01

    The Department of Energy's (DOE) Office of Science is among the world's premier supporters of basic research. The Office of Science enables the U.S. to maintain its competitive edge by funding science that can transform its energy future, supports its national security and seeks to understand the fundamentals of matter and energy itself. To do…

  9. Combotherapy and current concepts as well as future strategies for the treatment of Alzheimer’s disease

    PubMed Central

    Fan, Ling-Yun; Chiu, Ming-Jang

    2014-01-01

    It has been estimated that 35.6 million people globally had dementia in 2010 and the prevalence of dementia has been predicted to double every 20 years. Thus, 115.4 million people may be living with dementia in 2050. Alzheimer’s disease (AD) is the leading cause of dementia and is present in 60%–70% of people with dementia. Unfortunately, there are few approved drugs that can alleviate the cognitive or behavioral symptoms of AD dementia. Recent studies have revealed that pathophysiological changes related to AD occur decades before the appearance of clinical symptoms of dementia. This extended preclinical phase of AD provides a critical chance for disease-modifying agents to halt or delay the relentless process of AD. Although several trials targeting various pathological processes are ongoing, the examination of the combined use of different approaches to combat AD seems warranted. In this article, we will review current therapies, future strategies, and ongoing clinical trials for the treatment of AD with a special focus on combination therapies. Furthermore, preventive strategies for cognitively normal subjects in the presymptomatic stages of AD will also be addressed. In this review, we discuss current hypotheses of the disease process. In the decades since the approval of cholinesterase inhibitors, no new drug has ultimately demonstrated clear success in clinical trials. Given the difficulties that have been encountered in attempts to identify a single drug that can treat AD, we must pursue effective multi-target strategies, ie, combination therapies. The combination of cholinesterase inhibitors and memantine is considered well tolerated and safe, and this combination benefits patients with moderate-to-severe AD. In contrast, with the exception of adjuvant therapies of conventional drugs, combinations of different disease-modifying agents with different mechanisms may have promising synergic effects and benefit cognition, behavior, and daily living

  10. Accelerated repopulation as a cause of radiation treatment failure in non-small cell lung cancer: review of current data and future clinical strategies.

    PubMed

    Yom, Sue S

    2015-04-01

    Despite convincing evidence that the principles of accelerated repopulation would open up additional therapeutic opportunities in the treatment of advanced-stage non-small cell lung cancer, this strategy has been generally underexplored. The implementation of accelerated radiotherapy schedules has been hampered by logistical barriers, concerns about acute toxicity, and the prioritization of integrating concurrent chemotherapy into the standard treatment platform. At present, it is unclear to what extent accelerated fractionation will influence future treatment paradigms in non-small cell lung cancer, although technical advances in radiotherapy, allowing higher dose delivery with reduced toxicity, could permit the development of more convenient and tolerable forms of accelerated schedules. PMID:25771413

  11. Service strategies of the future

    SciTech Connect

    Wild, J.H.

    1998-07-01

    Service strategies of the future will have to take increasing account of the changes in the nature of global competition in the power generation market. Besides the key technical principles of availability and operational reliability, the costs for backup services such as overhauls, spare parts and retrofits will have to be lowered in order to boost competitiveness without, however, causing any unacceptable risks to plant operation. This objective can be achieved by OEM-integrated service contracts which include provisions relating to risk and profit sharing.

  12. Janus kinase inhibition as a potential strategy for the treatment of psoriasis: state of the art and future perspectives.

    PubMed

    Cassano, N; Vena, G A

    2012-01-01

    Research is focusing the attention on drugs acting on intracellular signaling as a possible strategy for various malignancies and autoimmune disorders, as well as prevention of transplant rejection. In such a context, an intriguing therapeutic target appears to be the signaling pathway mediated by Janus kinases (JAK)/signal transducers and activators of transcription (STAT) protein family. Several companies are developing and evaluating JAK inhibitors for immune-mediated disorders, including psoriasis. Among these drugs, ruxolitinib and especially tofacitinib have reached more advanced phases of clinical and experimental development. This review discusses the potential role of JAK inhibition in the treatment of psoriasis and presents the preliminary data regarding the clinical development of JAK inhibitors in this disease. PMID:23241109

  13. Strategies for treatment of dystonia.

    PubMed

    Dressler, Dirk; Altenmueller, Eckart; Bhidayasiri, Roongroj; Bohlega, Saeed; Chana, Pedro; Chung, Tae Mo; Frucht, Steven; Garcia-Ruiz, Pedro J; Kaelin, Alain; Kaji, Ryuji; Kanovsky, Petr; Laskawi, Rainer; Micheli, Federico; Orlova, Olga; Relja, Maja; Rosales, Raymond; Slawek, Jaroslaw; Timerbaeva, Sofia; Warner, Thomas T; Saberi, Fereshte Adib

    2016-03-01

    Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given. PMID:26370676

  14. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition.

    PubMed

    Finn, Richard S

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC. PMID:24159589

  15. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part II: Future compounds against influenza virus.

    PubMed

    Gasparini, R; Amicizia, D; Lai, P L; Bragazzi, N L; Panatto, D

    2014-12-01

    In the first part of this overview, we described the life cycle of the influenza virus and the pharmacological action of the currently available drugs. This second part provides an overview of the molecular mechanisms and targets of still-experimental drugs for the treatment and management of influenza. Briefly, we can distinguish between compounds with anti-influenza activity that target influenza virus proteins or genes, and molecules that target host components that are essential for viral replication and propagation. These latter compounds have been developed quite recently. Among the first group, we will focus especially on hemagglutinin, M2 channel and neuraminidase inhibitors. The second group of compounds may pave the way for personalized treatment and influenza management. Combination therapies are also discussed. In recent decades, few antiviral molecules against influenza virus infections have been available; this has conditioned their use during human and animal outbreaks. Indeed, during seasonal and pandemic outbreaks, antiviral drugs have usually been administered in mono-therapy and, sometimes, in an uncontrolled manner to farm animals. This has led to the emergence of viral strains displaying resistance, especially to compounds of the amantadane family. For this reason, it is particularly important to develop new antiviral drugs against influenza viruses. Indeed, although vaccination is the most powerful means of mitigating the effects of influenza epidemics, antiviral drugs can be very useful, particularly in delaying the spread of new pandemic viruses, thereby enabling manufacturers to prepare large quantities of pandemic vaccine. In addition, antiviral drugs are particularly valuable in complicated cases of influenza, especially in hospitalized patients. To write this overview, we mined various databases, including Embase, PubChem, DrugBank and Chemical Abstracts Service, and patent repositories. PMID:26137785

  16. Newer antiatherosclerosis treatment strategies

    PubMed Central

    Aggarwal, Amitesh; Singh, Safal

    2011-01-01

    Atherosclerosis has been a target of much clinical and molecular research. As a result of this extensive research, it is amply clear that atherogenesis is a multifactorial process involving an interplay of metabolic, immune and inflammatory mechanisms. Antiatherosclerotic strategies are today aiming for a multipronged approach targeting each arm of this multifactorial process. The newer agents under development can be divided into three broad categories: anti-inflammatory agents, modulators of intermediary metabolism and antiatherosclerosis vaccines. Potential targets for anti-inflammatory agents include inhibition of conversion of low-density lipoprotein (LDL) to oxidised LDL, blocking or downregulation of cell adhesion molecules, chemokine modulation and macrophage receptor blockade. Beyond inhibition of plaque formation, efforts are also ongoing to develop agents which stabilise the plaque by increasing its fibrous content and inhibiting its disruption. So far as research in the sphere of intermediary metabolism is concerned, the focus is now primarily on raising high-density lipoprotein and promoting reverse cholesterol transport; potential targets include cholesteryl ester transfer protein, liver X-receptor, lecithin cholesterol acyltransferase and high-density lipoprotein mimetics. Acyl-coenzymeA: cholesterol acyltransferase is another enzyme whose selective and differential inhibition is under active investigation. The concept of immunisation against a non-communicable disease such as atherosclerosis is still in its nascent stages. However, with increasing evidence to suggest the role of antigen-specific T-cell-mediated immunity in atherogenesis, this approach is potentially promising. Possible antigens under evaluation include oxidised LDL and its subparticles, heat-shock proteins and cholesteryl ester transfer protein. With cardiovascular disease being the single leading cause of death worldwide, the development of a safe and successful antiatherosclerosis

  17. Prevention strategies for cardioembolic stroke: present and future perspectives.

    PubMed

    Giacalone, Giacomo; Abbas, Mohammed Abballa; Corea, Francesco

    2010-01-01

    Atrial fibrillation (AF) is the most common cause of cardioembolism. An update on secondary prevention strategies, used to protect patients from the risk of stroke in many common cardiac conditions, is presented in the paper. The main line of actions of stroke prevention in cardioembolism is mostly connected with antithrombotic drugs, but also other, more invasive, techniques are quickly emerging. Also the classic pharmacological prevention with coumarins may soon be overcome by new generation anticoagulants. Is an aggressive treatment of Patent Foramen Ovale (PFO) always recommended? One of the main challenges of the future years will be to understand competitiveness between old and new preventive strategies. PMID:20721324

  18. OVERVIEW AND THE FUTURE OF OBESITY TREATMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This chapter addresses the future of obesity treatment. To provide a foundation for discussing the future, we begin with a brief background on the importance of obesity treatment and review of current interventions. We then examine issues and controversies that we believe will affect the future of...

  19. Treatment strategy for Boerhaave's syndrome.

    PubMed

    Ochiai, T; Hiranuma, S; Takiguchi, N; Ito, K; Maruyama, M; Nagahama, T; Kawano, T; Nagai, K; Nishikage, T; Noguchi, N; Takamatsu, S; Kawamura, T; Teramoto, K; Iwai, T; Arii, S

    2004-01-01

    Esophageal rupture is a potentially mortal condition. Rapid and correct diagnosis, and urgent surgical treatment with esophagectomy is indicated, but conservative and other surgical treatments have also been reported recently. The treatment strategies for esophageal rupture are discussed here, based on our experiences with four cases during the last 10 years. They were admitted urgently and each was treated by a different method. Three of them underwent emergency operations, one undergoing primary closure of the ruptured esophagus, another received a T-tube insertion from the ruptured site with omental flap, and the third an esophagogastrectomy. The fourth case was treated conservatively. All patients survived and were discharged 36-144 days post treatment. One of them was readmitted for debridement of necrotic rib. In conclusion, the prompt and accurate diagnosis of esophageal rupture is crucial for a subsequent successful treatment. Conservative treatment or operation including esophagectomy will be determined by the severity of the condition. PMID:15209751

  20. Future directions in treatment of brain metastases

    PubMed Central

    Barani, Igor J.; Larson, David A.; Berger, Mitchel S.

    2013-01-01

    Background: Brain metastases affect up to 30% of patients with cancer. Management of brain metastases continues to evolve with ever increasing focus on cognitive preservation and quality of life. This manuscript reviews current state of brain metastases management and discusses various treatment controversies with focus on future clinical trials. Stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) are discussed in context of multiple (4+ brain metastases) as well as new approaches combining radiation and targeted agents. A brief discussion of modified WBRT approaches, including hippocampal-avoidance WBRT (HA-WBRT) is included as well as a section on recently presented results of Radiation Therapy Oncology Group (RTOG) 0614, a randomized, double-blind, placebo-controlled trial of menantine for prevention of neurocognitive injury after WBRT. Methods: A search of selected studies relevant to management of brain metastases was performed in PubMed as well as in various published meeting abstracts. This data was collated and analyzed in context of contemporary management and future clinical trial plans. This data is presented in tabular form and discussed extensively in the text. Results: The published data demonstrate continued evolution of clinical trials and management strategies designed to minimize and/or prevent cognitive decline following radiation therapy management of brain metastases. Hippocampal avoidance whole-brain radiation therapy (HA-WBRT) and radiosurgery treatments for multiple brain metastases are discussed along with preliminary results of RTOG 0614, a trial of memantine therapy to prevent cognitive decline following WBRT. Trial results appear to support the use of memantine for prevention of cognitive decline. Conclusions: Different management strategies for multiple brain metastases (>4 brain metastases) are currently being evaluated in prospective clinical trials to minimize the likelihood of cognitive decline following WBRT. PMID

  1. Future launchers strategy : the ariane 2010 initiative

    NASA Astrophysics Data System (ADS)

    Bonnal, Ch.; Eymard, M.; Soccodato, C.

    2001-03-01

    With the new cryogenic upper stage ESC, the European heavy launcher Ariane 5+ is perfectly suited to the space market envisioned for the coming decade: flexible to cope with any payload and commercially attractive despite a fierce competition. Current Arianespace projections for the following years 2010-2020 indicate two major trends: satellites may still become larger and may require very different final orbits; today's market largely dominated by GEO may well evolve, influenced by LEO operations such as those linked to ISS or by constellations, to remain competitive, the launch cost has to be reduced. The future generation of the European heavy launcher has therefore to focus on an ever increased flexibility with a drastic cost reduction. Two strategies are possible to achieve this double goal: reusable launchers, either partially or totally, may ease the access to space, limiting costly expendable stages; the assessment of their technical feasibility and financial viability is undergoing in Europe under the Future Launchers Technology Program (FLTP), expendable launchers, derived from the future Ariane 5+. This second way started by CNES at the end of year 1999 is called the "Ariane 2010 initiative". The main objectives are simultaneously an increase of 25% in performance and a reduction of 30% in launch cost wrt Ariane 5+. To achieve these very ambitious goals, numerous major modifications are studied: technical improvements : modifications of the Solid Rocket Boosters may consist in filament winding casing, increased loading, simplified casting, improved grain, simplified Thrust Vector Control, … evolution of the Vulcain engine leading to higher efficiency despite a simplified design, flow separation controlled nozzle extension, propellant management of the two cryogenic stages, simplified electrical system, increased standardization, for instance on flanged interfaces and manufacturing processes, operational improvements such as launch cycle simplification

  2. New pharmacological treatment strategies for relapse prevention.

    PubMed

    Spanagel, Rainer; Vengeliene, Valentina

    2013-01-01

    Here we discuss treatment strategies that are based on pharmacological interventions to reduce craving and relapse in alcohol-dependent patients. We will first provide a historical overview about relapse prevention strategies. We will then review the development of disulfiram, naltrexone, acamprosate, and nalmefene and discuss their neurobiological modes of action. Then the concept of convergent genomic analysis will be introduced for the discovery of new molecular treatment targets. Finally, we will provide convincing evidence for the use of N-methyl-D-aspartate (NMDA) receptor channel blockers as substitution drugs. Important conclusions of this review are: (i) learning from other addictive substances is very helpful-e.g., substitution therapies as applied to opiate addiction for decades could also be translated to alcoholics, (ii) the glutamate theory of alcohol addiction provides a convincing framework for the use of NMDA receptor antagonists as substitution drugs for alcohol-dependent patients, (iii) a combination of behavioral and pharmacological therapies may be the optimal approach for future treatment strategies-one promising example concerns the pharmacological disruption of reconsolidation processes of alcohol cue memories, (iv) given that many neurotransmitter systems are affected by chronic alcohol consumption, numerous druggable targets have been identified; consequently, a "cocktail" of different compounds will further improve the treatment situation, (v) in silico psychopharmacology, such as drug repurposing will yield new medications, and finally, (vi) the whole organism has to be taken into consideration to provide the best therapy for our patients. In summary, there is no other field in psychiatric research that has, in recent years, yielded so many novel, druggable targets and innovative treatment strategies than for alcohol addiction. However, it will still be several years before the majority of the "treatment-seeking population" will benefit

  3. Cultural psychiatry: research strategies and future directions.

    PubMed

    Kirmayer, Laurence J; Ban, Lauren

    2013-01-01

    This chapter reviews some key aspects of current research in cultural psychiatry and explores future prospects. The first section discusses the multiple meanings of culture in the contemporary world and their relevance for understanding mental health and illness. The next section considers methodological strategies for unpacking the concept of culture and studying the impact of cultural variables, processes and contexts. Multiple methods are needed to address the many different components or dimensions of cultural identity and experience that constitute local worlds, ways of life or systems of knowledge. Quantitative and observational methods of clinical epidemiology and experimental science as well as qualitative ethnographic methods are needed to capture crucial aspects of culture as systems of meaning and practice. Emerging issues in cultural psychiatric research include: cultural variations in illness experience and expression; the situated nature of cognition and emotion; cultural configurations of self and personhood; concepts of mental disorder and mental health literacy; and the prospect of ecosocial models of health and culturally based interventions. The conclusion considers the implications of the emerging perspectives from cultural neuroscience for psychiatric theory and practice. PMID:23816867

  4. Multimedia strategy considers waste treatment

    SciTech Connect

    Phillips, J.B.

    1995-05-01

    The advent of multimedia pollution prevention programs has raised some interesting and challenging questions on the subject of facility operations. First and foremost is the goal of a multimedia pollution prevention program: how can industrial streams in an operating facility be treated to prevent pollutants from escaping in a particular effluent or waste streams without transferring the same pollutants to another medium? Once this is resolved, the next issue to be addressed is the fate of pollutants removed from effluent streams. EPA is moving toward discouraging destruction as an acceptable means of waste treatment. The strategies are presented for handling pollutants from one media without contaminating another.

  5. Current therapeutic strategies for premature ejaculation and future perspectives

    PubMed Central

    Xin, Zhong-Cheng; Zhu, Yi-Chen; Yuan, Yi-Ming; Cui, Wan-Shou; Jin, Zhe; Li, Wei-Ren; Liu, Tao

    2011-01-01

    Premature ejaculation (PE) is a common sexual disorder in men that is mediated by disturbances in the peripheral and central nervous systems. Although all pharmaceutical treatments for PE are currently used ‘off-label', some novel oral agents and some newer methods of drug administration now provide important relief to PE patients. However, the aetiology of this condition has still not been unified, primarily because of the lack of a standard animal model for basic research and the absence of a widely accepted definition and assessment tool for evidence-based clinical studies in patients with PE. In this review, we focus on the current therapeutic strategies and future treatment perspectives for PE. PMID:21532601

  6. Current and future treatment of amyloid diseases.

    PubMed

    Ankarcrona, M; Winblad, B; Monteiro, C; Fearns, C; Powers, E T; Johansson, J; Westermark, G T; Presto, J; Ericzon, B-G; Kelly, J W

    2016-08-01

    There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross-β-sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid β-peptide (Aβ) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit Aβ formation and aggregation or to enhance Aβ clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent Aβ aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases compromising multiple organ systems, caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, nonamyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as a promising treatment. PMID:27165517

  7. New treatment strategies for hepatitis C infection

    PubMed Central

    Ermis, Fatih; Senocak Tasci, Elif

    2015-01-01

    Hepatitis C infection can lead to cirrhosis and hepatocellular carcinoma and it is an important cause of mortality and morbidity. Achieving a sustained virological response has been the major aim for decades. Interferon treatment was the primarily developed therapy against the infection. Addition of the guanosine analog ribavirin to stop viral RNA synthesis increased the response rates as well as the adverse effects of the treatment. The increasing demands for alternative regimens led to the development of direct-acting antivirals (DAAs). The approval of sofosbuvir and simeprevir signaled a new era of antiviral treatment for hepatitis C infection. Although the majority of studies have been performed with DAAs in combination with interferon and resulted in a decrease in treatment duration and increase in response rates, the response rates achieved with interferon-free regimens provided hope for patients ineligible for therapy with interferon. Most DAA studies are in phase II leading to phase III. In the near future more DAAs are expected to be approved. The main disadvantage of the therapy remains the cost of the drugs. Here, we focus on new treatment strategies for hepatitis C infection as well as agents targeting hepatitis C virus replication that are in clinical development. PMID:26301052

  8. Cellular Learning: Strategy for the Future.

    ERIC Educational Resources Information Center

    Schrum, John

    1987-01-01

    Cellular learning refers to both arrangement of shop equipment and addition of new course materials for a contemporary manufacturing curriculum. The concept is an accumulation of ideas and strategies for the instruction and training of students. It also provides a method for consolidating old equipment and adding group technology. (CH)

  9. Future View: Web Navigation based on Learning User's Browsing Strategy

    NASA Astrophysics Data System (ADS)

    Nagino, Norikatsu; Yamada, Seiji

    In this paper, we propose a Future View system that assists user's usual Web browsing. The Future View will prefetch Web pages based on user's browsing strategies and present them to a user in order to assist Web browsing. To learn user's browsing strategy, the Future View uses two types of learning classifier systems: a content-based classifier system for contents change patterns and an action-based classifier system for user's action patterns. The results of learning is applied to crawling by Web robots, and the gathered Web pages are presented to a user through a Web browser interface. We experimentally show effectiveness of navigation using the Future View.

  10. EMPA-REG and Other Cardiovascular Outcome Trials of Glucose-lowering Agents: Implications for Future Treatment Strategies in Type 2 Diabetes Mellitus.

    PubMed

    Schernthaner, Guntram; Schernthaner-Reiter, Marie Helene; Schernthaner, Gerit-Holger

    2016-06-01

    reduce the CV burden of patients with T2DM, drugs influencing factors involved in atherogenesis (eg, insulin resistance, chronic inflammation, increase of HDL, prothrombotic state) are more promising. The recent IRIS (Insulin Resistance Intervention after Stroke) study documented a significant reduction in stroke and MI when pioglitazone instead of placebo was given to nondiabetic patients presenting with both stroke/transient ischemic attack and insulin resistance, confirming results from the PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events) study in patients with T2DM. Based on these new data, we suggest that the addition of both empagliflozin and pioglitazone to metformin might be the relative best option to reduce the high CV morbidity and mortality of patients with T2DM and already established CV complications. The very recent announcement that the CV outcome study with liraglutide (LEADER) also demonstrated a significant reduction of the composite endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) gives new hope for further beneficial treatment options for T2DM patients with established CVD. PMID:27210264

  11. Environmental scanning: a strategy for the future.

    PubMed

    Wolfe, P L; Stanton, M P

    1992-03-01

    The rapidity of change confronting nursing at all levels will continue to challenge nursing's ultimate capacity to adapt and remain a viable profession in the 21st century. The process of meeting the challenges can be proactive based on assessment of needs and available resources, or reactive based on the reaction to challenges. A strategy identified by the authors that can be used at all levels of nursing practice, administration, education, and research is environmental scanning. This methodology has been used effectively in other disciplines for strategic, long-term planning and can be readily adapted to a wide variety of nursing service, academic, or professional associations. PMID:1593290

  12. Current and future management strategies in intensive crop production systems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The root-knot nematode Control and Management Strategy chapter addresses the current and future developments in Meloidogyne spp. control in intensive crop production systems. Discussed are current nematode management strategies such as the use of cultural practices, host plant resistance, applicati...

  13. Counseling and the Future: Concepts, Issues, and Strategies.

    ERIC Educational Resources Information Center

    Hays, Donald G.

    Futurists and counselors both deal with the concept of change. This monograph examines some strategies counselors can use to help themselves adopt a future orientation and to assist their counselees in meeting the future confidently. The writings of Cornish, Fletcher and Conboy bring some focus to concepts and dimensions held by futurists and…

  14. Will Reforms Survive? Strategies for Sustaining Preparing Future Faculty Programs.

    ERIC Educational Resources Information Center

    Ferren, Ann; Gaff, Jerry G.; Clayton-Pedersen, Alma

    2002-01-01

    Observers of Preparing Future Faculty (PFF) programs reviewed a sample of campuses to discover the results of nearly 10 years of participation. Found significant factors in the programs, and strategies for sustaining their momentum, that provide insight into current practices in graduate education and what future faculty need. (EV)

  15. Powering nanorobotic devices: challenges and future strategies

    NASA Astrophysics Data System (ADS)

    Sankar, Krishna Moorthi

    2014-04-01

    Nanotechnology, even after 55 years since its foundation (1959 Richard Feynman's speech - `There is lot of space in the bottom'), is still in its infancy. However, of late, there has been a large increase in the research being done in this field in many prominent Universities and Research institutions across the globe. Nanorobotics is the combination of Nanotechnology and the science of Robotics, to create robots that are only a few nanometres (10-9 metres) in size. Nanobots are yet to be made. But with the current pace of ongoing researches, scientists predict that nanobots will be made a reality by next ten years. The main proposed function of nanobots is to use them in the medical field to interact with cells or intra-cellular substances and prevent or reverse structural and genetical problems and diseases. One of the major challenges faced while creating a nanobot to travel through human body is to power it. Nanobots would require a very small yet highly potential source of energy. There are many hypothesised energy sources for nanobots which are either already available within the human body naturally or which are to be supplied externally. But, all of these energy sources pose a few challenges which need to be addressed if they are to be used to power nanobots. These challenges can be overcome using a number of strategies that can be used to make an economically, ecologically and medically viable energy source.

  16. Molecular diagnostics: future probe-based strategies.

    PubMed

    Marsh, Peter; Cardy, Donald L N

    2004-01-01

    Nucleic acid amplification technologies (NAATs) represent powerful tools in clinical microbiology, particularly in areas where traditional culture-based methods alone prove insufficient. A notable advantage is in reducing the time from taking samples to reporting results. This, and the specificity and sensitivity imparted by NAATs, can help to improve patient care. Both thermal and isothermal NAATs have been adapted to aid diagnosis in clinical laboratories. Current molecular diagnostic assays are generally high-tech, and are expensive to buy and perform. Easy-to-use NAATs are beginning to appear, not only facilitating acceptable throughput in clinical laboratories, but also allowing tests to move out of the laboratory, closer to the point of care. Demand for simpler, miniaturized equipment and assays, and the trend toward personalized medicine, is leading towards the development of fully integrated automation and home-use kits. The integration of diverse disciplines, such as genomics, molecular biology, microelectromechanical systems, microfluidics, microfabrication, and organic chemistry, is behind the emerging DNA microarray technology. Development of DNA microchips allows the simultaneous detection of potentially thousands of target sequences, not only favoring high throughput, but also the potential for genotyping patient subsets with respect to their response to particular drug types (pharmakogenomics). It is envisaged that the future of probe-based technologies will see the development of fully integrated assays and devices suitable for nonskilled users. PMID:15148419

  17. Tissue engineering: current strategies and future directions.

    PubMed

    Olson, Jennifer L; Atala, Anthony; Yoo, James J

    2011-04-01

    Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, or other clinical issues. Currently, patients with diseased and injured organs are often treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and as the number of new cases of organ failure increases. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells that can circumvent the ethical issues associated with embryonic stem cells, have been discovered. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future. PMID:22111050

  18. Treatment Strategies for Mucocutaneous Leishmaniasis

    PubMed Central

    Palumbo, Emilio

    2010-01-01

    Mucocutaneous is an infection caused by a single celled parasite transmitted by sand fly bites. There are about 20 species of Leishmania that may cause mucocutaneous leishmaniasis. Some Leishmania species are closely linked to humans and are therefore found in cities (L. tropica) whereas some others are more traditionally associated with animal species and therefore considered zoonoses (L. major). The evidence for optimal treatment of mucocutaneous leishmaniasis is patchy. Although the cutaneous form of the disease is often self-limiting, it does result in significant scarring and can spread to more invasive, mucocutaneous disease. Therefore, treatment may be considered to prevent these complications. Drugs for systemic and topical treatment are presented and discussed with regard to their application, use and adverse effects. PMID:20606970

  19. Update and future of systemic acne treatment.

    PubMed

    Zouboulis, Christos C; Piquero-Martin, Jaime

    2003-01-01

    Systemic treatment is required in patients with moderate-to-severe acne, especially when acne scars start to occur. Antibiotics with anti-inflammatory properties, such as tetracyclines (oxytetracycline, tetracycline chloride, doxycycline, minocycline and limecycline) and macrolide antibiotics (erythromycin and azithromycin) are the agents of choice for papulopustular acne, even though the emerging resistant bacterial strains are minimizing their effect, especially regarding erythromycin. Systemic antibiotics should be administered during a period of 8-12 weeks. In severe papulopustular and in nodulocystic/conglobate acne, oral isotretinoin is the treatment of choice. Hormonal treatment represents an alternative regimen in female acne, whereas it is mandatory in resistant, severe pubertal or post-adolescent forms of the disease. Compounds with anti-androgenic properties include estrogens combined with progestins, such as ethinyl estradiol with cyproterone acetate, chlormadinone acetate, desogestrel, drospirenone, levonogestrel, norethindrone acetate, norgestimate, and other anti-androgens directly blocking the androgen receptor (flutamide) or inhibiting androgen activity at various levels, corticosteroids, spironolactone, cimetidine, and ketoconazole. After 3 months of treatment control of seborrhea and acne can be obtained. Low-dose corticosteroids (prednisone, prednisolone, or dexamethasone) are indicated in patients with adrenal hyperandrogenism or acne fulminans. New developments and future trends represent low-dose long-term isotretinoin regimens, new isotretinoin formulations (micronized isotretinoin), isotretinoin metabolites, combination treatments to reduce toxicity, insulin-sensitizing agents, 5alpha-reductase type 1 inhibitors, antisense oligonucleotide molecules, and, especially, new anti-inflammatory agents, such as lipoxygenase inhibitors. PMID:12566804

  20. Future perspectives: Moving towards NCL treatments.

    PubMed

    Cotman, Susan L; Mole, Sara E; Kohan, Romina

    2015-10-01

    Clinicians, basic researchers, representatives from pharma and families from around the world met in Cordoba, Argentina in October, 2014 to discuss recent research progress at the 14th International Congress on Neuronal Ceroid Lipofuscinoses (NCLs; Batten disease), a group of clinically overlapping fatal, inherited lysosomal disorders with primarily neurodegenerative symptoms. This brief review article will provide perspectives on the anticipated future directions of NCL basic and clinical research as we move towards improved diagnosis, care and treatment of NCL patients. This article is part of a Special Issue entitled: Current Research on the Neuronal Ceroid Lipofuscinoses (Batten Disease). PMID:25857620

  1. University Continuing Education: Strategies for an Uncertain Future.

    ERIC Educational Resources Information Center

    Baskett, H. K.; Hamilton, A. Bruce

    Some of the most common predictions relating to university continuing education units provide a base from which a discussion of future strategies can begin. These include the following: the Big Generation (i.e., baby boomers) is here; knowledge, not products, is the major focus of society; competition for the traditional university continuing…

  2. Soil Contamination and Remediation Strategies. Current research and future challenge

    NASA Astrophysics Data System (ADS)

    Petruzzelli, G.

    2012-04-01

    eliminating the source of pollution, but also on blocking the pathways from contaminants to receptors or reducing the exposure to contaminants,. Future challenge integration of sustainability into remediation decision-making. Soil is not a waste! There is a growing interest in the clean up approaches that maintain soil quality after remediation treatments. This issue is of great importance in the U.S.A. where the EPA from 2009 is promoting innovative clean-up strategies (Green Remediation). Green remediation is defined as the practice of considering all environmental effects of remedy and incorporating options to maximize environmental benefit of cleanup actions . These remediation strategies restore contaminated sites to productive use with a great attention to the global environmental quality, including the preservation of soil functionality according to the following principles: use minimally invasive technologies; use passive energy technologies such as bioremediation and phytoremediation as primary remedies or finishing steps where possible and effective; minimize soil and habitat disturbance; minimize bioavailability of contaminants trough adequate contaminant source and plume control If we move from the current definition of remedial targets based on total concentrations, technologies with low impact on the environment can be utilized reducing the wrong choice to disposal soil in landfill destroying quickly a not renewable essential resource.

  3. Current and future treatments for hepatocellular carcinoma

    PubMed Central

    Schlachterman, Alexander; Craft Jr, Willie W; Hilgenfeldt, Eric; Mitra, Avir; Cabrera, Roniel

    2015-01-01

    Hepatocellular carcinoma (HCC) represents a unique challenge for physicians and patients. There is no definitively curative treatment. Rather, many treatment and management modalities exist with differing advantages and disadvantages. Both current guidelines and individual patient concerns must be taken into account in order to properly manage HCC. In addition, quality of life issues are particularly complex in patients with HCC and these concerns must also be factored into treatment strategies. Thus, considering all the options and their various pros and cons can quickly become complex for both clinicians and patients. In this review, we systematically discuss the current treatment modalities available for HCC, detailing relevant clinical data, risks and rewards and overall outcomes for each approach. Surgical options discussed include resection, transplantation and ablation. We also discuss the radiation modalities: conformal radiotherapy, yttrium 90 microspheres and proton and heavy ion radiotherapy. The biologic agent Sorafenib is discussed as a promising new approach, and recent clinical trials are reviewed. We then detail currently described molecular pathways implicated in the initiation and progression of HCC, and we explore the potential of each pathway as an avenue for drug exploitation. We hope this comprehensive and forward-looking review enables both clinicians and patients to understand various options and thereby make more informed decisions regarding this disease. PMID:26229392

  4. Current treatment of craniosynostosis and future therapeutic directions.

    PubMed

    Wan, Derrick C; Kwan, Matthew D; Lorenz, H Peter; Longaker, Michael T

    2008-01-01

    Normal craniofacial development is contingent upon coordinated growth between the brain and overlying calvaria. Craniosynostosis, the premature fusion of one or more cranial sutures, perturbs this natural framework, resulting in dramatic dysmorphology of the skull and face along with a multitude of associated functional abnormalities. Traditional approaches to the treatment of craniosynostosis have employed complex surgical remodeling of the skull vault and facial deformities all aimed at increasing the amount of intracranial volume and restoring a more normal craniofacial appearance. Significant morbidity and mortality, however, have plagued these procedures, driving dramatic evolution in our approach towards the treatment of pathologically fused sutures. Recent clinical and genetic studies have identified multiple forms of human craniosynostosis, each associated with mutations within various cytokine signaling pathways. Knowledge garnered from these investigations bear promise for the future development of alternative strategies to enhance or perhaps even replace contemporary approaches for the treatment of craniosynostosis. PMID:18391503

  5. Lactic Acidosis: Current Treatments and Future Directions.

    PubMed

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-09-01

    Mortality rates associated with severe lactic acidosis (blood pH<7.2) due to sepsis or low-flow states are high. Eliminating the triggering conditions remains the most effective therapy. Although recommended by some, administration of sodium bicarbonate does not improve cardiovascular function or reduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment. PMID:27291485

  6. Viral encephalitis: current treatments and future perspectives.

    PubMed

    Domingues, Renan Barros

    2012-12-01

    Several viruses may cause central nervous system infections that lead to a broad range of clinical manifestations. The course of the viral encephalitis can be acute, sub acute, or chronic. Some viruses have the ability to enter into the brain and cause direct injury, while others activate inflammatory cells that attack the central nervous system (CNS) secondarily. Some types of viral encephalitis occur in previously healthy individuals, while others affect immunocompromised patients. The epidemiology of viral encephalitis has undergone changes in recent years. Factors such as evolving lifestyles and ecological changes have had a considerable impact on the epidemiology of some types of viral encephalitis. The result is a change in the etiology spectrum of viral encephalitis, with new types of encephalitis arising or returning from time to time. Many scientific achievements in neuroimaging, molecular diagnosis, antiviral therapy, immunomodulatory treatments, and neurointensive care have allowed more precise and earlier diagnoses and more efficient treatments, resulting in improved outcomes. Despite these advances, there is still considerable morbidity and mortality related to these disorders. This aim of this article is to review the current knowledge of the current drugs used in the management of the most important viral encephalitis, focusing on the mechanisms of action, efficacy, and side effects of the drugs. In addition, future perspectives in this area will be addressed. Despite the technological advances, much effort has yet to be undertaken to reduce the impact of these potentially devastating diseases. PMID:22640219

  7. Fractal Formation and Trend Trading Strategy in Futures Market

    NASA Astrophysics Data System (ADS)

    Masteika, Saulius; Rutkauskas, Aleksandras V.; Lopata, Audrius

    The paper presents the details of trend trading algorithm in futures market. A contribution of this paper lies in a modified chart pattern related to a fractal formation, nonlinearity and chaos theory, broadly discussed by Benoit B. Mandelbrot and Bill M. Williams. As typical fractal pattern often is being applied in conjunction with other forms of technical analysis, like moving averages, Elliott Waves analysis or MACD indicators the proposed pattern is presented as a basic indicator itself. The strategy can be applied as up-trend market forecasting tool. The efficiency of the proposed strategy was tested with the most active North American futures contracts using 10 years historical daily data. Experimental results showed better returns if compared to overall market average-CRB index.

  8. Overactive bladder syndrome pharmacotherapy: future treatment options

    PubMed Central

    2015-01-01

    Overactive bladder syndrome (OAB) is a lifestyle disease and its incidence increases with age. Although it is not a life-threatening disease, it is known to have a significant impact on the quality of life. The first-choice pharmacological treatment of OAB is antimuscarinics. However, their limited clinical effectiveness and unsatisfactory tolerance profile, combined with the advancement of knowledge on the aetiopathogenesis of the disease, have inspired research on new pharmacotherapy options for OAB. Basic research has provided foundations for the development of new OAB treatments, which seem very promising and can be applied in clinical practice. The mechanisms of the studied compounds are based on their effect on certain receptors and neurotransmitters that contribute to regulating the micturition reflex. These compounds are not only more receptor-specific as compared to currently used drugs, but also some of them are organ-specific. Some of such compounds have already passed the proof-of-concept stage of development and have the therapeutic potential to determine the future of OAB pharmacotherapy. This review focuses on the mechanisms of substances that are now undergoing pre-clinical and clinical tests and their effects on the micturition cycle, while also identifying opportunities for using them with specific groups of patients. Due to the fact that OAB is a disease of symptoms and its aetiopathogenesis is complex, it seems that modern treatment methods should be tailor-made and based on the pathophysiological mechanisms that induce disease symptoms, rather than only treating the symptoms by inhibiting the contractility of the urinary bladder. PMID:26848291

  9. Treatment of hemophilia in the near future.

    PubMed

    Peyvandi, Flora; Garagiola, Isabella

    2015-11-01

    Advancements and debacles have characterized hemophilia treatment over the past 50 years. The 1970s saw the availability of plasma-derived concentrates making prophylaxis and home therapy possible. This optimistic perception changed extremely in the early 1980s, when most people with hemophilia were infected with HIV and hepatitis viruses. Then, also in the 1980s, the rapid progress in molecular biology led to the development of recombinant therapeutic products. This important advancement was a huge technological leap fresh off from the earlier 1980s disaster. Now in the 21st century, the newer bioengineering drugs open a new hopeful phase for the management of hemophilia. The current efforts are concentrated on producing novel coagulation factors with prolonged bioavailability, increased potency, and resistance to inactivation and potentially reduced immunogenicity; this phase of evolution is improving very quickly. 2014 is the year of marketing approval by the Food and Drug Administration of the first bioengineered FVIII and FIX long-acting drugs, using Fc-fusion strategy. This represents the first significant advance in the hemophilia therapy that dramatically transforms patient management by substantially reducing the frequency of injections, improving compliance, and simplifying prophylaxis and, in turn, refining the quality of life of hemophilia patients, offering them a nearly normal life expectancy, particularly to newborns with hemophilia B. PMID:25703518

  10. Amblyopia treatment strategies and new drug therapies.

    PubMed

    Pescosolido, Nicola; Stefanucci, Alessio; Buomprisco, Giuseppe; Fazio, Stefano

    2014-01-01

    Amblyopia is a unilateral or bilateral reduction of visual acuity secondary to abnormal visual experience during early childhood. It is one of the most common causes of vision loss and monocular blindness and is commonly associated with strabismus, anisometropia, and visual deprivation (in particular congenital cataract and ptosis). It is clinically defined as a two-line difference of best-corrected visual acuity between the eyes. The purpose of this study was to understand the neural mechanisms of amblyopia and summarize the current therapeutic strategies. In particular, the authors focused on the concept of brain plasticity and its implication for new treatment strategies for children and adults with amblyopia. PMID:24410693

  11. [Drug delivery strategies for targeted treatment of inflammatory bowel disease].

    PubMed

    Lautenschläger, C; Schmidt, C; Lange, K; Stallmach, A

    2015-03-01

    Inflammatory bowel disease (IBD) is a frequently occurring disease in young people, which is characterized by chronic inflammation of the gastrointestinal tract. The therapy of IBD is dominated by the administration of anti-inflammatory and immunosuppressive agents, which suppress the intestinal inflammatory burden and improve the disease-related symptoms. Present treatment strategies are characterized by a limited therapeutical efficacy and the occurrence of adverse drug reactions. The development of novel disease-targeted drug delivery strategies is preferable for a more effective therapy and thus demonstrates the potential to address unmet medical needs. This review gives an overview about drug delivery strategies for the treatment of IBD. Therefore, established intestine-targeting strategies for a selective drug release into the diseased part of the gastrointestinal tract will be presented, including prodrugs, and dosage forms with pH-/time-dependent drug release. Furthermore future-oriented disease-targeting strategies for a selective drug release into the intestinal inflammation will be described, including micro-/nanosized synthetic and biologic drug carriers. This novel therapeutic approach may enable a more effective anti-inflammatory treatment of IBD with reduced risks of adverse reactions. PMID:25723326

  12. A treatment strategy for psychogenic vomiting.

    PubMed

    Willard, S G; Swain, B S; Winstead, D K

    1989-01-01

    Although the literature supports the existence of psychogenic vomiting as a distinct psychiatric disorder, the DSM III-R does not include it as a diagnostic category. Of the numerous articles in the literature which describe this disorder, few discuss treatment. The purposes of this paper are to review the existing literature, to describe the family dynamics which are thought to precipitate the evolution of psychogenic vomiting in the identified patient, and to describe a treatment protocol which has been successfully employed in an outpatient setting. The illness is characterized as an eating disorder in terms of etiology, symptomatology, and treatment. A treatment strategy is described which includes insight-oriented psychotherapy with cognitive/behavioral interventions and family therapy. Two case studies are included which illustrate that a combined therapy approach is efficacious in treating psychogenic vomiting. PMID:2813832

  13. Erection rehabilitation following prostatectomy - current strategies and future directions.

    PubMed

    Sopko, Nikolai A; Burnett, Arthur L

    2016-04-01

    Despite continued advances in urological surgery, erectile dysfunction (ED) remains a serious adverse effect of radical prostatectomy. In this setting, ED is predominantly caused by injury to the neurovascular bundles, which lie alongside the prostate and are responsible for initiating and maintaining the erectile response. Most men will experience some degree of ED after radical prostatectomy, although erectile function outcomes have already remarkably improved since the development of nerve-sparing surgical techniques. To further improve outcomes, erection rehabilitation strategies are being investigated, which emphasize early treatment regimens with the aim of preventing adverse remodelling after surgery and preserving erectile function. Strategies include pharmacological therapy, mechanical therapy and psychosocial support. In addition, novel therapeutic approaches involving new targets for small-molecule treatments and regenerative medicine therapies are being developed to aid in restoring erectile function. Although ED treatments can be effective following radical prostatectomy, no specific erection rehabilitation regimen has currently been shown to be superior to other investigated rehabilitation regimens. Nevertheless, the different strategies rightfully remain an area of intensive research, as preservation of erectile function is a critical part of providing comprehensive care for men with prostate cancer to ensure their overall well-being, in contrast to just treating a patient's tumour. PMID:26976244

  14. Nonsurgical Treatment Strategies after Osteoporotic Hip Fractures

    PubMed Central

    Song, Kwang-Soon; Bae, Ki-Cheor; Cho, Chul-Hyun; Son, Eun-Suck; Lee, Kyung-Jae

    2015-01-01

    Osteoporosis is a metabolic disease that is increasing in prevalence as people live longer. Because the orthopedic surgeon is frequently the first and often the only physician to manage patients with osteoporotic hip fractures, every effort should be made to prevent future fractures. A multidisciplinary approach is essential in treatment of osteoporotic fractures. Basic treatment includes calcium and vitamin D supplementation, fall prevention, hip protection, and balance and exercise programs. Currently available pharmacologic agents are divided into antiresorptive and anabolic groups. Antiresorptive agents such as bisphosphonates limit bone resorption through inhibition of osteoclastic activity. Anabolic agents such as parathyroid hormone promote bone formation.

  15. New Strategies for the Treatment of Phenylketonuria (PKU)

    PubMed Central

    Strisciuglio, Pietro; Concolino, Daniela

    2014-01-01

    Phenylketonuria (PKU) was the first inherited metabolic disease in which dietary treatment was found to prevent the disease’s clinical features. Treatment of phenylketonuria remains difficult due to progressive decrease in adherence to diet and the presence of neurocognitive defects despite therapy. This review aims to summarize the current literature on new treatment strategies. Additions to treatment include new, more palatable foods based on glycomacropeptide that contains very limited amount of aromatic amino acids, the administration of large neutral amino acids to prevent phenylalanine entry into the brain or tetrahydropterina cofactor capable of increasing residual activity of phenylalanine hydroxylase. Moreover, human trials have recently been performed with subcutaneous administration of phenylalanine ammonia-lyase, and further efforts are underway to develop an oral therapy containing phenylanine ammonia-lyase. Gene therapy also seems to be a promising approach in the near future. PMID:25375236

  16. Monkey Trial Offers Hope for Future Ebola Treatment for Humans

    MedlinePlus

    ... 157462.html Monkey Trial Offers Hope for Future Ebola Treatment for Humans Antibodies from 1995 survivor protected ... 25, 2016 (HealthDay News) -- An antibody treatment for Ebola might be able to protect people for up ...

  17. Current and future treatment options in SIADH

    PubMed Central

    Zietse, Robert; van der Lubbe, Nils; Hoorn, Ewout J.

    2009-01-01

    The treatment of hyponatraemia due to SIADH is not always as straightforward as it seems. Although acute treatment with hypertonic saline and chronic treatment with fluid restriction are well established, both approaches have severe limitations. These limitations are not readily overcome by addition of furosemide, demeclocycline, lithium or urea to the therapy. In theory, vasopressin-receptor antagonists would provide a more effective method to treat hyponatraemia, by virtue of their ability to selectively increase solute-free water excretion by the kidneys (aquaresis). In this review we explore the limitations of the current treatment of SIADH and describe emerging therapies for the treatment of SIADH-induced hyponatraemia. PMID:19881932

  18. Consolidation Strategies in Ovarian Cancer: Observations for Future Clinical Trials

    PubMed Central

    Sabbatini, Paul; Spriggs, David; Aghajanian, Carol; Hensley, Martee; Tew, William; Konner, Jason; Bell-McGuinn, Kathryn; Juretzka, Margrit; Iasonos, Alexia

    2013-01-01

    Purpose To describe the characteristics of a series of study populations of ovarian cancer patients with identical elegibility criteria in second or subsequent clinical remission (cCR) and to propose endpoint benchmarks for future consolidation studies. Patients and Methods The patient populations consisted of those 1) untreated - U (observed until progression), n = 35; 2) receiving imatinib - G, n = 32; 3) receiving goserelin and bicalutamide - A, n = 32; and 4) receiving vaccine - V, n = 68; total = 167. The endpoint of the combined analysis was progression-free survival in second remission (PFS 2). Patient characteristics were compared by Chi-square test, and factors predicting PFS 2 evaluated in multivariate Cox model. Results Groups were comparable for age, stage, grade, and debulking. Multivariate model to predict PFS 2 duration included histology, stage, optimal debulking, PFS 1 duration and the type of intervention. As a benchmark for future studies, the median PFS 2 of the combined population of G, A, U (removing V which had the most impact in prolonging PFS 2, n=68) was 11.3 months (95% CI: 10.4 – 12.5 months). The percent of patients with PFS 2 > PFS 1 was 14/90 (16%). At 12 months, 43% remain progression free. Conclusion Preliminary benchmarks for efficacy endpoints are suggested for future consolidation trials of patients in cCR. However, the suggested strategies will require validation in randomized trials and larger data sets. PMID:19836827

  19. Stereotactic body radiotherapy: current strategies and future development

    PubMed Central

    2016-01-01

    Stereotactic body radiotherapy (SBRT) has emerged as the standard treatment for medically inoperable early-staged non-small cell lung cancer (NSCLC). The local control rate after SBRT is over 90%. Some forms of tumour motion management and image-guided radiation delivery techniques are the prerequisites for fulfilment of its goal to deliver a high radiation dose to the tumour target without overdosing surrounding normal tissues. In this review, the current strategies of tumour motion management will be discussed, followed by an overview of various image-guided radiotherapy (RT) systems and devices available for clinical practice. Besides medically inoperable stage I NSCLC, SBRT has also been widely adopted for treatment of oligometastasis involving the lungs. Its possible applications in various other cancer illnesses are under extensive exploration. The progress of SBRT is critically technology-dependent. With advancement of technology, the ideal of personalised, effective and yet safe SBRT is already on the horizon. PMID:27606082

  20. Stereotactic body radiotherapy: current strategies and future development.

    PubMed

    Tsang, Maverick W K

    2016-07-01

    Stereotactic body radiotherapy (SBRT) has emerged as the standard treatment for medically inoperable early-staged non-small cell lung cancer (NSCLC). The local control rate after SBRT is over 90%. Some forms of tumour motion management and image-guided radiation delivery techniques are the prerequisites for fulfilment of its goal to deliver a high radiation dose to the tumour target without overdosing surrounding normal tissues. In this review, the current strategies of tumour motion management will be discussed, followed by an overview of various image-guided radiotherapy (RT) systems and devices available for clinical practice. Besides medically inoperable stage I NSCLC, SBRT has also been widely adopted for treatment of oligometastasis involving the lungs. Its possible applications in various other cancer illnesses are under extensive exploration. The progress of SBRT is critically technology-dependent. With advancement of technology, the ideal of personalised, effective and yet safe SBRT is already on the horizon. PMID:27606082

  1. Emerging treatment strategies for glioblastoma multiforme

    PubMed Central

    Carlsson, Steven K; Brothers, Shaun P; Wahlestedt, Claes

    2014-01-01

    Glioblastoma multiforme (GBM) is the deadliest form of brain tumor with a more than 90% 5-year mortality. GBM has a paltry median survival of 12.6 months attributed to the unique treatment limitations such as the high average age of onset, tumor location, and poor current understandings of the tumor pathophysiology. The resection techniques, chemotherapic strategies, and radiation therapy currently used to treat GBM have slowly evolved, but the improvements have not translated to marked increases in patient survival. Here, we will discuss the recent progress in our understanding of GBM pathophysiology, and the diagnostic techniques and treatment options. The discussion will include biomarkers, tumor imaging, novel therapies such as monoclonal antibodies and small-molecule inhibitors, and the heterogeneity resulting from the GBM cancer stem cell population. PMID:25312641

  2. The black aged: a strategy for future mental health services.

    PubMed

    Carter, J H

    1978-12-01

    The younger generation of today will become the elderly of tomorrow. The qualitative differences in life experiences of blacks versus whites lead to differences in the manifestations of emotional problems. Thus the need for a special psychiatric strategy for aged blacks in the future. The problems of blacks, regardless of age, are inextricably linked with beliefs regarding illness, health and institutionalized racism. The many psychiatric ghettoes stemming from the depopulation of mental hospitals reflect poor planning and an obvious disregard for the realities of the whole life situations of elderly blacks. There should be an end to living in squalor and being the victims of muggings, rape and all forms of exploitation. Psychiatry should step forward with some careful and significant plans. PMID:712025

  3. Combine or Separate Future Pain? The Impact of Current Pain on Decisions about Future Dental Treatments

    PubMed Central

    Andrade, Eduardo B.; Bianchini, Marco Aurélio; Lucchiari, Newton

    2013-01-01

    Patients are often given the option of undergoing future painful treatments in one or multiple sessions (e.g., extracting two wisdom teeth on one or two different days). In a randomized controlled field experiment, we investigated the impact of transient pain on patients’ decision to combine or separate future periodontal treatments. The main results show that most patients preferred to have the future treatments take place in one session when they made their choice after a painless examination (i.e., general clinical exam). However, the patients’ preference for combining the future treatments did not differ from chance when the choice was made immediately following a painful examination (i.e., pocketing and bleeding on probing exam). The impact of pain on decision making is observed within and between participants. Current pain seems to lead patients to question their ability to endure future painful treatments in one session. PMID:23704972

  4. Bone pain: current and future treatments.

    PubMed

    Frost, Charlotte Ørsted; Hansen, Rikke Rie; Heegaard, Anne-Marie

    2016-06-01

    Skeletal conditions are common causes of chronic pain and there is an unmet medical need for improved treatment options. Bone pain is currently managed with disease modifying agents and/or analgesics depending on the condition. Disease modifying agents affect the underlying pathophysiology of the disease and reduce as a secondary effect bone pain. Antiresorptive and anabolic agents, such as bisphosphonates and intermittent parathyroid hormone (1-34), respectively, have proven effective as pain relieving agents. Cathepsin K inhibitors and anti-sclerostin antibodies hold, due to their disease modifying effects, promise of a pain relieving effect. NSAIDs and opioids are widely employed in the treatment of bone pain. However, recent preclinical findings demonstrating a unique neuronal innervation of bone tissue and sprouting of sensory nerve fibers open for new treatment possibilities. PMID:26940053

  5. [Treatment of Alzheimer's disease and future approaches].

    PubMed

    Forette, Françoise; Hauw, Jean-Jacques

    2010-01-01

    The progressive neuronal loss in Alzheimer's disease leads to neurochemical abnormalities which provide the basis for symptomatic treatments. Four cholinesterase inhibitors were released in this indication. Meta-analyses have confirmed a beneficial effect on cognitive functioning and activities of daily living. The NMDA receptor antagonist, memantine, was also approved for the treatment of moderate to severe and may be associated. Progress in the patho-physiology of the disease offers some hope of new treatments acting on the cerebral lesions. The amyloid hypothesis allowed the emergence of active or passive immunotherapies, and of secretase inhibitors or modulators. Recent studies have targeted the P tau protein. The brain plasticity and the uses of stem cells offer more distant hope. PMID:21144478

  6. [Treatment strategy for advanced prostate cancer with bone metastases].

    PubMed

    Sugimoto, Mikio; Kakehi, Yoshiyuki

    2006-08-01

    The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases. PMID:16912523

  7. Entry inhibitors and future treatment of hepatitis C.

    PubMed

    Fofana, Isabel; Jilg, Nikolaus; Chung, Raymond T; Baumert, Thomas F

    2014-04-01

    Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Furthermore, HCV-induced liver disease is the leading indication for liver transplantation. The recent introduction of direct-acting antivirals (DAAs) has revolutionized HCV treatment by making possible the cure of the majority of patients. However, their efficacy and safety in difficult-to-treat patients such as patients receiving immunosuppression, those with advanced liver disease, co-morbidity and HIV/HCV-co-infection remain to be determined. Furthermore, prevention of liver graft infection remains a pressing issue. HCV entry inhibitors target the very first step of the HCV life cycle and efficiently inhibit cell-cell transmission - a key prerequisite for viral spread. Because of their unique mechanism of action on cell-cell transmission they may provide a promising and simple perspective for prevention of liver graft infection. A high genetic barrier to resistance and complementary mechanism of action compared to DAAs makes entry inhibitors attractive as a new strategy for treatment of multi-resistant or difficult-to-treat patients. Clinical studies are needed to determine the future role of entry inhibitors in the arsenal of antivirals to combat HCV infection. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." PMID:24525381

  8. Polyphenols: Potential Future Arsenals in the Treatment of Diabetes.

    PubMed

    Solayman, Md; Ali, Yousuf; Alam, Fahmida; Islam, Md Asiful; Alam, Nadia; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Diabetes mellitus (DM) is one of the most common endocrine metabolic disorders. In addition to exercise and diet, oral anti-diabetic drugs have been used as a part of the management strategy worldwide. Unfortunately, none of the conventional anti-diabetic drugs are without side effects, and these drugs pose an economic burden. Therefore, the investigation of novel anti-diabetic regimens is a major challenge for researchers, in which nature has been the primary resource for the discovery of potential therapeutics. Many plants have been shown to act as anti-diabetic agents, in which the main active constituents are believed to be polyphenols. Natural products containing high polyphenol levels can control carbohydrate metabolism by various mechanisms, such as protecting and restoring beta-cell integrity, enhancing insulin releasing activity, and increasing cellular glucose uptake. Blackberries, red grapes, apricots, eggplant and popular drinks such as coffee, cocoa and green tea are all rich in polyphenols, which may dampen insulin resistance and be natural alternatives in the treatment of diabetes. Therefore, the aim of this review is to report on the available anti-diabetic polyphenols (medicinal plants, fruits and vegetables), their mechanisms in the various pathways of DM and their correlations with DM. Additionally, this review emphasizes the types of polyphenols that could be potential future resources in the treatment of DM via either novel regimens or as supplementary agents. PMID:26601968

  9. The future of cancer treatment: immunomodulation, CARs and combination immunotherapy.

    PubMed

    Khalil, Danny N; Smith, Eric L; Brentjens, Renier J; Wolchok, Jedd D

    2016-05-01

    In the past decade, advances in the use of monoclonal antibodies (mAbs) and adoptive cellular therapy to treat cancer by modulating the immune response have led to unprecedented responses in patients with advanced-stage tumours that would otherwise have been fatal. To date, three immune-checkpoint-blocking mAbs have been approved in the USA for the treatment of patients with several types of cancer, and more patients will benefit from immunomodulatory mAb therapy in the months and years ahead. Concurrently, the adoptive transfer of genetically modified lymphocytes to treat patients with haematological malignancies has yielded dramatic results, and we anticipate that this approach will rapidly become the standard of care for an increasing number of patients. In this Review, we highlight the latest advances in immunotherapy and discuss the role that it will have in the future of cancer treatment, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended. PMID:26977780

  10. [Pathogenesis and treatment of presbyacusis. Current status and future perspectives].

    PubMed

    Mazurek, B; Stöver, T; Haupt, H; Gross, J; Szczepek, A

    2008-04-01

    Factors responsible for presbyacusis include physiological ageing processes as well as endogenous or exogenous causes. In the industrial countries, two main exogenous causes are exposure to loud noise and obesity. Pathomechanisms contributing to presbyacusis are hypoxia/ischemia, reactive species formation and oxidative stress, apoptotic and necrotic death of hair cells and spiral ganglion cells as well as inherited and acquired mutations in the mitochondrial DNA. Important for the successful treatment of presbyacusis is a timely fitting of hearing aids on both ears to improve communication and provide the auditory system with acoustic information. Using the hearing aids will also elevate the detection threshold of an existing tinnitus signal. At present, several therapeutic strategies based on pharmacological intervention are under discussion. The application of antioxidants or caloric restriction are considered to prevent or reduce oxidative stress-induced damage. Animal experiments evidenced that superoxide dismutase 2 (SOD2) strongly decreases in age; thus, a further approach may be the overexpression or modulation of the SOD2 within the cochlea. Adenoviral-mediated gene transfer technology would be a tempting approach to address this type of therapy. Finally, hair cell regeneration could be a possible treatment of presbyacusis in the future. PMID:18338147

  11. Hepatitis C treatment: current and future perspectives.

    PubMed

    Munir, Saira; Saleem, Sana; Idrees, Muhammad; Tariq, Aaliyah; Butt, Sadia; Rauff, Bisma; Hussain, Abrar; Badar, Sadaf; Naudhani, Mahrukh; Fatima, Zareen; Ali, Muhmmad; Ali, Liaqat; Akram, Madiha; Aftab, Mahwish; Khubaib, Bushra; Awan, Zunaira

    2010-01-01

    Hepatitis C virus (HCV) is a member of Flaviviridae family and one of the major causes of liver disease. There are about 175 million HCV infected patients worldwide that constitute 3% of world's population. The main route of HCV transmission is parental however 90% intravenous drug users are at highest risk. Standard interferon and ribavirin remained a gold standard of chronic HCV treatment having 38-43% sustained virological response rates. Currently the standard therapy for HCV is pegylated interferon (PEG-INF) with ribavirin. This therapy achieves 50% sustained virological response (SVR) for genotype 1 and 80% for genotype 2 & 3. As pegylated interferon is expensive, standard interferon is still the main therapy for HCV treatment in under developed countries. On the other hand, studies showed that pegylated IFN and RBV therapy has severe side effects like hematological complications. Herbal medicines (laccase, proanthocyandin, Rhodiola kirilowii) are also being in use as a natural and alternative way for treatment of HCV but there is not a single significant report documented yet. Best SVR indicators are genotype 3 and 2, < 0.2 million IU/mL pretreatment viral load, rapid virological response (RVR) rate and age <40 years. New therapeutic approaches are under study like interferon related systems, modified forms of ribavirin, internal ribosome entry site (HCV IRES) inhibitors, NS3 and NS5a inhibitors, novel immunomodulators and specifically targeted anti-viral therapy for hepatitis C compounds. More remedial therapies include caspase inhibitors, anti-fibrotic agents, antibody treatment and vaccines. PMID:21040548

  12. Biological treatment strategies for disc degeneration: potentials and shortcomings

    PubMed Central

    Nerlich, Andreas G.; Boos, Norbert

    2006-01-01

    Recent advances in molecular biology, cell biology and material sciences have opened a new emerging field of techniques for the treatment of musculoskeletal disorders. These new treatment modalities aim for biological repair of the affected tissues by introducing cell-based tissue replacements, genetic modifications of resident cells or a combination thereof. So far, these techniques have been successfully applied to various tissues such as bone and cartilage. However, application of these treatment modalities to cure intervertebral disc degeneration is in its very early stages and mostly limited to experimental studies in vitro or in animal studies. We will discuss the potential and possible shortcomings of current approaches to biologically cure disc degeneration by gene therapy or tissue engineering. Despite the increasing number of studies examining the therapeutic potential of biological treatment strategies, a practicable solution to routinely cure disc degeneration might not be available in the near future. However, knowledge gained from these attempts might be applied in a foreseeable future to cure the low back pain that often accompanies disc degeneration and therefore be beneficial for the patient. PMID:16983559

  13. The future of tic disorder treatment.

    PubMed

    Bennett, Shannon M; Keller, Alex E; Walkup, John T

    2013-11-01

    Competing theories on the etiology and treatment of chronic tic disorders and Tourette syndrome have long made the search for efficacious intervention more challenging for patients and families seeking to reduce functional impairment related to tic symptoms. These symptoms were historically posited to be either psychological in origin, leading to the long tradition of psychoanalytic psychotherapy for tics, or biological in nature, particularly since the advent of successful treatments using neuroleptic medications. Current thinking about the phenomenology of tic disorders comes from growing empirical evidence as well as advances in neuroscience and genetics research and reveals a biological vulnerability that is exacerbated by physiological arousal related to environmental or interpersonal stress. This manuscript summarizes the evolution of this knowledge base and describes current best-practice recommendations for patients, families, and clinicians. PMID:24175754

  14. Preparing Future Geoscience Professionals: Needs, Strategies, Programs, and Online Resources

    NASA Astrophysics Data System (ADS)

    Macdonald, H.; Manduca, C. A.; Ormand, C. J.; Dunbar, R. W.; Beane, R. J.; Bruckner, M.; Bralower, T. J.; Feiss, P. G.; Tewksbury, B. J.; Wiese, K.

    2011-12-01

    Geoscience faculty, departments, and programs play an important role in preparing future geoscience professionals. One challenge is supporting the diversity of student goals for future employment and the needs of a wide range of potential employers. Students in geoscience degree programs pursue careers in traditional geoscience industries; in geoscience education and research (including K-12 teaching); and opportunities at the intersection of geoscience and other fields (e.g., policy, law, business). The Building Strong Geoscience Departments project has documented a range of approaches that departments use to support the development of geoscience majors as professionals (serc.carleton.edu/departments). On the Cutting Edge, a professional development program, supports graduate students and post-doctoral fellows interested in pursuing an academic career through workshops, webinars, and online resources (serc.carleton.edu/NAGTWorkshops/careerprep). Geoscience departments work at the intersection of student interests and employer needs. Commonly cited program goals that align with employer needs include mastery of geoscience content; field experience; skill in problem solving, quantitative reasoning, communication, and collaboration; and the ability to learn independently and take a project from start to finish. Departments and faculty can address workforce issues by 1) implementing of degree programs that develop the knowledge, skills, and attitudes that students need, while recognizing that students have a diversity of career goals; 2) introducing career options to majors and potential majors and encouraging exploration of options; 3) advising students on how to prepare for specific career paths; 4) helping students develop into professionals, and 5) supporting students in the job search. It is valuable to build connections with geoscience employers, work with alumni and foster connections between students and alumni with similar career interests, collaborate with

  15. Treatment strategies for gastric cancer patients with peritoneal metastasis.

    PubMed

    Imano, Motohiro; Okuno, Kiyotaka

    2014-03-01

    Although the treatment of gastric cancer improves the clinical outcomes, the survival of gastric cancer patients with peritoneal metastasis is still very poor. Effective drugs against peritoneal metastasis, coupled with new therapeutic modalities, are needed to improve the prognoses of these patients. Paclitaxel and TS-1 are candidate drugs for peritoneal metastasis, and intraperitoneal chemotherapy and targeted therapy are potential new therapeutic modalities. Two phase II studies using TS-1 and intraperitoneal and systemic paclitaxel for gastric cancer patients with peritoneal metastasis showed respectable survival results. In addition, peritoneal metastatic lesions showed high levels of epithelial cellular adhesion molecule (ECAM) and very low levels of human epidermal growth factor receptor 2 (HER2), thus indicating that an anti-ECAM monoclonal antibody, catumaxomab, would be effective against gastric cancer-derived peritoneal metastasis. Although catumaxomab and intraperitoneally administered paclitaxel are not generally used in Japan at present, these treatment strategies might therefore be effectively used in Japan in the near future. PMID:23677598

  16. Inhalation injury: epidemiology, pathology, treatment strategies

    PubMed Central

    2013-01-01

    Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation. Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data

  17. Technology and the Future of Mental Health Treatment

    MedlinePlus

    ... Health Intervention Technology? Join a Study Learn More Technology and the Future of Mental Health Treatment Introduction ... What is NIMH’s Role in Mental Health Intervention Technology? Between FY2009 and FY2015, NIMH awarded 404 grants ...

  18. The Indonesian family planning program: its strategy for the future.

    PubMed

    Suyono, H; Parsons, J S; Teachman, J D

    1978-01-01

    This paper discusses the strategy of the Indonesian national family planning program for the coming 5-10 years, in which communities will be given greater responsibility for their own fertility limitation programs and a stronger alliance with other government programs will be sought in order to assure the long-term success of both family planning and development activities. The article explains why more vigorous fertility limitation efforts will be required in the future despite encouraging results so far, and describes the structure of the Indonesian national family planning program. The rationale behind the move away from clinics as depensers of family planning services is examined, and the community family planning approach in Bali is described and compared to that in Java. The differing approach to service delivery in the Outer Islands is then discussed. The relationship between development and the small family norm is discussed, and efforts underway to maximize cooperation between the family planning and development sector projects are described. PMID:12309781

  19. Bone regenerative medicine: classic options, novel strategies, and future directions

    PubMed Central

    2014-01-01

    This review analyzes the literature of bone grafts and introduces tissue engineering as a strategy in this field of orthopedic surgery. We evaluated articles concerning bone grafts; analyzed characteristics, advantages, and limitations of the grafts; and provided explanations about bone-tissue engineering technologies. Many bone grafting materials are available to enhance bone healing and regeneration, from bone autografts to graft substitutes; they can be used alone or in combination. Autografts are the gold standard for this purpose, since they provide osteogenic cells, osteoinductive growth factors, and an osteoconductive scaffold, all essential for new bone growth. Autografts carry the limitations of morbidity at the harvesting site and limited availability. Allografts and xenografts carry the risk of disease transmission and rejection. Tissue engineering is a new and developing option that had been introduced to reduce limitations of bone grafts and improve the healing processes of the bone fractures and defects. The combined use of scaffolds, healing promoting factors, together with gene therapy, and, more recently, three-dimensional printing of tissue-engineered constructs may open new insights in the near future. PMID:24628910

  20. Migraine: pathophysiology, pharmacology, treatment and future trends.

    PubMed

    Villalón, Carlos M; Centurión, David; Valdivia, Luis Felipe; de Vries, Peter; Saxena, Pramod R

    2003-03-01

    Migraine treatment has evolved into the scientific arena, but it seems still controversial whether migraine is primarily a vascular or a neurological dysfunction. Irrespective of this controversy, the levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter, seem to decrease during migraine (with associated carotid vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents invariably produce vasoconstriction in the external carotid circulation. The last decade has witnessed the advent of sumatriptan and second generation triptans (e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs, the 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the second-generation triptans have a higher oral bioavailability and longer plasma half-life. In line with the vascular and neurogenic theories of migraine, all triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and presynaptic inhibition of the trigeminovascular inflammatory responses implicated in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D (PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system without producing vasoconstriction. Nevertheless, PNU-142633 proved to be ineffective in the acute treatment of migraine, whilst LY344864 did show some efficacy when used in doses which interact with 5-HT1B receptors. Finally, although the triptans are effective antimigraine agents producing selective cranial vasoconstriction, efforts are being made to develop other effective antimigraine alternatives acting via the direct blockade of vasodilator mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors, inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully lead to fewer side effects. PMID:15320857

  1. Systematic Treatment Selection (STS): A Review and Future Directions

    ERIC Educational Resources Information Center

    Nguyen, Tam T.; Bertoni, Matteo; Charvat, Mylea; Gheytanchi, Anahita; Beutler, Larry E.

    2007-01-01

    Systematic Treatment Selection (STS) is a form of technical eclectism that develops and plans treatments using empirically founded principles of psychotherapy. It is a model that provides systematic guidelines for the utilization of different psychotherapeutic strategies based on patient qualities and problem characteristics. Historically, it…

  2. Water quality monitoring strategies - A review and future perspectives.

    PubMed

    Behmel, S; Damour, M; Ludwig, R; Rodriguez, M J

    2016-11-15

    The reliable assessment of water quality through water quality monitoring programs (WQMPs) is crucial in order for decision-makers to understand, interpret and use this information in support of their management activities aiming at protecting the resource. The challenge of water quality monitoring has been widely addressed in the literature since the 1940s. However, there is still no generally accepted, holistic and practical strategy to support all phases of WQMPs. The purpose of this paper is to report on the use cases a watershed manager has to address to plan or optimize a WQMP from the challenge of identifying monitoring objectives; selecting sampling sites and water quality parameters; identifying sampling frequencies; considering logistics and resources to the implementation of actions based on information acquired through the WQMP. An inventory and critique of the information, approaches and tools placed at the disposal of watershed managers was proposed to evaluate how the existing information could be integrated in a holistic, user-friendly and evolvable solution. Given the differences in regulatory requirements, water quality standards, geographical and geological differences, land-use variations, and other site specificities, a one-in-all solution is not possible. However, we advance that an intelligent decision support system (IDSS) based on expert knowledge that integrates existing approaches and past research can guide a watershed manager through the process according to his/her site-specific requirements. It is also necessary to tap into local knowledge and to identify the knowledge needs of all the stakeholders through participative approaches based on geographical information systems and adaptive survey-based questionnaires. We believe that future research should focus on developing such participative approaches and further investigate the benefits of IDSS's that can be updated quickly and make it possible for a watershed manager to obtain a

  3. Novel strategies for treatment of resistant hypertension.

    PubMed

    Judd, Eric K; Oparil, Suzanne

    2013-12-01

    Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of 3 or more antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires 4 or more agents to achieve control, occurs in a substantial proportion (>10%) of treated hypertensive patients. Refractory hypertension is a recently described subset of resistant hypertension that cannot be controlled with maximal medical therapy (⩾5 antihypertensive medications of different classes at maximal tolerated doses). Patients with resistant or refractory hypertension are at increased cardiovascular risk and comprise the target population for novel antihypertensive treatments. Device-based interventions, including carotid baroreceptor activation and renal denervation, reduce sympathetic nervous system activity and have effectively reduced BP in early clinical trials of resistant hypertension. Renal denervation interrupts afferent and efferent renal nerve signaling by delivering radiofrequency energy, other forms of energy, or norepinephrine-depleting pharmaceuticals through catheters in the renal arteries. Renal denervation has the advantage of not requiring general anesthesia, surgical intervention, or device implantation and has been evaluated extensively in observational proof-of-principle studies and larger randomized controlled trials. It has been shown to be safe and effective in reducing clinic BP, indices of sympathetic nervous system activity, and a variety of hypertension-related comorbidities. These include impaired glucose metabolism/insulin resistance, end-stage renal disease, obstructive sleep apnea, cardiac hypertrophy, heart failure, and cardiac arrhythmias. This article reviews the strengths, limitations, and future applications of novel device-based treatment, particularly renal denervation, for resistant hypertension and its comorbidities. PMID:25028641

  4. [Glioma treatment strategies using mesenchymal stem cells].

    PubMed

    Namba, Hiroki

    2010-10-01

    Because of the growth characteristics of malignant gliomas that are highly invasive and deeply infiltrate the surrounding brain area; the surgical resection of these gliomas with preservation of neural functions is almost always noncurative. The residual tumor cells are usually resistant to standard adjuvant radiochemotherapy, and therefore, the tumors inevitably recur after a certain period and finally cause the death of the patients. Neural and mesenchymal stem cells have been extensively studied for the development of new strategies for treating malignant gliomas because of these cells possess the intrinsic property of homing toward tumor cells. By using neural and mesenchymal stem cells as vehicles for drug carriers, it is possible to deliver anticancer drugs to the tumor cells that infiltrate functioning normal brain tissue and are difficult to remove. Several cytokines and suicide genes have been tested, and promising results have been reported in animal brain tumor models. However, further studies involving safety issues such as secondary cancer formation are required before human trials of stem cell therapies. In the present paper, the author has reviewed the recent concepts involved in the treatment of malignant gliomas with stem cells, especially mesenchymal stem cells that are much easier to obtain from the patients themselves. PMID:20940507

  5. Multimodal treatment strategies for advanced hilar cholangiocarcinoma.

    PubMed

    Weiss, Matthew J; Cosgrove, David; Herman, Joseph M; Rastegar, Neda; Kamel, Ihab; Pawlik, Timothy M

    2014-08-01

    Cholangiocarcinoma (CCA) is the second most common primary malignancy of the liver arising from malignant transformation and growth of biliary ductal epithelium. Approximately 50-70 % of CCAs arise at the hilar plate of the biliary tree, which are termed hilar cholangiocarcinoma (HC). Various staging systems are currently employed to classify HCs and determine resectability. Depending on the pre-operative staging, the mainstays of treatment include surgery, chemotherapy, radiation therapy, and photodynamic therapy. Surgical resection offers the only chance for cure of HC and achieving an R0 resection has demonstrated improved overall survival. However, obtaining longitudinal and radial surgical margins that are free of tumor can be difficult and frequently requires extensive resections, particularly for advanced HCs. Pre-operative interventions may be necessary to prepare patients for major hepatic resections, including endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, and portal vein embolization. Multimodal therapy that combines chemotherapy with external beam radiation, stereotactic body radiation therapy, bile duct brachytherapy, and/or photodynamic therapy are all possible strategies for advanced HC prior to resection. Orthotopic liver transplantation is another therapeutic option that can achieve complete extirpation of locally advanced HC in judiciously selected patients following standardized neoadjuvant protocols. PMID:24962146

  6. Optimizing Hypoxia Detection and Treatment Strategies

    PubMed Central

    Koch, Cameron J.; Evans, Sydney M.

    2015-01-01

    Clinical studies using Eppendorf® needle sensors have invariably documented the resistance of hypoxic human tumors to therapy. These studies first documented the need for individual patient measurement of hypoxia, since hypoxia varied from tumor-to-tumor. Furthermore, hypoxia in sarcomas & cervical cancer leads to distant metastasis or local/regional spread, respectively. For various reasons, the field has moved away from direct needle-sensor oxygen measurements to indirect assays (HIF-related changes; bioreductive metabolism) and the latter can be imaged non-invasively. Many of hypoxia’s detrimental therapeutic effects are reversible in mice but little treatment-improvement in hypoxic human tumors has been seen. The question is why? What factors cause human tumors to be refractory to anti-hypoxia strategies? We suggest the primary cause to be the complexity of hypoxia formation and its characteristics. Three basic types of hypoxia exist, encompassing various diffusional (distance from perfused vessel), temporal (on/off cycling) and perfusional (blood-flow efficiency) limitations. Surprisingly, there is no current information on their relative prevalence in human tumors and even animal models. This is important because different hypoxia sub-types are predicted to require different diagnostic and therapeutic approaches, but the implications of this remain unknown. Even more challenging, no agreement exists for the best way to measure hypoxia. Some results even suggest that hypoxia is unlikely to be targetable therapeutically. In this review, the authors will revisit various critical aspects of this field that are sometimes forgotten or misrepresented in the recent literature. Since most current non-invasive imaging studies involve PET-isotope-labelled 2-nitroimidazoles, we will emphasize key findings made in our studies using EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide] and F18-labelled EF5. These will show the importance of

  7. Cancer Treatment Strategies Targeting Sphingolipid Metabolism

    PubMed Central

    Oskouian, Babak; Saba, Julie D.

    2011-01-01

    Ceramide and sphingosine-1-phosphate are related sphingolipid metabolites that can be generated through a de novo biosynthetic route or derived from the recycling of membrane sphingomyelin. Both these lipids regulate cellular responses to stress, with generally opposing effects. Sphingosine-1-phosphate functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled receptors, whereas ceramide activates intrinsic and extrinsic apoptotic pathways through receptor-independent mechanisms. A growing body of evidence has implicated ceramide, sphingosine-1-phosphate and the genes involved in their synthesis, catabolism and signaling in various aspects of oncogenesis, cancer progression and drug- and radiation resistance. This may be explained in part by the finding that both lipids impinge upon the PI3K/AKT pathway, which represses apoptosis and autophagy. In addition, sphingolipids influence cell cycle progression, telomerase function, cell migration and stem cell biology. Considering the central role of ceramide in mediating physiological as well as pharmacologically stimulated apoptosis, ceramide can be considered a tumor-suppressor lipid. In contrast, sphingosine-1-phosphate can be considered a tumor-promoting lipid, and the enzyme responsible for its synthesis functions as an oncogene. Not surprisingly, genetic mutations that result in reduced ceramide generation, increased sphingosine-1-phosphate synthesis or which reduce steady state ceramide levels and increase sphingosine-1-phosphate levels have been identified as mechanisms of tumor progression and drug resistance in cancer cells. Pharmacological tools for modulating sphingolipid pathways are being developed and represent novel therapeutic strategies for the treatment of cancer. PMID:20919655

  8. Preparing Future Leaders: Project Management Strategies for Service Learning

    ERIC Educational Resources Information Center

    Munger, Roger; Gutowski, Amanda

    2008-01-01

    This article makes a case for teaching project management strategies in service-learning courses. The authors describe three specific documents students can create to help them manage a service-learning project and then present strategies that can help students manage their project teams. Such skills, the authors argue, provide the tools students…

  9. Personal strategies for maximizing your value in an uncertain future.

    PubMed

    Pannesi, R

    1997-11-01

    Because of the trend toward downsizing and the increase in job insecurity, managers need to consider strategies to ensure that they are not among those who will be laid off in the coming years. This article presents a set of such strategies, which mostly fall into the two categories of skill enhancement and management style adaptation. PMID:10173996

  10. Treatment for primary hypothyroidism: current approaches and future possibilities

    PubMed Central

    Chakera, Ali J; Pearce, Simon HS; Vaidya, Bijay

    2012-01-01

    Primary hypothyroidism is the most common endocrine disease. Although the diagnosis and treatment of hypothyroidism is often considered simple, there are large numbers of people with this condition who are suboptimally treated. Even in those people with hypothyroidism who are biochemically euthyroid on levothyroxine replacement there is a significant proportion who report poorer quality of life. This review explores the historical and current treatment options for hypothyroidism, reasons for and potential solutions to suboptimal treatment, and future possibilities in the treatment of hypothyroidism. PMID:22291465

  11. Closed Fuel Cycle Waste Treatment Strategy

    SciTech Connect

    Vienna, J. D.; Collins, E. D.; Crum, J. V.; Ebert, W. L.; Frank, S. M.; Garn, T. G.; Gombert, D.; Jones, R.; Jubin, R. T.; Maio, V. C.; Marra, J. C.; Matyas, J.; Nenoff, T. M.; Riley, B. J.; Sevigny, G. J.; Soelberg, N. R.; Strachan, D. M.; Thallapally, P. K.; Westsik, J. H.

    2015-02-01

    This study is aimed at evaluating the existing waste management approaches for nuclear fuel cycle facilities in comparison to the objectives of implementing an advanced fuel cycle in the U.S. under current legal, regulatory, and logistical constructs. The study begins with the Global Nuclear Energy Partnership (GNEP) Integrated Waste Management Strategy (IWMS) (Gombert et al. 2008) as a general strategy and associated Waste Treatment Baseline Study (WTBS) (Gombert et al. 2007). The tenets of the IWMS are equally valid to the current waste management study. However, the flowsheet details have changed significantly from those considered under GNEP. In addition, significant additional waste management technology development has occurred since the GNEP waste management studies were performed. This study updates the information found in the WTBS, summarizes the results of more recent technology development efforts, and describes waste management approaches as they apply to a representative full recycle reprocessing flowsheet. Many of the waste management technologies discussed also apply to other potential flowsheets that involve reprocessing. These applications are occasionally discussed where the data are more readily available. The report summarizes the waste arising from aqueous reprocessing of a typical light-water reactor (LWR) fuel to separate actinides for use in fabricating metal sodium fast reactor (SFR) fuel and from electrochemical reprocessing of the metal SFR fuel to separate actinides for recycle back into the SFR in the form of metal fuel. The primary streams considered and the recommended waste forms include; Tritium in low-water cement in high integrity containers (HICs); Iodine-129: As a reference case, a glass composite material (GCM) formed by the encapsulation of the silver Mordenite (AgZ) getter material in a low-temperature glass is assumed. A number of alternatives with distinct advantages are also considered including a fused silica waste form

  12. Future nanomedicine for the diagnosis and treatment of osteoarthritis

    PubMed Central

    Eichaker, Lauren R; Cho, Hongsik; Duvall, Craig L; Werfel, Thomas A; Hasty, Karen A

    2016-01-01

    Current treatments for osteoarthritis (OA) are largely palliative until the joints become totally dysfunctional and prosthetic replacement becomes necessary. Effective methods are needed for diagnosing OA and monitoring its progression during its early stages, when the effects of therapeutic drugs or biological agents are most likely to be effective. Theranostic nanosomes and nanoparticles have the potential to noninvasively detect, track and treat the early stages of OA. As articular cartilage does not regenerate once it is degraded, cell-based treatments aided by superparamagnetic iron oxide nanoparticle tracking are attractive future treatment modalities for the later stages of OA progression, when significant cartilage replacement is needed. This article will describe the current and future translational approaches for the detection and noninvasive treatment of degenerative OA. PMID:25405797

  13. Human Papillomavirus: Current and Future RNAi Therapeutic Strategies for Cervical Cancer

    PubMed Central

    Jung, Hun Soon; Rajasekaran, Nirmal; Ju, Woong; Shin, Young Kee

    2015-01-01

    Human papillomaviruses (HPVs) are small DNA viruses; some oncogenic ones can cause different types of cancer, in particular cervical cancer. HPV-associated carcinogenesis provides a classical model system for RNA interference (RNAi) based cancer therapies, because the viral oncogenes E6 and E7 that cause cervical cancer are expressed only in cancerous cells. Previous studies on the development of therapeutic RNAi facilitated the advancement of therapeutic siRNAs and demonstrated its versatility by siRNA-mediated depletion of single or multiple cellular/viral targets. Sequence-specific gene silencing using RNAi shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, siRNA-based targeting requires further validation of its efficacy in vitro and in vivo, for its potential off-target effects, and of the design of conventional therapies to be used in combination with siRNAs and their drug delivery vehicles. In this review we discuss what is currently known about HPV-associated carcinogenesis and the potential for combining siRNA with other treatment strategies for the development of future therapies. Finally, we present our assessment of the most promising path to the development of RNAi therapeutic strategies for clinical settings. PMID:26239469

  14. [Chronic complications in cardiac transplantation. Clinical implications and future strategies].

    PubMed

    Magaña-Serrano, José Antonio; Argüero-Sánchez, Rubén

    2005-01-01

    Chronic complications are situations which limit the long-term utility of cardiac transplantation. The allograft vasculopathy is the most important cause of death at 5 years alter transplantation. Another conditions are systemic arterial hypertension, nephropathies, diabetes mellitus, dyslipidemies and malignant neoplasies. The present manuscript summarizes the characteristics, clinical presentation and therapeutic strategies for this conditions. PMID:16524076

  15. A Critical Look at Communication Strategies: Possibilities for Future Research

    ERIC Educational Resources Information Center

    Doqaruni, Vahid Rahmani

    2015-01-01

    Like general theories of human communication, previous research into second language (L2) communication strategies (CSs) has also been characterized on either interactional conceived account or cognitively conceived one. However, this paper is a critical attempt to show that CSs' full significance can only be understood if the domain of CSs…

  16. Hybrid curcumin compounds: a new strategy for cancer treatment.

    PubMed

    Teiten, Marie-Hélène; Dicato, Mario; Diederich, Marc

    2014-01-01

    Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients. In order to overcome these pharmacokinetic deficits of curcumin, several strategies, such as the design of synthetic analogs, the combination with specific adjuvants or nano-formulations, have been developed. By taking into account the risk-benefit profile of drug combinations, as well as the knowledge about curcumin's structure-activity relationship, a new concept for the combination of curcumin with scaffolds from different natural products or components has emerged. The concept of a hybrid curcumin molecule is based on the incorporation or combination of curcumin with specific antibodies, adjuvants or other natural products already used or not in conventional chemotherapy, in one single molecule. The high diversity of such conjugations enhances the selectivity and inherent biological activities and properties, as well as the efficacy of the parental compound, with particular emphasis on improving the efficacy of curcumin for future clinical treatments. PMID:25514225

  17. Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag.

    PubMed

    Tsuchii, Isao

    2016-01-01

    Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies. PMID:27040334

  18. Management of aortic graft infections - the present strategy and future perspectives.

    PubMed

    Treska, V; Certik, B; Molacek, J

    2016-01-01

    Aortic graft infections (AGI) are serious complications of open and endovascular types of surgery with an incidence rate of 0.6-3 %. AGI are associated with 30-60 % perioperative mortality and 40-60 % morbidity rate with limb amputation rates between 10 % and 40 %. The economic cost of AGI is substantial. At the time of aortic reconstruction, almost 90 % of patients have one or more predisposing factors for AGI. The diagnosis is based on clinical symptomatology, laboratory markers, microbial cultures, and imaging modalities. The general principle of surgical treatment lies in the removal of infected graft, debridement of infected periprosthetic tissues, and vascular reconstruction by in situ or extra-anatomic bypass with long-term antibiotic therapy. The conservative treatment is used only for selected patients with endograft infection. This review summarizes the current knowledge about the incidence, predisposing factors, etiology, diagnosis, treatment options, and prevention of aortic vascular graft and endograft infections. With the growing number of endovascular procedures we can expect more cases of infected aortic endografts in patients with severe comorbidities in the near future, where the recent radical surgical approach (graft excision, debridement, and new revascularization) cannot be used. Therefore the less invasive, sophisticated and individualized treatment strategies will have to be used in search of the best therapeutic approach to each specific patient (Fig. 4, Ref. 82). PMID:26925740

  19. Current Treatment Strategies in Pediatric Alopecia Areata

    PubMed Central

    Wang, Etienne; Lee, Joyce SS; Tang, Mark

    2012-01-01

    Alopecia areata (AA) is a non-scarring autoimmune disease of the hair follicle that can present at any age. Pediatric cases are commonly seen in a dermatology clinic, and management can potentially be challenging, with a small proportion of cases experiencing a chronic relapsing course marked by distressing hair loss that can bring about significant psychosocial morbidity. We review the established treatments for pediatric alopecia areata, alongside second and third line therapies that have shown to be efficacious. We also offer a treatment algorithm as a guide to the treatment of pediatric AA. PMID:23248364

  20. Immunotherapy strategies for multiple myeloma: the present and the future

    PubMed Central

    Locke, Frederick L; Nishihori, Taiga; Alsina, Melissa; Kharfan-Dabaja, Mohamed A

    2015-01-01

    Growing knowledge of the complexities of the immune system have led to a better understanding of how it can be harnessed for the purpose of anticancer therapy. Moreover, recent success with immunotherapies for solid tumors, combined with novel therapeutic strategies against myeloma, heighten excitement at the prospect of improving clinical outcomes for myeloma by improving antitumor immunity. Increased understanding of myeloma tumor-associated antigens, availability of more potent vaccines, expanded immune-modulating therapies, development of agents that block immune-suppressive pathways, increased sophistication of adoptive cell therapy techniques and capitalization upon standard autologous transplant are all important standalone or combination strategies that might ultimately improve prognosis of patients with multiple myeloma. PMID:23998734

  1. Bridge to a sustainable future: National environmental technology strategy

    SciTech Connect

    1995-04-01

    For the past two years the Administration has sought the views of Congress, the states, communities, industry, academia, nongovernmental organizations, and interested citizens on ways to spur the development and use of a new generation of environmental technologies. This document represents the views of thousands of individuals who participated in events around the country to help craft a national environmental technology strategy that will put us on the path to sustainable development.

  2. Current treatment strategies in autoimmune hemolytic disorders.

    PubMed

    Barcellini, Wilma

    2015-10-01

    Autoimmune hemolytic anemia (AIHA) is a heterogeneous disease usually classified according to the thermal range of the autoantibody in warm, cold and mixed forms. The treatment of AIHA is still not evidence-based. Corticosteroids are the first-line therapy for warm AIHA. For refractory/relapsed cases, the choice is between splenectomy (effective in ∼70% cases but with a presumed cure rate of 20%) and rituximab (effective in ∼70-80% of cases), which is becoming the preferred second-line treatment, and thereafter any of the immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporin, mycophenolate mofetil). Additional therapies are intravenous immunoglobulins and danazol. For severe or refractory cases, last option treatments are plasma-exchange, high-dose cyclophosphamide and alemtuzumab. As regards cold agglutinin disease, rituximab is now recommended as first-line treatment. PMID:26343892

  3. Gynecologic cancer: Diagnosis and treatment strategies

    SciTech Connect

    Rutledge, F.N.; Freedman, R.S.; Gershenson, D.M.

    1987-01-01

    This book contains 36 chapters divided into seven sections. The section headings are: Heath Memorial Award Lecture; Ovarian Cancer; Cervical and Vulvar Cancer; Endometrial Cancer; Trophoblastic Disease; Diagnostic Procedures; and New Treatment Modalities.

  4. The treatment strategy for tracheoesophageal fistula

    PubMed Central

    Wu, Xuemei; Zeng, Junli

    2015-01-01

    With the development of endoscopic techniques, the treatment of tracheoesophageal fistula (TEF) has made marked progress. As surgical intervention is often not an advisable option due to advanced malignancy and poor performance status of the patients, bronchoscopic intervention provides a good choice to palliate symptoms and reconstruct the airway and esophagus. In this review, we focus on the application of interventional therapy of TEF, especially the application of airway stenting, and highlight some representative cases referred to our department for treatment. PMID:26807286

  5. Future trends in environmental mercury concentrations: implications for prevention strategies.

    PubMed

    Sunderland, Elsie M; Selin, Noelle E

    2013-01-01

    In their new paper, Bellanger and coauthors show substantial economic impacts to the EU from neurocognitive impairment associated with methylmercury (MeHg) exposures. The main source of MeHg exposure is seafood consumption, including many marine species harvested from the global oceans. Fish, birds and other wildlife are also susceptible to the impacts of MeHg and already exceed toxicological thresholds in vulnerable regions like the Arctic. Most future emissions scenarios project a growth or stabilization of anthropogenic mercury releases relative to present-day levels. At these emissions levels, inputs of mercury to ecosystems are expected to increase substantially in the future, in part due to growth in the legacy reservoirs of mercury in oceanic and terrestrial ecosystems. Seawater mercury concentration trajectories in areas such as the North Pacific Ocean that supply large quantities of marine fish to the global seafood market are projected to increase by more than 50% by 2050. Fish mercury levels and subsequent human and biological exposures are likely to also increase because production of MeHg in ocean ecosystems is driven by the supply of available inorganic mercury, among other factors. Analyses that only consider changes in primary anthropogenic emissions are likely to underestimate the severity of future deposition and concentration increases associated with growth in mercury reservoirs in the land and ocean. We therefore recommend that future policy analyses consider the fully coupled interactions among short and long-lived reservoirs of mercury in the atmosphere, ocean, and terrestrial ecosystems. Aggressive anthropogenic emission reductions are needed to reduce MeHg exposures and associated health impacts on humans and wildlife and protect the integrity of one of the last wild-food sources globally. In the near-term, public health advice on safe fish consumption choices such as smaller species, younger fish, and harvests from relatively unpolluted

  6. Monitoring the effects of wastewater treatment strategies.

    PubMed

    de-la-Ossa-Carretero, J A; Del-Pilar-Ruso, Y; Giménez-Casalduero, F; Sánchez-Lizaso, J L

    2016-02-01

    Wastewater disposal in coastal waters causes widespread environmental problems. Secondary treatment is expected to reduce the adverse effects of insufficiently treated wastewater. The environmental impact of sewage disposal via 18 wastewater treatment plants was analysed using the benthic opportunistic polychaetes and amphipods (BOPA) index. In previous studies this index proved to be an effective tool for monitoring sewage pollution. The impact of these discharges was highly related to treatment level, which ranged from pre-treatment to biological, as well as to flow rates and outfall position. Locations affected by pre-treated wastewater showed environmental degradation, especially marked near outfalls with higher flow rates. At most locations, biologically treated wastewater did not cause a significant impact and an improvement in ecological integrity was detected after this secondary treatment had been implemented. The impact of discharge was highly related to chemical oxygen demand (COD), suspended solids and nutrient concentrations, which are all lower in biologically treated wastewater. A 'moderate' ecological status was observed not only near sewage outfalls with high wastewater flow rates (>1,500,000 m(3)/month) with a COD over 200 mg/l but also near those with lower flow rates but with a COD over 400 mg/l. To reduce the impact of sewage disposal, it is necessary to carry out adequate treatment, have site outfalls deep enough, and implement water recycling. PMID:26801153

  7. [Treatment strategies for advanced prostate cancer].

    PubMed

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  8. Emerging strategies for the treatment of gastroparesis.

    PubMed

    Langworthy, James; Parkman, Henry P; Schey, Ron

    2016-07-01

    Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction. Symptoms can be debilitating, affect nutritional states, and significantly impact patients' quality of life. The management of these patients can prove quite difficult to many providers. This article will review the current management recommendations of gastroparesis, discuss investigational medications and interventions, and summarize future directions of therapies targeting the underlying disease process. Current therapies are subdivided into those improving gastric motility and those directly targeting symptoms. Non-pharmacologic interventions, including gastric stimulator implantation and intra-pyloric botulinum toxic injection are reviewed. A discussion of expert opinion in the field, a look into the future of gastroparesis management, and a key point summary conclude the article. PMID:26840446

  9. Treatment of myasthenia gravis: current practice and future directions.

    PubMed

    Ciafaloni, Emma; Sanders, Donald B

    2002-09-01

    Myasthenia gravis is the best understood of the autoimmune diseases and a number of treatments are currently used to produce clinical improvement. However, due to the scarcity of evidence-based and comparative data, there is still no consensus on many therapeutic issues. Even a widely accepted treatment like thymectomy has never been proven effective by a well-designed trial. These are just some of the unanswered questions: What is the best treatment algorithm and safest long-term management of myasthenia gravis? What patients are likely to benefit from thymectomy? How long should myasthenia gravis patients be treated? Is it possible to discontinue immunotherapy once remission has been achieved? What are the risks associated with long-term immunosuppression? In this article, we review current therapeutic strategies and these unresolved questions about myasthenia gravis treatment. PMID:19810991

  10. SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

    SciTech Connect

    TW, CRAWFORD

    2008-07-17

    This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

  11. Factors influencing the future need for treatment of root surfaces.

    PubMed

    Ettinger, R L; Hand, J S

    1994-10-01

    This paper discusses the current status of root surface caries in the elderly population and the need for treatment of this condition in the future. Although root surface exposure and root caries have been reported for adults at all ages, the people at greatest risk for these conditions are the elderly. In the United States, life expectancy and the population aged 65 years and older has increased substantially, and the proportion of the elderly population who are dentate has increased and is projected to increase further. Utilization of dental services by the elderly is similar to that of employed adults. Interpretation of studies of the prevalence and incidence of root surface caries are difficult due to differences in sampling, definition of lesions, and reporting conventions. Root surface caries prevalence is related to age and continues to be a significant problem for this population as they age. Factors that may affect the future need for treatment are explored. PMID:7986448

  12. The Current and Future Treatment of Brain Metastases.

    PubMed

    Hardesty, Douglas A; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient's overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood-brain barrier transgression, cell-cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  13. The Current and Future Treatment of Brain Metastases

    PubMed Central

    Hardesty, Douglas A.; Nakaji, Peter

    2016-01-01

    Brain metastases are the most common intracranial malignancy, accounting for significant morbidity and mortality in oncology patients. The current treatment paradigm for brain metastasis depends on the patient’s overall health status, the primary tumor pathology, and the number and location of brain lesions. Herein, we review the modern management options for these tumors, including surgical resection, radiotherapy, and chemotherapy. Recent operative advances, such as fluorescence, confocal microscopy, and brachytherapy, are highlighted. With an increased understanding of the pathophysiology of brain metastasis come increased future therapeutic options. Therapy targeted to specific tumor molecular pathways, such as those involved in blood–brain barrier transgression, cell–cell adhesion, and angiogenesis, are also reviewed. A personalized plan for each patient, based on molecular characterizations of the tumor that are used to better target radiotherapy and chemotherapy, is undoubtedly the future of brain metastasis treatment. PMID:27252942

  14. Acute behavioral interventions and outpatient treatment strategies with suicidal adolescents

    PubMed Central

    O’Brien, Kimberly H. McManama; Singer, Jonathan B.; LeCloux, Mary; Duarté-Vélez, Yovanska; Spirito, Anthony

    2015-01-01

    Despite the prevalence of suicidal thoughts and behaviors among adolescents, there is limited knowledge of effective interventions to use with this population. This paper reviews the findings of studies on behavioral interventions for adolescents who are at acute suicide risk, as well as outpatient treatment and risk management strategies with suicidal adolescents. The importance of addressing comorbid behaviors and enhancing protective factors are discussed. Cultural considerations in working with suicidal adolescents and strategies for conducting culturally competent treatment are explored. PMID:26279646

  15. Archiving strategy for USGS EROS center and our future direction

    USGS Publications Warehouse

    Faundeen, John L.

    2010-01-01

    The U. S. Geological Survey's Earth Resources Observation and Science Center has the responsibility to acquire, manage, and preserve our Nation's land observations. These records are obtained primarily from airplanes and satellites dating back to the 1930s. The ability to compare landscapes from the past with current information enables change analysis at local and global scales. With new observations added daily, the records management challenges are daunting, involving petabytes of electronic data and tens of thousands of rolls of analog film. This paper focuses upon the appraisal and preservation functions employed to ensure that these records are available for current and future generations.

  16. Treatment strategies for tics in Tourette syndrome

    PubMed Central

    Eddy, Clare M.; Rickards, Hugh E.; Cavanna, Andrea E.

    2011-01-01

    Tourette syndrome (TS) is a chronic neurodevelopmental disorder characterized by tics: repetitive, involuntary movements and vocalizations. These symptoms can have a significant impact on patients’ daily functioning across many domains. Tics tend to be most severe in child and adolescent sufferers, so their presence has the potential to impact a period of life that is both critical for learning and is often associated with the experience of greater social tension and self-consciousness than adulthood. Furthermore, control over tics that lead to physical impairment or self-injurious behaviour is of vital importance in maintaining health and quality of life. There are numerous complicating factors in the prescription of treatment for tics, due to both the side effects associated with alleviating agents and patient characteristics, such as age and comorbid conditions. This review summarizes literature pertaining to the efficacy and safety of both traditionally prescribed and more modern medications. We also discuss the merits of behavioural and surgical techniques and highlight newer emerging treatments. Although treatment response is to some extent variable, there are a number of agents that are clearly useful as first-line treatments for TS. Other interventions may be of most benefit to patients exhibiting refractory tics or more specific symptom profiles. PMID:21339906

  17. Treatment-resistant depression: therapeutic trends, challenges, and future directions

    PubMed Central

    Al-Harbi, Khalid Saad

    2012-01-01

    Background Patients with major depression respond to antidepressant treatment, but 10%–30% of them do not improve or show a partial response coupled with functional impairment, poor quality of life, suicide ideation and attempts, self-injurious behavior, and a high relapse rate. The aim of this paper is to review the therapeutic options for treating resistant major depressive disorder, as well as evaluating further therapeutic options. Methods In addition to Google Scholar and Quertle searches, a PubMed search using key words was conducted, and relevant articles published in English peer-reviewed journals (1990–2011) were retrieved. Only those papers that directly addressed treatment options for treatment-resistant depression were retained for extensive review. Results Treatment-resistant depression, a complex clinical problem caused by multiple risk factors, is targeted by integrated therapeutic strategies, which include optimization of medications, a combination of antidepressants, switching of antidepressants, and augmentation with non-antidepressants, psychosocial and cultural therapies, and somatic therapies including electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy, deep brain stimulation, transcranial direct current stimulation, and vagus nerve stimulation. As a corollary, more than a third of patients with treatment-resistant depression tend to achieve remission and the rest continue to suffer from residual symptoms. The latter group of patients needs further study to identify the most effective therapeutic modalities. Newer biomarker-based antidepressants and other drugs, together with non-drug strategies, are on the horizon to address further the multiple complex issues of treatment-resistant depression. Conclusion Treatment-resistant depression continues to challenge mental health care providers, and further relevant research involving newer drugs is warranted to improve the quality of life of patients

  18. [The pharmacological treatment of obesity: past, present and future].

    PubMed

    Simonyi, Gábor; Pados, Gyula; Medvegy, Mihály; Bedros, J Róbert

    2012-03-11

    Currently, obesity presents one of the biggest health problems. Management strategies for weight reduction in obese individuals include changes in life style such as exercise and diet, behavioral therapy, and pharmacological treatment, and in certain cases surgical intervention. Diet and exercise are best for both prevention and treatment, but both require much discipline and are difficult to maintain. Drug treatment of obesity offer a possible adjunct, but it may only have modest results, limited by side effects; furthermore, the weight lowering effects last only as long as the drug is being taken and, unfortunately, as soon as the administration is stopped, the weight is regained. These strategies should be used in a combination for higher efficacy. Drugs used to induce weight loss have various effects: they increase satiety, reduce the absorption of nutrients or make metabolism faster; but their effect is usually moderate. In the past, several drugs were used in the pharmacological therapy of weight reduction including thyroid hormone, dinitrophenol, amphetamines and their analogues, e.g. fenfluramine, At present, only orlistat is available in the long term treatment (≥ 24 weeks) of obesity as sibutramine and rimonabant were withdrawn form the market. Several new anti-obesity drugs are being tested at present, and liraglutide, a GLP-1 analogue (incretin mimetic), is the most promising one. PMID:22370224

  19. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies.

    PubMed

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-06-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  20. Bone marrow mesenchymal stem cell therapy in ischemic stroke: mechanisms of action and treatment optimization strategies

    PubMed Central

    Li, Guihong; Yu, Fengbo; Lei, Ting; Gao, Haijun; Li, Peiwen; Sun, Yuxue; Huang, Haiyan; Mu, Qingchun

    2016-01-01

    Animal and clinical studies have confirmed the therapeutic effect of bone marrow mesenchymal stem cells on cerebral ischemia, but their mechanisms of action remain poorly understood. Here, we summarize the transplantation approaches, directional migration, differentiation, replacement, neural circuit reconstruction, angiogenesis, neurotrophic factor secretion, apoptosis, immunomodulation, multiple mechanisms of action, and optimization strategies for bone marrow mesenchymal stem cells in the treatment of ischemic stroke. We also explore the safety of bone marrow mesenchymal stem cell transplantation and conclude that bone marrow mesenchymal stem cell transplantation is an important direction for future treatment of cerebral ischemia. Determining the optimal timing and dose for the transplantation are important directions for future research. PMID:27482235

  1. Developing adaptive treatment strategies in substance abuse research.

    PubMed

    Murphy, Susan A; Lynch, Kevin G; Oslin, David; McKay, James R; TenHave, Tom

    2007-05-01

    For many individuals, substance abuse possesses characteristics of chronic disorders in that individuals experience repeated cycles of cessation and relapse; hence viewing drug dependence as a chronic, relapsing disorder is increasingly accepted. The development of a treatment for a chronic disorder requires consideration of the ordering of treatments, the timing of changes in treatment, and the use of measures of response, burden and adherence collected during treatment to make further treatment decisions. Adaptive treatment strategies provide a vehicle through which these issues can be addressed and thus provide a means toward improving and informing the clinical management of chronic substance abuse disorders. The sequential multiple assignment randomized trial (SMART) is particularly useful in developing adaptive treatment strategies. Simple analyses that can be used with the SMART design are described. Furthermore, the SMART design is compared with standard experimental designs. PMID:17056207

  2. Reducing hospital readmission rates: current strategies and future directions.

    PubMed

    Kripalani, Sunil; Theobald, Cecelia N; Anctil, Beth; Vasilevskis, Eduard E

    2014-01-01

    New financial penalties for institutions with high readmission rates have intensified efforts to reduce rehospitalization. Several interventions that involve multiple components (e.g., patient needs assessment, medication reconciliation, patient education, arranging timely outpatient appointments, and providing telephone follow-up) have successfully reduced readmission rates for patients discharged to home. The effect of interventions on readmission rates is related to the number of components implemented; single-component interventions are unlikely to reduce readmissions significantly. For patients discharged to postacute care facilities, multicomponent interventions have reduced readmissions through enhanced communication, medication safety, advanced care planning, and enhanced training to manage medical conditions that commonly precipitate readmission. To help hospitals direct resources and services to patients with greater likelihood of readmission, risk-stratification methods are available. Future work should better define the roles of home-based services, information technology, mental health care, caregiver support, community partnerships, and new transitional care personnel. PMID:24160939

  3. Capability Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William; Merida, Sofia; Adumitroaie, Virgil; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future missions are ready as needed. The responsibilities include development of a Strategic Plan (Antonsson, E., 2005). As part of the planning effort, a structured approach to technology prioritization, based upon the work of the START (Strategic Assessment of Risk and Technology) (Weisbin, C.R., 2004) team, was developed. The purpose of this paper is to describe this approach and present its current status relative to the JPL technology investment.

  4. Temporal Investment Strategy to Enable JPL Future Space Missions

    NASA Technical Reports Server (NTRS)

    Lincoln, William P.; Hua, Hook; Weisbin, Charles R.

    2006-01-01

    The Jet Propulsion Laboratory (JPL) formulates and conducts deep space missions for NASA (the National Aeronautics and Space Administration). The Chief Technologist of JPL has the responsibility for strategic planning of the laboratory's advanced technology program to assure that the required technological capabilities to enable future JPL deep space missions are ready as needed; as such he is responsible for the development of a Strategic Plan. As part of the planning effort, he has supported the development of a structured approach to technology prioritization based upon the work of the START (Strategic Assessment of Risk and Technology) team. A major innovation reported here is the addition of a temporal model that supports scheduling of technology development as a function of time. The JPL Strategic Technology Plan divides the required capabilities into 13 strategic themes. The results reported here represent the analysis of an initial seven.

  5. Treatment resistant depression: strategies for primary care.

    PubMed

    Preston, Taylor C; Shelton, Richard C

    2013-07-01

    Depression is commonly diagnosed and treated in primary care. Recent evidence indicates that the majority of depressed patients will not fully recover with an initial antidepressant treatment. This paper reviews commonly used options for treatment after an inadequate initial antidepressant response. The alternatives range widely, and include escalating the dose of the initial antidepressant, switching to an alternative medication, combining two antidepressants with different mechanisms of action (e.g., bupropion + SSRI or mirtazapine + venlafaxine), adding other medications such as lithium or certain atypical antipsychotics (olanzapine, aripiprazole, or quetiapine) to the antidepressant, adding a natural product such as l-methylfolate or s-adenosylmethionine (SAMe), or adding cognitive behavioral psychotherapy. What agent to be used will depend on the comfort level of the primary care practitioner and the availability of Psychiatry referral. However, it is reasonable to take one or more additional steps to attempt to achieve remission. PMID:23712721

  6. Portfolio Strategies, Relinquishment, the Urban School System of the Future, and Smart Districts

    ERIC Educational Resources Information Center

    Hill, Paul; Jochim, Ashley; Campbell, Christine

    2013-01-01

    This brief outlines how new K-12 public education governance proposals--relinquishment, smart districts, and the urban school system of the future--are complements, not alternatives, to the portfolio strategy. The portfolio strategy defines the role of government, or how it can steer in public education; the other proposals show how, once…

  7. Pre-Service Teachers' Use of Reading Strategies in Their Own Readings and Future Classrooms

    ERIC Educational Resources Information Center

    Akyol, Hayati; Ulusoy, Mustafa

    2010-01-01

    The main purpose of this study was to determine pre-service teachers' use of reading strategies in their own readings. In addition, pre-service teachers' use of these strategies in their future teaching practices was also investigated. The subjects for this study were 505 pre-service teachers enrolled in one of the major universities in Ankara.…

  8. Amalgamation of Future Time Orientation, Epistemological Beliefs, Achievement Goals and Study Strategies: Empirical Evidence Established

    ERIC Educational Resources Information Center

    Phan, Huy P.

    2009-01-01

    Background: Recently research evidence emphasizes two main lines of inquiry, namely the relations between future time perspective (FTP), achievement goals (mastery, performance-approach, and performance-avoidance) and study processing strategies, and the relations between epistemological beliefs, achievement goals and study processing strategies.…

  9. Female urinary incontinence: effective treatment strategies.

    PubMed

    Castro, R A; Arruda, R M; Bortolini, M A T

    2015-04-01

    Urinary incontinence is a dysfunction that tremendously affects women's quality of life, involving social, emotional and economic aspects. Although various treatments for urinary incontinence have been described, it is important to know which of them are truly effective. This review seeks to determine the current available therapies for women with stress urinary incontinence and overactive bladder syndrome, based on the best scientific evidence. PMID:25307986

  10. The future for electrocoagulation as a localised water treatment technology.

    PubMed

    Holt, Peter K; Barton, Geoffrey W; Mitchell, Cynthia A

    2005-04-01

    Electrocoagulation is an electrochemical method of treating polluted water whereby sacrificial anodes corrode to release active coagulant precursors (usually aluminium or iron cations) into solution. Accompanying electrolytic reactions evolve gas (usually as hydrogen bubbles) at the cathode. Electrocoagulation has a long history as a water treatment technology having been employed to remove a wide range of pollutants. However electrocoagulation has never become accepted as a 'mainstream' water treatment technology. The lack of a systematic approach to electrocoagulation reactor design/operation and the issue of electrode reliability (particularly passivation of the electrodes over time) have limited its implementation. However recent technical improvements combined with a growing need for small-scale decentralised water treatment facilities have led to a re-evaluation of electrocoagulation. Starting with a review of electrocoagulation reactor design/operation, this article examines and identifies a conceptual framework for electrocoagulation that focuses on the interactions between electrochemistry, coagulation and flotation. In addition detailed experimental data are provided from a batch reactor system removing suspended solids together with a mathematical analysis based on the 'white water' model for the dissolved air flotation process. Current density is identified as the key operational parameter influencing which pollutant removal mechanism dominates. The conclusion is drawn that electrocoagulation has a future as a decentralised water treatment technology. A conceptual framework is presented for future research directed towards a more mechanistic understanding of the process. PMID:15763088

  11. Treatment compliance in chronic illness: Current situation and future perspectives.

    PubMed

    Conthe, P; Márquez Contreras, E; Aliaga Pérez, A; Barragán García, B; Fernández de Cano Martín, M N; González Jurado, M; Ollero Baturone, M; Pinto, J L

    2014-01-01

    Long-term chronic diseases have a high mortality rate around the world, affecting both genders equally. Despite improvements in the diagnosis and treatment of various health problems, lack of treatment compliance remains an obstacle to improving health and patient quality of life, and it carries a high associated socio-healthcare cost. The objectives of this study were to develop the concept of «therapeutic adherence», which includes both pharmacological compliance as well as non-pharmacological (level of agreement and patient involvement, lifestyle changes, etc.) treatments. The study also aimed to establish the clinical and socio-health impact of non-compliance, the reasons for non-compliance, and methods and strategies to improve compliance. The results of this study support therapeutic adherence as an essential goal of the healthcare system that encompasses all stakeholders involved in patient health. PMID:24816042

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

    PubMed

    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. PMID:26939412

  13. Vaccination against Alzheimer disease: an update on future strategies.

    PubMed

    Fettelschoss, Antonia; Zabel, Franziska; Bachmann, Martin F

    2014-01-01

    Alzheimer disease is a devastating chronic disease without adequate therapy. More than 10 years ago, it was demonstrated in transgenic mouse models that vaccination may be a novel, disease-modifying therapy for Alzheimer. Subsequent clinical development has been a roller-coaster with some positive and many negative news. Here, we would like to summarize evidence that next generation vaccines optimized for old people and focusing on patients with mild disease stand a good chance to proof efficacious for the treatment of Alzheimer. PMID:24535580

  14. Palmoplantar Psoriasis and Palmoplantar Pustulosis: Current Treatment and Future Prospects.

    PubMed

    Raposo, Inês; Torres, Tiago

    2016-08-01

    Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics. PMID:27113059

  15. Cancer Treatment Using Peptides: Current Therapies and Future Prospects

    PubMed Central

    Thundimadathil, Jyothi

    2012-01-01

    This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or can act as a carrier of cytotoxic agents and radioisotopes by specifically targeting cancer cells. Peptide-based hormonal therapy has been extensively studied and utilized for the treatment of breast and prostate cancers. Tremendous amount of clinical data is currently available attesting to the efficiency of peptide-based cancer vaccines. Combination therapy is emerging as an important strategy to achieve synergistic effects in fighting cancer as a single method alone may not be efficient enough to yield positive results. Combining immunotherapy with conventional therapies such as radiation and chemotherapy or combining an anticancer peptide with a nonpeptidic cytotoxic drug is an example of this emerging field. PMID:23316341

  16. Burnout: Treatment and Prevention Strategies for College Student Affairs Professionals.

    ERIC Educational Resources Information Center

    Keener, Roger

    1990-01-01

    Presents possible prevention and treatment strategies for combating burnout among college student affairs professionals. Includes definition of burnout, review of symptoms of burnout, discussion of causes of burnout, and suggestions for treatment and prevention of burnout. Interventions discussed include personal counseling, using stress…

  17. [Phantom limb pain. Psychological treatment strategies].

    PubMed

    Diers, M; Flor, H

    2013-04-01

    Similar to other pain syndromes phantom limb pain is characterized by learning and memory processes that maintain the pain and increase maladaptive plastic changes of the brain: therefore, psychological interventions that change maladaptive memory processes are useful. In addition to traditional psychological interventions, such as pain management training and biofeedback, more recent developments that involve sensory discrimination training, mirror treatment, graded motor imagery, prosthesis training and training in virtual reality are interesting. These interventions not only reduce phantom limb pain but also reverse the associated maladaptive brain changes. PMID:23588803

  18. Research strategies for the treatment of biothreats.

    PubMed

    Cherwonogrodzky, John W

    2005-10-01

    Whether it is a layperson in the street or a politician in the Senate, there is widespread fear over the consequences of biothreats. In response to these fears, a wide range of treatments has been developed. These include antibiotics (conventional and unconventional uses), nucleic acids (analogues, antisense, ribozymes and DNAzymes), immunomodulators, antibodies, bacteriophage therapy and micro-encapsulation. Furthermore, there are often additional benefits when these therapeutics are used in combination, rather than alone. Although there has been much investment in therapeutics against a terrorist threat for reasons of national security, there are likely to be far greater benefits and applications on domestic and world health. PMID:16084772

  19. HDT mixtures treatment strategies by gas chromatography

    SciTech Connect

    Laquerbe, C.; Contreras, S.; Demoment, J.

    2008-07-15

    Gas phase chromatographic processes are of interest for the separation of hydrogen isotopes from an HDT mixture. For a certain quantity, they are very competitive and present several benefits. Nevertheless no active packing material allows to have simultaneously good enrichment performances for tritium production and high decontamination capabilities for HD gases. The influence of the packing material is first described in this article. Then two specific processes (TCAP and Reverse Chromatography), each well adapted to perform one target, are presented. Finally, the problematic to propose an optimized treatment scheme associating these two processes is formulated. (authors)

  20. Pharmacologic Strategies for Treatment of Poisonings.

    PubMed

    Roberts, Eric; Gooch, Michael D

    2016-03-01

    Poisoning is the leading cause of injury-related mortality in the United States. Data suggest that nonmedical use of pharmaceuticals is increasing, along with a proportional increase in subsequent adverse events. The widespread use of illegal drugs contributes to the challenge, because these drugs may produce a wide array of clinical presentations that warrant time-critical recognition and treatment. Common legal and illegal poisonings highlighting clinical presentations in terms of toxidromes as a means of categorically recognizing these emergencies is the focus of this article. To optimize outcomes for situations such as these, pharmacologic considerations are discussed and explored. PMID:26897424

  1. Whole Cell Vaccines — Past Progress and Future Strategies

    PubMed Central

    Keenan, Bridget P.; Jaffee, Elizabeth M.

    2012-01-01

    Cancer vaccines have shown success in curing tumors in pre-clinical models. Accumulating evidence also supports their ability to induce immune responses in patients. In many cases, these responses correlate with improved clinical outcomes. However, cancer vaccines have not yet demonstrated their true potential in clinical trials. This is likely due to the difficulty in mounting a significant antitumor response in patients with advanced disease because of preexisting tolerance mechanisms that are actively turning off immune recognition in cancer patients. This review will examine the recent progress being made in the design and implementation of whole cell cancer vaccines, one vaccine approach that simultaneously targets multiple tumor antigens to activate the immune response. These vaccines have been shown to induce antigen specific T cell responses. Pre-clinical studies evaluating these vaccines given in sequence with other agents and cancer treatment modalities support the use of immunomodulating doses of chemotherapy and radiation, as well as immune modulating pathway targeted monoclonal antibodies, to enhance the efficacy of cancer vaccines. Based on emerging pre-clinical data, clinical trials are currently exploring the use of combinatorial immune based therapies for the treatment of cancer. PMID:22595050

  2. European Fusion Materials Research Program - Recent Results and Future Strategy

    SciTech Connect

    Diegele, E.; Andreani, R.; Laesser, R.; Schaaf, B. van der

    2005-05-15

    The paper reviews the objectives and the status of the current EU long-term materials program. It highlights recent results, discusses some of the key issues and major existing problems to be resolved and presents an outlook on the R and D planned for the next few years. The main objectives of the Materials Development program are the development and qualification of reduced activation structural materials for the Test Blanket Modules (TBMs) in ITER and of low activation structural materials resistant to high fluence neutron irradiation for in-vessel components such as breeding blanket, divertor and first wall in DEMO. The EU strategy assumes: (i) ITER operation starting in 2015 with DEMO relevant Test Blanket Modules to be installed from day one of operation, (ii) IFMIF operation in 2017 and (iii) DEMO final design activities in 2022 to 2025. The EU candidate structural material EUROFER for TBMs has to be fully code qualified for licensing well before 2015. In parallel, research on materials for operation at higher temperatures is conducted following a logical sequence, by supplementing EUROFER with the oxide dispersion strengthened ferritic steels and, thereafter, with fibre-reinforced Silicon Carbide (SiC{sub f}/SiC). Complementary, tungsten alloys are developed as structural material for high temperature applications such as gas-cooled divertors.

  3. Evolving Strategies for Cancer and Autoimmunity: Back to the Future

    PubMed Central

    Lane, Peter J. L.; McConnell, Fiona M.; Anderson, Graham; Nawaf, Maher G.; Gaspal, Fabrina M.; Withers, David R.

    2014-01-01

    Although current thinking has focused on genetic variation between individuals and environmental influences as underpinning susceptibility to both autoimmunity and cancer, an alternative view is that human susceptibility to these diseases is a consequence of the way the immune system evolved. It is important to remember that the immunological genes that we inherit and the systems that they control were shaped by the drive for reproductive success rather than for individual survival. It is our view that human susceptibility to autoimmunity and cancer is the evolutionarily acceptable side effect of the immune adaptations that evolved in early placental mammals to accommodate a fundamental change in reproductive strategy. Studies of immune function in mammals show that high affinity antibodies and CD4 memory, along with its regulation, co-evolved with placentation. By dissection of the immunologically active genes and proteins that evolved to regulate this step change in the mammalian immune system, clues have emerged that may reveal ways of de-tuning both effector and regulatory arms of the immune system to abrogate autoimmune responses whilst preserving protection against infection. Paradoxically, it appears that such a detuned and deregulated immune system is much better equipped to mount anti-tumor immune responses against cancers. PMID:24782861

  4. Present and New Treatment Strategies in the Management of Glaucoma

    PubMed Central

    Kolko, M

    2015-01-01

    Glaucoma is a neurodegenerative disease characterized by retinal ganglion cell (RGC) death and axonal loss. It remains a major cause of blindness worldwide. All current modalities of treatment are focused on lowering intraocular pressure (IOP), and it is evident that increased IOP is an important risk factor for progression of the disease. However, it is clear that a significant number of glaucoma patients show disease progression despite of pressure lowering treatments. Much attention has been given to the development of neuroprotective treatment strategies, but the identification of such has been hampered by lack of understanding of the etiology of glaucoma. Hence, in spite of many attempts no neuroprotective drug has yet been clinically approved. Even though neuroprotection is without doubt an important treatment strategy, many glaucoma subjects are diagnosed after substantial loss of RGCs. In this matter, recent approaches aim to rescue RGCs and regenerate axons in order to restore visual function in glaucoma. The present review seeks to provide an overview of the present and new treatment strategies in the management of glaucoma. The treatment strategies are divided into current available glaucoma medications, new pressure lowering targets, prospective neuroprotective interventions, and finally possible neuroregenrative strategies. PMID:26069521

  5. Nanotechnology-based water treatment strategies.

    PubMed

    Kumar, Sandeep; Ahlawat, Wandit; Bhanjana, Gaurav; Heydarifard, Solmaz; Nazhad, Mousa M; Dilbaghi, Neeraj

    2014-02-01

    The most important component for living beings on the earth is access to clean and safe drinking water. Globally, water scarcity is pervasive even in water-rich areas as immense pressure has been created by the burgeoning human population, industrialization, civilization, environmental changes and agricultural activities. The problem of access to safe water is inevitable and requires tremendous research to devise new, cheaper technologies for purification of water, while taking into account energy requirements and environmental impact. This review highlights nanotechnology-based water treatment technologies being developed and used to improve desalination of sea and brackish water, safe reuse of wastewater, disinfection and decontamination of water, i.e., biosorption and nanoadsorption for contaminant removal, nanophotocatalysis for chemical degradation of contaminants, nanosensors for contaminant detection, different membrane technologies including reverse osmosis, nanofiltration, ultrafiltration, electro-dialysis etc. This review also deals with the fate and transport of engineered nanomaterials in water and wastewater treatment systems along with the risks associated with nanomaterials. PMID:24749460

  6. Heart Failure in Adult Congenital Heart Disease: Nonpharmacologic Treatment Strategies.

    PubMed

    LeMond, Lisa; Mai, Tuan; Broberg, Craig S; Muralidaran, Ashok; Burchill, Luke J

    2015-11-01

    In early stages, heart failure (HF) in adult congenital heart disease (ACHD) remains an elusive diagnosis. Many ACHD patients seem well-compensated owing to chronic physical and psychological adaptations. HF biomarkers and cardiopulmonary exercise tests are often markedly abnormal, although patients report stable health and good quality of life. Treatment differs from acquired HF. Evidence for effective drug therapy in ACHD-related HF is lacking. Residual ventricular, valvular, and vascular abnormalities contribute to HF pathophysiology, leading to an emphasis on nonpharmacologic treatment strategies. This article reviews emerging perspectives on nonpharmacologic treatment strategies, including catheter-based interventions, surgical correction, and palliative care. PMID:26471822

  7. Genetics, diagnosis, and future treatment strategies for primary ciliary dyskinesia

    PubMed Central

    Daniels, M. Leigh Anne; Noone, Peadar G.

    2015-01-01

    Introduction Primary ciliary dyskinesia (PCD) is a genetically heterogeneous recessive disorder resulting in chronic oto-sino-pulmonary disease. While PCD is estimated to occur in 1 in 20,000 individuals, fewer than 1,000 patients in the US have a well-established diagnosis. Areas Covered We provide an overview of the clinical manifestations of PCD, describe the evolution of diagnostic methods, and critique the literature on management of PCD. Expert Opinion Although interest in clinical studies in non-CF bronchiectasis has increased in recent years, some of whom enroll patients with PCD, the literature regarding therapy for PCD as a distinct entity is lacking, as the numbers are small, and there have been no sub-analyses published. However, with improved screening and diagnostic methods, the development of clinical and research consortiums, and actively enrolling registries of PCD patients, the environment is conducive to perform longitudinal studies of disease course and therapeutic studies to alter that course. PMID:26998415

  8. Future therapeutical strategies dictated by pre-clinical evidence in ALS.

    PubMed

    Fornai, Francesco; Meininger, Vincent; Silani, Vincent

    2011-03-01

    Classic concepts on amyotrophic lateral sclerosis led to define the disease as a selective degeneration of upper and lower motor neurons. At present such selectivity is questioned by novel findings. For instance, the occurrence of frontotemporal dementia is now increasingly recognized in the course of ALS. Again, areas outside the central nervous system are targeted in ALS. In keeping with motor areas other cell types surrounding motor neurons such as glia and interneurons are key in the pathogenesis of ALS. This multiple cell involvement may be due to a prion-like diffusion of specific misfolded proteins which are altered in ALS. This is the case of FUS and TDP-43 which harbor a prion domain prone to pathological misfolding. These misfolded proteins are metabolized by the autophagy, but in ALS there is evidence for a specific deficit of autophagy which impedes the clearance of these proteins. These concepts lead to re-analyze the potential therapeutics of ALS. In fact, mere cell substitution (stem cell) therapy appears insufficient to contrast all the alterations in the various pathways affected by ALS. Although preclinical data speed the application of stem cells in human clinical trials, several hurdles limit their translation into new therapies. Future treatments are expected to consider the need to target both motor neurons and neighboring cells which may contribute to the diffusion and persistence of the disease. On this basis the present manuscript describes which future strategies need to be pursued in order to design optimal therapeutic trial in ALS. PMID:21412723

  9. Current treatment and future prospects of dopa-induced dyskinesias.

    PubMed

    Mazzucchi, S; Frosini, D; Bonuccelli, U; Ceravolo, R

    2015-05-01

    Levodopa-induced dyskinesias (LID) are one of the main issues in the management of Parkinson's disease (PD); once these dyskinesias are established treatment becomes difficult, so preventive strategies should be first evaluated. Although levodopa (LD) treatment has recently been related as risk factor for LID, the main strategy to delay LID is to start PD treatment with dopamine agonists, adding LD at low doses. After LID onset, approaches include reducing single LD doses, reducing or discontinuing monoamine oxidase type B/catechol O-methyltransferase (MAO-B/COMT) inhibitors and extended-release (ER) LD. Amantadine represents the best antidyskinetic tool, and ER amantadine is the most promising upcoming antidyskinetic drug. New LD formulations such as IPX-066 (able to provide continuous dopaminergic stimulation) also represent promising new approaches. The involvement of a nondopaminergic system in the pathogenesis of LID suggests that the modulation of glutamate, serotonin and adenosine could have potential as new upcoming drug targets, but the role of such drugs will still need to be confirmed in randomized controlled trials. PMID:26097904

  10. Treatment strategies for aggressive lymphomas: what works?

    PubMed

    Wilson, Wyndham H

    2013-01-01

    Over the past 30 years, many treatment platforms have been developed for diffuse large B-cell lymphoma, but none proved better than CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone). In the immunochemotherapy era, however, there is convincing evidence for superior chemotherapy platforms. A randomized study from the Groupe d'Etude des Lymphomes de l'Adulte showed that R-ACVBP (rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) was superior to rituximab plus CHOP (R-CHOP) in patients under 60 years of age, but toxicity limits its use to younger patients. Studies also suggest that DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) is more effective in some subtypes of diffuse large B-cell lymphoma and a randomized comparison with R-CHOP is now nearing completion. The simplicity and safety of R-CHOP and the long history of failed contenders, however, has set a high bar for new approaches. PMID:24319235

  11. Unilateral condylar hyperplasia: a treatment strategy.

    PubMed

    Ferreira, Sabrina; da Silva Fabris, André Luis; Ferreira, Gabriel Ramalho; Faverani, Leonardo Perez; Francisconi, Giovanna Barbosa; Souza, Francisley Avila; Garcia, Idelmo Rangel

    2014-05-01

    Condylar hyperplasia (CH) is a pathologic condition that causes overdevelopment of the condylar head and neck as well as the mandible. Slowly progressive unilateral enlargement of the head and the neck of the condyle causes crossbite malocclusion, facial asymmetry, and shifting of the midpoint of the chin to the unaffected side. The etiology and the pathogenesis of CH remain uncertain. The diagnosis is made by clinical and radiologic examinations and bone scintigraph. A difference in uptake of 10% or more between condyles is regarded as indicative of CH, and the affected condyles had a relative uptake of 55% or more. When the diagnosis of active CH is established, the treatment consists of removal of the growth center by a partial condylectomy. The authors present the case of a 46-year-old male patient with right active type II CH or hemimandibular hyperplasia who underwent a high condylectomy. PMID:24820728

  12. Endovascular Treatment Strategies in Aortoiliac Occlusion

    SciTech Connect

    Ozkan, Ugur Oguzkurt, Levent Tercan, Fahri Gumus, Burcak

    2009-05-15

    The aim of this study was to report our experience in endovascular treatment of total aortoiliac occlusion. Five patients who underwent endovascular recanalization procedures including manual aspiration thrombectomy, balloon angioplasty, and stent placement for total aortoiliac occlusion in a 4-year period were reviewed retrospectively. The mean age of patients was 51 years (range, 43 to 58 years). All patients had abdominal aorta and bilateral common iliac artery occlusion with or without external iliac artery occlusion. All patients either had a contraindication to surgery or refused it. Initial technical success was obtained in four of five (80%) patients. Endovascular techniques were successful in four patients who had good distal runoff and short-segment aortoiliac occlusion, but failed in a patient who had the worst distal runoff and long-segment aortoiliac occlusion. We observed two major complications, one of which was bilateral rupture of the common iliac arteries treated with covered stent placement. Another patient had extension of intra-aortic thrombus into the iliac stent after primary stenting. This was successfully treated with manual aspiration thrombectomy. Aortic and iliac stents remained patent during the follow-up period (median, 18 months; range, 3 to 26 months) in four patients. Primary patency rates at 6, 12, and 24 months were all 80%. In conclusion, endovascular treatment can be an alternative for aortoiliac occlusion in selected patients. Short- to midterm follow-up so far is satisfactory. Removal of intra-aortic thrombus with manual aspiration thrombectomy before balloon angioplasty and/or stenting is possible and a good alternative to thrombolysis.

  13. Future directions in the treatment of neuropathic pain: a review on various therapeutic targets.

    PubMed

    Gangadhar, Matharasala; Mishra, Ram Kumar; Sriram, Dharmarajan; Yogeeswari, Perumal

    2014-02-01

    Neuropathic pain is caused by structural lesion leading to functional abnormalities in central and peripheral nervous system. Neuropathic pain in itself is not always a disease, as it arises due to consequences of other diseases like diabetes, spinal cord injury, degenerative neuronal diseases and cancer. Current strategies of neuropathic pain treatment have provided relief to the patients to some extent, but complete cure is still a distant dream. In the future, it is hoped that a combination of new and improved pharmaceutical developments combined with careful clinical trials and increased understanding of neuroplasticity will lead to improved and effective pain management strategies leading to improved quality of life. In this review we have discussed various therapeutic targets of neuropathic pain and their pathophysiological mechanisms. Current status of drugs used for treatment of neuropathic pain have also been discussed in the review. PMID:24152326

  14. 17 CFR 30.7 - Treatment of foreign futures or foreign options secured amount.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Treatment of foreign futures... FUTURES TRADING COMMISSION FOREIGN FUTURES AND FOREIGN OPTIONS TRANSACTIONS § 30.7 Treatment of foreign futures or foreign options secured amount. (a) Except as provided in this section, a futures...

  15. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives

    PubMed Central

    Pavlovic, Dejan; Patera, Andriani C.; Nyberg, Fredrik; Gerber, Marianne; Liu, Maggie

    2015-01-01

    Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system, primarily affecting individuals with chronically and severely suppressed immune systems. The disease was relatively obscure until the outbreak of HIV/AIDS, when it presented as one of the more frequent opportunistic infections in this immune deficiency syndrome. It attracted additional attention from the medical and scientific community following the discovery of significant PML risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing–remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and treatment of PML are focused on immune reconstitution, restoration of immune responses to JC virus infection, and eventual suppression of immune reconstitution inflammatory syndrome. This approach was successful in reducing the incidence of PML and improved survival of PML patients with HIV infection. However, the outcome for the majority of PML patients, regardless of their medical history, is still relatively poor. There is a high unmet need for both prophylaxis and treatment of PML. The aim of this review is to discuss potential drug candidates for prophylaxis and treatment of PML with a critical review of previously conducted and completed PML treatment studies as well as to provide perspectives for future therapies. PMID:26600871

  16. Progressive multifocal leukoencephalopathy: current treatment options and future perspectives.

    PubMed

    Pavlovic, Dejan; Patera, Andriani C; Nyberg, Fredrik; Gerber, Marianne; Liu, Maggie

    2015-11-01

    Progressive multifocal leukoencephalopathy (PML) is a rare but debilitating and frequently fatal viral disease of the central nervous system, primarily affecting individuals with chronically and severely suppressed immune systems. The disease was relatively obscure until the outbreak of HIV/AIDS, when it presented as one of the more frequent opportunistic infections in this immune deficiency syndrome. It attracted additional attention from the medical and scientific community following the discovery of significant PML risk associated with natalizumab, a monoclonal antibody used for treatment of relapsing-remitting multiple sclerosis. This was followed by association of PML with other immunosuppressive or immunomodulating drugs. PML is currently untreatable disease with poor outcomes, so it is a significant concern when developing new immunotherapies. Current prophylaxis and treatment of PML are focused on immune reconstitution, restoration of immune responses to JC virus infection, and eventual suppression of immune reconstitution inflammatory syndrome. This approach was successful in reducing the incidence of PML and improved survival of PML patients with HIV infection. However, the outcome for the majority of PML patients, regardless of their medical history, is still relatively poor. There is a high unmet need for both prophylaxis and treatment of PML. The aim of this review is to discuss potential drug candidates for prophylaxis and treatment of PML with a critical review of previously conducted and completed PML treatment studies as well as to provide perspectives for future therapies. PMID:26600871

  17. Perimenstrual asthma: from pathophysiology to treatment strategies.

    PubMed

    Graziottin, Alessandra; Serafini, Audrey

    2016-01-01

    The prevalence of asthma is about 9,7 % in women and 5,5 % in men. Asthma can deteriorate during the perimenstrual period, a phenomenon known as perimenstrual asthma (PMA), which represents a unique, highly symptomatic asthma phenotype. It is distinguished from traditional allergic asthma by aspirin sensitivity, less atopy, and lower lung capacity. PMA incidence is reported to vary between 19 and 40 % of asthmatic women. The presence of PMA has been related to increases in asthma-related emergency department visits, hospitalizations and emergency treatment including intubations. It is hypothesized that hormonal status may influence asthma in women, focusing on the role of sex hormones, and specifically on the impact of estrogens' fluctuations at ovulation and before periods. This paper will focus on the pathophysiology of hormone triggered cycle related inflammatory/allergic events and their relation with asthma. We reviewed the scientific literature on Pubmed database for studies on PMA. Key word were PMA, mastcells, estrogens, inflammation, oral contraception, hormonal replacement therapy (HRT), and hormone free interval (HFI). Special attention will be devoted to the possibility of reducing the perimenstrual worsening of asthma and associated symptoms by reducing estrogens fluctuations, with appropriate hormonal contraception and reduced HFI. This novel therapeutical approach will be finally discussed. PMID:27482380

  18. Present and Future in the Treatment of Diabetic Kidney Disease

    PubMed Central

    de Arriba, Gabriel

    2015-01-01

    Diabetic kidney disease is the leading cause of end-stage renal disease. Albuminuria is recognized as the most important prognostic factor for chronic kidney disease progression. For this reason, blockade of renin-angiotensin system remains the main recommended strategy, with either angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. However, other antiproteinuric treatments have begun to be studied, such as direct renin inhibitors or aldosterone blockers. Beyond antiproteinuric treatments, other drugs such as pentoxifylline or bardoxolone have yielded conflicting results. Finally, alternative pathogenic pathways are being explored, and emerging therapies including antifibrotic agents, endothelin receptor antagonists, or transcription factors show promising results. The aim of this review is to explain the advances in newer agents to treat diabetic kidney disease, along with the background of the renin-angiotensin system blockade. PMID:25945357

  19. Anal cancer treatment: Current status and future perspectives

    PubMed Central

    Ghosn, Marwan; Kourie, Hampig Raphael; Abdayem, Pamela; Antoun, Joelle; Nasr, Dolly

    2015-01-01

    Anal cancers (AC) are relatively rare tumors. Their incidence is increasing, particularly among men who have sex with other men due to widespread infection by human papilloma virus. The majority of anal cancers are squamous cell carcinomas, and they are treated according to stage. In local and locally advanced AC, concomitant chemoradiation therapy based on mitomycin C and 5-Fluorouracil (5-FU) is the current best treatment, while metastatic AC, chemotherapy with 5-FU and cisplatin remains the gold standard. There are no indications for induction or maintenance therapies in locally advanced tumors. Many novel strategies, such as targeted therapies, vaccination, immunotherapy and photodynamic therapy are in clinical trials for the treatment of AC, with promising results in some indications. PMID:25741135

  20. Diagnostic and treatment strategies in mucopolysaccharidosis VI

    PubMed Central

    Vairo, Filippo; Federhen, Andressa; Baldo, Guilherme; Riegel, Mariluce; Burin, Maira; Leistner-Segal, Sandra; Giugliani, Roberto

    2015-01-01

    Mucopolysaccharidosis VI (MPS VI) is a very rare autosomal recessive disorder caused by mutations in the ARSB gene, which lead to deficient activity of the lysosomal enzyme ASB. This enzyme is important for the breakdown of the glycosaminoglycans (GAGs) dermatan sulfate and chondroitin sulfate, which accumulate in body tissues and organs of MPS VI patients. The storage of GAGs (especially dermatan sulfate) causes bone dysplasia, joint restriction, organomegaly, heart disease, and corneal clouding, among several other problems, and reduced life span. Despite the fact that most cases are severe, there is a spectrum of severity and some cases are so attenuated that diagnosis is made late in life. Although the analysis of urinary GAGs and/or the measurement of enzyme activity in dried blood spots are useful screening methods, the diagnosis is based in the demonstration of the enzyme deficiency in leucocytes or fibroblasts, and/or in the identification of pathogenic mutations in the ARSB gene. Specific treatment with enzyme replacement has been available since 2005. It is safe and effective, bringing measurable benefits and increased survival to patients. As several evidences indicate that early initiation of therapy may lead to a better outcome, newborn screening is being considered for this condition, and it is already in place in selected areas where the incidence of MPS VI is increased. However, as enzyme replacement therapy is not curative, associated therapies should be considered, and research on innovative therapies continues. The management of affected patients by a multidisciplinary team with experience in MPS diseases is highly recommended. PMID:26586959

  1. Water management in cities of the future using emission control strategies for priority hazardous substances.

    PubMed

    Eriksson, E; Revitt, D M; Ledin, A; Lundy, L; Holten Lützhøft, H C; Wickman, T; Mikkelsen, P S

    2011-01-01

    Cities of the future face challenges with respect to the quantity and quality of water resources, and multiple managerial options need to be considered in order to safeguard urban surface water quality. In a recently completed project on 'Source control options for reducing emissions of Priority Pollutants' (ScorePP), seven emission control strategies (ECSs) were developed and tested within a semi-hypothetical case city (SHCC) to evaluate their potential to reduce the emission of selected European priority hazardous substances (PHSs) to surface waters. The ECSs included (1) business-as-usual, (2) full implementation of relevant European (EU) directives, (3) ECS2 in combination with voluntary options for household, municipalities and industry, (4) ECS2 combined with industrial treatment and best available technologies (BAT), (5) ECS2 in combination with stormwater and combined sewer overflow treatment, (6) ECS2 in combination with advanced wastewater treatment, and (7) combinations of ECS3-6. The SHCC approach was chosen to facilitate transparency, to allow compensating for data gaps and to decrease the level of uncertainty in the results. The selected PHSs: cadmium (Cd), hexachlorobenzene (HCB), nonylphenol (NP) and pentabromodiphenyl ether (PBDE) differ in their uses and environmental fate and therefore accumulate in surface waters to differing extents in response to the application of alternative ECS. To achieve the required reduction in PHS levels in urban waters the full implementation of existing EU regulation is prioritised and feasible combinations of managerial and technological options (source control and treatment) can be highly relevant for mitigating releases. PMID:22105136

  2. Nitroimidazoles for the treatment of TB: past, present and future

    PubMed Central

    Mukherjee, Tathagata; Boshoff, Helena

    2011-01-01

    Tuberculosis remains a leading cause of death resulting from an infectious agent, and the spread of multi- and extensively drug-resistant strains of Mycobacterium tuberculosis poses a threat to management of global health. New drugs that effectively shorten the duration of treatment and are active against drug-resistant strains of this pathogen are urgently required to develop effective chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683, are currently in Phase II clinical trials for the treatment of TB and the outcome of these may determine the future directions of drug development for anti-tubercular nitroimidazoles. In this review we summarize the development of these nitroimidazoles and alternative analogs in these series that may offer attractive alternatives to PA-824 and OPC-67683 for further development in the drug-discovery pipeline. Lastly, the potential pitfalls in the development of nitroimidazoles as drugs for TB are discussed. PMID:21879846

  3. Treatment Strategy Profiles in Substance Use Disorder Treatment Programs: A Latent Class Analysis

    PubMed Central

    Aletraris, Lydia; Paino, Maria; Roman, Paul M.

    2015-01-01

    Background Modern treatment options for substance use disorder are diverse. While studies have analyzed the adoption of individual evidence-based practices in treatment centers, little is known about the specific make-up of treatment strategy profiles in treatment centers throughout the United States. The current study used latent class analysis to profile underlying treatment strategies and to evaluate philosophical and structural supports associated with each profile. Methods Utilizing three aggregated and secondary datasets of nationally representative samples of substance use disorder treatment centers (N=775), we employed latent class analysis to determine treatment strategy profiles. Using multinomial logistic regression, we then examined organizational characteristics associated with each profile. Results We found three distinct treatment strategy profiles: Centers that primarily relied on Motivational Interviewing and Motivational Enhancement Therapy, centers that utilized psychosocial and alternative therapies, and centers that employed comprehensive treatments including pharmacotherapy. The multinomial logistic regression revealed that philosophical and structural center characteristics were associated with membership in the comprehensive class. Centers with philosophical orientations conducive to holistic care and pharmacotherapy-acceptance, resource-rich infrastructures, and an entrepreneurial reliance on insured clients were more likely to offer diverse interventions. All associations were significant at the .05 level. Principle Conclusion The findings from this study help us understand the general strategies of treatment centers. From a practical perspective, practitioners and clients should be aware of the variation in treatment center practices where they may offer or receive treatment. PMID:26105707

  4. Current treatment for Alzheimer disease and future prospects.

    PubMed

    Tariot, Pierre N; Federoff, Howard J

    2003-01-01

    A cascade of pathophysiological events is triggered in Alzheimer disease (AD) that ultimately involves common cellular signaling pathways and leads to cellular and network dysfunction, failure of neurotransmission, cell death, and a common clinical outcome. The process is asynchronous, meaning that viable neurons remain as targets for therapy even in the diseased state, and each stage of the cascade affords the possibility for therapeutic intervention. Cholinesterase inhibitors are the only available treatment in the United States for patients with mild to moderate AD, helping maintain cognitive and functional abilities in most patients and conferring beneficial behavioral effects in some. Memantine is an NMDA receptor antagonist that has recently been approved in Europe for treatment of moderately severe to severe AD and is under investigation in the United States. Its mechanism of action may include enhanced neurotransmission in several systems as well as antiexcitotoxic effects. There are data regarding the effectiveness of the combination of memantine with cholinesterase inhibitors that will be useful for the practicing clinician. Other agents have shown some benefit in clinical trials, including the antioxidants vitamin E, selegiline, and Ginkgo biloba extracts, although the weight of evidence regarding their effects is not sufficient to define clinical practice. Potential future therapies currently are in development that target multiple aspects of the illness cascade, including aberrant inflammation, neurotrophic function, and processing of beta amyloid and tau proteins. These newer approaches hold promise for disease modification but are as yet unproven. Whether or not disease-modifying or preventive therapies become a reality, clinicians will be faced with AD patients who require treatment at all stages of illness for the indefinite future. Cholinergic and emerging noncholinergic medications will likely prevail as the standards of treatment for years to

  5. Metastatic melanoma - a review of current and future treatment options.

    PubMed

    Maverakis, Emanual; Cornelius, Lynn A; Bowen, Glen M; Phan, Tiffany; Patel, Falin B; Fitzmaurice, Sarah; He, Young; Burrall, Barbara; Duong, Christopher; Kloxin, April M; Sultani, Hawa; Wilken, Reason; Martinez, Steve R; Patel, Forum

    2015-05-01

    Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment. PMID:25520039

  6. Huntington's disease: present treatments and future therapeutic modalities.

    PubMed

    Bonelli, Raphael M; Wenning, Gregor K; Kapfhammer, Hans P

    2004-03-01

    Huntington's disease (HD) is a devastating neuropsychiatric disorder for which therapeutic interventions have been rather fruitless to date, except in a slight symptomatic relief. Even the discovery of the gene related to HD in 1993 has not effectively advanced treatments. This article is essentially a review of available double-blind, placebo-controlled trials of therapy for this condition which also includes relevant open label trials. Unfortunately, HD research has tended to concentrate on the motor aspects of the disorder, whereas the major problems are behavioural (e.g. dementia, depression, psychosis), and the chorea is often least relevant in terms of management. We conclude that there is definitely poor evidence in management of HD. The analysis of the 24 best studies fails to result in a treatment recommendation of clinical relevance. Based on data of open-label studies, or even case reports, we recommend riluzole, olanzapine and amantadine for the treatment of the movement disorders associated with HD, selective serotonin reuptake inhibitors and mirtazapine for the treatment of depression, and atypical antipsychotic drugs for HD psychosis and behavioural problems. Moreover, adjuvant psychotherapy, physiotherapy and speech therapy should be applied to supply the optimal management. Finally, some cellular mechanisms are discussed in this paper because they are essential for future neuroprotective modalities, such as minocycline, unsaturated fatty acids or riluzole. PMID:15076012

  7. Advanced gastric cancer: Current treatment landscape and future perspectives

    PubMed Central

    Digklia, Antonia; Wagner, Anna Dorothea

    2016-01-01

    Gastric cancer currently ranks fourth in cancer-related mortality worldwide. In the western world, it is most often diagnosed at an advanced stage, after becoming metastatic at distant sites. Patients with advanced disease (locally advanced or metastatic) have a somber prognosis, with a median overall survival of 10-12 mo, and palliative chemotherapy is the mainstay of treatment. In recent years, novel approaches using inhibition of human epidermal growth factor receptor 2 (HER2) have demonstrated significant improvements in progression-free and overall survival, compared with chemotherapy alone, in first-line treatment of patients with overexpression of HER2. In addition, both second-line chemotherapy and treatment with the vascular endothelial growth factor receptor-inhibitor ramucirumab demonstrated significant benefits in terms of overall survival, compared with best supportive care, in randomized studies. Moreover, ramucirumab in combination with chemotherapy demonstrated further significant benefits in terms of progression-free and overall survival, compared with chemotherapy alone, in second-line treatment for patients with metastatic gastric cancer. A recently published molecular classification of gastric cancer is expected to improve patient stratification and selection for clinical trials and provide a roadmap for future drug development. Nevertheless, despite these developments the prognosis of patients with advanced gastric cancer remains poor. In this review we discuss current standards of care and outline major topics of drug development in gastric cancer. PMID:26937129

  8. [Diagnosis and Treatment of Peptic Ulcer Disease: Present and Future Perspective].

    PubMed

    Kim, Byung Wook

    2016-06-25

    Peptic ulcer disease is one of the most commonly encountered diseases in gastroenterology clinics. After the discovery of Helicobacter pylori by Warren and Marshall, it has been identified as the most important cause of peptic ulcer. Eradication of H. pylori markedly reduces the post-treatment recurrence rate of peptic ulcer. However, as human populations age, the incidence of cardiovascular and musculoskeletal diseases increases and consequent use of aspirin and non-steroidal anti-in-flammatory drugs increases. Thus causes and presenting patterns of peptic ulcer have changed. In this review, I describe new diagnostic and therapeutic strategies for peptic ulcer disease and explore future perspectives. PMID:27312832

  9. Novel therapeutic strategies for treatment of visceral leishmaniasis.

    PubMed

    Jain, Keerti; Jain, Narendra K

    2013-12-01

    Leishmaniasis reveals itself in two forms, cutaneous and visceral, but the later exerts serious complications and may lead to death, if untreated. The availability of limited number of antileishmanial chemotherapeutic agents, the high cost of treatment, growing incidences of resistance to first line drugs as well as severe toxicities associated with the drugs complicate the treatment of visceral leishmaniasis. To overcome these problems, critical investigation of new therapeutic strategies with potential antileishmanial activity and good tolerability are essential. In this review we explore the different facets of novel therapeutic strategies for treatment of visceral leishmaniasis with a purpose to summarize all the possible treatment tactics, which will help scientists working in this arena to implement their research in a systematic manner. PMID:23973338

  10. Platinum-induced neurotoxicity and preventive strategies: past, present, and future.

    PubMed

    Avan, Abolfazl; Postma, Tjeerd J; Ceresa, Cecilia; Avan, Amir; Cavaletti, Guido; Giovannetti, Elisa; Peters, Godefridus J

    2015-04-01

    models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution. PMID:25765877

  11. Platinum-Induced Neurotoxicity and Preventive Strategies: Past, Present, and Future

    PubMed Central

    Avan, Abolfazl; Postma, Tjeerd J.; Ceresa, Cecilia; Avan, Amir; Cavaletti, Guido; Giovannetti, Elisa

    2015-01-01

    models and appropriate trials planning should be integrated into the future design of neuroprotective strategies to find the best patient-oriented solution. PMID:25765877

  12. The multimodal treatment of acromegaly: current status and future perspectives.

    PubMed

    Espinosa, Etual; Ramirez, Claudia; Mercado, Moises

    2014-01-01

    Acromegaly is a chronic systemic disorder caused by a GH-secreting pituitary adenoma. Active acromegaly results in a poor quality of life due to symptoms such as headache, fatigue, arthralgia, depression, sexual dysfunction and hyperhidrosis; an increased prevalence of co-morbidities like diabetes, hypertension as well as cancer risk and a reduced life expectancy. Appropriate, modern, multimodal treatment of acromegaly has led to a significant improvement in quality of life, an adequate control of co-morbidities and a drastic reduction in the mortality rates that used to prevail in the past. This multimodal strategy includes an adequate selection of patients who are likely to benefit from surgical treatment (which has to be performed by a skilled pituitary neurosurgeon), the use of pharmacological interventions such as somatostatin analogs and dopamine agonists, which target the pituitary adenoma; and pegvisomant, a GH mutant acting as a competitive antagonist of the GH receptor. Radiation therapy is an important tool, particularly in parts of the World where resources are limited. The ultimate outcome of the individual patient depends on the judicious use of all these treatment options, which are critically analyzed in this mini-review. PMID:24915854

  13. [North Rhine-Westphalia Scientific Rehabilitation Group--"future strategies for rehabilitation"].

    PubMed

    Fischer, J; Raschke, F

    1998-11-01

    This Northrine-Westfalian integrated research system in rehabilitation aims at the development of future strategies for medical rehabilitation. The well known deficits of rehabilitation have led to different complementary projects. These comprise research on the lack of evidence in efficacy, predictors for outcomes, international cooperation, university related curricula in training, implementation of health economics and disease management, and finally the need for an actual adaptation of social legislation. The research topics have been transformed into key themes which will be coherently integrated by additional external expert knowledge acquired in workshops organized by a task force group for the development of future strategies. PMID:10065489

  14. Treatment of Helicobacter pylori infection: Past, present and future

    PubMed Central

    Papastergiou, Vasilios; Georgopoulos, Sotirios D; Karatapanis, Stylianos

    2014-01-01

    Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection. PMID:25400982

  15. Treatment of Helicobacter pylori infection: Past, present and future.

    PubMed

    Papastergiou, Vasilios; Georgopoulos, Sotirios D; Karatapanis, Stylianos

    2014-11-15

    Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection. PMID:25400982

  16. Phenylketonuria: a review of current and future treatments

    PubMed Central

    Al Hafid, Naz

    2015-01-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  17. Present and future treatment possibilities in macular degeneration

    NASA Astrophysics Data System (ADS)

    Fisher, E.; Wegner, A.; Pfeiler, T.; Mertz, M.

    2005-11-01

    Purpose: To discuss present and future treatment possibilities in different types of choroidal neovascularisation. Methods: Presented are angiographic- and OCT-findings in patients with macular degeneration of different origin. Choroidal neovascularisations, which are not likely to respond positively to established procedures like thermal laser coagulation or photodynamic therapy will be discussed. Results and conclusions: Present study-guidelines and new methods of pharmacological intervention are analysed in different patterns of macular degeneration. Conventional laser coagulation in the treatment of classic, extrafoveal CNV and photodynamic therapy of predominantly classic subfoveal CNV still represent a gold standard. There are new recommendations, loosening the tight criteria of the TAP and VIP-guidelines, which cover, for instance, wider visual acuity ranges and the treatment of juxtafoveally located choroidal neovascularisations. Positive findings in literature confirm the role of PDT in pathologic myopia and other non-AMD CNV. Studies about surgical procedures, like macula- or RPE-translocation after surgical removal or thermal laser destruction of the CNV are in progress and are expected to show promising results. Phase II/III studies will soon point out the effect of anti-VEGF agents. The application of intravitreal (triamcinolone) or peribulbar (anecortave acetat) steroids could be useful. The combination with surgical or laser techniques could bring further benefit to the patient.

  18. Phenylketonuria: a review of current and future treatments.

    PubMed

    Al Hafid, Naz; Christodoulou, John

    2015-10-01

    Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID:26835392

  19. Understanding latent tuberculosis: the key to improved diagnostic and novel treatment strategies

    PubMed Central

    Esmail, Hanif; Barry, Clifton E; Wilkinson, Robert J

    2012-01-01

    Treatment of latent tuberculosis (LTBI) is a vital component of tuberculosis elimination but is not efficiently implemented with available diagnostics and therapeutics. The tuberculin skin test and interferon gamma release assays can inform that infection has occurred but do not prove that it persists. Treatment of LTBI with isoniazid targets actively replicating bacilli but not non-replicating populations, prolonging treatment duration. Developing more predictive diagnostic tests and treatments of shorter duration requires a greater understanding of the biology of latent tuberculosis, from both host and bacillary perspectives. In this article we discuss the basis of current diagnosis and treatment of LTBI and review recent developments in understanding the biology of latency that may enable future improved diagnostic and treatment strategies. PMID:22198298

  20. Treatment strategies for acute metabolic disorders in neonates

    PubMed Central

    Mohamed, Sarar

    2011-01-01

    Acute metabolic emergencies in neonates represent a challenge to the medical and nursing staff. If not treated optimally, these disorders are associated with poor outcome. Early diagnosis, supportive therapy and specific measures addressing the derranged metabolic process are the gold standards for favorable results. This review highlights treatment strategies for Inborn Errors of Metabolism (IEM) presenting in the neonatal period.

  1. Novel Interventional Strategies for the Treatment of Atrial Fibrillation

    PubMed Central

    Siontis, Konstantinos C; Oral, Hakan

    2016-01-01

    The landscape of the invasive management of atrial fibrillation, the most common sustained arrhythmia in humans, has changed dramatically in the last decade owing to numerous advances in arrhythmia mapping and ablation technologies. The current review critically appraises novel interventional strategies for the treatment of atrial fibrillation with a focus on clinical effectiveness and safety. PMID:27403294

  2. The future of pharmacogenetics in the treatment of heart failure.

    PubMed

    Anwar, Mohamed Subhan; Iskandar, Muhammad Zaid; Parry, Helen M; Doney, Alex S; Palmer, Colin N; Lang, Chim C

    2015-11-01

    Heart failure is a common disease with high levels of morbidity and mortality. Current treatment comprises β-blockers, ACE inhibitors, aldosterone antagonists and diuretics. Variation in clinical response seen in patients begs the question of whether there is a pharmacogenetic component yet to be identified. To date, the genes most studied involve the β-1, β-2, α-2 adrenergic receptors and the renin-angiotensin-aldosterone pathway, mainly focusing on SNPs. However results have been inconsistent. Genome-wide association studies and next-generation sequencing are seen as alternative approaches to discovering genetic variations influencing drug response. Hopefully future research will lay the foundations for genotype-led drug management in these patients with the ultimate aim of improving their clinical outcome. PMID:26555119

  3. Future agents and treatment directions in multiple myeloma

    PubMed Central

    Ocio, Enrique M.; Mitsiades, Constantine S.; Orlowski, Robert; Anderson, Kenneth C.

    2014-01-01

    Summary The development of bortezomib and IMIDs resulted in a revolution in the treatment of MM. Moreover, second-generation proteasome inhibitors (carfilzomib) and IMIDs (pomalidomide) have recently been approved. Nevertheless, the incurability of this disease requires other drugs with different mechanisms of action to either prolong the survival of patients refractory to current therapies, or achieve cure. Active research has been done exploring the pathogenesis of MM and searching for novel druggable targets. In this regard, some of these novel agents seem promising, such as monoclonal antibodies (anti-CD38 - daratumumab or anti-CS1 - elotuzumab) or the kinesin protein inhibitor Arry-520. Other agents under investigation are kinase inhibitors, signaling pathways inhibitors or deacetylase inhibitors. With so many novel agents under investigation, future therapy in MM will probably involve the combined use of the already approved drugs with some of those newly discovered. PMID:24350987

  4. Optimal management of familial hypercholesterolemia: treatment and management strategies

    PubMed Central

    Nemati, Mohammad Hassan; Astaneh, Behrooz

    2010-01-01

    Familial hypercholesterolemia is an autosomally dominant disorder caused by various mutations in low-density lipoprotein receptor genes. This will lead to elevated levels of total and low-density lipoprotein cholesterol, which may in turn lead to premature coronary atherosclerosis and cardiac-related death. The symptoms are more severe in the homozygous type of the disease. Different options for the treatment of affected patients are now available. Diet therapy, pharmacologic therapy, lipid apheresis, and liver transplantation are among the various treatments. We clinically review the treatment and management strategies for the disease in order to shed light on the optimal management of familial hypercholesterolemia. PMID:21191428

  5. Noninfectious uveitis: strategies to optimize treatment compliance and adherence

    PubMed Central

    Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Díaz-Llopis, Manuel; Cunningham, Emmett T; Arévalo, J Fernando

    2015-01-01

    Noninfectious uveitis includes a heterogenous group of sight-threatening ocular and systemic disorders. Significant progress has been made in the treatment of noninfectious uveitis in recent years, particularly with regard to the effective use of corticosteroids and non-corticosteroid immunosuppressive drugs, including biologic agents. All of these therapeutic approaches are limited, however, by any given patient’s ability to comply with and adhere to their prescribed treatment. In fact, compliance and adherence are among the most important patient-related determinants of treatment success. We discuss strategies to optimize compliance and adherence. PMID:26316689

  6. Treatment-resistant Schizophrenia: Evidence-based Strategies

    PubMed Central

    Englisch, Susanne; Zink, Mathias

    2012-01-01

    Treatment-resistant symptoms complicate the clinical course of schizophrenia, and a large proportion of patients do not reach functional recovery. In consequence, polypharmacy is frequently used in treatment-refractory cases, addressing psychotic positive, negative and cognitive symptoms, treatment-emergent side effects caused by antipsychotics and comorbid depressive or obsessive-compulsive symptoms. To a large extent, such strategies are not covered by pharmacological guidelines which strongly suggest antipsychotic monotherapy. Add-on strategies comprise combinations of several antipsychotic agents and augmentations with mood stabilizers; moreover, antidepressants and experimental substances are applied. Based on the accumulated evidence of clinical trials and meta-analyses, combinations of clozapine with certain second-generation antipsychotic agents and the augmentation of antipsychotics with antidepressants seem recommendable, while the augmentation with mood stabilizers cannot be considered superior to placebo. Forthcoming investigations will have to focus on innovative pharmacological agents, the clinical spectrum of cognitive deficits and the implementation of cognitive behavioral therapy. PMID:22654380

  7. Rehabilitating antisocial personalities: treatment through self-governance strategies.

    PubMed

    McRae, Leon

    2013-02-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  8. Rehabilitating antisocial personalities: treatment through self-governance strategies

    PubMed Central

    McRae, Leon

    2012-01-01

    Offenders with antisocial personality disorder (ASPD) are widely assumed to reject psychotherapeutic intervention. Some commentators, therefore, argue that those with the disorder are better managed in the criminal justice system, where, following the introduction of indeterminate sentences, engagement with psychological treatment is coercively linked to the achievement of parole. By comparison, National Institute of Clinical Excellence guidelines on the management and treatment of ASPD recommend that those who are treatment seeking should be considered for admission to specialist psychiatric hospitals. The rationale is that prison-based interventions are underresourced, and the treatment of ASPD is underprioritised. The justification is that offenders with ASPD can be rehabilitated, if they are motivated. One problem, however, is that little is known about why offenders with ASPD seek treatment or what effect subsequent treatment has on their self-understanding. The aim of this paper is to address these unresolved issues. It draws on the findings of Economic and Social Research Council (ESRC) funded qualitative study examining the experiences of sentenced male offenders admitted to a specialist personality disorder ward within the medium secure estate and the medical practitioners who treat them. The data are analysed with reference to Michel Foucault's work on governmentality and strategy in power relations. Two arguments are advanced: first, offenders with ASPD are motivated by legal coercive pressures to implement a variety of Foucauldian-type strategies to give the false impression of treatment progress. Second, and related, treatment does not result in changes in self-understanding in the resistive client with ASPD. This presupposes that, in respect of this group at least, Foucault was mistaken in his claim that resistive behaviours merely mask the effectiveness of treatment norms over time. Nevertheless, the paper concludes that specialist treatment in the

  9. The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy

    ERIC Educational Resources Information Center

    Kahlenberg, Richard D., Ed.

    2012-01-01

    The Century Foundation released The Future of School Integration: Socioeconomic Diversity as an Education Reform Strategy, edited by senior fellow Richard D. Kahlenberg. The volume seeks to answer important questions about how socioeconomic integration plans are faring and to provide guidance for how they can be sustained and expanded in the…

  10. Strategies for Teaching African American History: Musings from the Past, Ruminations for the Future

    ERIC Educational Resources Information Center

    Dagbovie, Pero Gaglo

    2006-01-01

    The analysis of the existing body of scholarship on the teaching of African American history shows that various new relevant pedagogies should be adopted to utilize the past reflections for future teaching strategies. The author demonstrates the need for a more rigorous scholarship on the philosophies, methodologies and techniques of teaching…

  11. Neurogenic ejaculatory disorders: focus on current and future treatments.

    PubMed

    Calabrò, Rocco S; Polimeni, Giovanni; Ciurleo, Rosella; Casella, Carmela; Bramanti, Placido

    2011-09-01

    Ejaculation is a complex and still poorly understood neurological mechanism, at both spinal and cerebral levels as it is closely associated with orgasm. Physiologically, ejaculation is defined as the expulsion of seminal fluid from the urethral meatus and consists of two phases, namely emission and expulsion. Ejaculation is mediated by a spinal control center, referred to as a spinal pattern generator that coordinates sympathetic, parasympathetic and motor (somatic) outflows, integrating the latter with the inputs from the supraspinal sites in brainstem, hypothalamus and preoptic area. Premature ejaculation (PE) is the most common sexual dysfunction among young men, and it has been considered mostly psychogenic in origin, although it can be associated to diverse urological and neurological diseases. On the contrary, retrograde ejaculation and anejaculation are predominantly related to organic causes, particularly to neurogenic ones. Since ejaculation is mostly a spinal reflex, it is comprehensible that ejaculatory disorders are more frequent in spinal cord injury than in other neurological disorders. Over the past decades, research has focused on PE, and evidence from clinical studies showed a beneficial effect of antidepressants for the treatment of men with PE. Other ejaculatory disorders, especially painful ejaculation, have been less investigated and the proper therapy is still controversial. Aim of this review is to provide a comprehensive description of both currently available treatments and most promising future therapies, including assigned patents, for the neurogenic ejaculatory disorders. PMID:21834782

  12. Logistics modeling of future solid waste storage, treatment, and disposal

    SciTech Connect

    Holter, G.M.; Stiles, D.L.; Shaver, S.R.; Armacost, L.L.

    1993-11-01

    Logistics modeling is a powerful analytical technique for effective planning of waste storage, treatment, and disposal activities. Logistics modeling facilitates analyses of alternate scenarios for future waste flows, facility schedules, and processing or handling capacities. These analyses provide an increased understanding of the specific needs for waste storage, treatment, and disposal while adequate time remains to plan accordingly. They also help to determine the sensitivity of these needs to various system parameters. This paper discusses a logistics modeling system developed by the Pacific Northwest Laboratory (PNL) to aid in solid waste planning for a large industrial complex managing many different types and classifications of waste. The basic needs for such a system are outlined, and the approach adopted in developing the system is described. A key component of this approach is the development of a conceptual model that provides a flexible framework for modeling the waste management system and addressing the range of logistics and economic issues involved. Developing an adequate description of the waste management system being analyzed is discussed. Examples are then provided of the types of analyses that have been conducted. The potential application of this modeling system to different settings is also examined.

  13. Effective rheumatoid arthritis treatment requires comprehensive management strategies.

    PubMed

    Boomershine, Chad S

    2009-01-01

    Work by Lee and colleagues has shown that decreased sleep quality and increased psychiatric distress increase pain sensitivity at both articular and nonarticular sites in rheumatoid arthritis (RA) patients. This work is consistent with prior studies showing that factors independent of RA disease activity can influence RA outcome measures. Owing to increasing pressure on rheumatologists to use outcome measures to inform treatment decisions, the work by Lee and colleagues highlights the need for comprehensive RA management strategies to understand and address the human factors that influence outcomes measures. Such strategies will ensure appropriate use of increasingly expensive therapies while maximizing patient satisfaction and reimbursement. PMID:20067592

  14. Effective rheumatoid arthritis treatment requires comprehensive management strategies

    PubMed Central

    2009-01-01

    Work by Lee and colleagues has shown that decreased sleep quality and increased psychiatric distress increase pain sensitivity at both articular and nonarticular sites in rheumatoid arthritis (RA) patients. This work is consistent with prior studies showing that factors independent of RA disease activity can influence RA outcome measures. Owing to increasing pressure on rheumatologists to use outcome measures to inform treatment decisions, the work by Lee and colleagues highlights the need for comprehensive RA management strategies to understand and address the human factors that influence outcomes measures. Such strategies will ensure appropriate use of increasingly expensive therapies while maximizing patient satisfaction and reimbursement. PMID:20067592

  15. Practical strategies for enhancing adherence to treatment regimen in inflammatory bowel disease.

    PubMed

    Greenley, Rachel N; Kunz, Jennifer H; Walter, Jennifer; Hommel, Kevin A

    2013-06-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  16. Practical Strategies for Enhancing Adherence to Treatment Regimen in Inflammatory Bowel Disease

    PubMed Central

    Greenley, Rachel N.; Kunz, Jennifer H.; Walter, Jennifer; Hommel, Kevin A.

    2013-01-01

    Promoting adherence to treatment among pediatric and adult patients with inflammatory bowel disease (IBD) is a critical yet challenging task for health care providers. Several existing interventions to enhance adherence among individuals with IBD offer useful information about practical strategies to enhance adherence. The current review article has 3 goals. First, the review provides a context for understanding treatment regimen adherence in IBD by reviewing key definitional, measurement, and conceptual challenges in this area. Next, published studies focused on interventions to enhance adherence in IBD are briefly summarized, followed by a synthesis of practical adherence promotion strategies for use in IBD by health care providers. Strategies are distinguished by the level of evidence supporting their utility as well as by age group. Finally, recommendations for future research to facilitate the development and implementation of practical, evidence-based strategies for adherence promotion in IBD are provided. Findings from the literature review suggest that strategies including education, regimen simplification, and use of reminder systems and organizational strategies (e.g., pill boxes) are likely to be best suited for addressing accidental nonadherence. In contrast, addressing motivational issues, teaching problem-solving skills, and addressing problematic patterns of family functioning are more likely to benefit individuals displaying intentional nonadherence. PMID:23635715

  17. Strategies for maximizing clinical effectiveness in the treatment of schizophrenia.

    PubMed

    Tandon, Rajiv; Targum, Steven D; Nasrallah, Henry A; Ross, Ruth

    2006-11-01

    The ultimate clinical objective in the treatment of schizophrenia is to enable affected individuals to lead maximally productive and personally meaningful lives. As with other chronic diseases that lack a definitive cure, the individual's service/recovery plan must include treatment interventions directed towards decreasing manifestations of the illness, rehabilitative services directed towards enhancing adaptive skills, and social support mobilization aimed at optimizing function and quality of life. In this review, we provide a conceptual framework for considering approaches for maximizing the effectiveness of the array of treatments and other services towards promoting recovery of persons with schizophrenia. We discuss pharmacological, psychological, and social strategies that decrease the burden of the disease of schizophrenia on affected individuals and their families while adding the least possible burden of treatment. In view of the multitude of treatments necessary to optimize outcomes for individuals with schizophrenia, effective coordination of these services is essential. In addition to providing best possible clinical assessment and pharmacological treatment, the psychiatrist must function as an effective leader of the treatment team. To do so, however, the psychiatrist must be knowledgeable about the range of available services, must have skills in clinical-administrative leadership, and must accept the responsibility of coordinating the planning and delivery of this multidimensional array of treatments and services. Finally, the effectiveness of providing optimal individualized treatment/rehabilitation is best gauged by measuring progress on multiple effectiveness domains. Approaches for efficient and reliable assessment are discussed. PMID:17122696

  18. Multimodality treatment strategies have changed prognosis of peritoneal metastases.

    PubMed

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-15

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with "terminal status/despair". The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists' perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  19. Multimodality treatment strategies have changed prognosis of peritoneal metastases

    PubMed Central

    Lungoci, Corneliu; Mironiuc, Aurel Ion; Muntean, Valentin; Oniu, Traian; Leebmann, Hubert; Mayr, Max; Piso, Pompiliu

    2016-01-01

    For a long time, treatment of peritoneal metastases (PM) was mostly palliative and thus, this status was link with “terminal status/despair”. The current multimodal treatment strategy, consisting of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), has been strenuously achieved over time, but seems to be the best treatment option for PM patients. As we reviewed the literature data, we could emphasize some milestones and also, controversies in the history of proposed multimodal treatment and thus, outline the philosophy of this approach, which seems to be an unusual one indeed. Initially marked by nihilism and fear, but benefiting from a remarkable joint effort of human and material resources (multi-center and -institutional research), over a period of 30 years, CRS and HIPEC found their place in the treatment of PM. The next 4 years were dedicated to the refinement of the multimodal treatment, by launching research pathways. In selected patients, with requires training, it demonstrated a significant survival results (similar to the Hepatic Metastases treatment), with acceptable risks and costs. The main debates regarding CRS and HIPEC treatment were based on the oncologists’ perspective and the small number of randomized clinical trials. It is important to statement the PM patient has the right to be informed of the existence of CRS and HIPEC, as a real treatment resource, the decision being made by multidisciplinary teams. PMID:26798438

  20. [Current Conservative Treatment and Management Strategies of Skeletal Muscle Injuries].

    PubMed

    Hotfiel, T; Carl, H-D; Swoboda, B; Heinrich, M; Heiß, R; Grim, C; Engelhardt, M

    2016-06-01

    Muscle injuries frequently occur during sport and are one of the commonest injuries. The diagnosis and treatment of muscle injuries impose high demands on medical treatment, in order to ensure successful regeneration and a rapid return to sport. Most of the injuries can be treated conservatively, as skeletal muscles have a high endogenous capacity for repair and regeneration. Conservative treatment includes initial on-field therapy. This is known as the "RICE" principle and is common and recommended for initial treatment for most sports injuries. The primary therapy target is to reduce pain, swelling and bleeding and thus to limit the initial inflammatory process and prevent further damage. During the first days after injury, brief immobilization helps to reduce the re-injury rate and accelerates the formation of granulation tissue. There are many possible additional treatments, including intramuscular injections, manipulation of the sacroiliac joint or rehabilitation programs, including stretching and strengthening. If the acute treatment phase is complete after 3 to 5 days, more active treatment, including trunk stabilisation, stretching and strengthening, can be started gradually. Despite their high prevalence, there have only been a few studies on the treatment and management of these injuries. The aim of this manuscript is to review the literature on the classification, pathobiology and treatment strategies for muscle injuries. PMID:27351158

  1. Benign Paroxysmal Positional Vertigo (BPPV): History, Pathophysiology, Office Treatment and Future Directions

    PubMed Central

    Hornibrook, Jeremy

    2011-01-01

    BPPV is the most common cause of vertigo. It most often occurs spontaneously in the 50 to 70 year age group. In younger individuals it is the commonest cause of vertigo following head injury. There is a wide spectrum of severity from inconsistent positional vertigo to continuous vertigo provoked by any head movement. It is likely to be a cause of falls and other morbidity in the elderly. Misdiagnosis can result in unnecessary tests. The cardinal features and a diagnostic test were clarified in 1952 by Dix and Hallpike. Subsequently, it has been established that the symptoms are attributable to detached otoconia in any of the semicircular canals. BPPV symptoms can resolve spontaneously but can last for days, weeks, months, and years. Unusual patterns of nystagmus and nonrepsonse to treatment may suggest central pathology. Diagnostic strategies and the simplest “office” treatment techniques are described. Future directions for research are discussed. PMID:21808648

  2. Comparison of different treatment strategies for industrial landfill leachate.

    PubMed

    Gotvajn, A Zgajnar; Tisler, T; Zagorc-Koncan, J

    2009-03-15

    The aim of our research was to determine appropriate treatment technique for effective treatment of heavily polluted tannery landfill leachate. We have accomplished several treatment experiments: (i) aerobic biological treatment, (ii) air stripping at various pH, (iii) adsorption to activated carbon, (iv) coagulation-flocculation and (v) advanced oxidation process with Fe(2+)/H(2)O(2). Efficiency of each procedure was monitored by chemical analysis and changes in biodegradability and acute toxicity were also evaluated (Vibrio fischeri and Daphnia magna). Biological treatment of raw leachate was effective only for very diluted leachate (up to 6Vol.%). It has been confirmed that air stripping at pH 11.0 effectively removed volatile organics and ammonia for 33% and 84%, respectively and contributed to lower toxicity of the leachate. Fenton's oxidation was the most effective among all used treatment procedures. COD removal reached 86%, biodegradability has been increased and toxicity reduced. Adsorption to activated carbon increased BOD(5)/COD ratio from 0.18 to 0.56 and it removed 40% of organics. Coagulation and flocculation procedures with FeCl(3) were also very effective. At lowered pH and added flocculant treatment efficiency reached 50%. But no method alone was effective enough to meet effluent limits for release into local surface waters. Future work was focused on the study of different promising treatment schemes, especially combination of Fenton's oxidation and biological treatment. PMID:18650010

  3. High Priority Future Research Needs for Obstructive Sleep Apnea Diagnosis and Treatment

    PubMed Central

    Patel, Kamal; Moorthy, Denish; Chan, Jeffrey A.; Concannon, Thomas W.; Ratichek, Sara J.; Chung, Mei; Balk, Ethan M.

    2013-01-01

    Study Objectives: To identify and prioritize future research needs (FRN) topics for diagnosis and treatment of obstructive sleep apnea (OSA). Methods: Twenty-one panel members represented six stake-holder categories: patients and the public, providers; purchasers of health care, payers, policymakers, and principal investigators. Building on a recently completed comparative effectiveness review, stakeholders nominated and discussed potential FRN topics. Stakeholders then nominated their top priority FRN topics based on the Agency for Healthcare Research and Quality Effective Health Care Program Selection Criteria. From these nominations, the highest priority FRN topics were determined and were elaborated upon to include possible study designs to address the topics. Results: Thirty-seven topics were discussed and prioritized. The nine highest priority FRN topics included: cost-effectiveness of management strategies, defining age- and sex-specific criteria for OSA, evaluating routine preoperative screening for OSA, evaluating involvement of a sleep medicine specialist in diagnosis of OSA, evaluating clinical prediction rules, assessing the effect of treating sleep disordered breathing and long-term clinical outcomes, comparing treatments for patients who do not tolerate positive airway pressure, evaluating strategies to improve treatment compliance, and evaluating the association between sleep apnea severity and long-term clinical outcomes. Conclusions: While there are numerous specific research questions with low or insufficient strength of evidence for OSA management, OSA patients, their healthcare providers, and society at large would benefit from refocusing research efforts into the prioritized research questions and away from simple comparisons of short-term outcomes between specific interventions. Citation: Patel K; Moorthy D; Chan JA; Concannon TW. High priority future research needs for obstructive sleep apnea diagnosis and treatment. J Clin Sleep Med 2013

  4. Transportation Energy Futures: Combining Strategies for Deep Reductions in Energy Consumption and GHG Emissions (Brochure)

    SciTech Connect

    Not Available

    2013-03-01

    This fact sheet summarizes actions in the areas of light-duty vehicle, non-light-duty vehicle, fuel, and transportation demand that show promise for deep reductions in energy use. Energy efficient transportation strategies have the potential to simultaneously reduce oil consumption and greenhouse gas (GHG) emissions. The Transportation Energy Futures (TEF) project examined how the combination of multiple strategies could achieve deep reductions in GHG emissions and petroleum use on the order of 80%. Led by NREL, in collaboration with Argonne National Laboratory, the project's primary goal was to help inform domestic decisions about transportation energy strategies, priorities, and investments, with an emphasis on underexplored opportunities. TEF findings reveal three strategies with the potential to displace most transportation-related petroleum use and GHG emissions: 1) Stabilizing energy use in the transportation sector through efficiency and demand-side approaches. 2) Using additional advanced biofuels. 3) Expanding electric drivetrain technologies.

  5. Novel treatment strategies for patients with relapsed classical Hodgkin lymphoma

    PubMed Central

    Jona, Adam; Younes, Anas

    2011-01-01

    The treatment of patients with relapsed and refractory Hodgkin lymphoma (HL), especially those who relapse after autologous stem cell transplantation, remains challenging. Patients with HL whose disease relapses after stem cell transplantation are rarely cured with current treatment modalities, and have a median survival is less than 3 years. With no new drugs have been approved by the FDA for HL in more than three decades, there is a clear unmet medical need for drug development for this patients population. New treatment strategies that are based on targeting oncogenic signaling pathways are currently explored. This review will focus on emerging new treatment modalities that are currently under investigation for patients with relapsed classical HL. PMID:20828898

  6. Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies

    PubMed Central

    Hawk, Kathryn F.; Vaca, Federico E.; D’Onofrio, Gail

    2015-01-01

    The opioid overdose epidemic is a major threat to the public’s health, resulting in the development and implementation of a variety of strategies to reduce fatal overdose [1-3]. Many strategies are focused on primary prevention and increased access to effective treatment, although the past decade has seen an exponential increase in harm reduction initiatives. To maximize identification of opportunities for intervention, initiatives focusing on prevention, access to effective treatment, and harm reduction are examined independently, although considerable overlap exists. Particular attention is given to harm reduction approaches, as increased public and political will have facilitated widespread implementation of several initiatives, including increased distribution of naloxone and policy changes designed to increase bystander assistance during a witnessed overdose [4-7]. PMID:26339206

  7. Treatment strategies in early and advanced Parkinson disease.

    PubMed

    Ossig, Christiana; Reichmann, Heinz

    2015-02-01

    The initiation of therapy in Parkinson disease (PD), altering the medication, adding new substances, and switching to alternative therapies throughout the disease is always a matter of debate. In the past, experts in PD have propagated different medication strategies. Even though there is no new medical treatment on the horizon, much has changed in consideration of the known treatments in the early and advanced therapy for PD. Therapeutic regimens have to be adapted and adjusted on a regular basis to accomplish the best medical care for the predominant symptom of the individual patient with PD. PMID:25432721

  8. Assessment and treatment strategies for rotator cuff tears

    PubMed Central

    Al-Hakim, Wisam; Noorani, Ali

    2014-01-01

    Tears of the rotator cuff are common and becoming an increasingly frequent problem. There is a vast amount of literature on the merits and limitations of the various methods of clinical and radiological assessment of rotator cuff tears. This is also the case with regard to treatment strategies. Certain popular beliefs and principles practiced widely and the basis upon which they are derived may be prone to inaccuracy. We provide an overview of the historical management of rotator cuff tears, as well as an explanation for how and why rotator cuff tears should be managed, and propose a structured methodology for their assessment and treatment.

  9. [Pleural empyema - treatment strategies in light of etiology].

    PubMed

    Hecker, E; Hecker, H C; Hecker, K A

    2013-06-01

    The variety of strategies in the treatment of parapneumonic pleural empyema demonstrates the ambiguity for the method of choice. Parapneumonic pleural empyema has been classified into different stages and classes. While the American Thoracic Society (ATS) classification is based on the natural course of the disease, or according to the radiological, physical and biochemical characteristics respectively, the American College of Chest Physicians (ACCP) has categorized the patients with pleural empyema according to the risk of a poor outcome. The British Thoracic Society (BTS) developed a treatment algorithm based on a systematic review of peer-reviewed literature. With regard to this classification the management of parapneumonic and postoperative pleural empyema is based on the stage of the disease. Therapeutic strategies include chest tube alone, chest tube with fibrinolysis, thoracoscopic debridement and decortication in open or minimally invasive techniques, closed empyemectomy, or treatment with thoracomyoplasty, open window treatment or vacuum clothing with negative pressure. The different conservative and operative therapeutic possibilities determinate the central treatment function of thoracic surgery. PMID:23807591

  10. New strategies for local treatment of vaginal infections.

    PubMed

    Palmeira-de-Oliveira, Rita; Palmeira-de-Oliveira, Ana; Martinez-de-Oliveira, José

    2015-09-15

    Vaginal infections are extremely prevalent, particularly among women of reproductive age. Although they do not result in high mortality rates, these infections are associated with high levels of anxiety and reduction of quality of life. In most cases, topical treatment of vaginal infections has been shown to be at least as effective as oral treatment, resulting in higher local drug concentrations, with fewer drug interactions and adverse effects. Furthermore, the emergence of microbial resistance to chemotherapeutics and the difficulties in managing infection recurrences sustain the need for more effective local treatments. However, conventional dosage forms have been associated with low retention in the vagina and discomfort. Formulation strategies such as the development of bioadhesive, thermogelling systems and microtechnological or nanotechnological approaches have been proposed to improve delivery of traditional drugs, and other treatment modalities such as new drugs, plant extracts, and probiotics are being studied. This article reviews the recent strategies studied to improve the treatment and prevention of the commonest vaginal infections-namely, vaginal bacteriosis, aerobic vaginitis, vulvovaginal candidosis, and trichomoniasis-through the intravaginal route. PMID:26144995

  11. Treatment Strategies for Patients with an INTERMACS I Profile

    PubMed Central

    Abu Saleh, Walid K.; Jabbari, Odeaa Al; Guha, Ashrith; Loebe, Matthias; Bruckner, Brian A.

    2015-01-01

    Treatment of patients with INTERMACS class I heart failure can be very challenging, and temporary long-term device support may be needed. In this article, we review the currently available temporary support devices in order to support these severely ill patients with decompensated heart failure. Strategies of using a temporary assist as a bridge to long-term device support are also discussed. PMID:25793022

  12. Treatment strategies for patients with an INTERMACS I profile.

    PubMed

    Abu Saleh, Walid K; Jabbari, Odeaa Al; Guha, Ashrith; Loebe, Matthias; Bruckner, Brian A

    2015-01-01

    Treatment of patients with INTERMACS class I heart failure can be very challenging, and temporary long-term device support may be needed. In this article, we review the currently available temporary support devices in order to support these severely ill patients with decompensated heart failure. Strategies of using a temporary assist as a bridge to long-term device support are also discussed. PMID:25793022

  13. Future challenges for the treatment of liver tumors.

    PubMed

    Di Carlo, Isidoro; Toro, Adriana

    2013-04-01

    The annual World Congress of the International Association of Surgeons, Gastroenterologists and Oncologists (IASGO) was held in Bangkok, Thailand, from 5-9 December 2012, hosted under the auspices of the President of the Association, Masatoshi Makuuchi and the General Secretary Nicolas Lygidakis. The President of the Congress and of the local committee was Nopadol Wora-Urai from Bangkok University (Bangkok, Thailand). The organization of the congress was excellent, and both the location and the kindness of the local people were marvellous. The congress was supported by 665 participants from 62 countries, including speakers from Europe, America, Africa, Asia and Australia. The program included symposia, videos, free papers and poster sessions. The scientific sessions also provided live surgery and lunch lectures. The congress offered the opportunity to exchange knowledge about the challenges and controversies involved in the management of abdominal diseases. This paper analyzes current possibilities and future expectations for the diagnosis and treatment of liver tumors, especially hepatocellular carcinomas and liver metastases from colorectal cancer. PMID:23560371

  14. Traumatic brain injury: future assessment tools and treatment prospects

    PubMed Central

    Flanagan, Steven R; Cantor, Joshua B; Ashman, Teresa A

    2008-01-01

    Traumatic brain injury (TBI) is widespread and leads to death and disability in millions of individuals around the world each year. Overall incidence and prevalence of TBI are likely to increase in absolute terms in the future. Tackling the problem of treating TBI successfully will require improvements in the understanding of normal cerebral anatomy, physiology, and function throughout the lifespan, as well as the pathological and recuperative responses that result from trauma. New treatment approaches and combinations will need to be targeted to the heterogeneous needs of TBI populations. This article explores and evaluates the research evidence in areas that will likely lead to a reduction in TBI-related morbidity and improved outcomes. These include emerging assessment instruments and techniques in areas of structural/chemical and functional neuroimaging and neuropsychology, advances in the realms of cell-based therapies and genetics, promising cognitive rehabilitation techniques including cognitive remediation and the use of electronic technologies including assistive devices and virtual reality, and the emerging field of complementary and alternative medicine. PMID:19183780

  15. Therapeutic Strategies for Treatment of Pulmonary Lymphangioleiomyomatosis (LAM)

    PubMed Central

    Krymskaya, Vera P.

    2015-01-01

    Introduction Pulmonary lymphangioleiomyomatosis (LAM) is a rare progressive lung disease affecting almost exclusively women. Neoplastic growth of atypical smooth muscle-like cells in the lung induces destruction of lung parenchyma leading to the formation of lung cysts, rupture of which results in spontaneous pneumothorax. LAM occurs sporadically or in association with inherited hamartoma syndrome tuberous sclerosis complex (TSC). Progression of LAM often results in loss of pulmonary function and death. Increasing understanding of neoplastic LAM cell growth is driving the development of therapeutic approaches targeting the disease progression. Areas covered This review provides background to understand the rationale for current treatments used in patients with LAM, to critically appraise the evidence for these treatments, and to discuss future treatment approaches. The literature review includes publications from PubMed and clinicaltrials.gov/. Expert Opinion Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. A number of other treatment options have been investigated and are currently tested in clinical trials to target LAM cell survival and metastasis. Key remaining and poorly understood areas for development and validation of therapeutic targeting in LAM are destruction of lungs, pathological lymphangiogenesis, and hormonal regulation. Future will reveal whether they could be targeted therapeutically. PMID:26779398

  16. 17 CFR 1.30 - Loans by futures commission merchants; treatment of proceeds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 1 2010-04-01 2010-04-01 false Loans by futures commission merchants; treatment of proceeds. 1.30 Section 1.30 Commodity and Securities Exchanges COMMODITY FUTURES... Property § 1.30 Loans by futures commission merchants; treatment of proceeds. Nothing in these...

  17. 17 CFR 1.30 - Loans by futures commission merchants; treatment of proceeds.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... merchants; treatment of proceeds. 1.30 Section 1.30 Commodity and Securities Exchanges COMMODITY FUTURES... Property § 1.30 Loans by futures commission merchants; treatment of proceeds. Nothing in these regulations shall prevent a futures commission merchant from lending its own funds to commodity or option...

  18. 17 CFR 1.30 - Loans by futures commission merchants; treatment of proceeds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Loans by futures commission merchants; treatment of proceeds. 1.30 Section 1.30 Commodity and Securities Exchanges COMMODITY FUTURES... Property § 1.30 Loans by futures commission merchants; treatment of proceeds. Nothing in the regulations...

  19. 17 CFR 1.30 - Loans by futures commission merchants; treatment of proceeds.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Loans by futures commission merchants; treatment of proceeds. 1.30 Section 1.30 Commodity and Securities Exchanges COMMODITY FUTURES... Property § 1.30 Loans by futures commission merchants; treatment of proceeds. Nothing in these...

  20. Economic and financial restructuring of the petroleum industry: strategies for the future

    SciTech Connect

    Malik, K.A.

    1987-01-01

    The relationship between economics, finance, and geopolitics in the oil market is examined. Furthermore, the structural changes that have occurred in the petroleum industry are analyzed. Recent developments have greatly influenced oil prices, and the supply of and demand for oil. The research clearly points to an increasing U.S. reliance on the Middle East oil in the future. Large U.S. oil companies are emphasizing overseas oil exploration and development. The volatility and competitiveness in the market have led to a new oil-pricing mechanisms in international oil trade. Netback pricing, the growth of the crude-oil futures market, and an increase in barter agreements are important developments. Several factors, including the decline in oil prices, and the lack of investor interest in oil investments have reduced the capital available to the industry. This has created the need for new financing techniques. Companies are devising strategies to protect their financial strength. A survey of the restructuring of the petroleum industry was conducted. The survey examined the problems of the petroleum industry, strategies of the oil companies, and the future role of OPEC. The consensus amongst the respondents was that misjudgment regarding future oil prices was the leading cause of the industry's problems, and that the U.S. will be more vulnerable to oil-supply disruptions in the future.

  1. Water and wastewater in developing countries: present reality and strategy for the future.

    PubMed

    Ujang, Z; Buckley, C

    2002-01-01

    This paper summarises the paper presentation sessions at the Conference, as well giving insights on the issues related to developing countries. It also discusses the present status of practice and research on water and wastewater management, and projected future scenario based not only on the papers presented in the Conference, but also on other sources. The strategy is presented to overcome many problems in developing countries such as rapid urbanization, industrialization, population growth, financial and institutional problems and, depleting water resources. The strategy consists of Integrated Urban Water Management (IUWM), cleaner industrial production, waste minimisation and financial arrangements. PMID:12448446

  2. High-energy physics strategies and future large-scale projects

    NASA Astrophysics Data System (ADS)

    Zimmermann, F.

    2015-07-01

    We sketch the actual European and international strategies and possible future facilities. In the near term the High Energy Physics (HEP) community will fully exploit the physics potential of the Large Hadron Collider (LHC) through its high-luminosity upgrade (HL-LHC). Post-LHC options include a linear e+e- collider in Japan (ILC) or at CERN (CLIC), as well as circular lepton or hadron colliders in China (CepC/SppC) and Europe (FCC). We conclude with linear and circular acceleration approaches based on crystals, and some perspectives for the far future of accelerator-based particle physics.

  3. Strategies for microwave thermal treatment planning, navigation, and assessment

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.

    2011-03-01

    Thermal treatment is commonly performed interstitially in either surgical or percutaneous procedures, using microwave antenna sources at 915 or 2540 MHz. There are a number of tools or aids as well as challenges for clinicians performing these procedures in the course of patient treatment. These challenges will be present whether the procedure is surgical, laparoscopic, or percutaneous, and include treatment planning, image guidance, navigation, coregistration in 3D, and treatment assessment. Treatment planning has been used historically in hyperthermia for microwave antenna arrays, but has yet to be properly applied in thermal ablation. Image assessment of thermal treatment is not typically performed in real time, although these tools will provide the clinician with further information to understand the extent of treatment and whether further treatment is needed. 3D imaging is available, but not coregistered to patient space. Navigation has been used in many medical specialties, but is also not in the clinician's toolbox in thermal treatment. Although treatment planning will lay out the skin entry and trajectory for each antenna placed, subsequently, each antenna needs to be tracked to accurately show placement in the patient and overlaid in patient space, along with the tumor target location. Some patient treatments may consist of multiple, but sequential single placements of an antenna, and guidance is even more critical to track positions and plan for the next insertion. Lastly, real-time image assessment will show the extent and shape of the coagulated lesion and which targets may have been undertreated. If used synchronously in arrays, MW power steering may also aid in filling in the ablation as the treatment progresses. This paper will analyze the present state-of-the art as well as a strategy to incorporate the various facets of planning, guidance, and assessment of treatment. The integration of thermal treatment planning, navigation and guidance, robotics

  4. Improving Care for Depression & Suicide Risk in Adolescents: Innovative Strategies for Bringing Treatments to Community Settings

    PubMed Central

    Asarnow, Joan Rosenbaum; Miranda, Jeanne

    2015-01-01

    This article reviews the literature on interventions and services for depression and suicide prevention among adolescents, with the goals of placing this science within the context of current changing health care environments and highlighting innovative models for improving health and mental health. We examine the: challenges and opportunities offered by new initiatives and legislation designed to transform the U.S. health and mental healthcare systems; summarize knowledge regarding the treatment of depression and suicidality/self-harm in adolescents; and describe innovative models for partnering with health systems and communities. This review demonstrates that treatment models and service delivery strategies are currently available for increasing evidence-based care, particularly for depression, and concludes with recommendations for future research and quality improvement initiatives aimed at inspiring additional efforts to put science to work, bridge science and community practice, and develop strategies for partnering with communities to improve care, mental health, and well-being among adolescents. PMID:24437432

  5. SMARTer Discontinuation Trial Designs for Developing an Adaptive Treatment Strategy

    PubMed Central

    Compton, Scott N.; Rynn, Moira A.; Walkup, John T.; Murphy, Susan A.

    2012-01-01

    Abstract Objective Developing evidenced-based practices for the management of childhood psychiatric disorders requires research studies that address how to treat children during both the acute phase of the disorder and beyond. Given the selection of a medication for acute treatment, discontinuation trials are used to evaluate the effects of treatment duration (e.g., time on medication) and/or maintenance strategies following successful acute-phase treatment. Recently, sequential multiple assignment randomized trials (SMART) have been proposed for use in informing sequences of critical clinical decisions such as those mentioned. The objective of this article is to illustrate how a SMART study is related to the standard discontinuation trial design, while addressing additional clinically important questions with similar trial resources. Method The recently completed Child/Adolescent Anxiety Multimodal Study (CAMS), a randomized trial that examined the relative efficacy of three acute-phase treatments for pediatric anxiety disorders, along with a next logical step, a standard discontinuation trial design, is used to clarify the ideas. This example is used to compare the discontinuation trial design relative to the SMART design. Results We find that the standard discontinuation trial can be modified slightly using a SMART design to yield high-quality data that can be used to address a wider variety of questions in addition to the impact of treatment duration. We discuss how this innovative trial design is ultimately more efficient and less costly than the standard discontinuation trial, and may result in more representative comparisons between treatments. Conclusions Mental health researchers who are interested in addressing questions concerning the effects of continued treatment (for different durations) following successful acute-phase treatment should consider SMART designs in place of discontinuation trial designs in their research. SMART designs can be used to

  6. Bioengineering Strategies for the Treatment of Type I Diabetes.

    PubMed

    Liu, Xiaoyan; Li, Xiaowei; Zhang, Ning; Zhao, Zhanzheng; Wen, Xuejun

    2016-04-01

    Diabetes mellitus, the third most common disease in the world, is a chronic metabolic disorder caused by a failure of insulin production and/or an inability to respond to insulin. Specifically, type 1 diabetes is a disease resulted by the autoimmune destruction of a patient's β-cell population within the pancreatic islets of Langerhans. The current primary treatment for type 1 diabetes is daily multiple insulin injections. However, this treatment cannot provide sustained physiological release, and the insulin amount is not finely tuned to glycemia. Pancreatic transplants or islet transplants would be the preferred treatment method but the lack of donor tissue and immunoincompatibility has been shown to be a roadblock to their widespread use. Bioengineering strategies are poised to combat these challenges. In this review, bioengineering approaches for the treatment of type 1 diabetes, including insulin controlled release systems, strategies for immunoisolation of transplanted islets, and cell-based therapies, such as β-cells and stem cells, are discussed. PMID:27301187

  7. Optimal Pharmacologic Treatment Strategies in Obesity and Type 2 Diabetes

    PubMed Central

    Goswami, Gayotri; Shinkazh, Nataliya; Davis, Nichola

    2014-01-01

    The prevalence of obesity has increased to pandemic levels worldwide and is related to increased risk of morbidity and mortality. Metabolic comorbidities are commonly associated with obesity and include metabolic syndrome, pre-diabetes, and type 2 diabetes. Even if the prevalence of obesity remains stable until 2030, the anticipated numbers of people with diabetes will more than double as a consequence of population aging and urbanization. Weight reduction is integral in the prevention of diabetes among obese adults with pre-diabetes. Lifestyle intervention and weight reduction are also key in the management of type 2 diabetes. Weight loss is challenging for most obese patients, but for those with diabetes, it can pose an even greater challenge due to the weight gain associated with many treatment regimens. This article will review optimal treatment strategies for patients with comorbid obesity and type 2 diabetes. The role of anti-obesity agents in diabetes will also be reviewed. This literature review will provide readers with current strategies for the pharmacologic treatment of obesity and diabetes with a focus on the weight outcomes related to diabetes treatments. PMID:26237392

  8. 4D Proton treatment planning strategy for mobile lung tumors

    SciTech Connect

    Kang Yixiu; Zhang Xiaodong; Chang, Joe Y.; Wang He; Wei Xiong; Liao Zhongxing; Komaki, Ritsuko; Cox, James D.; Balter, Peter A.; Liu, Helen; Zhu, X. Ronald; Mohan, Radhe; Dong Lei . E-mail: ldong@mdanderson.org

    2007-03-01

    Purpose: To investigate strategies for designing compensator-based 3D proton treatment plans for mobile lung tumors using four-dimensional computed tomography (4DCT) images. Methods and Materials: Four-dimensional CT sets for 10 lung cancer patients were used in this study. The internal gross tumor volume (IGTV) was obtained by combining the tumor volumes at different phases of the respiratory cycle. For each patient, we evaluated four planning strategies based on the following dose calculations: (1) the average (AVE) CT; (2) the free-breathing (FB) CT; (3) the maximum intensity projection (MIP) CT; and (4) the AVE CT in which the CT voxel values inside the IGTV were replaced by a constant density (AVE{sub R}IGTV). For each strategy, the resulting cumulative dose distribution in a respiratory cycle was determined using a deformable image registration method. Results: There were dosimetric differences between the apparent dose distribution, calculated on a single CT dataset, and the motion-corrected 4D dose distribution, calculated by combining dose distributions delivered to each phase of the 4DCT. The AVE{sub R}IGTV plan using a 1-cm smearing parameter had the best overall target coverage and critical structure sparing. The MIP plan approach resulted in an unnecessarily large treatment volume. The AVE and FB plans using 1-cm smearing did not provide adequate 4D target coverage in all patients. By using a larger smearing value, adequate 4D target coverage could be achieved; however, critical organ doses were increased. Conclusion: The AVE{sub R}IGTV approach is an effective strategy for designing proton treatment plans for mobile lung tumors.

  9. Recent Strategies in Treatment of Pulmonary Arterial Hypertension, A Review

    PubMed Central

    Fallah, Flora

    2015-01-01

    Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. The pulmonary circulation has to accommodate the entire cardiac output in each cardiac cycle and evolution has adapted to this by making it a low-pressure high-flow system. However, pathology can affect both the arterial and venous components of this system. Pulmonary venous hypertension mainly refers to diseases that result in elevated venous pressure and occurs mainly from mitral valve and left-sided heart disease. Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers. Newer treatments include prostacyclin analogues, endothelin receptor antago¬nists, and phosphodiesterase type 5 inhibitors. This article reviews the current treatments strategies for PAH and provides guidelines for its management. PMID:25946920

  10. Advanced therapies for the treatment of hemophilia: future perspectives

    PubMed Central

    2012-01-01

    Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression. PMID:23237078

  11. Evidence-based Management Strategies for Treatment of Chronic Wounds

    PubMed Central

    Werdin, Frank; Tennenhaus, Mayer; Schaller, Hans-Eberhardt; Rennekampff, Hans-Oliver

    2009-01-01

    The care and management of patients with chronic wounds and their far-reaching effects challenge both the patient and the practitioner. Further complicating this situation is the paucity of evidence-based treatment strategies for chronic wound care. After searching both MEDLINE and Cochrane databases, we reviewed currently available articles concerning chronic wound care. Utilizing this information, we have outlined a review of current, evidence-based concepts as they pertain to the treatment of chronic wounds, focusing on fundamental treatment principles for the management of venous, arterial, diabetic, and pressure ulcers. Individualized treatment options as well as general wound management principles applicable to all varieties of chronic wounds are described. Classification and treatment guidelines as well as the adoption of the TIME acronym facilitate an organized conceptional approach to wound care. In so doing, individual aspects of generalized wound care such as debridement, infection, and moisture control as well as attention to the qualities of the wound edge are comprehensively evaluated, communicated, and addressed. Effective adjuvant agents for the therapy of chronic wounds including nutritional and social support measures are listed, as is a brief review of strategies helpful for preventing recurrence. An appreciation of evidence-based treatment pathways and an understanding of the pathophysiology of chronic wounds are important elements in the management of patients with chronic wounds. To achieve effective and long-lasting results, a multidisciplinary approach to patient care, focused on the education and coordination of patient, family as well as medical and support staff can prove invaluable. PMID:19578487

  12. [Adherence to psychopharmacological treatment: Psychotherapeutic strategies to enhance adherence].

    PubMed

    Lencer, R; Korn, D

    2015-05-01

    Effective psychopharmacological medication with good tolerability represents the cornerstone of treatment for severe mental illness; however, the 1-year adherence rates are only approximately 50%. The term adherence emphasizes the collaborative responsibility of the clinician and the patient for a positive treatment outcome. Reasons for non-adherence are manifold and include patient-specific factors, such as self-stigmatization, lack of social and familial support, cognitive impairment and substance use besides insufficient effectiveness and the occurrence of side effects of the psychotropic drugs. To enhance adherence, both clinician and patient have to fully understand all the reasons for and against adherence to medication before a collaborative decision is made on future long-term treatment. A positive attitude towards medication critically depends on whether patients feel that the medication supports the attainment of the individual goals. PMID:25903501

  13. Update on prolactinomas. Part 2: Treatment and management strategies.

    PubMed

    Wong, Anni; Eloy, Jean Anderson; Couldwell, William T; Liu, James K

    2015-10-01

    The authors present an update on the various treatment modalities and discuss management strategies for prolactinomas. Prolactinomas are the most common type of functional pituitary tumor. Effective hyperprolactinemia treatment is of great importance, due to its potential deleterious effects including infertility, gonadal dysfunction and osteoporosis. Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy. PMID:26243714

  14. Has the DOTS Strategy Improved Case Finding or Treatment Success? An Empirical Assessment

    PubMed Central

    Obermeyer, Ziad; Abbott-Klafter, Jesse; Murray, Christopher J. L.

    2008-01-01

    Background Nearly fifteen years after the start of WHO's DOTS strategy, tuberculosis remains a major global health problem. Given the lack of empirical evidence that DOTS reduces tuberculosis burden, considerable debate has arisen about its place in the future of global tuberculosis control efforts. An independent evaluation of DOTS, one of the most widely-implemented and longest-running interventions in global health, is a prerequisite for meaningful improvements to tuberculosis control efforts, including WHO's new Stop TB Strategy. We investigate the impact of the expansion of the DOTS strategy on tuberculosis case finding and treatment success, using only empirical data. Methods and Findings We study the effect of DOTS using time-series cross-sectional methods. We first estimate the impact of DOTS expansion on case detection, using reported case notification data and controlling for other determinants of change in notifications, including HIV prevalence, GDP, and country-specific effects. We then estimate the effect of DOTS expansion on treatment success. DOTS programme variables had no statistically significant impact on case detection in a wide range of models and specifications. DOTS population coverage had a significant effect on overall treatment success rates, such that countries with full DOTS coverage benefit from at least an 18% increase in treatment success (95% CI: 5–31%). Conclusions The DOTS technical package improved overall treatment success. By contrast, DOTS expansion had no effect on case detection. This finding is less optimistic than previous analyses. Better epidemiological and programme data would facilitate future monitoring and evaluation efforts. PMID:18320042

  15. Creating the laboratory`s future; A strategy for Lawrence Livermore National Laboratory

    SciTech Connect

    1997-09-01

    ``Creating The Laboratory`s Future`` describes Livermore`s roles and responsibilities as a Department of Energy (DOE) national laboratory and sets the foundation for decisions about the Laboratory`s programs and operations. It summarizes Livermore`s near-term strategy, which builds on recent Lab achievements and world events affecting their future. It also discusses their programmatic and operational emphases and highlights program areas that the authors believe can grow through application of Lab science and technology. Creating the Laboratory`s Future reflects their very strong focus on national security, important changes in the character of their national security work, major efforts are under way to overhaul their administrative and operational systems, and the continuing challenge of achieving national consensus on the role of the government in energy, environment, and the biosciences.

  16. [Pharmacological treatment strategy and mirror visual feedback treatment for neuropathic pain].

    PubMed

    Sumitani, Masahiko; Miyauchi, Satoru; Yamada, Yoshitsugu

    2012-11-01

    Neuropathic pain is a debilitating condition, and pharmacotherapy is the most established treatment strategy. A variety of pharmacotherapies is used for neuropathic pain management: however, pharmacotherapies with evidence for analgesic potency are less common. Several pharmacotherapeutic treatment guidelines for neuropathic pain treatment recommend the first- to third-line drugs on the basis of evidence-based medicine; however, neuropathic pain is often resistant to pharmacotherapies. We have treated pharmacotherapy-resistant neuropathic pain with neurorehabilitation techniques such as mirror visual feedback (MVF) treatment. Further to our clinical experience using MVF, we discuss the cerebral mechanism associated with neuropathic pain in this study. PMID:23131739

  17. Dietary Strategies for the Treatment of Cadmium and Lead Toxicity

    PubMed Central

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2014-01-01

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

  18. Combined bacterial and viral treatment: a novel anticancer strategy

    PubMed Central

    2015-01-01

    An idea for a new combination therapy will be described herein. It is a proposition to combine viral and bacterial anticancer therapies and make them fight cancer in concert. We analyzed biological anticancer therapies and found overlapping advantages and disadvantages which led us to the conclusion that the combination therapy has the potential to create a new therapeutic quality. It is surprising how many weaknesses of viral anticancer therapy are the strengths of bacterial anticancer therapies and the other way round. We review the facts behind this concept and try to assess its value. We propose a few strategies how to combine these two therapies but as far as the review can go, final answers will have to come from the experiments. This review is the first attempt to describe a new strategy and understand the means for this idea but also to raise new questions and discuss new ways to look at anti-cancer treatment. PMID:26648783

  19. Dietary strategies for the treatment of cadmium and lead toxicity.

    PubMed

    Zhai, Qixiao; Narbad, Arjan; Chen, Wei

    2015-01-01

    Cadmium (Cd) and lead (Pb) are toxic heavy metals that cause adverse health effects in humans and animals. Chelation therapy, the conventional treatment for heavy metal toxicity, is reported to have a number of safety and efficacy issues. Recent studies have shown that dietary supplements play important roles in protecting against Cd and Pb toxicity. This paper reviews the evidence for protective effects of essential metals, vitamins, edible plants, phytochemicals, probiotics and other dietary supplements against Cd and Pb toxicity and describes the proposed possible mechanisms. Based on these findings, dietary strategies are recommended for people at risk of Cd and Pb exposure. The application of these strategies is advantageous for both the prevention and alleviation of Cd and Pb toxicity, as such supplements can be added easily and affordably to the daily diet and are expected to have very few side effects compared to the chelation therapy. PMID:25594439

  20. Novel treatment strategies for brain tumors and metastases

    PubMed Central

    El-Habashy, Salma E.; Nazief, Alaa M.; Adkins, Chris E.; Wen, Ming Ming; El-Kamel, Amal H.; Hamdan, Ahmed M.; Hanafy, Amira S.; Terrell, Tori O.; Mohammad, Afroz S.; Lockman, Paul R.; Nounou, Mohamed Ismail

    2015-01-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood–brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  1. Novel treatment strategies for brain tumors and metastases.

    PubMed

    El-Habashy, Salma E; Nazief, Alaa M; Adkins, Chris E; Wen, Ming Ming; El-Kamel, Amal H; Hamdan, Ahmed M; Hanafy, Amira S; Terrell, Tori O; Mohammad, Afroz S; Lockman, Paul R; Nounou, Mohamed Ismail

    2014-05-01

    This review summarizes patent applications in the past 5 years for the management of brain tumors and metastases. Most of the recent patents discuss one of the following strategies: the development of new drug entities that specifically target the brain cells, the blood-brain barrier and the tumor cells, tailor-designing a novel carrier system that is able to perform multitasks and multifunction as a drug carrier, targeting vehicle and even as a diagnostic tool, direct conjugation of a US FDA approved drug with a targeting moiety, diagnostic moiety or PK modifying moiety, or the use of innovative nontraditional approaches such as genetic engineering, stem cells and vaccinations. Until now, there has been no optimal strategy to deliver therapeutic agents to the CNS for the treatment of brain tumors and metastases. Intensive research efforts are actively ongoing to take brain tumor targeting, and novel and targeted CNS delivery systems to potential clinical application. PMID:24998288

  2. Looking into a Deaf Child's Future: A Brief Treatment Approach.

    ERIC Educational Resources Information Center

    Harvey, Michael A.; Green, Christine L.

    1990-01-01

    A hearing mother who reported obsessional thoughts about her deaf child's future underwent brief psychotherapy. Clinical hypnosis modified the mother's negative images of her child's future, and meetings attended by the mother, a vocational counselor, and deaf adults affirmed the more positive images. Theoretical descriptions and personal…

  3. PD-1 and PD-L1 inhibitors in melanoma treatment: past success, present application and future challenges.

    PubMed

    Lee, Jenny; Kefford, Richard; Carlino, Matteo

    2016-06-01

    Anti-programmed death (PD)-1 antibodies have now become the standard of care for advanced melanoma, with two drugs gaining US FDA approval in recent years: nivolumab and pembrolizumab. Both have demonstrated significant activity and durable response with a manageable toxicity profile. Despite initial success, ongoing challenges include patient selection and predictors of response, innate resistance and optimizing combination strategies. In this overview, we take a closer look at the history and development of therapeutic targets to the PD-1/PD-ligand (L)1 pathway, clinical evidence, availability of biomarkers and their limitations in clinical practice and future strategies to improve treatment outcomes. PMID:27197541

  4. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future.

    PubMed

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment. PMID:27118982

  5. Therapeutic Effects of Traditional Chinese Medicine on Spinal Cord Injury: A Promising Supplementary Treatment in Future

    PubMed Central

    Zhang, Qian; Yang, Hao; An, Jing; Zhang, Rui; Chen, Bo; Hao, Ding-Jun

    2016-01-01

    Objective. Spinal cord injury (SCI) is a devastating neurological disorder caused by trauma. Pathophysiological events occurring after SCI include acute, subacute, and chronic phases, while complex mechanisms are comprised. As an abundant source of natural drugs, Traditional Chinese Medicine (TCM) attracts much attention in SCI treatment recently. Hence, this review provides an overview of pathophysiology of SCI and TCM application in its therapy. Methods. Information was collected from articles published in peer-reviewed journals via electronic search (PubMed, SciFinder, Google Scholar, Web of Science, and CNKI), as well as from master's dissertations, doctoral dissertations, and Chinese Pharmacopoeia. Results. Both active ingredients and herbs could exert prevention and treatment against SCI, which is linked to antioxidant, anti-inflammatory, neuroprotective, or antiapoptosis effects. The detailed information of six active natural ingredients (i.e., curcumin, resveratrol, epigallocatechin gallate, ligustrazine, quercitrin, and puerarin) and five commonly used herbs (i.e., Danshen, Ginkgo, Ginseng, Notoginseng, and Astragali Radix) was elucidated and summarized. Conclusions. As an important supplementary treatment, TCM may provide benefits in repair of injured spinal cord. With a general consensus that future clinical approaches will be diversified and a combination of multiple strategies, TCM is likely to attract greater attention in SCI treatment. PMID:27118982

  6. Glucagon-Like Peptide-1 Formulation--the Present and Future Development in Diabetes Treatment.

    PubMed

    Lee, Chooi Yeng

    2016-03-01

    Type 2 diabetes mellitus is a chronic metabolic disorder that has become the fourth leading cause of death in the developed countries. The disorder is characterized by pancreatic β-cells dysfunction, which causes hyperglycaemia leading to several other complications. Treatment by far, which focuses on insulin administration and glycaemic control, has not been satisfactory. Glucagon-like peptide-1 (GLP1) is an endogenous peptide that stimulates post-prandial insulin secretion. Despite being able to mimic the effect of insulin, GLP1 has not been the target drug in diabetes treatment due to the peptide's metabolic instability. After a decade-long effort to improve the pharmacokinetics of GLP1, a number of GLP1 analogues are currently available on the market. The current Minireview does not discuss these drugs but presents strategies that were undertaken to address the weaknesses of the native GLP1, particularly drug delivery techniques used in developing GLP1 nanoparticles and modified GLP1 molecule. The article highlights how each of the selected preparations has improved the efficacy of GLP1, and more importantly, through an overview of these studies, it will provide an insight into strategies that may be adopted in the future in the development of a more effective oral GLP1 formulation. PMID:26551045

  7. Adherence to Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnea: Implications for Future Interventions

    PubMed Central

    Weaver, Terri E.; Sawyer, Amy M.

    2010-01-01

    Adherence to continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) is a critical problem with adherence rates ranging from 30–60%. Poor adherence to CPAP is widely recognized as a significant limiting factor in treating OSA, reducing the overall effectiveness of the treatment and leaving many OSA patients at heightened risk for comorbid conditions, impaired function and quality of life. The extant literature examining adherence to CPAP provides critical insight to measuring adherence outcomes, defining optimal adherence levels, and predicting CPAP adherence. This research has revealed salient factors that are associated with or predict CPAP adherence and may guide the development of interventions to promote CPAP adherence. Over the past 10 years, intervention studies to promote CPAP adherence have incorporated a multitude of strategies including education, support, cognitive behavioral approaches, and mixed strategies. This review of the current state of science of CPAP adherence will (1) synthesize the extant literature with regard to measuring, defining, and predicting CPAP adherence, (2) review published intervention studies aimed at promoting CPAP adherence, and (3) suggest directions for future empiric study of adherence to CPAP that will have implications for translational science. Our current understanding of CPAP adherence suggests that adherence is a multi-factorial, complex clinical problem that requires similarly designed approaches to effectively address poor CPAP adherence in the OSA population. PMID:20308750

  8. [Child and adolescent obesity, psychosocial consequences and treatment strategies].

    PubMed

    Hartmann, A S; Hilbert, A

    2013-04-01

    Being overweight and obese in childhood and adolescence is associated with various somatic and psychosocial sequelae. Psychosocial problems can negatively influence the future weight trajectory. Therefore, weight reduction or stabilization should be complemented by the treatment of significant psychosocial problems. This review provides an overview of the psychosocial problems associated with being overweight and obese in childhood and adolescence. Evidence on weight-related stigmatization and discrimination, eating disorder symptoms, general psychopathology, impaired quality of life, lowered self-esteem, social skill deficits, as well as academic problems is summarized. Furthermore, state-of-the-art diagnostic and therapeutic procedures for the psychosocial problems are summarized. Future research should focus on the development of interventions targeting the destigmatization of obesity, as experiences of stigmatization and discrimination likely aggravate the psychosocial sequelae of overweight and obesity. PMID:23529599

  9. Energy Efficiency Strategies for Municipal Wastewater Treatment Facilities

    SciTech Connect

    Daw, J.; Hallett, K.; DeWolfe, J.; Venner, I.

    2012-01-01

    Water and wastewater systems are significant energy consumers with an estimated 3%-4% of total U.S. electricity consumption used for the movement and treatment of water and wastewater. Water-energy issues are of growing importance in the context of water shortages, higher energy and material costs, and a changing climate. In this economic environment, it is in the best interest for utilities to find efficiencies, both in water and energy use. Performing energy audits at water and wastewater treatment facilities is one way community energy managers can identify opportunities to save money, energy, and water. In this paper the importance of energy use in wastewater facilities is illustrated by a case study of a process energy audit performed for Crested Butte, Colorado's wastewater treatment plant. The energy audit identified opportunities for significant energy savings by looking at power intensive unit processes such as influent pumping, aeration, ultraviolet disinfection, and solids handling. This case study presents best practices that can be readily adopted by facility managers in their pursuit of energy and financial savings in water and wastewater treatment. This paper is intended to improve community energy managers understanding of the role that the water and wastewater sector plays in a community's total energy consumption. The energy efficiency strategies described provide information on energy savings opportunities, which can be used as a basis for discussing energy management goals with water and wastewater treatment facility managers.

  10. Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities

    Cancer.gov

    Cancer Treatment-Related Cardiotoxicity: Understanding the Current State of Knowledge and Developing Future Research Priorities, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

  11. Toxin-Specific Antibodies for the Treatment of Clostridium difficile: Current Status and Future Perspectives †

    PubMed Central

    Hussack, Greg; Tanha, Jamshid

    2010-01-01

    Therapeutic agents targeting bacterial virulence factors are gaining interest as non-antibiotic alternatives for the treatment of infectious diseases. Clostridium difficile is a Gram-positive pathogen that produces two primary virulence factors, enterotoxins A and B (TcdA and TcdB), which are responsible for Clostridium difficile-associated disease (CDAD) and are targets for CDAD therapy. Antibodies specific for TcdA and TcdB have been shown to effectively treat CDAD and prevent disease relapse in animal models and in humans. This review summarizes the various toxin-specific antibody formats and strategies under development, and discusses future directions for CDAD immunotherapy, including the use of engineered antibody fragments with robust biophysical properties for systemic and oral delivery. PMID:22069622

  12. Treatment strategies for Middle East respiratory syndrome coronavirus

    PubMed Central

    Modjarrad, Kayvon

    2016-01-01

    Middle East respiratory syndrome coronavirus (MERS-CoV), an emerging infectious disease of growing global importance, has caused severe acute respiratory disease in more than 1600 people, resulting in almost 600 deaths. The high case fatality rate, growing geographic distribution and vaguely defined epidemiology of this novel pathogen have created an urgent need for effective public health countermeasures, including safe and effective treatment strategies. Despite the relatively few numbers of cases to date, research and development of MERS-CoV therapeutic candidates is advancing quickly. This review surveys the landscape of these efforts and assesses their potential for use in affected populations. PMID:26866060

  13. Effective treatment of bipolar depression: monotherapy and combination strategies.

    PubMed

    Manning, J Sloan

    2015-11-01

    Managing patients with bipolar disorder remains a challenge due to its chronic nature. In addition, bipolar depression remains understudied even though patients spend more time in depressive episodes than in manic ones. Effective treatment requires an accurate and timely diagnosis, psychoeducation, psychotherapy, pharmacotherapy, and implementation of elements of the chronic care model. Pharmacologic strategies for treating bipolar depression differ from those for bipolar mania as well as those for unipolar depression and require knowledge of the efficacy and safety of agents including mood stabilizers, atypical antipsychotics, and antidepressants both as monotherapy and in combination. PMID:26646048

  14. Chronic type B aortic dissection: indications and strategies for treatment.

    PubMed

    Rohlffs, F; Tsilimparis, N; Diener, H; Larena-Avellaneda, A; Von Kodolitsch, Y; Wipper, S; Debus, E S; Kölbel, T

    2015-04-01

    Chronic type B aortic dissection is a distinctive condition that needs individual treatment strategies and different considerations than in therapy of acute or subacute type B aortic dissection. The most common indication for treatment of this complex disease is aneurysmal dilatation of the dissected aortic segment. While open repair of the enlarged dissected aorta remains the best option for good-risk patients and patients with connective tissue disorders in high-volume centers with respective expertise, endovascular management of chronic type B aortic dissection with postdissection aneurysms has significantly gained ground in the past years. But the concept of TEVAR with implantation of a tubular stent-graft into the thoracic aorta to seal the proximal entry tear and reroute the blood flow into the true lumen alone, is not associated with satisfactory results. This is mainly due to the sparse remodeling capacity of the aortic tissue compared to earlier stages of the disease as the aortic wall and the dissection membrane are thickened and more rigid. On the other hand, it is restricted by the most limiting factor for endovascular success in chronic type B aortic dissection: persistent false lumen perfusion. This problem also affects patients with residual dissection after surgical repair of a DeBakey type I aortic dissection or dissection after ascending aortic repair for other pathologies. Hence, it is evident that strategies to achieve endovascular false lumen occlusion are of increasing importance and novel techniques have been introduced to solve the problem of persisting false lumen flow. Thus, the evolution of a large variety of techniques to address the false lumen perfusion issue indicates that complicated chronic type B dissection involves a high diversity in clinical presentation and morphology. A large armamentarium of catheter skills as well as critical individualized treatment strategies are required to address the heterogenous morphological disease

  15. Treatment strategies for atopic dermatitis: optimizing the available therapeutic options.

    PubMed

    Paller, Amy S; Simpson, Eric L; Eichenfield, Lawrence F; Ellis, Charles N; Mancini, Anthony J

    2012-09-01

    Bathing and moisturization to control dryness, applications of topical anti-inflammatory agents (including corticosteroids and calcineurin inhibitors [TCIs]) to control flares, minimization of the risk for infection, and relief of pruritus are the cornerstones of effective therapy for atopic dermatitis. Education of parents and patients is crucial to enhance adherence. Strategies for reduced Staphylococcus aureus colonization may help control re-emergence of flares following cessation of antimicrobial treatment for infection; these include dilute bleach baths and minimizing the risk for contamination of topical agents. In severe, refractory cases, more aggressive therapy with systemic immunosuppressants may be considered, but appropriate laboratory testing must be included as part of patient monitoring during treatment. The value of adjuvant therapy with wet wraps to "cool down" particularly erythematous and pruritic flares is becoming increasingly recognized. PMID:23021780

  16. Climate Change: A Future of Less Water and More people - Strategies for a Water Constrained World

    NASA Astrophysics Data System (ADS)

    Nahai, D.

    2010-12-01

    Today, the fact that the Earth is warming is indisputable. The evidence of climate change is already all around us, with the occurence of ever more intense weather events, droughts, heat waves, floods and sea level rise. Predictions of greater calamities in the future without swift action must be taken seriously. However, while international summits have focused on means to reduce greenhouse gas emissions, these are largely strategies of containment, not of cure. Even if emissions were to cease today, the current effects of climate change would remain with us for millenia. This is clear from the 2007 report of the Intergovernmental Panel on Climate Change. The world must not only tackle the causes of global warming; it must adapt to the damage already done. This need is most acute where water supply is concerned. The world already faces daunting chalenges. According to United Nations' reports, even today 1.8 million children under 5 die from water related diseases every year; 900 million people lack access to safe drinking water; and 2.6 billion go without basic sanitation. In the developing world, 90% of sewage is discharged to water bodies without adequate treatment contributing to "dead zones". Population increases will make matters worse (an addition of around 3 billion people by 2050 is expected) and climate change will compound the crisis. It is forecast that, as the Earth warms, deserts will expand and droughts will intensify causing demographic shifts even as the world's population burgeons. We are already seeing different regions react to water shortages. Many countries are pursuing seawater desalination. However, seawater desalination has numerous drawbacks; it remains the most expensive of water treatment options and the most energy intensive. Some societies may have no choice but to turn to the sea; others should look to other alternatives first. Such frontrunners could include: (1) enhanced conservation, utilizing public education programs, price

  17. Clean option: Berkeley Pit water treatment and resource recovery strategy

    SciTech Connect

    Gerber, M.A.; Orth, R.J.; Elmore, M.R.; Monzyk, B.F.

    1995-09-01

    The US Department of Energy (DOE), Office of Technology Development, established the Resource Recovery Project (RRP) in 1992 as a five-year effort to evaluate and demonstrate multiple technologies for recovering water, metals, and other industrial resources from contaminated surface and groundwater. Natural water resources located throughout the DOE complex and the and western states have been rendered unusable because of contamination from heavy metals. The Berkeley Pit, a large, inactive, open pit copper mine located in Butte, Montana, along with its associated groundwater system, has been selected by the RRP for use as a feedstock for a test bed facility located there. The test bed facility provides the infrastructure needed to evaluate promising technologies at the pilot plant scale. Data obtained from testing these technologies was used to assess their applicability for similar mine drainage water applications throughout the western states and at DOE. The objective of the Clean Option project is to develop strategies that provides a comprehensive and integrated approach to resource recovery using the Berkeley Pit water as a feedstock. The strategies not only consider the immediate problem of resource recovery from the contaminated water, but also manage the subsequent treatment of all resulting process streams. The strategies also employ the philosophy of waste minimization to optimize reduction of the waste volume requiring disposal, and the recovery and reuse of processing materials.

  18. Strategies to reduce indoor tanning: current research gaps and future opportunities for prevention.

    PubMed

    Holman, Dawn M; Fox, Kathleen A; Glenn, Jeffrey D; Guy, Gery P; Watson, Meg; Baker, Katie; Cokkinides, Vilma; Gottlieb, Mark; Lazovich, DeAnn; Perna, Frank M; Sampson, Blake P; Seidenberg, Andrew B; Sinclair, Craig; Geller, Alan C

    2013-06-01

    Exposure to ultraviolet radiation from indoor tanning device use is associated with an increased risk of skin cancer, including risk of malignant melanoma, and is an urgent public health problem. By reducing indoor tanning, future cases of skin cancer could be prevented, along with the associated morbidity, mortality, and healthcare costs. On August 20, 2012, the CDC hosted a meeting to discuss the current body of evidence on strategies to reduce indoor tanning as well as research gaps. Using the Action Model to Achieve Healthy People 2020 Overarching Goals as a framework, the current paper provides highlights on the topics that were discussed, including (1) the state of the evidence on strategies to reduce indoor tanning; (2) the tools necessary to effectively assess, monitor, and evaluate the short- and long-term impact of interventions designed to reduce indoor tanning; and (3) strategies to align efforts at the national, state, and local levels through transdisciplinary collaboration and coordination across multiple sectors. Although many challenges and barriers exist, a coordinated, multilevel, transdisciplinary approach has the potential to reduce indoor tanning and prevent future cases of skin cancer. PMID:23683986

  19. Advances in Risk Classification and Treatment Strategies for Neuroblastoma.

    PubMed

    Pinto, Navin R; Applebaum, Mark A; Volchenboum, Samuel L; Matthay, Katherine K; London, Wendy B; Ambros, Peter F; Nakagawara, Akira; Berthold, Frank; Schleiermacher, Gudrun; Park, Julie R; Valteau-Couanet, Dominique; Pearson, Andrew D J; Cohn, Susan L

    2015-09-20

    Risk-based treatment approaches for neuroblastoma have been ongoing for decades. However, the criteria used to define risk in various institutional and cooperative groups were disparate, limiting the ability to compare clinical trial results. To mitigate this problem and enhance collaborative research, homogenous pretreatment patient cohorts have been defined by the International Neuroblastoma Risk Group classification system. During the past 30 years, increasingly intensive, multimodality approaches have been developed to treat patients who are classified as high risk, whereas patients with low- or intermediate-risk neuroblastoma have received reduced therapy. This treatment approach has resulted in improved outcome, although survival for high-risk patients remains poor, emphasizing the need for more effective treatments. Increased knowledge regarding the biology and genetic basis of neuroblastoma has led to the discovery of druggable targets and promising, new therapeutic approaches. Collaborative efforts of institutions and international cooperative groups have led to advances in our understanding of neuroblastoma biology, refinements in risk classification, and stratified treatment strategies, resulting in improved outcome. International collaboration will be even more critical when evaluating therapies designed to treat small cohorts of patients with rare actionable mutations. PMID:26304901

  20. European Perspective on Multiple Myeloma Treatment Strategies in 2014

    PubMed Central

    Sonneveld, Pieter; Davies, Faith; Bladé, Joan; Boccadoro, Mario; Cavo, Michele; Morgan, Gareth; de la Rubia, Javier; Delforge, Michel; Dimopoulos, Meletios; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Moreau, Philippe; Nahi, Hareth; Plesner, Torben; San-Miguel, Jesús; Hajek, Roman; Sondergeld, Pia; Palumbo, Antonio

    2014-01-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on “fitness,” with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. PMID:25063227

  1. European perspective on multiple myeloma treatment strategies in 2014.

    PubMed

    Ludwig, Heinz; Sonneveld, Pieter; Davies, Faith; Bladé, Joan; Boccadoro, Mario; Cavo, Michele; Morgan, Gareth; de la Rubia, Javier; Delforge, Michel; Dimopoulos, Meletios; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Moreau, Philippe; Nahi, Hareth; Plesner, Torben; San-Miguel, Jesús; Hajek, Roman; Sondergeld, Pia; Palumbo, Antonio

    2014-08-01

    The treatment of multiple myeloma has undergone significant changes and has resulted in the achievement of molecular remissions, the prolongation of remission duration, and extended survival becoming realistic goals, with a cure being possible in a small but growing number of patients. In addition, nowadays it is possible to categorize patients more precisely into different risk groups, thus allowing the evaluation of therapies in different settings and enabling a better comparison of results across trials. Here, we review the evidence from clinical studies, which forms the basis for our recommendations for the management of patients with myeloma. Treatment approaches depend on "fitness," with chronological age still being an important discriminator for selecting therapy. In younger, fit patients, a short three drug-based induction treatment followed by autologous stem cell transplantation (ASCT) remains the preferred option. Consolidation and maintenance therapy are attractive strategies not yet approved by the European Medicines Agency, and a decision regarding post-ASCT therapy should only be made after detailed discussion of the pros and cons with the individual patient. Two- and three-drug combinations are recommended for patients not eligible for transplantation. Treatment should be administered for at least nine cycles, although different durations of initial therapy have only rarely been compared so far. Comorbidity and frailty should be thoroughly assessed in elderly patients, and treatment must be adapted to individual needs, carefully selecting appropriate drugs and doses. A substantial number of new drugs and novel drug classes in early clinical development have shown promising activity. Their introduction into clinical practice will most likely further improve treatment results. PMID:25063227

  2. The Leader of the Future. New Visions, Strategies, and Practices for the Next Era. First Edition. Drucker Foundation Future Series.

    ERIC Educational Resources Information Center

    Hesselbein, Frances, Ed.; And Others

    The 31 papers in this volume address the requirements and qualities of leadership and leaders in the organization of the future. Papers are grouped into the following categories: Leading the Organization of the Future, Future Leaders in Action, Learning to Lead for Tomorrow, and Executives on the Future of Leadership. Some of the papers included…

  3. Immunocytokines for cancer treatment: past, present and future.

    PubMed

    Neri, Dario; Sondel, Paul M

    2016-06-01

    Immunocytokines are antibody-cytokine fusion proteins, with the potential to preferentially localize on tumor lesions and to activate anticancer immunity at the site of disease. Various tumor targets (e.g., cell membrane antigens and extracellular matrix components) and antibody formats (e.g., intact IgG and antibody fragments) have been considered for immunocytokine development and some products have advanced to clinical trials. In this review, we present relevant concepts and strategies for the design and use of anticancer immunocytokine products. In addition, we discuss emerging strategies for the pharmaceutical development and clinical application of this promising class of biopharmaceuticals. PMID:27060634

  4. Extra vascular interventional treatment of liver cancer, present and future.

    PubMed

    Hou, Wenjing; Zhu, Xiaolin

    2015-10-01

    Interventional therapy for liver cancer is a new type of treatment, and its progress has been influenced by the development of the large scale imaging instrument and various therapeutic apparatus. This article, from these two aspects, discusses the status and progress of interventional treatment of liver cancer. PMID:26632542

  5. Bio-nano hybrid materials based on bacteriorhodopsin: Potential applications and future strategies.

    PubMed

    Mahyad, Baharak; Janfaza, Sajjad; Hosseini, Elaheh Sadat

    2015-11-01

    This review presents an overview of recent progress in the development of bio-nano hybrid materials based on the photoactive protein bacteriorhodopsin (bR). The interfacing of bR with various nanostructures including colloidal nanoparticles (such as quantum dots and Ag NPs) and nanoparticulate thin films (such as TiO2 NPs and ZnO NPs,) has developed novel functional materials. Applications of these materials are comprehensively reviewed in two parts: bioelectronics and solar energy conversion. Finally, some perspectives on possible future strategies in bR-based nanostructured devices are presented. PMID:26506028

  6. Breast cancer: Actual methods of treatment and future trends

    PubMed Central

    Murawa, Paweł; Murawa, Dawid; Adamczyk, Beata; Połom, Karol

    2014-01-01

    The recent ten to twenty years have seen a substantial progress in the diagnosis and treatment of breast cancer. A rapid development of various curative options has led to the improvement of treatment outcomes, while paying more and more attention to the aspects of quality of life and cosmetic effect. In our publication, we wish to outline certain trends in the development of modern treatment of breast cancer. Among topics discussed are new forms of molecular diagnostics, new approach to the idea of sentinel node biopsy, as well as new techniques for delivery of medical procedures, the increasing use of nomograms, progress in the techniques of breast conservative treatment, modern approach to occult breast lesions, the increasing use of neoadjuvant treatment and intraoperative radiotherapy. PMID:24936340

  7. Coronary microvascular dysfunction, microvascular angina, and treatment strategies.

    PubMed

    Marinescu, Mark A; Löffler, Adrián I; Ouellette, Michelle; Smith, Lavone; Kramer, Christopher M; Bourque, Jamieson M

    2015-02-01

    Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10% to 30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50% to 65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively-defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve or myocardial perfusion reserve <2.5 by positron emission tomography, cardiac magnetic resonance imaging, dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 papers met the strict inclusion criteria. The papers were heterogeneous, using different treatments, endpoints, and definitions of CMD. The small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded published data. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD. PMID:25677893

  8. Targeted cancer therapies: the future of cancer treatment.

    PubMed

    Kumar, Manoj; Nagpal, Ravinder; Hemalatha, R; Verma, Vinod; Kumar, Ashok; Singh, Satvinder; Marotta, Francesco; Jain, Shalini; Yadav, Hariom

    2012-12-01

    For decades, the hallmark of medical treatment for cancer has been intravenous cytotoxic chemotherapy, where these drugs target rapidly dividing cells, including cancer cells and certain normal tissues. As a result, many patients experience the classic toxicities of alopecia, gastrointestinal symptoms, and myelosuppression. In the past decade, however, a dramatic shift has been witnesses in the cancer therapy. Although traditional cytotoxic chemotherapy still remains the treatment of choice for many malignancies, targeted therapies are now a component of treatment for many types of cancer, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. PMID:23762999

  9. Current and future treatments of osteoporosis in men.

    PubMed

    Kaufman, Jean-Marc; Lapauw, Bruno; Goemaere, Stefan

    2014-12-01

    One in three osteoporotic fractures occur in men and the consequences of a fracture in men tend to be more severe than in women. Still, only a small minority of men with high risk of fracture are detected and treated. Although there are gender differences in the pathophysiology of osteoporosis, such as in the pattern of bone loss, similarities predominate, which is also the case for clinical risk factors. It seems appropriate to consider treatment for men and women with a similar 10 year fracture risk. Drugs now approved for treatment of osteoporosis in men include the anti-resorptive bisphosphonates alendronate, residronate and zoledronic acid, the anti-resorptive drug denosumab, the bone-forming agent teriparatide, and (not in the US) strontium ranelate with mild opposite effects on resorption and formation. Although the evidence level for efficacy and safety of these drugs in men is still relatively limited, available data indicate that treatment effects in men are very similar to what has been observed in the treatment of postmenopausal osteoporosis. Denosumab is also approved for treatment in men receiving androgen deprivation therapy for non-metastatic prostate cancer; bisphosphonates and teriparatide are also available to clinicians for treatment of glucocorticoid-induced osteoporosis in men. Testosterone treatment may be indicated in men with documented symptomatic hypogonadism, but osteoporosis is neither a sufficient nor a specific indication for testosterone treatment. New compounds with well advanced clinical development include odanacatib, a selective inhibitor of the cysteine protease cathepsin-K, and romosozumab, a monoclonal antibody against sclerostin. PMID:25432358

  10. Treatment of Helicobacter pylori infection: Current and future insights.

    PubMed

    Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza

    2016-01-16

    Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626

  11. Treatment of Cannabis Use Disorder: Current Science and Future Outlook.

    PubMed

    Sherman, Brian J; McRae-Clark, Aimee L

    2016-05-01

    Cannabis is the most commonly used illicit substance in the United States. Rates of cannabis use and cannabis use disorder (CUD) have increased in the past decade, paralleling changes in the legal and political climate favoring legalization. Almost 20 million people 12 years or older report past-month cannabis use, and 8 million report daily or near-daily use. Concurrently, the perception that cannabis use poses a significant risk of negative consequences has decreased. Contrary to this perception, heavy cannabis use is associated with cognitive impairment, increased risk for psychotic disorders and other mental health problems, lower education attainment, and unemployment. Clinical trials of various treatments for CUD have likewise increased, focusing primarily on psychotherapy treatments, specifically motivational enhancement therapy, cognitive behavioral therapy, and contingency management. Their findings suggest that a combination of these three modalities produces the best abstinence outcomes, although abstinence rates remain modest and decline after treatment. More recently, pharmacotherapy trials have been conducted as adjunctive interventions to psychosocial treatment. N-acetylcysteine and gabapentin are two of the most promising medications, although no pharmacologic treatment has emerged as clearly efficacious. In this review, we provide a detailed summary of clinical trials that evaluated psychotherapy and pharmacotherapy for treating CUD and discuss emerging areas of clinical research and cannabis-specific barriers to treatment. PMID:27027272

  12. Treatment of Helicobacter pylori infection: Current and future insights

    PubMed Central

    Safavi, Maliheh; Sabourian, Reyhaneh; Foroumadi, Alireza

    2016-01-01

    Helicobacter pylori (H. pylori) is an important major cause of peptic ulcer disease and gastric malignancies such as mucosa-associated lymphoid tissue lymphoma and gastric adenocarcinoma worldwide. H. pylori treatment still remains a challenge, since many determinants for successful therapy are involved such as individual primary or secondary antibiotics resistance, mucosal drug concentration, patient compliance, side-effect profile and cost. While no new drug has been developed, current therapy still relies on different mixture of known antibiotics and anti-secretory agents. A standard triple therapy consisting of two antibiotics and a proton-pump inhibitor proposed as the first-line regimen. Bismuth-containing quadruple treatment, sequential treatment or a non-bismuth quadruple treatment (concomitant) are also an alternative therapy. Levofloxacin containing triple treatment are recommended as rescue treatment for infection of H. pylori after defeat of first-line therapy. The rapid acquisition of antibiotic resistance reduces the effectiveness of any regimens involving these remedies. Therefore, adding probiotic to the medications, developing anti-H. pylori photodynamic or phytomedicine therapy, and achieving a successful H. pylori vaccine may have the promising to present synergistic or additive consequence against H. pylori, because each of them exert different effects. PMID:26798626

  13. Prevention, diagnosis, and treatment of influenza: current and future options.

    PubMed

    Poehling, K A; Edwards, K M

    2001-02-01

    Because influenza significantly affects the health of children, this review describes the current and future options for preventing, diagnosing, and treating influenza infections. Currently, the inactivated influenza vaccine is recommended for prevention of influenza; however, the live, attenuated, intranasal influenza vaccine is a potential future option. For diagnosis, viral culture is the gold standard, although four rapid diagnostic tests are available for more immediate results. The impetus for rapid results is the availability of effective antiviral agents indicated for early influenza infection. The four currently approved antiviral agents are amantadine, rimantadine, zanamivir [Relenza, Glaxo Wellcome, Inc., Research Triangle Park, NC] and oseltamivir [Tamiflu, Roche Pharmaceuticals, Nutley, NJ]. The indications, benefits, side effects and ages for which each drug is approved are reviewed. PMID:11176246

  14. Current and emerging strategies for treatment of childhood dystonia.

    PubMed

    Bertucco, Matteo; Sanger, Terence D

    2015-01-01

    Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al, 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies. PMID:25835254

  15. Novel Strategies for the Treatment of Pseudomonas aeruginosa Infections.

    PubMed

    Wagner, Stefanie; Sommer, Roman; Hinsberger, Stefan; Lu, Cenbin; Hartmann, Rolf W; Empting, Martin; Titz, Alexander

    2016-07-14

    Infections with Pseudomonas aeruginosa have become a concerning threat in hospital-acquired infections and for cystic fibrosis patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. These diverse strategies span from killing (new antibiotics) to disarming (antivirulence) the pathogen. Particular emphasis lies on the development of compounds that inhibit biofilms formed in chronic infections to restore susceptibility toward antibiotics. Numerous promising results are summarized in this perspective. Antibiotics with a novel mode of action will be needed to avoid cross resistance against currently used therapeutic agents. Importantly, antivirulence drugs are expected to yield a significantly reduced rate of resistance development. Most developments are still far from the application. It can however be expected that combination therapies, also containing antivirulence agents, will pave the way toward novel treatment options against P. aeruginosa. PMID:26804741

  16. Comparison of treatment strategies for space motion sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1991-01-01

    Treatment strategies for space motion sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of space motion sickness were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through private medical conferences with the crew. A symptom matrix was analyzed for nineteen crewmembers treated with an oral combination of scopolomine and dextroamphetamine (scopdex) and fifteen crewmembers treated with promethazine delivered by intramuscular or suppository routes. Scopdex has been given preflight as prophylaxis for space motion sickness but analysis showed delayed symptom presentation in nine crewmembers or failed to prevent symptoms in seven.

  17. Current and emerging strategies for treatment of childhood dystonia

    PubMed Central

    Bertucco, Matteo; Sanger, Terence D.

    2014-01-01

    Childhood dystonia is a movement disorder characterized by involuntary sustained or intermittent muscle contractions causing twisting and repetitive movements, abnormal postures, or both (Sanger et al. 2003). Dystonia is a devastating neurological condition that prevents the acquisition of normal motor skills during critical periods of development in children. Moreover, it is particularly debilitating in children when dystonia affects the upper extremities such that learning and consolidation of common daily motor actions are impeded. Thus, the treatment and rehabilitation of dystonia is a challenge that continuously requires exploration of novel interventions. This review will initially describe the underlying neurophysiological mechanisms of the motor impairments found in childhood dystonia followed by the clinical measurement tools that are available to document the presence and severity of symptoms. Finally, we will discuss the state-of-the-art of therapeutic options for childhood dystonia, with particular emphasis on emergent and innovative strategies. PMID:25835254

  18. Treatment strategies in obstructed defecation and fecal incontinence

    PubMed Central

    Khaikin, Marat; Wexner, Steven D

    2006-01-01

    Obstructed defecation (OD) and fecal incontinence (FI) are challenging clinical problems, which are commonly encountered in the practice of colorectal surgeons and gastroenterologists. These disorders socially and psychologically distress patients and greatly impair their quality of life. The underlying anatomical and pathophysiological changes are complex, often incompletely understood and cannot always be determined. As a consequence, many medical, surgical, and behavioral approaches have been described, with no panacea. Over the past decade, advances in an understanding of these disorders together with rational and similar methods of evaluation in anorectal physiology laboratories (ARP), radiology studies, and new surgical techniques have led to promising results. In this brief review, we discuss treatment strategies and recent updates on clinical and therapeutic aspects of obstructed defecation and fecal incontinence. PMID:16718835

  19. Biomaterial Design Strategies for the Treatment of Spinal Cord Injuries

    PubMed Central

    Straley, Karin S.; Po Foo, Cheryl Wong

    2010-01-01

    Abstract The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates biomaterial scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of biomaterial-scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these scaffolds to deliver cells and biomolecules. Developing scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue. PMID:19698073

  20. Knowledge of, and treatment strategies for, endometriosis among general practitioners.

    PubMed

    van der Zanden, Moniek; Nap, Annemiek W

    2016-05-01

    Endometriosis is the most common benign gynaecological disorder. The general practitioner (GP) plays an important role in identifying women at early stages of the disease. This study was conducted to acquire information about awareness and knowledge of endometriosis among Dutch GPs, and clinical strategies taken. A total of 101 GPs completed a questionnaire either by email or at a local education meeting. The GPs annually encounter 2.8 women they suspect of having endometriosis. The estimated time to diagnosis was 65.7 months (39.1 months patient delay and 26.6 months doctors delay); 56.7% of GPs primarily refer to a gynaecologist for consultation or diagnostic tests. The GPs answered on average 16.6 out of 28 knowledge questions correctly. Seventy-six out of 87 GPs stated that they needed further education. The results of this study indicate that if a GP considers endometriosis as a diagnosis, adequate action is undertaken. As only limited numbers of women with endometriosis are encountered in their practice, GPs do not recognize immediately the symptoms that may be caused by endometriosis, leading to diagnostic delay. Our findings may help to set up teaching programmes and awareness strategies for first-line medical professionals to enhance timely diagnosis and treatment of endometriosis. PMID:26947452

  1. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies

    PubMed Central

    Hove, Michael J.; Keller, Peter E.

    2014-01-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson’s disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients’ gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient’s walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with Parkinson patients’ footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  2. Impaired movement timing in neurological disorders: rehabilitation and treatment strategies.

    PubMed

    Hove, Michael J; Keller, Peter E

    2015-03-01

    Timing abnormalities have been reported in many neurological disorders, including Parkinson's disease (PD). In PD, motor-timing impairments are especially debilitating in gait. Despite impaired audiomotor synchronization, PD patients' gait improves when they walk with an auditory metronome or with music. Building on that research, we make recommendations for optimizing sensory cues to improve the efficacy of rhythmic cuing in gait rehabilitation. Adaptive rhythmic metronomes (that synchronize with the patient's walking) might be especially effective. In a recent study we showed that adaptive metronomes synchronized consistently with PD patients' footsteps without requiring attention; this improved stability and reinstated healthy gait dynamics. Other strategies could help optimize sensory cues for gait rehabilitation. Groove music strongly engages the motor system and induces movement; bass-frequency tones are associated with movement and provide strong timing cues. Thus, groove and bass-frequency pulses could deliver potent rhythmic cues. These strategies capitalize on the close neural connections between auditory and motor networks; and auditory cues are typically preferred. However, moving visual cues greatly improve visuomotor synchronization and could warrant examination in gait rehabilitation. Together, a treatment approach that employs groove, auditory, bass-frequency, and adaptive (GABA) cues could help optimize rhythmic sensory cues for treating motor and timing deficits. PMID:25773624

  3. [Peritoneal carcinomatosis: new strategies for more efficacious treatment].

    PubMed

    Zanon, Claudio

    2002-09-01

    The peritoneal carcinomatosis is considered an unlikely treatable disease using standard procedures as surgery or systemic chemotherapy. New improvements in the knowledge of the peritoneum are inducing to consider the mesothelium of the abdominal cavity as an organ similar to the other body organs. This new consideration, unified with the understanding of conditions permitting the implant of the tumor cell into the peritoneal space previous or during the surgical manipulation of the abdominal cancers, leads to the application of news strategies as the advanced cytoreduction with every nodes reduced less than 2.5 mm followed by the chemohyperthermic peritoneal perfusion (CHPP). Last papers indicate improvements in overall survival and quality of the life in ovarian, colonic and gastric cancer treated with an extensive surgical debulking plus CHPP. These results induce surgeons and oncologists to avoid incorrect strategies in the treatment of peritoneal carcinomatosis originating from ovarian and gastrointestinal tumors. In case of malignant untreatable ascites a peritoneo-venous shunt allows a control of the ascites avoiding several hospital admissions for continuous fastidious and sometime dangerous paracentesis. A palliative surgical operation in selected patients effected by trained surgical group permits an improvement of the patient's conditions in more than 80% with a positive feed back on his or her psychological behavior. PMID:12355981

  4. Potential regenerative treatment strategies for intervertebral disc degeneration in dogs

    PubMed Central

    2014-01-01

    Pain due to spontaneous intervertebral disc (IVD) disease is common in dogs. In chondrodystrophic (CD) dogs, IVD disease typically develops in the cervical or thoracolumbar spine at about 3–7 years of age, whereas in non-chondrodystrophic (NCD) dogs, it usually develops in the caudal cervical or lumbosacral spine at about 6–8 years of age. IVD degeneration is characterized by changes in the biochemical composition and mechanical integrity of the IVD. In the degenerated IVD, the content of glycosaminoglycan (GAG, a proteoglycan side chain) decreases and that of denatured collagen increases. Dehydration leads to tearing of the annulus fibrosus (AF) and/or disc herniation, which is clinically characterized by pain and/or neurological signs. Current treatments (physiotherapy, anti-inflammatory/analgesic medication, surgery) for IVD disease may resolve neurological deficits and reduce pain (although in many cases insufficient), but do not lead to repair of the degenerated disc. For this reason, there is interest in new regenerative therapies that can repair the degenerated disc matrix, resulting in restoration of the biomechanical function of the IVD. CD dogs are considered a suitable animal model for human IVD degeneration because of their spontaneous IVD degeneration, and therefore studies investigating cell-, growth factor-, and/or gene therapy-based regenerative therapies with this model provide information relevant to both human and canine patients. The aim of this article is to review potential regenerative treatment strategies for canine IVD degeneration, with specific emphasis on cell-based strategies. PMID:24387033

  5. Ants in the Hospital Environment: Ecological Parameters as Support for Future Management Strategies.

    PubMed

    de Castro, M M; Almeida, M; Fernandes, E F; Prezoto, F

    2016-06-01

    Urban ants cause many losses to human society, and they represent a potential threat to public health in hospital environments due to their ability to transport pathogenic organisms. We evaluated several ecological parameters (richness, abundance, constancy, and evenness), their fluctuation during the seasons, and identified species that occur outside the natural range of the ant fauna of a hospital environment, as support for future management strategies. Ant sampling was held every 2 months by using attractive bait traps in the morning and evening, leading to the sampling of 10,342 individuals belonging to six subfamilies and 26 species. Myrmicinae showed higher richness (n = 12) and abundance (n = 7336), with Pheidole susannae Forel being the most abundant species. The most constant species (100%) were P. susannae and Tetramorium simillimum (Smith). Among the most abundant species, Monomorium floricola (Jerdon) and Tapinoma melanocephalum (Fabricius) are considered as species that occur outside the natural range. No difference was observed between species richness and abundance. The Shannon (2.247), dominance (0.1395) and evenness indices (0.6897) indicated a stability of the community throughout the year with high diversity and low dominance of species. The sampled data constitute a new series of information on a long-term ecological approach to support future management strategies in hospital environments and allow for more efficient pest control. PMID:26883447

  6. Novel Strategies in the Prevention and Treatment of Urinary Tract Infections

    PubMed Central

    Lüthje, Petra; Brauner, Annelie

    2016-01-01

    Urinary tract infections are one of the most common bacterial infections, especially in women and children, frequently treated with antibiotics. The alarming increase in antibiotic resistance is a global threat to future treatment of infections. Therefore, alternative strategies are urgently needed. The innate immune system plays a fundamental role in protecting the urinary tract from infections. Antimicrobial peptides form an important part of the innate immunity. They are produced by epithelial cells and neutrophils and defend the urinary tract against invading bacteria. Since efficient resistance mechanisms have not evolved among bacterial pathogens, much effort has been put into exploring the role of antimicrobial peptides and possibilities to utilize them in clinical practice. Here, we describe the impact of antimicrobial peptides in the urinary tract and ways to enhance the production by hormones like vitamin D and estrogen. We also discuss the potential of medicinal herbs to be used in the prophylaxis and the treatment of urinary tract infections. PMID:26828523

  7. Application of Multi-Model CMIP5 Analysis in Future Drought Adaptation Strategies

    NASA Astrophysics Data System (ADS)

    Casey, M.; Luo, L.; Lang, Y.

    2014-12-01

    Drought influences the efficacy of numerous natural and artificial systems including species diversity, agriculture, and infrastructure. Global climate change raises concerns that extend well beyond atmospheric and hydrological disciplines - as climate changes with time, the need for system adaptation becomes apparent. Drought, as a natural phenomenon, is typically defined relative to the climate in which it occurs. Typically a 30-year reference time frame (RTF) is used to determine the severity of a drought event. This study investigates the projected future droughts over North America with different RTFs. Confidence in future hydroclimate projection is characterized by the agreement of long term (2005-2100) multi-model precipitation (P) and temperature (T) projections within the Coupled model Intercomparison Project Phase 5 (CMIP5). Drought severity and the propensity of extreme conditions are measured by the multi-scalar, probabilistic, RTF-based Standard Precipitation Index (SPI) and Standard Precipitation Evapotranspiration Index (SPEI). SPI considers only P while SPEI incorporates Evapotranspiration (E) via T; comparing the two reveals the role of temperature change in future hydroclimate change. Future hydroclimate conditions, hydroclimate extremity, and CMIP5 model agreement are assessed for each Representative Concentration Pathway (RCP 2.6, 4.5, 6.0, 8.5) in regions throughout North America for the entire year and for the boreal seasons. In addition, multiple time scales of SPI and SPEI are calculated to characterize drought at time scales ranging from short to long term. The study explores a simple, standardized method for considering adaptation in future drought assessment, which provides a novel perspective to incorporate adaptation with climate change. The result of the analysis is a multi-dimension, probabilistic summary of the hydrological (P, E) environment a natural or artificial system must adapt to over time. Studies similar to this with

  8. Future Directions for Pharmacotherapies for Treatment-resistant Bipolar Disorder.

    PubMed

    Dodd, Seetal; Fernandes, Brisa S; Dean, Olivia M

    2015-01-01

    Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has historically been discovered through serendipity. There is now scope for new drug development, focused on the underlying biology of BD that is not targeted by current therapies. The need for novel treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate (NMDA)-receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by lack of corporate interest. PMID:26467413

  9. Future Directions for Pharmacotherapies for Treatment-resistant Bipolar Disorder

    PubMed Central

    Dodd, Seetal; Fernandes, Brisa S.; Dean, Olivia M.

    2015-01-01

    Current pharmacological treatments for bipolar disorder (BD) are limited and efficacy has historically been discovered through serendipity. There is now scope for new drug development, focused on the underlying biology of BD that is not targeted by current therapies. The need for novel treatments is urgent when considering treatment resistant BD, where current therapies have failed. While established drugs targeting the monoamine systems continue to be worthwhile, new biological targets including inflammatory and oxidative an nitrosative pathways, apoptotic and neurotrophic pathways, mitochondrial pathways, the N-methyl-Daspartate (NMDA)–receptor complex, the purinergic system, neuropeptide system, cholinergic system and melatonin pathways are all being identified as potential anchors for the discovery of new agents. Many agents are experimental and efficacy data is limited, however further investigation may provide a new line for drug discovery, previously stalled by lack of corporate interest. PMID:26467413

  10. Water law as an adaptation strategy for global water scarcity in the future

    NASA Astrophysics Data System (ADS)

    Kakinuma, K.; Yoshikawa, S.; Endo, T.; Kanae, S.

    2014-12-01

    Water scarcity due to climate changes and growing human population is a major concern for the world. Adaptation and mitigation strategies should be developed for water scarcity in the future. Previous studies assessed the future water availability by hard technology (e.g., reservoirs, reclaimed and desalinated water plants) as adaptation strategies. On the other hand, soft path such as water law and policy would also be important for adaptation strategies. Water transfers is reallocation of water among water users. For example, distribution of the amount of available water is often heterogeneous especially during drought periods. If water transfers are permitted in these areas, water can be moved from surplus areas/sections to critical need areas/sections. There are several studies which describe the water transfer at the local scales (i.e., water bank in California), however the factors that determined the establishment of water transfer are not clear. If we can detect the factors, it could be used to estimate in which areas the water transfer would come into existence. This in turn would reduce the water stress. Here, we focus on historical interaction between human activity and water environments. Generally, rules of water use are developed by repeated discussion among water users. The frequency of these discussions would be related with their land use, frequency of drought and water resource sizes. For example, people in rice crop area need to discuss about water allocation compared to wheat crop area. Therefore, we examine the relationship between the permission of water transfer and factors such as water environment and human activity in the world.

  11. Part 1: Vesicoureteral reflux treatment: the past, present, and future.

    PubMed

    Hensle, Terry W; Grogg, Amy L

    2007-09-01

    The purpose of this manuscript is to provide clinicians with highlights of key findings pertaining to our current understanding and treatment of the condition of vesicoureteral reflux (VUR). This includes a review of the disease, patient characteristics, current treatment options, challenges for managed care and patients, and opportunities for improvements in care. This is not intended as a comprehensive review of VUR. This manuscript does, however, serve to introduce three additional manuscripts contained within this supplement. The first article in this series is designed to provide the clinician with real-world data pertaining to treatment patterns and outcomes in patients with VUR (Examining pediatric vesicoureteral reflux: a real-world evaluation of treatment patterns and outcomes: Hensle TW, Hyun G, Grogg AL, Eaddy M). The second article considers the efficacy of prophylactic antibiotics in reducing the likelihood of urinary tract infections (UTIs) when compared with endoscopic injection with dextranomer/hyaluronic acid (Endoscopic injection versus antibiotic prophylaxis in the reduction of urinary tract infection in patients with vesicoureteral reflux: Elder JS, Shah MB, Batiste LR, et al.). The third article explores the role medication noncompliance plays in contributing to antibiotic resistance, the consequences associated with resistance (longer lasting illness and costs), and the difficulties with resistance specific to UTI pathogens in children (Considerations regarding the medical management of VUR: what have we really learned?: Koyle MA, Caldamone A). This supplement is intended to provide the clinician with valuable information regarding the treatment patterns, the role of compliance, and the efficacy of treatments for pediatric patients with VUR. PMID:17931478

  12. Treatment of Prosthetic Valve Thrombosis: Current Evidence and Future Directions

    PubMed Central

    Biteker, Murat; Altun, Ibrahim; Basaran, Ozcan; Dogan, Volkan; Yildirim, Birdal; Ergun, Gokhan

    2015-01-01

    Prosthetic heart valve thrombosis (PVT) is a rare but serious complication with high morbidity and mortality. The optimal treatment of the PVT is controversial and depends on thrombus location and size, the patient’s functional class, the risk of surgery or thrombolysis, and the clinician’s experience. Although surgical therapy has been the traditional therapeutic approach, studies with low-dose and slow-infusion rates of thrombolytic agents have revealed excellent results. This article reviews the various treatment options in patient with PVT. PMID:26566406

  13. Update on xerostomia: current treatment modalities and future trends.

    PubMed

    Givens, Edward

    2006-01-01

    This article discusses some of the current treatment modalities available to those who suffer from xerostomia and looks at some therapies currently being explored to ameliorate the condition. With the number of elderly patients in the U.S. population expected to increase--concomitant with the increase in incidence of xerostomia in this group as well as other special patient population groups (that is, postradiation, Sjogren's syndrome, and so forth)--it is increasingly important that dentists maintain an awareness of the clinical implications of xerostomia and a knowledge of appropriate treatment recommendations. PMID:16689063

  14. Future: new strategies for hospitalists to overcome challenges in teaching on today's wards.

    PubMed

    Martin, Shannon K; Farnan, Jeanne M; Arora, Vineet M

    2013-07-01

    Changes in the clinical learning environment under resident duty hours restrictions have introduced a number of challenges on today's wards. Additionally, the current group of medical trainees is largely represented by the Millennial Generation, a generation characterized by an affinity for technology, interaction, and group-based learning. Special attention must be paid to take into account the learning needs of a generation that has only ever known life with duty hours. A mnemonic for strategies to augment teaching rounds for hospitalists was created using an approach that considers time limitations due to duty hours as well as the preferences of Millennial learners. These strategies to enhance learning during teaching rounds are Flipping the Wards, Using Documentation to Teach, Technology-Enabled Teaching, Using Guerilla Teaching Tactics, Rainy Day Teaching, and Embedding Teaching Moments into Rounds (FUTURE). Hospitalists serving as teaching attendings should consider these possible strategies as ways to enhance teaching in the post-duty hours era. These techniques appeal to the preferences of today's learners in an environment often limited by time constraints. Hospitalists are well positioned to champion innovative approaches to teaching in a dynamic and evolving clinical learning environment. PMID:23757149

  15. Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions.

    PubMed

    Otto, Michael W; Kredlow, M Alexandra; Smits, Jasper A J; Hofmann, Stefan G; Tolin, David F; de Kleine, Rianne A; van Minnen, Agnes; Evins, A Eden; Pollack, Mark H

    2016-08-15

    Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning). PMID:26520240

  16. Treatment of Thrombotic Antiphospholipid Syndrome: The Rationale of Current Management—An Insight into Future Approaches

    PubMed Central

    Ubiali, Tania; Meroni, Pier Luigi

    2015-01-01

    Vascular thrombosis and pregnancy morbidity represent the clinical manifestations of antiphospholipid syndrome (APS), which is serologically characterized by the persistent positivity of antiphospholipid antibodies (aPL). Antiplatelet and anticoagulant agents currently provide the mainstay of APS treatment. However, the debate is still open: controversies involve the intensity and the duration of anticoagulation and the treatment of stroke and refractory cases. Unfortunately, the literature cannot provide definite answers to these controversial issues as it is flawed by many limitations, mainly due to the recruitment of patients not fulfilling laboratory and clinical criteria for APS. The recommended therapeutic management of different aPL-related clinical manifestations is hereby presented, with a critical appraisal of the evidence supporting such approaches. Cutting edge therapeutic strategies are also discussed, presenting the pioneer reports about the efficacy of novel pharmacological agents in APS. Thanks to a better understanding of aPL pathogenic mechanisms, new therapeutic targets will soon be explored. Much work is still to be done to unravel the most controversial issues about APS management: future studies are warranted to define the optimal management according to aPL risk profile and to assess the impact of a strict control of cardiovascular risk factors on disease control. PMID:26075289

  17. Inflammation and human cerebral aneurysms: current and future treatment prospects

    PubMed Central

    Hudson, Joseph S; Hoyne, Danielle S; Hasan, David M

    2013-01-01

    The formation of cerebral aneurysms and their rupture propensity is of immediate clinical importance. Current management includes observation with expectant management, microsurgical clipping and/or endovascular coiling. The surgical options are invasive and are not without increased risk despite the technological advances. Recent human and animal studies have shown that inflammation plays a critical role in aneurysm formation and progression to rupture. Modulating this inflammatory process may prove to be clinically significant. This review will discuss cerebral aneurysm pathogenesis with a focus on current and future research of potential use of pharmaceutical agents that attenuate inflammation in the aneurysm wall leading to decreased risk of aneurysm rupture. PMID:24376373

  18. [Strategies for the treatment of postoperative sternal infections].

    PubMed

    Akil, A; Schnorr, P; Wiebe, K

    2016-02-01

    Postoperative sternal infections are associated with significant morbidity and mortality. An incidence of up to 8 % has to be expected. Typically, a highly inflammatory acute infection with a marked soft tissue component is observed. However, the infection may also be present as a less symptomatic reaction and localised chronic osteomyelitis with fistula formation. The treatment strategy for a deep sternal wound infection consists of several steps. A radical debridement of the wound requires the opening of all abscesses, the resection of non-vital bone and the removal of all infected allomaterial. This is followed by a period of VAC therapy (Vacuum-Assisted Closure Therapy) for infection treatment and conditioning of the wound. Secondary closure of the wound may be planned only after the infection is completely controlled. The sternum is stabilised by osteosynthesis. Sternal defects are covered. In most cases adequate soft tissue coverage is achieved by mobilisation of both pectoral muscles together with the precostal soft tissues. Following resection of the sternum, the reconstruction of the thoracic wall requires the implantation of material for stabilisation as well as soft tissue coverage. For complicated or large defects various muscle flaps and the omentum majus have been advocated. The latissimus dorsi muscle with skin is the muscle flap most frequently used. PMID:26492536

  19. Comparison of treatment strategies for Space Motion Sickness

    NASA Astrophysics Data System (ADS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    Treatment strategies for Space Motion Sickness (SMS) were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of SMS were graded as mild, moderate, or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular i.m. or suppository routes. Scopdex has been given preflight as prophylaxis for SMS, but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only 3 crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with i.m. promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 1-2h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96h. We conclude that promethazine is an effective treatment of SMS symptoms inflight. NASA policy currently recommends treating crewmembers with SMS after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  20. Tissue Engineering Strategies as Tools for Personalized Meningioma Treatment.

    PubMed

    Ferroni, Letizia; Della Puppa, Alessandro; D'Avella, Domenico; Isola, Maurizio; Scienza, Renato; Gardin, Chiara; Zavan, Barbara

    2015-07-01

    Pharmacogenomics, the science of how genetic makeup influences an individual's reaction to drugs, is an innovative tool for providing critical insights into how a patient will respond to a particular treatment. In the present work, we constructed cancer-like tissues to be used as tools for determining the most effective drug for an individual patient. Using tissue engineering strategies, we generated two different solid tumor-like tissues in vitro, a neuronal tumor (meningioma) and a nonmelanoma skin cancer. Samples were tested by both histological and genetic approaches (using a comparative genomic hybridization array, and the relative World Health Organization classification of the samples was compared with the results obtained by the molecular analyses. Our data confirmed the ability of the cells to maintain their phenotype in three-dimensional scaffolds as well as the strong relationship between chromosomal alterations and histological malignancy grades. We then validated the in vitro construction of tumor-like tissues as a potential tool for developing personalized drug treatments. PMID:25894852

  1. A review of current treatment strategies for gestational diabetes mellitus

    PubMed Central

    Kelley, Kristi W; Carroll, Dana G; Meyer, Allison

    2015-01-01

    Approximately 90% of diabetes cases in pregnant women are considered gestational diabetes mellitus (GDM). It is well known that uncontrolled glucose results in poor pregnancy outcomes in both the mother and fetus. Worldwide there are many guidelines with recommendations for appropriate management strategies for GDM once lifestyle modifications have been instituted and failed to achieve control. The efficacy and particularly the safety of other treatment modalities for GDM has been the source of much debate in recent years. Studies that have demonstrated the safety and efficacy of both glyburide and metformin in the management of patients with GDM will be reviewed. There is a lack of evidence with other oral and injectable non-insulin agents to control blood glucose in GDM. The role of insulin will be discussed, with emphasis on insulin analogs. Ideal patient characteristics for each treatment modality will be reviewed. In addition, recommendations for postpartum screening of patients will be described as well as recommendations for use of agents to manage subsequent type 2 diabetes in patients who are breastfeeding. PMID:26213555

  2. Various Strategies for Pain-Free Root Canal Treatment

    PubMed Central

    Parirokh, Masoud; V. Abbott, Paul

    2014-01-01

    Introduction: Achieving successful anesthesia and performing pain-free root canal treatment are important aims in dentistry. This is not always achievable and therefore, practitioners are constantly seeking newer techniques, equipments, and anesthetic solutions for this very purpose. The aim of this review is to introduce strategies to achieve profound anesthesia particularly in difficult cases. Materials and Methods: A review of the literature was performed by electronic and hand searching methods for anesthetic agents, techniques, and equipment. The highest level of evidence based investigations with rigorous methods and materials were selected for discussion. Results: Numerous studies investigated to pain management during root canal treatment; however, there is still no single technique that will predictably provide profound pulp anesthesia. One of the most challenging issues in endodontic practice is achieving a profound anesthesia for teeth with irreversible pulpitis especially in mandibular posterior region. Conclusion: According to most investigations, achieving a successful anesthesia is not always possible with a single technique and practitioners should be aware of all possible alternatives for profound anesthesia. PMID:24396370

  3. Strategies for implementation of harm reduction in treatment settings.

    PubMed

    Denning, P

    2001-01-01

    Harm reduction is a set of strategies that we all use everyday to protect us from the harms of living in a complex world. Central to the principles of harm reduction is the need to respect the client's autonomy and develop a relationship of mutual collaboration with the goal of reducing drug- and alcohol-related harm. Additional principles stress the need to develop a hierarchy of client needs, a list that includes all other services, with the importance for each set by the client. Harm reduction implementation includes a range of interventions including abstinence. Some interventions are controversial, including needle exchange, but most are traditional health promotion activities such as videos, health fairs, and drug education. Essential to implementing harm reduction is a recognition that, even for those who wish to become abstinent, this goal is difficult to achieve and maintain. We must acknowledge this and stop the practice of imposing punitive sanctions on clients who use drugs while in treatment. Exclusion or expulsion from treatment settings does nothing to reduce drug use and greatly increases the harm to the client. In conclusion, just as we need to respect diversity among our clients, staff must find a way to respect each others' ideas and concerns as we develop new ways to implement harm reduction in our work. PMID:11332997

  4. Current Research Therapeutic Strategies for Alzheimer's Disease Treatment

    PubMed Central

    Folch, Jaume; Petrov, Dmitry; Ettcheto, Miren; Abad, Sonia; Sánchez-López, Elena; García, M. Luisa; Olloquequi, Jordi; Beas-Zarate, Carlos; Auladell, Carme; Camins, Antoni

    2016-01-01

    Alzheimer's disease (AD) currently presents one of the biggest healthcare issues in the developed countries. There is no effective treatment capable of slowing down disease progression. In recent years the main focus of research on novel pharmacotherapies was based on the amyloidogenic hypothesis of AD, which posits that the beta amyloid (Aβ) peptide is chiefly responsible for cognitive impairment and neuronal death. The goal of such treatments is (a) to reduce Aβ production through the inhibition of β and γ secretase enzymes and (b) to promote dissolution of existing cerebral Aβ plaques. However, this approach has proven to be only modestly effective. Recent studies suggest an alternative strategy centred on the inhibition of the downstream Aβ signalling, particularly at the synapse. Aβ oligomers may cause aberrant N-methyl-D-aspartate receptor (NMDAR) activation postsynaptically by forming complexes with the cell-surface prion protein (PrPC). PrPC is enriched at the neuronal postsynaptic density, where it interacts with Fyn tyrosine kinase. Fyn activation occurs when Aβ is bound to PrPC-Fyn complex. Fyn causes tyrosine phosphorylation of the NR2B subunit of metabotropic glutamate receptor 5 (mGluR5). Fyn kinase blockers masitinib and saracatinib have proven to be efficacious in treating AD symptoms in experimental mouse models of the disease. PMID:26881137

  5. Adapting to a Changing Colorado River: Making Future Water Deliveries More Reliable Through Robust Management Strategies

    NASA Astrophysics Data System (ADS)

    Groves, D.; Bloom, E.; Fischbach, J. R.; Knopman, D.

    2013-12-01

    The U.S. Bureau of Reclamation and water management agencies representing the seven Colorado River Basin States initiated the Colorado River Basin Study in January 2010 to evaluate the resiliency of the Colorado River system over the next 50 years and compare different options for ensuring successful management of the river's resources. RAND was asked to join this Basin Study Team in January 2012 to help develop an analytic approach to identify key vulnerabilities in managing the Colorado River basin over the coming decades and to evaluate different options that could reduce this vulnerability. Using a quantitative approach for planning under uncertainty called Robust Decision Making (RDM), the RAND team assisted the Basin Study by: identifying future vulnerable conditions that could lead to imbalances that could cause the basin to be unable to meet its water delivery objectives; developing a computer-based tool to define 'portfolios' of management options reflecting different strategies for reducing basin imbalances; evaluating these portfolios across thousands of future scenarios to determine how much they could improve basin outcomes; and analyzing the results from the system simulations to identify key tradeoffs among the portfolios. This talk will describe RAND's contribution to the Basin Study, focusing on the methodologies used to to identify vulnerabilities for Upper Basin and Lower Basin water supply reliability and to compare portfolios of options. Several key findings emerged from the study. Future Streamflow and Climate Conditions Are Key: - Vulnerable conditions arise in a majority of scenarios where streamflows are lower than historical averages and where drought conditions persist for eight years or more. - Depending where the shortages occur, problems will arise for delivery obligations for the upper river basin and the lower river basin. The lower river basin is vulnerable to a broader range of plausible future conditions. Additional Investments in

  6. Empirically Supported Treatment Endeavour: A Successful Future or Inevitable Debacle?

    ERIC Educational Resources Information Center

    Foley, Jessica M.

    2004-01-01

    The Empirically Supported Treatment (EST) endeavour began with and has persisted through prodigious skepticism among practising clinical psychologists. Despite such criticism, however, the advent of managed care guidelines, growing emphasis on biological psychiatry, promotion of scientific interests, and the need for better patient care have…

  7. Strategy for the treatment of Helicobacter pylori infection.

    PubMed

    Shiota, Seiji; Yamaoka, Yoshio

    2014-01-01

    The eradication of Helicobacter pylori not only heals peptic ulcers but also prevents their recurrence and reduces the risk of development of gastric cancer and other H. pylori-associated disorders. H. pylori eradication heals gastritis and may prevent the spread of infection, reducing the future costs required for the treatment of subsequent H. pylori-associated diseases. There are various guidelines for the management of H. pylori infection worldwide, such as the guidelines of the American College of Gastroenterology, Maastricht IV, the Second Asia-Pacific Consensus Conference, and Japan. The Japanese health insurance system approved H. pylori eradication therapy for H. pylori-related chronic gastritis in 2013. Triple therapy regimens comprising 1 proton pump inhibitor and 2 antimicrobial agents such as amoxicillin, clarithromycin, metronidazole, levofloxacin, or tetracycline have been widely used to eradicate this bacterium. The rate of successful eradication has declined owing to the increased rate of drug resistance stemming from the wide usage of antibiotics. This issue is of particular relevance with regard to clarithromycin. In worldwide, clarithromycin-based triple therapy should be abandoned, as it is no longer effective. Quadruple therapy and sequential therapy are reasonable alternatives for initial therapy. First-line treatment should be recommended on the basis of an understanding of the local prevalence of H. pylori antimicrobial resistance. PMID:24180402

  8. Current management strategies and emerging treatments for functional dyspepsia.

    PubMed

    Camilleri, Michael; Stanghellini, Vincenzo

    2013-03-01

    Functional dyspepsia refers to painful and nonpainful symptoms that are perceived to arise in the upper digestive tract but are not secondary to organic, systemic or metabolic diseases. The symptoms of this syndrome often overlap with those of GERD and IBS, making its management far from simple. If Helicobacter pylori infection is diagnosed in patients with functional dyspepsia, it should be treated. In patients with mild or intermittent symptoms, reassurance and lifestyle advice might be sufficient; in patients not responding to these measures, or in those with more severe symptoms, drug therapy should be considered. Both PPIs and prokinetics can be used in initial empirical pharmacotherapy based on symptom patterns--a PPI is more likely to be effective in the presence of retrosternal or epigastric burning or epigastric pain, whereas a prokinetic is more effective in dyspepsia with early satiation or postprandial fullness. Although combinations of PPIs and prokinetics might have additive symptomatic effects, single-drug therapy is initially preferable. Antidepressants or referral to a psychiatrist or psychotherapist can be considered in nonresponders and in those whose symptoms have a marked effect on daily functioning. Despite extensive research, functional dyspepsia treatment often remains unsatisfactory. Better characterization of dyspeptic subgroups and understanding of underlying mechanisms will enable treatment advances to be made in the future. PMID:23381190

  9. Current and emerging treatment strategies for Duchenne muscular dystrophy.

    PubMed

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  10. Current and emerging treatment strategies for Duchenne muscular dystrophy

    PubMed Central

    Mah, Jean K

    2016-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying

  11. Application of nitrogen sufficiency conversion strategy for microalgae-based ammonium-rich wastewater treatment.

    PubMed

    Wang, Jinghan; Zhou, Wenguang; Yang, Haizhen; Ruan, Roger

    2016-10-01

    Ammonium ([Formula: see text]-N)-rich wastewater, a main cause for eutrophication, can serve as a promising medium for fast microalgae cultivation with efficient [Formula: see text]-N removal. To achieve this goal, a well-controlled three-stage treatment process was developed. Two trophic modes (mixotrophy and heterotrophy) in Stage 1 and Stage 2, with two nitrogen availability conditions (N sufficient and N deprived) in Stage 2, and different [Formula: see text]-N concentrations in Stage 3 were compared to investigate the effects of nitrogen sufficiency conversion on indigenous strain UMN266 for [Formula: see text]-N removal. Results showed that mixotrophic cultures in the first two stages with N deprivation in Stage 2 was the optimum treatment strategy, and higher [Formula: see text]-N concentration in Stage 3 facilitated both microalgal growth and [Formula: see text]-N removal, with average and maximum biomass productivity of 55.3 and 161.0 mg L(-1) d(-1), and corresponding removal rates of 4.2 and 15.0 mg L(-1) d(-1), respectively, superior to previously published results. Observations of intracellular compositions confirmed the optimum treatment strategy, discovering excellent starch accumulating property of strain UMN266 as well. Combination of bioethanol production with the proposed three-stage process using various real wastewater streams at corresponding stages was suggested for future application. PMID:26979571

  12. Future scientific drilling in the Arctic Ocean: Key objectives, areas, and strategies

    NASA Astrophysics Data System (ADS)

    Stein, R.; Coakley, B.; Mikkelsen, N.; O'Regan, M.; Ruppel, C.

    2012-04-01

    Past, Present and Future Changes in Arctic Terrestrial and Marine Systems" (Kananaskis, Alberta/Canada, February 2012). During these workshops, key areas and key scientific themes as well as drilling and site-survey strategies were discussed. Major scientific themes for future Arctic drilling will include: - The Arctic Ocean during the transition from greenhouse to icehouse conditions and millennial scale climate changes; - Physical and chemical changes of the evolving Polar Ocean and Arctic gateways; - Impact of Pleistocene/Holocene warming and sea-level rise on upper continental slope and shelf gas hydrates and on shelf permafrost; - Land-ocean interactions; - Tectonic evolution and birth of the Arctic Ocean basin: Arctic ridges, sea floor spreading and global lithosphere processes. When thinking about future Arctic drilling, it should be clearly emphasized that for the precise planning of future Arctic Ocean drilling campaigns, including site selection, evaluation of proposed drill sites for safety and environmental protection, etc., comprehensive site survey data are needed first. This means that the development of a detailed site survey strategy is a major challenge for the coming years. Here, an overview of perspectives and plans for future Arctic Ocean drilling will be presented.

  13. The antimicrobial armamentarium: evaluating current and future treatment options.

    PubMed

    Bosso, John A

    2005-10-01

    The development and introduction of new antibiotics has, unfortunately, not kept pace with the development of bacterial resistance, and the need for new agents is becoming acute. Although some currently marketed agents remain valuable tools in the treatment of infectious diseases, few new drugs have reached the market in the last decade. In recent years, antibiotics with activity against certain problematic resistant bacteria such as methicillin-resistant Staphylococcus aureus, including linezolid and daptomycin, have been approved for clinical practice. Recently, tigecycline, a minocycline derivative, received approval by the United States Food and Drug Administration for treatment of complicated skin and skin structure and intraabdominal infections; the agent is also active against a variety of multidrug-resistant bacteria. Of the other agents in phase III development, ceftobiprole--a cephalosporin, and faropenem and doripenem--both carbapenems, have wide antibacterial spectra. Antimicrobial agents in the pipeline with marked gram-positive activity include dalbavancin, telavancin, and oritavancin. PMID:16178676

  14. Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives.

    PubMed

    Bregou Bourgeois, Aline; Aubry-Rozier, Bérengère; Bonafé, Luisa; Laurent-Applegate, Lee; Pioletti, Dominique P; Zambelli, Pierre-Yves

    2016-01-01

    Osteogenesis imperfecta is an inherited connective tissue disorder with wide phenotypic and molecular heterogeneity. A common issue associated with the molecular abnormality is a disturbance in bone matrix synthesis and homeostasis inducing bone fragility. In very early life, this can lead to multiple fractures and progressive bone deformities, including long bone bowing and scoliosis. Multidisciplinary management improves quality of life for patients with osteogenesis imperfecta. It consists of physical therapy, medical treatment and orthopaedic surgery as necessary. Medical treatment consists of bone-remodelling drug therapy. Bisphosphonates are widely used in the treatment of moderate to severe osteogenesis imperfecta, from infancy to adulthood. Other more recent drug therapies include teriparatide and denosumab. All these therapies target the symptoms and have effects on the mechanical properties of bone due to modification of bone remodelling, therefore influencing skeletal outcome and orthopaedic surgery. Innovative therapies, such as progenitor and mesenchymal stem cell transplantation, targeting the specific altered pathway rather than the symptoms, are in the process of development. PMID:27346233

  15. Current primary open-angle glaucoma treatments and future directions

    PubMed Central

    Beidoe, Gabriel; Mousa, Shaker A

    2012-01-01

    Primary open-angle glaucoma (POAG) is a leading cause of blindness with no known cure. Management of the disease focuses on lowering intraocular pressure (IOP) with current classes of drugs like prostaglandin analogs, beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. These treatments have not helped all patients. Some patients continue to experience deterioration in the optic nerve even though their IOPs are within the normal range. New views have surfaced about other pathophysiological processes (such as oxidative stress, vascular dysfunction, and retinal cell apoptosis) being involved in POAG progression, and adjunctive treatments with drugs like memantine, bis(7)-tacrine, nimodipine, and mirtogenol are advocated. This review examines the current and proposed treatments for POAG. Some of the proposed drugs (bis(7)-tacrine, nimodipine, vitamin E, and others) have shown good promise, mostly as monotherapy in various clinical trials. It is recommended that both the current and proposed drugs be put through further robust trials in concurrent administration and evaluated. PMID:23118520

  16. Chronic urticaria: aetiology, management and current and future treatment options.

    PubMed

    Kozel, Martina M A; Sabroe, Ruth A

    2004-01-01

    Chronic urticaria is a common condition that can be very disabling when severe. A cause for chronic idiopathic urticaria (CIU) is only infrequently identified. Potential causes include reactions to food and drugs, infections (rarely) and, apart from an increased incidence of thyroid disease, uncomplicated urticaria is not usually associated with underlying systemic disease or malignancy. About one-third of patients with CIU have circulating functional autoantibodies against the high affinity IgE receptor or against IgE, although it is not known why such antibodies are produced, or how the presence of such antibodies alters the course of the disease or response to treatment. There are only a few publications relating to childhood urticaria, but it is probably similar to the adult form, except that adult urticaria is more common. The diagnosis is based on patient history and it is vital to spend time documenting this in detail. Extensive laboratory tests are not required in the vast majority of patients. Chronic urticaria resolves spontaneously in 30-55% of patients within 5 years, but it can persist for many years. Treatment is aimed firstly at avoiding underlying causative or exacerbating factors. Histamine H1 receptor antagonists remain the mainstay of oral treatment for all forms of urticaria. The newer low-sedating antihistamines desloratadine, fexofenadine, levocetirizine and mizolastine should be tried first. Sedating antihistamines have more adverse effects but are useful if symptoms are causing sleep disturbance. Low-dose dopexin is effective and especially suitable for patients with associated depression. There is controversy as to whether the addition of an histamine H2 receptor antagonist or a leukotriene antagonist is helpful. For CIU, second-line agents include ciclosporin (cyclosporine) [which is effective in approximately 75% of patients], short courses of oral corticosteroids, intravenous immunoglobulins and plasmapheresis, although the last two were

  17. Current and future systemic treatment options in metastatic pancreatic cancer

    PubMed Central

    Arslan, Cagatay

    2014-01-01

    Although pancreatic adenocarcinoma is the fourth leading cause of cancer death, only modest improvement has been observed in the past two decades, single agent gemcitabine has been the only standard treatment in patients with advanced disease. Recently newer agents such as nab-paclitaxel, nimotuzumab and regimens such as FOLFIRINOX have been shown to have promising activity being superior to gemcitabine as a single agent. With better understanding of tumour biology coupled with the improvements in targeted and immunotherapies, there is increasing expectation for better response rates and extended survival in pancreatic cancer. PMID:25083302

  18. Ecological models supporting environmental decision making: a strategy for the future

    USGS Publications Warehouse

    Schmolke, Amelie; Thorbek, Pernille; DeAngelis, Donald L.; Grimm, Volker

    2010-01-01

    Ecological models are important for environmental decision support because they allow the consequences of alternative policies and management scenarios to be explored. However, current modeling practice is unsatisfactory. A literature review shows that the elements of good modeling practice have long been identified but are widely ignored. The reasons for this might include lack of involvement of decision makers, lack of incentives for modelers to follow good practice, and the use of inconsistent terminologies. As a strategy for the future, we propose a standard format for documenting models and their analyses: transparent and comprehensive ecological modeling (TRACE) documentation. This standard format will disclose all parts of the modeling process to scrutiny and make modeling itself more efficient and coherent.

  19. A Survey of Strategies to Modulate the Bone Morphogenetic Protein Signaling Pathway: Current and Future Perspectives

    PubMed Central

    2016-01-01

    Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the TGF-β family of ligands and are unequivocally involved in regulating stem cell behavior. Appropriate regulation of canonical BMP signaling is critical for the development and homeostasis of numerous human organ systems, as aberrations in the BMP pathway or its regulation are increasingly associated with diverse human pathologies. In this review, we provide a wide-perspective on strategies that increase or decrease BMP signaling. We briefly outline the current FDA-approved approaches, highlight emerging next-generation technologies, and postulate prospective avenues for future investigation. We also detail how activating other pathways may indirectly modulate BMP signaling, with a particular emphasis on the relationship between the BMP and Activin/TGF-β pathways. PMID:27433166

  20. Past Strategies and Future Directions for Identifying AMP-Activated Protein Kinase (AMPK) Modulators

    PubMed Central

    Sinnett, Sarah E.; Brenman, Jay E.

    2014-01-01

    AMP-activated protein kinase (AMPK) is a promising therapeutic target for cancer, type II diabetes, and other illnesses characterized by abnormal energy utilization. During the last decade, numerous labs have published a range of methods for identifying novel AMPK modulators. The current understanding of AMPK structure and regulation, however, has propelled a paradigm shift in which many researchers now consider ADP to be an additional regulatory nucleotide of AMPK. How can the AMPK community apply this new understanding of AMPK signaling to translational research? Recent insights into AMPK structure, regulation, and holoenzyme-sensitive signaling may provide the hindsight needed to clearly evaluate the strengths and weaknesses of past AMPK drug discovery efforts. Improving future strategies for AMPK drug discovery will require pairing the current understanding of AMPK signaling with improved experimental designs. PMID:24583089

  1. Future therapeutic treatment of COPD: Struggle between oxidants and cytokines

    PubMed Central

    de Boer, Willem I; Yao, Hongwei; Rahman, Irfan

    2007-01-01

    Chronic obstructive pulmonary disease (COPD) is a global health problem. Being a progressive disease characterized by inflammation and predominantly caused by tobacco smoking, it deteriorates pulmonary and skeletal muscle functioning, and reduces physical behavior, societal participation and quality of life. During the last two decades studies were focused on the airway and systemic inflammation, oxidative stress, and airway and/or parenchymal remodeling. Macrophages, neutrophils and T cells are thought to be important key players, as well as structural cells like fibroblasts, epithelial, endothelial and smooth muscle cells. Mediators and proteins including cytokines, chemokines, growth factors, proteinases, and oxidants seem to be involved differentially in its pathogenesis. Current pharmacological treatments are directed to reducing airway inflammation, boosting the endogenous levels of anti-oxidants and relieving airway contraction and sputum production. Most agents were primarily used for treating asthma. But in contrast to asthma, these treatments are not very effective in COPD. As a result, novel more specifically acting interventional drugs with less side effects are being developed to treat chronic inflammatory diseases, including COPD. This review highlights studies on novel or potential drug antioxidants such as dietary antioxidants supplementation, N-acetyl-L-cysteine, N-acystelyn, endosteine, antioxidant enzyme mimetics, and anti-inflammatory agents like antagonists of cytokines, such as tumor necrosis factor (TNF)-α, CXCL8, and CCL2, and inhibitors of signal transduction proteins including phosphodiesterase 4, MAPK p38, Pl-3k, and NFκB. PMID:18229560

  2. Future of the Prevention and Treatment of Coronary Artery Disease.

    PubMed

    Steg, Philippe Gabriel; Ducrocq, Grégory

    2016-04-25

    With ongoing progress in the prevention and treatment of coronary artery disease (CAD), a continued decrease in prevalence and lethality is expected in high-income countries. Prevention will include lipid-lowering, antithrombotic and anti-inflammatory therapies. With respect to the former, potent, safe and prolonged drugs (such as generic forms of PCSK9 inhibitors relying on monoclonal antibodies or miRNA) should result in a decreased incidence of acute coronary syndromes. Another key aspect will be the ability to identify genetic predictors of CAD and therefore implement targeted personalized prevention early in life. Curative treatment will involve a short course of potent and reversible antithrombotics, but long-term therapy will rely on the ability to stabilize or even regress plaque (eg, using PCSK9 inhibition or modified high-density lipoprotein infusions or anti-inflammatory therapies). Antithrombotic therapy will rely on highly reversible agents (or agents with specific titratable antagonists), and on personalized therapies in which the doses, combinations and duration of therapy will be determined differentially for each patient on the basis of clinical characteristics, genetic profiling and biomarkers. Finally, the need for revascularization in stable CAD will be rare, given the expected progress in prevention. The main challenge, 20 years from now, is likely to be the provision of such effective care at acceptable costs in low- and middle-income countries. (Circ J 2016; 80: 1067-1072). PMID:27063295

  3. Current and future treatment options for polycythemia vera.

    PubMed

    Griesshammer, Martin; Gisslinger, Heinz; Mesa, Ruben

    2015-06-01

    Patients with polycythemia vera (PV), a myeloproliferative neoplasm characterized by an elevated red blood cell mass, are at high risk of vascular and thrombotic complications and have reduced quality of life due to a substantial symptom burden that includes pruritus, fatigue, constitutional symptoms, microvascular disturbances, and bleeding. Conventional therapeutic options aim at reducing vascular and thrombotic risk, with low-dose aspirin and phlebotomy as first-line recommendations for patients at low risk of thrombotic events and cytoreductive therapy (usually hydroxyurea or interferon alpha) recommended for high-risk patients. However, long-term effective and well-tolerated treatments are still lacking. The discovery of mutations in Janus kinase 2 (JAK2) as the underlying molecular basis of PV has led to the development of several targeted therapies, including JAK inhibitors, and results from the first phase 3 clinical trial with a JAK inhibitor in PV are now available. Here, we review the current treatment landscape in PV, as well as therapies currently in development. PMID:25832853

  4. Future treatment options with capecitabine in solid tumours.

    PubMed

    Wilke, H

    2002-02-01

    The oral fluoropyrimidine, capecitabine is attracting great interest in the context of tumour-selective therapy and rationally designed combination regimens. Agents such as taxanes upregulate thymidine phosphorylase (TP), and there is therefore a clear rationale for their combination with capecitabine. Preclinical studies of capecitabine/taxane combination therapy demonstrated synergistic antitumour activity and phase I studies showed encouraging efficacy. Therefore, a randomised, phase III trial (docetaxel versus docetaxel/capecitabine) has been initiated in anthracycline-refractory metastatic breast cancer patients. Recruitment is complete. In colorectal cancer, capecitabine/oxaliplatin combination therapy is promising and a phase I, dose-finding trial has been conducted in patients with refractory metastatic solid tumours. A similar trial has evaluated capecitabine/irinotecan combination treatment. Capecitabine is also being investigated as adjuvant therapy for colorectal and breast cancers. The primary objective of the ongoing X-ACT trial in almost 2000 Dukes' C colon cancer patients is to demonstrate at least equivalent disease-free survival between capecitabine and the Mayo Clinic regimen. In addition, the CALGB is planning a randomised, phase III trial of capecitabine versus doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/5-fluorouracil (CMF) as adjuvant treatment in high-risk, node-negative breast cancer patients aged >65 years. PMID:11841932

  5. Targeted treatment of pruritus: a look into the future.

    PubMed

    Tey, H L; Yosipovitch, G

    2011-07-01

    Recent advances in pruritus research have elucidated mediators and neuronal pathways involved in itch transmission, and this fast emerging knowledge may possibly be translated into new therapies in the near future. In the skin and peripheral nerves, potential mediator and receptor therapeutic targets include the H4 histamine receptor, protease-activated receptor 2, serine proteases, cathepsin S, peripheral mu- and kappa-opioid receptors, interleukin-31, transient receptor potential vanilloid 1 and 3, fatty acid amide hydrolase, nerve growth factor and its receptor, acetylcholine, and the Mas-related G protein-coupled receptors. In the spinal cord, gastrin-related peptide and its receptor, as well as substance P and its receptor neurokinin receptor-1 serve as potential therapeutic targets. In the brain, reduction of itch perception and modulation of emotions may possibly be achieved through drugs acting on the anterior cingulate cortex. Clinically, management of pruritus should be instituted early and should address the skin pathology, peripheral neuropathy, central sensitization, and the cognito-affective aspects of the disease. PMID:21219293

  6. Targeted treatment of pruritus - a look into the future

    PubMed Central

    Tey, H.L.; Yosipovitch, G

    2011-01-01

    Recent advances in pruritus research have elucidated mediators and neuronal pathways involved in itch transmission and this fast-emerging knowledge may possibly be translated into new therapies in the near future. In the skin and peripheral nerves, potential mediator and receptor therapeutic targets include the H4 histamine receptor, proteinase-activated receptor 2, serine proteases, Cathepsin S, peripheral mu- and kappa-opioid receptors, interleukin-31, transient receptor potential vanilloid 1 and 3, fatty acid amide hydrolase, nerve growth factor and its receptor, acetylcholine, and the Mas-related G-protein-coupled receptor. In the spinal cord, gastrin-related peptide and its receptor, as well as substance P and its receptor neurokinin receptor-1 serve as potential therapeutic targets. In the brain, reduction of itch perception and modulation of emotions may possibly be achieved through drugs acting on the anterior cingulate cortex. Clinically, management of pruritus should be instituted early and address the skin pathology, peripheral neuropathy, central sensitisation, and the cognito-affective aspects of the disease. PMID:21219293

  7. District heating and cooling systems of the future: Strategies for global change

    SciTech Connect

    McCabe, R.E.

    1996-12-31

    The future of district heating and cooling, also known as district energy, will be a function of economic and regulatory forces in the US. Typically a district energy system provides thermal energy in the form of steam, hot water, or chilled water from a central plant, and distributes the energy through pipes to two or more buildings. At the present time, district energy is under-utilized and serves only 1.3 percent of US energy needs, providing a total of 1.1 quadrillion Btu of energy annually. A brief review of the historical development of district energy, the status of the technology in the US, and a few basics on world energy consumption lead in to the economic and environmental advantages of district energy. District energy systems have been retrofitted to comply wit h the regulations of the Clean Air Act (CAA); presently emissions of greenhouse gases, such as CO{sub 2}, are not regulated by the CAA. If the results of ongoing investigation on global climate change determine that regulation is warranted, several strategies exist for district energy systems to offer significant reductions in greenhouse gas emissions. Projections of district energy`s reaction to the ongoing forces are possible with the use of energy consumption forecasts through the year 2015, and a discussion of trend setting concepts being applied involving: gas turbines, cogeneration, fuel cells, chillers, advanced transmission fluids, renewable energies, and CO{sub 2} capture. District energy has potential to be an important part of the evolving strategies for global climate change. For this reason, combined with technology advancements and a supportive economic climate, a new era in district energy has begun. Growth and development of district energy into the foreseeable future is expected to be strong.

  8. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment

    PubMed Central

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum – Saint John’s wort – has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID:27200032

  9. Radiation treatment of brain tumors: Concepts and strategies

    SciTech Connect

    Marks, J.E. )

    1989-01-01

    Ionizing radiation has demonstrated clinical value for a multitude of CNS tumors. Application of the different physical modalities available has made it possible for the radiotherapist to concentrate the radiation in the region of the tumor with relative sparing of the surrounding normal tissues. Correlation of radiation dose with effect on cranial soft tissues, normal brain, and tumor has shown increasing effect with increasing dose. By using different physical modalities to alter the distribution of radiation dose, it is possible to increase the dose to the tumor and reduce the dose to the normal tissues. Alteration of the volume irradiated and the dose delivered to cranial soft tissues, normal brain, and tumor are strategies that have been effective in improving survival and decreasing complications. The quest for therapeutic gain using hyperbaric oxygen, neutrons, radiation sensitizers, chemotherapeutic agents, and BNCT has met with limited success. Both neoplastic and normal cells are affected simultaneously by all modalities of treatment, including ionizing radiation. Consequently, one is unable to totally depopulate a tumor without irreversibly damaging the normal tissues. In the case of radiation, it is the brain that limits delivery of curative doses, and in the case of chemical additives, it is other organ systems, such as bone marrow, liver, lung, kidneys, and peripheral nerves. Thus, the major obstacle in the treatment of malignant gliomas is our inability to preferentially affect the tumor with the modalities available. Until it is possible to directly target the neoplastic cell without affecting so many of the adjacent normal cells, the quest for therapeutic gain will go unrealized.72 references.

  10. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. PMID:26645661

  11. Comparison of treatment strategies for Space Motion Sickness

    NASA Technical Reports Server (NTRS)

    Davis, J. R.; Jennings, R. T.; Beck, B. G.

    1992-01-01

    Treatment strategies for Space Motion Sickness were compared using the results of postflight oral debriefings. Standardized questionnaires were administered to all crewmembers immediately following Space Shuttle flights by NASA flight surgeons. Cases of Space Motion Sickness were graded as mild, moderate or severe based on published criteria, and medication effectiveness was judged based on subjective reports of symptom relief. Since October 1989, medication effectiveness is reported inflight through Private Medical Conferences with the crew. A symptom matrix was analyzed for 19 crewmembers treated with an oral combination of scopolamine and dextroamphetamine (scopdex) and 15 crewmembers treated with promethazine delivered by intramuscular (IM) or suppository routes. Scopdex has been given preflight as prophaxis for Space Motion Sickness but analysis showed delayed symptom presentation in 9 crewmembers or failed to prevent symptoms in 7. Only three crewmembers who took scopdex had no symptoms inflight. Fourteen out of 15 crewmembers treated with IM promethazine and 6 of 8 treated with promethazine suppositories after symptom development had immediate (within 12 h) symptom relief and required no additional medication. There were no cases of delayed symptom presentation in the crewmembers treated with promethazine. This response is in contrast to untreated crewmembers who typically have slow symptom resolution over 72-96 h. We conclude that promethazine is an effective treatment of Space Motion Sickness symptoms inflight. NASA policy currently recommends treating crewmembers with Space Motion Sickness after symptom development, and no longer recommends prophylaxis with scopdex due to delayed symptom development and apparent variable absorption of oral medications during early flight days.

  12. Solitary Large Hepatocellular Carcinoma: Staging and Treatment Strategy

    PubMed Central

    Liu, Po-Hong; Su, Chien-Wei; Hsu, Chia-Yang; Hsia, Cheng-Yuan; Lee, Yun-Hsuan; Huang, Yi-Hsiang; Lee, Rheun-Chuan; Lin, Han-Chieh; Huo, Teh-Ia

    2016-01-01

    Background & Aims Controversies exist on staging and management of solitary large (>5 cm) hepatocellular carcinoma (HCC). This study aims to evaluate the impact of tumor size on Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy. Methods BCLC stage A and B patients were included and re-classified as single tumor 2–5 cm or up to 3 tumors ≤3 cm (group A; n = 657), single tumor >5 cm (group SL; n = 224), and multiple tumors >3 cm (group B; n = 351). Alternatively, 240 and 229 patients with solitary large HCC regardless of tumor stage received surgical resection (SR) and transarterial chemoembolization (TACE), respectively. The propensity score analysis identified 156 pairs of patients from each treatment arm for survival comparison. Results The survival was significantly higher for group A but was comparable between group SL and group B patients. Of patients with solitary large HCC, the 1-, 3- and 5-year survival rates were 88% versus 74%, 76% versus 44%, and 63% versus 35% between SR and TACE group, respectively (p<0.001). When baseline demographics were adjusted in the propensity model, the respective 1-, 3- and 5-year survival rates were 87% versus 79%, 76% versus 46%, and 61% versus 36% (p<0.001). The Cox proportional hazards model identified TACE with a 2.765-fold increased risk of mortality compared with SR (95% confidence interval: 1.853–4.127, p<0.001). Conclusions Patients with solitary large HCC should be classified at least as intermediate stage HCC. SR provides significantly better survival than TACE for solitary large HCC regardless of tumor stage. Further amendment to the BCLC classification is mandatory. PMID:27176037

  13. Conservation Strategies in the Genus Hypericum via Cryogenic Treatment.

    PubMed

    Bruňáková, Katarína; Čellárová, Eva

    2016-01-01

    In the genus Hypericum, cryoconservation offers a strategy for maintenance of remarkable biodiversity, emerging from large inter- and intra-specific variability in morphological and phytochemical characteristics. Long-term cryostorage thus represents a proper tool for preservation of genetic resources of endangered and threatened Hypericum species or new somaclonal variants with unique properties. Many representatives of the genus are known as producers of pharmacologically important polyketides, namely naphthodianthrones and phloroglucinols. As a part of numerous in vitro collections, the nearly cosmopolitan Hypericum perforatum - Saint John's wort - has become a suitable model system for application of biotechnological approaches providing an attractive alternative to the traditional methods for secondary metabolite production. The necessary requirements for efficient cryopreservation include a high survival rate along with an unchanged biochemical profile of plants regenerated from cryopreserved cells. Understanding of the processes which are critical for recovery of H. perforatum cells after the cryogenic treatment enables establishment of cryopreservation protocols applicable to a broad number of Hypericum species. Among them, several endemic taxa attract a particular attention due to their unique characteristics or yet unrevealed spectrum of bioactive compounds. In this review, recent advances in the conventional two-step and vitrification-based cryopreservation techniques are presented in relation to the recovery rate and biosynthetic capacity of Hypericum spp. The pre-cryogenic treatments which were identified to be crucial for successful post-cryogenic recovery are discussed. Being a part of genetic predisposition, the freezing tolerance as a necessary precondition for successful post-cryogenic recovery is pointed out. Additionally, a beneficial influence of cold stress on modulating naphthodianthrone biosynthesis is outlined. PMID:27200032

  14. Treatment of spinal cord injury with intravenous immunoglobulin G: preliminary evidence and future perspectives.

    PubMed

    Tzekou, Apostolia; Fehlings, Michael G

    2014-07-01

    Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease, with a good safety profile. Thus, it is a promising treatment candidate for SCI. Indeed, IVIg has been shown by our team to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J Neuroinflammation 9:224, 2012). Here we review published data in the context of relevant mechanisms of action that have been proposed for IVIg in other conditions. We hope that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation. PMID:24722853

  15. [Indications and future perspectives in the pharmacological treatment of hypercortisolism].

    PubMed

    Stigliano, Antonio; Toscano, Vincenzo

    2016-03-01

    The hypercortisolism is a rare endocrine disease characterized by an autonomous steroid secretion or excessive adrenal stimulation by ACTH. the Surgical removal of the lesion directly responsible hypercortisolism represents the treatment of choice. When neurosurgery for pituitary adenoma is contraindicated, radiotherapy is candidate as the second line of therapy. Currently, the recent advances in medical therapy provide a viable alternative to surgery and radiotherapy, when these are not feasible or followed by relapses (present in more than one third of cases) of the underlying disease. Recently, also in Italy, are available pharmacological agents with central activity (pasireotide) specifically indicated for treating Cushing's disease together with peripherally acting drugs (metyrapone and ketoconazole) that are used in a broader spectrum of hypercortisolemic clinical pictures. In addition, drugs active in the inhibition of steroidogenesis provide a valid support to the patient's surgical preparation allowing the reduction or normalization of plasma cortisol levels. PMID:27030224

  16. Current and future medical treatment in primary dystonia

    PubMed Central

    Delnooz, Cathérine C.S.

    2012-01-01

    Dystonia is a hyperkinetic movement disorder, characterized by involuntary and sustained contractions of opposing muscles causing twisting movements and abnormal postures. It is often a disabling disorder that has a significant impact on physical and psychosocial wellbeing. The medical therapeutic armamentarium used in practice is quite extensive, but for many of these interventions formal proof of efficacy is lacking. Exceptions are the use of botulinum toxin in patients with cervical dystonia, some forms of cranial dystonia (in particular, blepharospasm) and writer’s cramp; deep brain stimulation of the pallidum in generalized and segmental dystonia; and high-dose trihexyphenidyl in young patients with segmental and generalized dystonia. In order to move this field forward, we not only need better trials that examine the effect of current treatment interventions, but also a further understanding of the pathophysiology of dystonia as a first step to design and test new therapies that are targeted at the underlying biologic and neurophysiologic mechanisms. PMID:22783371

  17. Treatment paradigms for cataplexy in narcolepsy: past, present, and future

    PubMed Central

    Swick, Todd J

    2015-01-01

    Cataplexy is defined as episodes of sudden loss of voluntary muscle tone triggered by emotions generally lasting <2 minutes. Cataplexy is most commonly associated with and considered pathognomonic for narcolepsy, a sleep disorder affecting ~0.05% of the general population. Knowledge of the pathophysiology of cataplexy has advanced through study of canine, murine, and human models. It is now generally considered that loss of signaling by hypothalamic hypocretin/orexin-producing neurons plays a key role in the development of cataplexy. Although the cause of hypocretin/orexin neuron loss in narcolepsy with cataplexy is unknown, an autoimmune etiology is widely hypothesized. Despite these advances, a literature review shows that treatment of cataplexy remains limited. Multiple classes of antidepressants have been commonly used off-label for cataplexy in narcolepsy and are suggested for this use in expert consensus guidelines based on traditional practice, case reports, and small trials. However, systematic research evidence supporting antidepressants for cataplexy is lacking. The single pharmacotherapy indicated for cataplexy and the guideline-recommended first-line treatment in Europe and the US is sodium oxybate, the sodium salt of gamma-hydroxybutyrate. Clinical trial evidence of its efficacy and safety in cataplexy is robust, and it is hypothesized that its therapeutic effects may occur through gamma-aminobutyric acid receptor type B-mediated effects at noradrenergic, dopaminergic, and thalamocortical neurons. Additional possible mechanisms for cataplexy therapy suggested by preliminary research include antagonism of the histamine H3 autoreceptor with pitolisant and intravenous immunoglobulin therapy for amelioration of the presumed autoimmune-mediated hypocretin/orexin cell loss. Further research and development of therapeutic approaches to cataplexy are needed. PMID:26715865

  18. Drug treatment of pulmonary arterial hypertension: current and future agents.

    PubMed

    Hoeper, Marius M

    2005-01-01

    During the last decade we have witnessed substantial improvements in the therapeutic options for pulmonary arterial hypertension (PAH), including true innovations targeting some of the mechanisms involved in the pathogenesis of this devastating disease. Intravenous epoprostenol was the first drug to improve symptoms and survival of patients with PAH. Novel prostanoids, including subcutaneous treprostinil and inhaled iloprost, also have beneficial effects in many patients, although their long-term efficacy is less well known. Among the newer treatments for PAH, endothelin receptor antagonists and phosphodiesterase type 5 (PDE5) inhibitors have reshaped clinical practice. The endothelin receptor antagonist bosentan has been approved in many parts of the world and most current guidelines recommend this drug as first-line treatment for patients with PAH in functional class III. Novel endothelin receptor antagonists such as sitaxsentan sodium and ambrisentan are currently being investigated. The PDE5 sildenafil is also being intensively studied in patients with pulmonary hypertension, and most of the available data look promising, although approval for PAH is still pending. Other PDE5 inhibitors have not yet undergone extensive study in PAH. The increasing insight into the pathogenesis of PAH opens several new therapeutic opportunities, which include vasoactive intestinal peptide, selective serotonin reuptake inhibitors, adrenomedullin and HMG-CoA reductase inhibitors (statins). However, PAH is a complex disorder and targeting a single pathway can not be expected to be uniformly successful. Thus, combining substances with different modes of action is expected to improve symptoms, haemodynamics and survival in PAH patients, although combination therapy has yet to undergo the scrutiny of large randomised clinical trials. PMID:15977967

  19. [Pathology and strategies for the treatment of ischemic brain injury].

    PubMed

    Takagi, Norio

    2009-10-01

    Cerebral ischemia, a pathological condition in which brain tissue experiences a shortage or lack of glucose and oxygen, provokes an irreversible neurodegenerative disorder that may lead clinically to a progressive dementia and global cognitive deterioration. Accumulating evidence indicates many biochemical cascades that lead ultimately to ischemia-induced cell death. However, the cellular and molecular aspects of cerebral ischemia are not yet fully understood. Since the pattern of pathophysiological alterations is not the same for all cells in the ischemic brain, a good understanding of the cellular and molecular alterations induced by cerebral ischemia is needed to develop strategies for the treatment of stroke. This review summarizes recent advances concerning the pathophysiological alterations caused by cerebral ischemia, focusing on the modification of properties of glutamate receptors, which modification may be linked to the development of cerebral infarction. Furthermore, the effects of hepatocyte growth factor on learning dysfunction and cerebral vessel injury after cerebral ischemia are also summarized. Finally, this review describes a possible ameliorative effect of the injection of exogenous neural progenitor cells on cerebral ischemia-induced learning and memory dysfunction. PMID:19797876

  20. [Pilon fractures. Part 1: Diagnostics, treatment strategies and approaches].

    PubMed

    Krettek, C; Bachmann, S

    2015-01-01

    Intraarticular fractures of the distal tibia (pilon fractures) are caused by axial forces, usually in combination with torsional moments. Routine diagnostics include plain films and three dimensional (3D) imaging with computed tomography (CT). Treatment is often impaired by complex fracture configurations and thin soft tissue layers. The management of complex pilon fractures with soft tissue injuries has seen many trends, with changes toward staged protocols of temporary external fixation followed by delayed open reduction and internal fixation (ORIF), minimally invasive percutaneous plate osteosynthesis (MIPPO) techniques and special implants, the benefits of negative pressure wound sealing and early "fix and flap" efforts to reconstruct soft tissue defects. Reduction and fixation must involve respectful management and careful handling of soft tissues in order to minimize the well-known complications of this difficult fracture. The proper approach is one of the keys to success. Approach planning is based on the careful and thorough analysis of the fracture pattern in the 3D data set, which is the basis for a successful strategy for articular reconstruction. PMID:25591416

  1. Treatment strategies for infertile women with polycystic ovary syndrome.

    PubMed

    Vitek, Wendy; Hoeger, Kathleen; Legro, Richard S

    2016-08-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder that can be diagnosed when two of the following three criteria are present: menstrual irregularity, hyperandrogenism and polycystic ovaries. Factors such as the individual's body weight influence the severity of the phenotype and risk of metabolic comorbidities. While anovulatory infertility is a common issue among lean and obese reproductive-aged women with PCOS, obesity is associated with resistance to oral ovulation induction agents, lower pregnancy rates and a higher risk of pregnancy complications. Lifestyle modification is recommended as first line therapy among obese women with PCOS in order to optimize their outcomes. Among lean and obese women with PCOS, ovulation induction can be achieved with aromatase inhibitors, selective estrogen receptor modulators, insulin sensitizing agents, gonadotropins and ovarian drilling with varying rates of ovulation, live birth and multiple gestations. Assisted reproductive technologies are reserved for women who do not conceive despite restoration of ovulation or couples with additional factors contributing to their infertility. This review will outline treatment strategies for achieving a healthy pregnancy among lean and obese women with PCOS and infertility. PMID:26765152

  2. Drug delivery strategies for the treatment of Helicobacter pylori infections.

    PubMed

    Conway, B R

    2005-01-01

    Helicobacter pylori is one of the most common pathogenic bacterial infections, colonising an estimated half of all humans. It is associated with the development of serious gastroduodenal disease - including peptic ulcers, gastric lymphoma and acute chronic gastritis. Current recommended regimes are not wholly effective and patient compliance, side-effects and bacterial resistance can be problematic. Drug delivery to the site of residence in the gastric mucosa may improve efficacy of the current and emerging treatments. Gastric retentive delivery systems potentially allow increased penetration of the mucus layer and therefore increased drug concentration at the site of action. Proposed gastric retentive systems for the enhancement of local drug delivery include floating systems, expandable or swellable systems and bioadhesive systems. Generally, problems with these formulations are lack of specificity, limited to mucus turnover or failure to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue, penetrating the mucus layer and prolonging activity at the mucus-epithelial interface. This review appraises gastroretentive delivery strategies specifically with regard to their application as a delivery system to target Helicobacter. As drug-resistant strains emerge, the development of a vaccine to eradicate and prevent reinfection is an attractive proposition. Proposed prophylactic and therapeutic vaccines have been delivered using a number of mucosal routes using viral and non-viral vectors. The delivery form, inclusion of adjuvants, and delivery regime will influence the immune response generated. PMID:15777232

  3. From Hippocrates to tissue engineering: surgical strategies in wound treatment.

    PubMed

    Nicoli Aldini, Nicolò; Fini, Milena; Giardino, Roberto

    2008-09-01

    The history of wound treatment has been virtually the history of surgery for many centuries and also is a history of alliance and conflicts between the physician and nature. The Hippocratic statement about natura medicatrix has been well known since antiquity, but often was neglected. Suppuration was considered a necessary event in the healing process and was elicited by the surgeons with traumatic and painful procedures. The concept of simplicity in treating the wounds was suggested by Teodorico Borgognone and Henry de Mondeville in 13th century and was confirmed only three centuries later by the works of Ambroise Paré and Cesare Magati. The history of wound management has been characterized by empiricism since the 18th century, but it took a physiopathological direction during the 19th century when Virchow investigated tissue reaction to injuries, and Lister introduced antiseptic procedures in surgery. By establishing the basis for a biological method to treat wounds, the seeds were sown to enhance the pathways involved in tissue repair, also with the support of new strategies and technology. PMID:18581166

  4. Pharmacologic Treatment Strategies in Children with Type 2 Diabetes Mellitus

    PubMed Central

    Urakami, Tatsuhiko; Kuwabara, Remi; Habu, Masako; Yoshida, Ayako; Okuno, Misako; Suzuki, Junichi; Takahashi, Shori; Mugishima, Hideo

    2013-01-01

    We treated 80 obese and 28 nonobese children diagnosed as having type 2 diabetes mellitus (T2DM). Among these patients, 26 obese and 23 nonobese children were assigned to pharmacologic therapies during the course of diabetes. Pharmacologic therapies were started if the HbA1c (NGSP) value exceeded 7.0% despite dietary and exercise management. For the 26 obese patients, metformin alone or in combination with an additional medication was frequently used. Only 2 patients independently received sulfonylureas (SUs) in the form of glimepiride. In addition, 9 patients were treated with basal insulin supported with oral hypoglycemic drugs (OHDs) or biphasic premix insulin. On the other hand, the 23 nonobese patients were frequently treated with insulin alone or in combination with an additional medication followed by SUs. The nonobese patients tended to require pharmacologic therapies, in particular insulin, at an earlier stage of diabetes as compared with the obese patients. New antidiabetic drugs, DPP-4 inhibitors and GLP-1 receptor agonists, seemed to exert positive effects on glycemic control without occurrence of hypoglycemic episodes in some patients regardless of the type of diabetes. These results suggest that pharmacologic treatment strategies in childhood T2DM should be tailored to individual patient characteristics. PMID:23966754

  5. Imaging of coronary atherosclerosis - evolution towards new treatment strategies.

    PubMed

    Dweck, Marc R; Doris, Mhairi K; Motwani, Manish; Adamson, Philip D; Slomka, Piotr; Dey, Damini; Fayad, Zahi A; Newby, David E; Berman, Daniel

    2016-09-01

    Coronary atherosclerosis and the precipitation of acute myocardial infarction are highly complex processes, which makes accurate risk prediction challenging. Rapid developments in invasive and noninvasive imaging technologies now provide us with detailed, exquisite images of the coronary vasculature that allow direct investigation of a wide range of these processes. These modalities include sophisticated assessments of luminal stenoses and myocardial perfusion, complemented by novel measures of the atherosclerotic plaque burden, adverse plaque characteristics, and disease activity. Together, they can provide comprehensive, individualized assessments of coronary atherosclerosis as it occurs in patients. Not only can this information provide important pathological insights, but it can also potentially be used to guide personalized treatment decisions. In this Review, we describe the latest advances in both established and emerging imaging techniques, focusing on the strengths and weakness of each approach. Moreover, we discuss how these technological advances might be translated from attractive images into novel imaging strategies and definite improvements in clinical risk prediction and patient outcomes. This process will not be easy, and the many potential barriers and difficulties are also reviewed. PMID:27226154

  6. WEEE recovery strategies and the WEEE treatment status in China.

    PubMed

    He, Wenzhi; Li, Guangming; Ma, Xingfa; Wang, Hua; Huang, Juwen; Xu, Min; Huang, Chunjie

    2006-08-25

    The electric and electronic equipment has been developed, applied, and consumed world wide at a very high speed. Subsequently, the ever-increasing amount of waste electric and electronic equipment (WEEE) has become a common problem facing the world. In view of the deleterious effects of WEEE on the environment and the valuable materials that can be reused in them, legislations in many countries have focused their attention on the management of WEEE, and new techniques have been developed for the recovery of WEEE. In China, rapid economic growth, coupled with urbanization and growing demand for consumer goods, has increased the consumption of EEE in large quantity, thus made the WEEE manifold rapidly, posing a severe threat to the environment and the sustainable economic growth as well. This article reviewed the implementation of strategies of WEEE treatment and the recovery technologies of WEEE. It presented the current status of WEEE and corresponding responses adopted so far in China. The concept and implementation of scientific development is critical to the sector of electronics, one of the important industrial sectors in China's economy. To achieve this objective, it is significant to recycle WEEE sufficiently to comply with regulations regarding WEEE management, and to implement green design and cleaner production concepts within the electronics industry to comply with the upcoming EU and China legislation in a proactive manner. PMID:16820262

  7. Sustainability of irrigated crops under future climate: the interplay of irrigation strategies and cultivar responses

    NASA Astrophysics Data System (ADS)

    De Lorenzi, F.; Bonfante, A.; Alfieri, S.; Patanè, C.; Basile, A.; Di Tommasi, P.; Monaco, E.; Menenti, M.

    2012-04-01

    Climate evolution will cause significant changes in the quality and availability of water resources, affecting many sectors including food production, where available water resources for irrigation play a crucial role. Strategies focused on managing and conserving water are one way to deal with the impact; moreover concurring adaptation measurements will be needed to cope with the foreseen decline of water resource. This work deals with i) the impacts of climate change on water requirements of an horticultural crop, determined in an irrigated district in Southern Italy, ii) the possible irrigation scheduling options and their sustainability in the future, iii) the adaptation measurements that can be undertaken to protect production, relying on intra-specific biodiversity of agricultural crops. Two climate scenarios were considered: present climate (1961-90) and future climate (2021-2050), the former from climatic statistics, and the latter from statistical downscaling of general circulation models (AOGCM). Climatic data set consists of daily time series of maximum and minimum temperature, and rainfall on a grid with spatial resolution of 35 km. The analysis of climate scenarios showed that significant increases in summer maximum daily temperature could be expected in 2021-2050 period. Soil water regime was determined by means of a mechanistic model (SWAP) of water flow in the soil-plant-atmosphere system. Twenty? soil units were identified in the district (in Sele Plain, Campania Region) and simulations were performed accounting for hydro-pedological properties of different soil units. Parameters of a generic tomato crop, in a rotation typical of the area, were used in simulations. Soil water balance was simulated in the present and future climate, both with optimal water availability and under constrains that irrigation schemes will pose. Indicators of soil water availability were calculated, in terms of soil water or evapotranspiration deficit. For several tomato

  8. Genomics, microRNA, epigenetics, and proteomics for future diagnosis, treatment and monitoring response in upper GI cancers.

    PubMed

    Brücher, Björn L D M; Li, Yan; Schnabel, Philipp; Daumer, Martin; Wallace, Timothy J; Kube, Rainer; Zilberstein, Bruno; Steele, Scott; Voskuil, Jan L A; Jamall, Ijaz S

    2016-12-01

    One major objective for our evolving understanding in the treatment of cancers will be to address how a combination of diagnosis and treatment strategies can be used to integrate patient and tumor variables with an outcome-oriented approach. Such an approach, in a multimodal therapy setting, could identify those patients (1) who should undergo a defined treatment (personalized therapy) (2) in whom modifications of the multimodal therapy due to observed responses might lead to an improvement of the response and/or prognosis (individualized therapy), (3) who might not benefit from a particular toxic treatment regimen, and (4) who could be identified early on and thereby be spared the morbidity associated with such treatments. These strategies could lead in the direction of precision medicine and there is hope of integrating translational molecular data to improve cancer classifications. In order to achieve these goals, it is necessary to understand the key issues in different aspects of biotechnology to anticipate future directions of personalized and individualized diagnosis and multimodal treatment strategies. Providing an overview of translational data in cancers proved to be a challenge as different methods and techniques used to obtain molecular data are used and studies are based on different tumor entities with different tumor biology and prognoses as well as vastly different therapeutic approaches. The pros and cons of the available methodologies and the potential response data in genomics, microRNA, epigenetics and proteomics with a focus on upper gastrointestinal cancers are considered herein to allow for an understanding of where these technologies stand with respect to cancer diagnosis, prognosis and treatment. PMID:27053248

  9. Real-time nutrient monitoring in rivers: adaptive sampling strategies, technological challenges and future directions

    NASA Astrophysics Data System (ADS)

    Blaen, Phillip; Khamis, Kieran; Lloyd, Charlotte; Bradley, Chris

    2016-04-01

    Excessive nutrient concentrations in river waters threaten aquatic ecosystem functioning and can pose substantial risks to human health. Robust monitoring strategies are therefore required to generate reliable estimates of river nutrient loads and to improve understanding of the catchment processes that drive spatiotemporal patterns in nutrient fluxes. Furthermore, these data are vital for prediction of future trends under changing environmental conditions and thus the development of appropriate mitigation measures. In recent years, technological developments have led to an increase in the use of continuous in-situ nutrient analysers, which enable measurements at far higher temporal resolutions than can be achieved with discrete sampling and subsequent laboratory analysis. However, such instruments can be costly to run and difficult to maintain (e.g. due to high power consumption and memory requirements), leading to trade-offs between temporal and spatial monitoring resolutions. Here, we highlight how adaptive monitoring strategies, comprising a mixture of temporal sample frequencies controlled by one or more 'trigger variables' (e.g. river stage, turbidity, or nutrient concentration), can advance our understanding of catchment nutrient dynamics while simultaneously overcoming many of the practical and economic challenges encountered in typical in-situ river nutrient monitoring applications. We present examples of short-term variability in river nutrient dynamics, driven by complex catchment behaviour, which support our case for the development of monitoring systems that can adapt in real-time to rapid environmental changes. In addition, we discuss the advantages and disadvantages of current nutrient monitoring techniques, and suggest new research directions based on emerging technologies and highlight how these might improve: 1) monitoring strategies, and 2) understanding of linkages between catchment processes and river nutrient fluxes.

  10. Risk factor adapted treatment of Hodgkin's lymphoma: strategies and perspectives.

    PubMed

    Loeffler, M; Pfreundschuh, M; Rühl, U; Hiller, E; Gerhartz, H; Roloff, R; Adler, M; Schoppe, W; Hagen-Aukamp, U; Schmitt, G

    1989-01-01

    prognostic impact. In contrast, a pretreatment erythrocyte sedimentation rate (ESR) above 80 mm/h and a serum alkaline phosphatase (AP) above 230 IU/ml each appeared as significant prognostic factors (P less than 0.01; relative risk, 2.3). The two parameters can be combined to separate two groups (A: ESR and AP both low; B: ESR and/or AP high) which differ significantly for FFTF (P less than 0.001) and survival (P less than 0.04). The decision for risk-adapted treatment requires identification of groups of patients in the frame of specified diagnostic and therapeutic strategies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2690225

  11. Osteogenesis imperfecta : current treatment options and future prospects.

    PubMed

    Devogelaer, Jean-Pierre; Coppin, Christine

    2006-01-01

    Osteogenesis imperfecta is a heritable condition characterized by abnormally brittle bones, with an approximate prevalence of 1/20 000 births. Fractures are the main cause of suffering and disability, but owing to the abundance and wide distribution of the defective type I collagen in the body, a variety of symptoms occur. Several types of osteogenesis imperfecta (I-VII) have been described that vary in severity. For many years, therapy consisted of rehabilitation and orthopedic surgery. Presently, pharmacologic therapies aimed at strengthening bone are available, which decrease the pain and fracture rate associated with this condition, and allow more appropriate rehabilitation programs that will hopefully result in a less marked failure to thrive in affected children. In particular, the bisphosphonates, especially pamidronate, have been used for several years. They have been successful in increasing bone mineral density (BMD) and improving bone resistance, leading to a decrease in the fracture rate. Various regimens have been proposed, but it is the therapeutic regimen first used by Glorieux and co-workers in Montreal that has been the most frequently applied.However, as yet there is no definite consensus regarding the indications for therapy, the osteogenesis imperfecta types that are of the greatest concern, the appropriate age at the outset of therapy, and the treatment duration, without yet speaking about the best bisphosphonate regimen for use. The authors have proposed some personal recommendations for the clinical use of bisphosphonates, based on their own experience with the management of patients with this condition; these include the indications for therapy, based on the clinical status, and the treatment duration. These recommendations will certainly not be unanimously endorsed, but they should help to stimulate discussion. Ameliorating BMD is an important step, but will not prevent all fractures because bisphosphonate therapy does not correct the

  12. Lysyl oxidase: from basic science to future cancer treatment.

    PubMed

    Nishioka, Takeshi; Eustace, Amanda; West, Catharine

    2012-01-01

    In this mini-review, we discuss the physiological and pathological roles of lysyl oxidase (LOX) and its family, LOX-like proteins (LOXL), in relation to prognosis of major cancers. The number of reports on LOX family is numerous. We have decided to review the articles that were recently published (i.e. past 5 years). Experimental techniques in molecular biology have advanced surprisingly in the past decade. Accordingly, the results of the studies are more reliable. Most studies reached the same conclusion; a higher LOX- or LOXL- expression is associated with a poor prognosis. Molecular experiments have already started aiming for clinical application, and the results are encouraging. Suppressing LOX or LOXL activities resulted in lower cell motility in collagen gel and, moreover, succeeded in reducing metastases in mice. LOX family members were originally recognized as molecules that cross-link collagen fibers in the extracellular matrix. Recent studies demonstrated that they are also involved in a phenomenon called Epithelial Mesenchymal Transition (EMT). This may affect cell movement and cancer cell invasiveness. LOX and LOXL2 are regulated by hypoxia, a major factor in the failure of cancer treatment. Here we discuss the molecular biology of the LOX family in relation to its role in tumor biology. PMID:22453058

  13. Treatment of Nonalcoholic Steatohepatitis in Adults: Present and Future

    PubMed Central

    Gitto, S.; Vitale, G.; Villa, E.; Andreone, P.

    2015-01-01

    Nonalcoholic steatohepatitis has become one of the most common liver-related health problems. This condition has been linked to an unhealthy diet and weight gain, but it can also be observed in nonobese people. The standard of care is represented by the lifestyle intervention. However, because this approach has several limitations, such as a lack of compliance, the use of many drugs has been proposed. The first-line pharmacological choices are vitamin E and pioglitazone, both showing a positive effect on transaminases, fat accumulation, and inflammation. Nevertheless, vitamin E has no proven effect on fibrosis and on long-term morbidity and mortality and pioglitazone has a negative impact on weight. Other drugs have been studied such as metformin, ursodeoxycholic acid, statins, pentoxiphylline, and orlistat with only partially positive results. Among the emerging treatments, telmisartan is particularly interesting as it seems to have an impact on insulin resistance, liver steatosis, inflammation, and fibrosis. However, the pathogenesis of steatohepatitis is highly complex and is determined by different parallel hits; indeed, the association of different drugs that act on various levels has been suggested. In conclusion, lifestyle intervention should be optimised and the associations of different drugs should be tested in large studies with long-term outcomes. PMID:25866507

  14. Neuroimmune mechanisms of cytokine-induced depression: Current theories and novel treatment strategies

    PubMed Central

    Loftis, Jennifer M.; Huckans, Marilyn; Morasco, Benjamin J.

    2010-01-01

    The relationships between immune and neural function are an increasingly important area of study for neuropsychiatric disorders, in particular depression. This is exemplified by the growing number of publications on cytokines and depression during the last 10 years, as compared to earlier decades. This review summarizes the current theories and novel treatment strategies for depression, with a focus on cytokine-induced depression. Neuroimmune mechanisms are now viewed as central to the development of depressive symptoms and emerging evidence is beginning to identify the neural circuits involved in cytokine-induced depression. The current diagnostic categories for depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders, however, are not etiologically or biologically derived, and it has been proposed that “depression”, likely reflects multiple pathogeneses leading to varying symptom constellations. As we move toward a better biological understanding of depression-related symptom constellations or syndromes, the term “depression” may prove inadequately broad, and an integration of interdisciplinary literatures will increase in importance. Future research should aim to characterize these depression-related symptom constellations or syndromes better with the goal of optimizing treatment strategies. PMID:19944762

  15. The History and Future of Treatment of Hypothyroidism.

    PubMed

    McAninch, Elizabeth A; Bianco, Antonio C

    2016-01-01

    Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine monotherapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone-treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism. PMID:26747302

  16. The History and Future of Treatment of Hypothyroidism

    PubMed Central

    McAninch, Elizabeth A.; Bianco, Antonio C.

    2016-01-01

    Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine mono-therapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism. PMID:26747302

  17. Ultrasound-targeted microbubble destruction: toward a new strategy for diabetes treatment.

    PubMed

    Mozafari, Masoud; Shimoda, Masayuki; Urbanska, Aleksandra M; Laurent, Sophie

    2016-04-01

    Ultrasound-targeted microbubble destruction (UTMD) is a promising technique with an immense target-specific gene delivery potential deep inside the human body. The potential of this technique has recently been confirmed for diabetic patients. This technology allows the genes to transfer specifically into the inefficient pancreas using ultrasound energy without viral vector utilization. It has been speculated that this idea and the advent of modern gene therapy techniques could result in significant future advances. Undoubtedly, this strategy needs further investigation and many critical questions have to be answered before it can be successfully advanced. Herein, we introduce the salient features of this approach, the hurdles that must be overcome, the hopes associated with it and practical constraints to develop this method for diabetes treatment. PMID:26646254

  18. Improving outcomes of refractory celiac disease – current and emerging treatment strategies

    PubMed Central

    Woodward, Jeremy

    2016-01-01

    Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. PMID:27536154

  19. Improving outcomes of refractory celiac disease - current and emerging treatment strategies.

    PubMed

    Woodward, Jeremy

    2016-01-01

    Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness. PMID:27536154

  20. Future tendencies of climate indicators important for adaptation and mitigation strategies in forestry

    NASA Astrophysics Data System (ADS)

    Galos, Borbala; Hänsler, Andreas; Gulyas, Krisztina; Bidlo, Andras; Czimber, Kornel

    2014-05-01

    impact analyses and build an important basis of the future adaptation strategies in forestry, agriculture and water management. Funding: The research is supported by the TÁMOP-4.2.2.A-11/1/KONV-2012-0013 and TÁMOP-4.1.1.C-12/1/KONV-2012-0012 (ZENFE) joint EU-national research projects. Keywords: climate indices, climate change impacts, forestry, regional climate modelling

  1. Strategies for automatic online treatment plan reoptimization using clinical treatment planning system: A planning parameters study

    SciTech Connect

    Li, Taoran; Wu, Qiuwen; Zhang, You; Vergalasova, Irina; Lee, W. Robert; Yin, Fang-Fang; Wu, Q. Jackie

    2013-11-15

    Purpose: Adaptive radiation therapy for prostate cancer using online reoptimization provides an improved control of interfractional anatomy variations. However, the clinical implementation of online reoptimization is currently limited by the low efficiency of current strategies and the difficulties associated with integration into the current treatment planning system. This study investigates the strategies for performing fast (∼2 min) automatic online reoptimization with a clinical fluence-map-based treatment planning system; and explores the performance with different input parameters settings: dose-volume histogram (DVH) objective settings, starting stage, and iteration number (in the context of real time planning).Methods: Simulated treatments of 10 patients were reoptimized daily for the first week of treatment (5 fractions) using 12 different combinations of optimization strategies. Options for objective settings included guideline-based RTOG objectives, patient-specific objectives based on anatomy on the planning CT, and daily-CBCT anatomy-based objectives adapted from planning CT objectives. Options for starting stages involved starting reoptimization with and without the original plan's fluence map. Options for iteration numbers were 50 and 100. The adapted plans were then analyzed by statistical modeling, and compared both in terms of dosimetry and delivery efficiency.Results: All online reoptimized plans were finished within ∼2 min with excellent coverage and conformity to the daily target. The three input parameters, i.e., DVH objectives, starting stage, and iteration number, contributed to the outcome of optimization nearly independently. Patient-specific objectives generally provided better OAR sparing compared to guideline-based objectives. The benefit in high-dose sparing from incorporating daily anatomy into objective settings was positively correlated with the relative change in OAR volumes from planning CT to daily CBCT. The use of the

  2. Preparing the future nurses for nursing research: a creative teaching strategy for RN-to-BSN students.

    PubMed

    Tsai, Hsiu-Min; Cheng, Ching-Yu; Chang, Chia-Hao; Liou, Shwu-Ru

    2014-02-01

    Developing effective teaching strategies to stimulate students' interest and enthusiasm are urgently needed in current research courses. The purposes of the study were to implement the Cookie Experiments teaching strategy in research course and examine the effects of the strategy on students' attitudes towards nursing research. The study was a pretest-post-test design with 95 students at a Registered Nurses to Bachelor of Science in Nursing (RN-to-BSN) program enrolled in the nursing research course. Results indicated that there was a significant effect of the Cookie Experiments teaching strategy on students' attitudes towards research. Although students perceived a median high score of pressure from the research course, they regarded that the pressure is conducive to their learning of research. Students highly suggested to continuously applying this teaching strategy in the future nursing research courses. Developing and using various teaching strategies with attractive and hands-on methods to motivate nurse students, learning research is strongly recommended. PMID:24580972

  3. Future Directions in the Treatment of Gastrointestinal and Pancreatic Neuroendocrine Tumors.

    PubMed

    Asmis, Timothy

    2016-07-01

    Recently, the landscape of the diagnosis and treatment of patients with well-differentiated gastrointestinal/pancreatic neuroendocrine tumors (previously referred to as carcinoid tumors) has changed dramatically. We will need to work with all of the stakeholders including clinicians, patients, regulatory agencies, and industry to best navigate future treatment and research. Future protocols will require us to define clinically relevant end points. In designing future clinical trials, we will need to determine which patients will be included in these studies. Future research will need to address the best way to image and follow patient's disease both in the clinic and on research studies. Timely access to new therapies will be the utmost importance to both current and future patients. We must work together to establish relevant clinical questions and to pursue collaborative research that promotes the health of our patients. PMID:27295530

  4. Management strategies in the treatment of neonatal and pediatric gastroenteritis

    PubMed Central

    Ciccarelli, Simona; Stolfi, Ilaria; Caramia, Giuseppe

    2013-01-01

    Acute gastroenteritis, characterized by the onset of diarrhea with or without vomiting, continues to be a major cause of morbidity and mortality in children in mostly resource-constrained nations. Although generally a mild and self-limiting disease, gastroenteritis is one of the most common causes of hospitalization and is associated with a substantial disease burden. Worldwide, up to 40% of children aged less than 5 years with diarrhea are hospitalized with rotavirus. Also, some microorganisms have been found predominantly in resource-constrained nations, including Shigella spp, Vibrio cholerae, and the protozoan infections. Prevention remains essential, and the rotavirus vaccines have demonstrated good safety and efficacy profiles in large clinical trials. Because dehydration is the major complication associated with gastroenteritis, appropriate fluid management (oral or intravenous) is an effective and safe strategy for rehydration. Continuation of breastfeeding is strongly recommended. New treatments such as antiemetics (ondansetron), some antidiarrheal agents (racecadotril), and chemotherapeutic agents are often proposed, but not yet universally recommended. Probiotics, also known as “food supplement,” seem to improve intestinal microbial balance, reducing the duration and the severity of acute infectious diarrhea. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition and the European Society of Paediatric Infectious Diseases guidelines make a stronger recommendation for the use of probiotics for the management of acute gastroenteritis, particularly those with documented efficacy such as Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Saccharomyces boulardii. To date, the management of acute gastroenteritis has been based on the option of “doing the least”: oral rehydration-solution administration, early refeeding, no testing, no unnecessary drugs. PMID:24194646

  5. Nutritional strategies in the prevention and treatment of metabolic syndrome.

    PubMed

    Feldeisen, Sabrina E; Tucker, Katherine L

    2007-02-01

    The metabolic syndrome (MetS) is a clustering of metabolic abnormalities that increase the risk of developing atherosclerotic cardiovascular disease and type 2 diabetes. The exact etiology remains unclear, but it is known to be a complex interaction between genetic, metabolic, and environmental factors. Among environmental factors, dietary habits are of central importance in the prevention and treatment of this condition. However, there is currently no firm consensus on the most appropriate dietary recommendations. General recommendations include decreasing obesity, increasing physical activity, and consuming an anti-atherogenic diet, and have traditionally focused on low total fat intake. A major problem with the focus on low fat is that high-carbohydrate diets can contribute to increasing triglyceride and decreasing high-density lipoprotein (HDL) concentrations. Low-carbohydrate diets have been popular in recent years. However, such diets are typically higher in saturated fat and lower in fruits, vegetables, and whole grains than national dietary recommendations. More recently the quality of carbohydrate has been studied in relation to MetS, including a focus on dietary fiber and glycemic index. Similarly, there has been a move from limiting total fat to a focus on the quality of the fat, with evidence of beneficial effects of replacing some carbohydrate with monounsaturated fat. Other nutrients examined for possible importance include calcium, vitamin D, and magnesium. Together, the evidence suggests that the components of diet currently recommended as "healthy" are likely also protective against MetS, including low saturated and trans fat (rather than low total fat) and balanced carbohydrate intake rich in dietary fiber, as well as high fruit and vegetable intake (rather than low total carbohydrate); and the inclusion of low-fat dairy foods. Accelerating research on gene-diet interactions is likely to contribute interesting information that may lead to further

  6. Systemic treatment strategies for triple-negative breast cancer.

    PubMed

    Yadav, Budhi Singh; Sharma, Suresh C; Chanana, Priyanka; Jhamb, Swaty

    2014-05-10

    Triple-negative breast cancer (TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival (PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitors in combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success. PMID:24829859

  7. Systemic treatment strategies for triple-negative breast cancer

    PubMed Central

    Yadav, Budhi Singh; Sharma, Suresh C; Chanana, Priyanka; Jhamb, Swaty

    2014-01-01

    Triple-negative breast cancer (TNBC) is defined by the lack of immunohistochemical expression of the estrogen and progesterone receptors and human epidermal growth factor receptor 2 (EGFR2). Most TNBC has a basal-like molecular phenotype by gene expression profiling and shares clinical and pathological features with hereditary BRCA1 related breast cancers. This review evaluates the activity of available chemotherapy and targeted agents in TNBC. A systematic review of PubMed and conference databases was carried out to identify randomised clinical trials reporting outcomes in women with TNBC treated with chemotherapy and targeted agents. Our review identified TNBC studies of chemotherapy and targeted agents with different mechanisms of action, including induction of synthetic lethality and inhibition of angiogenesis, growth and survival pathways. TNBC is sensitive to taxanes and anthracyclins. Platinum agents are effective in TNBC patients with BRCA1 mutation, either alone or in combination with poly adenosine diphosphate polymerase 1 inhibitors. Combinations of ixabepilone and capecitabine have added to progression-free survival (PFS) without survival benefit in metastatic TNBC. Antiangiogenic agents, tyrosine kinase inhibitors and EGFR inhibitors in combination with chemotherapy produced only modest gains in PFS and had little impact on survival. TNBC subgroups respond differentially to specific targeted agents. In future, the treatment needs to be tailored for a specific patient, depending on the molecular characteristics of their malignancy. TNBC being a chemosensitive entity, combination with targeted agents have not produced substantial improvements in outcomes. Appropriate patient selection with rationale combinations of targeted agents is needed for success. PMID:24829859

  8. Vascular surgery-related organ injury and protective strategies: update and future prospects.

    PubMed

    Yang, B; Fung, A; Pac-Soo, C; Ma, D

    2016-09-01

    Whilst there has been a reduction in the prevalence of peripheral vascular disease worldwide, a significant proportion of the world's growing population is still affected by disease of the aorta, carotid, iliac and lower limb arteries. These if left untreated can result in severe morbidity and mortality. However vascular surgery, the main definitive treatment for such conditions, is associated with subsequent injury to vital organs including the kidneys, heart, brain, intestines and lungs, with a consequent increase in both morbidity and mortality. The current thinking is that the underlying mechanism of injury is direct organ ischaemia and ischaemia induced formation of free radicals, cytokine release and mitochondrial failure. Various methods to alleviate such injuries have been investigated including pre- and postconditioning strategies, pharmacological therapies including volatile anaesthetic and alpha2 adrenoceptor agonist drugs and more recently remote conditioning strategies. Although these interventions have demonstrated some reduction in the biomarkers for organ injury, attempts to translate these benefits into clinical practice have not been successful in terms of morbidity, mortality or length of hospital stay. For this reason, further research is needed in this area to facilitate the translation of the potential interventional benefits from bench to bedside. PMID:27566807

  9. Developing America's Shale Reserves - Water Strategies For A Sustainable Future (Invited)

    NASA Astrophysics Data System (ADS)

    Shephard, L. E.; Oshikanlu, T.

    2013-12-01

    The development of shale oil and gas reserves over the last several years has had a significant impact on securing America's energy future while making substantial contributions to our nation's economic prosperity. These developments have also raised serious concerns about potential detrimental impacts to our environment (i.e., land, air and water) with much media attention focused on the impacts to our nation's fresh water supply. These concerns are being discussed across the nation often with little or no distinction that the nature of the water issues vary depending on local circumstances (e.g., depth of aquifer and reservoir zone, water demand and availability, availability of discharge wells, regulatory framework, etc.) and regional shale reservoir development strategies (depth of wells, length of laterals, fluid-type used for fracturing, etc.). Growing concerns over long standing drought conditions in some areas and competing demands for water from other sectors (e.g., agriculture, domestic, etc.) add even greater uncertainty relative to fresh water. Water demands for gas and oil wells vary from region to region but nominally range from 10 to 15 acre feet of water (4 to 6 million gallons) for drilling and hydraulic fracturing applications. Flowback water from the hydraulic fracturing process varies and can range from 5 to 40 % of the water used for drilling and 'fracing'. Produced water can be substantial, leading to significant volumes of 'disposed water' where injection wells are available. A science-based systems approach to water lifecycle management that incorporates leading-edge technology development and considers economic and social impacts is critical for the long-term sustainable development of shale reserves. Various water recycling and reuse technologies are being deployed within select regions across the nation with each having limited success depending on region. The efficacy of reuse technology will vary based on produced water quantity and

  10. Recent improvements in oily wastewater treatment: Progress, challenges, and future opportunities.

    PubMed

    Jamaly, Sanaa; Giwa, Adewale; Hasan, Shadi Wajih

    2015-11-01

    Oily wastewater poses significant threats to the soil, water, air and human beings because of the hazardous nature of its oil contents. The objective of this review paper is to highlight the current and recently developed methods for oily wastewater treatment through which contaminants such as oil, fats, grease, and inorganics can be removed for safe applications. These include electrochemical treatment, membrane filtration, biological treatment, hybrid technologies, use of biosurfactants, treatment via vacuum ultraviolet radiation, and destabilization of emulsions through the use of zeolites and other natural minerals. This review encompasses innovative and novel approaches to oily wastewater treatment and provides scientific background for future work that will be aimed at reducing the adverse impact of the discharge of oily wastewater into the environment. The current challenges affecting the optimal performance of oily wastewater treatment methods and opportunities for future research development in this field are also discussed. PMID:26574084

  11. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

    PubMed Central

    Saliba, Antoine N; Harb, Afif R; Taher, Ali T

    2015-01-01

    Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT) and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. PMID:26124688

  12. [Therapeutic strategies for obsessive-compulsive disorder refractory to treatment].

    PubMed

    Mussa, Alexis

    2008-01-01

    Obsessive-compulsive disorder (OCD) is a chronic disabling disease with profound implications for social functioning. OCD affects all spheres of functioning of patients who suffer the disorder. Treatment with serotonin reuptake inhibitors is effective in 40% to 60% of patients with OCD, but a large percentage of patients are non responsive to treatment. Those patients who do respond often do not fully remit, which should be the standard goal of treatment in OCD. Treatment refractory patients with OCD are those who undergo adequate trials of first-line therapies without a satisfactory response. Conventional treatment and alternative treatment options for this population are reviewed. PMID:18997908

  13. Targeting transcription factors by small compounds-Current strategies and future implications.

    PubMed

    Hagenbuchner, Judith; Ausserlechner, Michael J

    2016-05-01

    Transcription factors are central regulators of gene expression and critically steer development, differentiation and death. Except for ligand-activated nuclear receptors, direct modulation of transcription factor function by small molecules is still widely regarded as "impossible". This "un-druggability" of non-ligand transcription factors is due to the fact that the interacting surface between transcription factor and DNA is huge and subject to significant changes during DNA-binding. Besides some "success studies" with compounds that directly interfere with DNA binding, drug targeting approaches mostly address protein-protein interfaces with essential co-factors, transcription factor dimerization partners, chaperone proteins or proteins that regulate subcellular shuttling. An alternative strategy represent DNA-intercalating, alkylating or DNA-groove-binding compounds that either block transcription factor-binding or change the 3D-conformation of the consensus DNA-strand. Recently, much interest has been focused on chromatin reader proteins that steer the recruitment and activity of transcription factors to a gene transcription start site. Several small compounds demonstrate that these epigenetic reader proteins are exciting new drug targets for inhibiting lineage-specific transcription in cancer therapy. In this research update we will discuss recent advances in targeting transcription factors with small compounds, the challenges that are related to the complex function and regulation of these proteins and also the possible future directions and applications of transcription factor drug targeting. PMID:26686579

  14. Breaking the Cycle: Future Faculty Begin Teaching with Learner-Centered Strategies after Professional Development

    PubMed Central

    Ebert-May, Diane; Derting, Terry L.; Henkel, Timothy P.; Middlemis Maher, Jessica; Momsen, Jennifer L.; Arnold, Bryan; Passmore, Heather A.

    2015-01-01

    The availability of reliable evidence for teaching practices after professional development is limited across science, technology, engineering, and mathematics disciplines, making the identification of professional development “best practices” and effective models for change difficult. We aimed to determine the extent to which postdoctoral fellows (i.e., future biology faculty) believed in and implemented evidence-based pedagogies after completion of a 2-yr professional development program, Faculty Institutes for Reforming Science Teaching (FIRST IV). Postdocs (PDs) attended a 2-yr training program during which they completed self-report assessments of their beliefs about teaching and gains in pedagogical knowledge and experience, and they provided copies of class assessments and video recordings of their teaching. The PDs reported greater use of learner-centered compared with teacher-centered strategies. These data were consistent with the results of expert reviews of teaching videos. The majority of PDs (86%) received video ratings that documented active engagement of students and implementation of learner-centered classrooms. Despite practice of higher-level cognition in class sessions, the items used by the PDs on their assessments of learning focused on lower-level cognitive skills. We attributed the high success of the FIRST IV program to our focus on inexperienced teachers, an iterative process of teaching practice and reflection, and development of and teaching a full course. PMID:26033870

  15. The Future of Public Health Informatics: Alternative Scenarios and Recommended Strategies

    PubMed Central

    Edmunds, Margo; Thorpe, Lorna; Sepulveda, Martin; Bezold, Clem; Ross, David A.

    2014-01-01

    Background: In October 2013, the Public Health Informatics Institute (PHII) and Institute for Alternative Futures (IAF) convened a multidisciplinary group of experts to evaluate forces shaping public health informatics (PHI) in the United States, with the aim of identifying upcoming challenges and opportunities. The PHI workshop was funded by the Robert Wood Johnson Foundation as part of its larger strategic planning process for public health and primary care. Workshop Context: During the two-day workshop, nine experts from the public and private sectors analyzed and discussed the implications of four scenarios regarding the United States economy, health care system, information technology (IT) sector, and their potential impacts on public health in the next 10 years, by 2023. Workshop participants considered the potential role of the public health sector in addressing population health challenges in each scenario, and then identified specific informatics goals and strategies needed for the sector to succeed in this role. Recommendations and Conclusion: Participants developed recommendations for the public health informatics field and for public health overall in the coming decade. These included the need to rely more heavily on intersectoral collaborations across public and private sectors, to improve data infrastructure and workforce capacity at all levels of the public health enterprise, to expand the evidence base regarding effectiveness of informatics-based public health initiatives, and to communicate strategically with elected officials and other key stakeholders regarding the potential for informatics-based solutions to have an impact on population health. PMID:25848630

  16. Breaking the cycle: future faculty begin teaching with learner-centered strategies after professional development.

    PubMed

    Ebert-May, Diane; Derting, Terry L; Henkel, Timothy P; Middlemis Maher, Jessica; Momsen, Jennifer L; Arnold, Bryan; Passmore, Heather A

    2015-01-01

    The availability of reliable evidence for teaching practices after professional development is limited across science, technology, engineering, and mathematics disciplines, making the identification of professional development "best practices" and effective models for change difficult. We aimed to determine the extent to which postdoctoral fellows (i.e., future biology faculty) believed in and implemented evidence-based pedagogies after completion of a 2-yr professional development program, Faculty Institutes for Reforming Science Teaching (FIRST IV). Postdocs (PDs) attended a 2-yr training program during which they completed self-report assessments of their beliefs about teaching and gains in pedagogical knowledge and experience, and they provided copies of class assessments and video recordings of their teaching. The PDs reported greater use of learner-centered compared with teacher-centered strategies. These data were consistent with the results of expert reviews of teaching videos. The majority of PDs (86%) received video ratings that documented active engagement of students and implementation of learner-centered classrooms. Despite practice of higher-level cognition in class sessions, the items used by the PDs on their assessments of learning focused on lower-level cognitive skills. We attributed the high success of the FIRST IV program to our focus on inexperienced teachers, an iterative process of teaching practice and reflection, and development of and teaching a full course. PMID:26033870

  17. Targeting MIF in Cancer: Therapeutic Strategies, Current Developments, and Future Opportunities.

    PubMed

    O'Reilly, Ciaran; Doroudian, Mohammad; Mawhinney, Leona; Donnelly, Seamas C

    2016-04-01

    Strong evidence has been presented linking chronic inflammation to the onset and pathogenesis of cancer. The multifunctional pro-inflammatory protein macrophage migration inhibitory factor (MIF) occupies a central role in the inflammatory pathway and has been implicated in the tumorigenesis, angiogenesis, and metastasis of many cancer phenotypes. This review highlights the current state of the art, which presents MIF, and the second member of the MIF structural superfamily, d-DT (MIF2), as significant mediators in the inflammatory-cancer axis. Although the mechanism by which MIF asserts its biological activity has yet to be fully understood, it has become clear in recent years that for certain phenotypes of cancer, MIF represents a valid therapeutic target. Current research efforts have focused on small molecule approaches that target MIF's unique tautomerase active site and neutralization of MIF with anti-MIF antibodies. These approaches have yielded promising results in a number of preclinical murine cancer models and have helped to increase our understanding of MIF biological activity. More recently, MIF's involvement in a number of key protein-protein interactions, such as with CD74 and HSP90, has been highlighted and provides a novel platform for the development of anti-MIF chemotherapeutic strategies in the future. PMID:26777977

  18. The dieselization of America: An integrated strategy for future transportation fuels

    SciTech Connect

    Eberhardt, J.J.

    1997-12-31

    The Diesel Cycle engine has already established itself as the engine-of-choice for the heavy duty transport industry because of its fuel efficiency, durability, and reliability. In addition, it has also been shown to be capable of using alternative fuels, albeit at efficiencies lower than that achieved with petroleum-derived diesel fuel. Alternative fuel dedicated engines have not made significant penetration of the heavy duty truck market because truck fleet operators need a cost-competitive fuel and reliable supply and fueling infrastructure. In lieu of forcing diverse fuels from many diverse domestic feedstocks onto the end-users, the Office of Heavy Vehicle Technologies envisions that a future fuels strategy for the heavy duty transport sector is one where the diverse feedstocks are utilized to provide a single fuel specification (dispensed from the existing fueling infrastructure) that would run efficiently in a single high efficiency energy conversion device, the Diesel Cycle engine. In so doing, the US Commercial transport industry may gain a measure of security from the rapid fuel price increases by relying less on a single feedstock source to meet its increasing fuel requirements.

  19. Radium and Other Radiological Chemicals: Drinking Water Treatment Strategies

    EPA Science Inventory

    Radium and Other Radiological Chemicals: Drinking Water Treatment Technologies Topics include: Introduction to Rad Chemistry, Summary of the Rad, Regulations Treatment Technology, and Disposal. The introductions cover atoms, ions, radium and uranium and the removal of radioac...

  20. Randomized Trial of Drug Abuse Treatment-Linkage Strategies

    ERIC Educational Resources Information Center

    Sorenson, James L.; Masson, Carmen L.; Delucchi, Kevin; Sporer, Karl; Barnett, Paul G.; Mitsuishi, Fumi; Lin, Christine; Song, Yong; Chen, TeChieh; Hall, Sharon M.

    2005-01-01

    A clinical trial contrasted 2 interventions designed to link opioid-dependent hospital patients to drug abuse treatment. The 126 out-of-treatment participants were randomly assigned to (a) case management, (b) voucher for free methadone maintenance treatment (MMT), (c) case management plus voucher, or (d) usual care. Services were provided for 6…

  1. The economic effects of whole-herd versus selective anthelmintic treatment strategies in dairy cows.

    PubMed

    Charlier, J; Levecke, B; Devleesschauwer, B; Vercruysse, J; Hogeveen, H

    2012-06-01

    Current control practices against gastrointestinal nematodes in dairy cows rely strongly on anthelmintic use. To reduce the development of anthelmintic resistance or disposition of drug residues in the environment, novel control approaches are currently proposed that target anthelmintic treatment to individual animals instead of the whole herd. However, such selective treatment strategies come with additional costs for labor and diagnostics and, so far, no studies have addressed whether they could be economically sustainable. The objectives of this study were to (1) investigate the economic effects at farm level of whole-herd versus more selective anthelmintic treatment strategies in adult dairy cows, and (2) determine how these economic effects depend on level of infection and herd size. A Monte Carlo simulation, fed by current epidemiological and economical knowledge, was used to estimate the expected economic effects and possible variation of different control strategies under Belgian conditions. Four treatment strategies were compared with a baseline situation in which no treatments were applied: whole herd at calving (S1), selective at calving with (S2) or without (S3) treatment of the first-calf cows, and whole-herd when animals are moved from grazing to the barn in the fall (housing treatment, S4). The benefit per lactation for an average dairy herd varied between -$2 and $131 (average $64) for S1, between -$2 and $127 (average $62) for S2, between -$17 and $104 (average $43) for S3, and between -$41 and $72 (average $15) for S4. The farmer's risk associated with any treatment strategy, as indicated by the width of the 95% credible intervals of economic benefit of anthelmintic treatment, decreased with increasing level of exposure, as assessed by bulk tank milk ELISA. The order of the different strategies when sorted by expected benefit was robust to changes in economic input parameters. We conclude that, on average, strategies applying anthelmintic

  2. Applying Future Studies Methods to Understanding the Impact of University Information and Communication Technology Strategies on Learning

    ERIC Educational Resources Information Center

    Aczel, J. C.; Hardy, P.

    2007-01-01

    This article aims to explore the potential of certain future studies techniques to provide insight into the question of the impact of higher education information and communication technology (ICT) strategies on student learning. The approach is to consider three case studies of new universities in different countries, and to identify the main…

  3. Attributions to Failure: The Effects of Effort, Ability, and Learning Strategy Use on Perceptions of Future Goals and Emotional Responses.

    ERIC Educational Resources Information Center

    Holschuh, Jodi Patrick; Nist, Sherrie L.; Olejnik, Stephen

    2001-01-01

    Examines college students' attributions to failure in an introductory biology course. Determines how males and females viewed the attributions of ability, effort, and learning strategy use. Concludes that collectively, results indicate differences in patterns of responses between future goal and emotional items. Notes the importance for…

  4. The microenvironment in mature B-cell malignancies: a target for new treatment strategies

    PubMed Central

    Ghia, Paolo; Rosenwald, Andreas

    2009-01-01

    Despite major therapeutic advances, most mature B-cell malignancies remain incurable. Compelling evidence suggests that crosstalk with accessory stromal cells in specialized tissue microenvironments, such as the bone marrow and secondary lymphoid organs, favors disease progression by promoting malignant B-cell growth and drug resistance. Therefore, disrupting the crosstalk between malignant B cells and their milieu is an attractive novel strategy for treating selected mature B-cell malignancies. Here we summarize the current knowledge about the cellular and molecular interactions between neoplastic B lymphocytes and accessory cells that shape a supportive microenvironment, and the potential therapeutic targets that are emerging, together with the new problems they raise. We discuss clinically relevant aspects and provide an outlook into future biologically oriented therapeutic strategies. We anticipate a paradigm shift in the treatment of selected B-cell malignancies, moving from targeting primarily the malignant cells toward combining cytotoxic drugs with agents that interfere with the microenvironment's proactive role. Such approaches hopefully will help eliminating residual disease, thereby improving our current therapeutic efforts. PMID:19636060

  5. Evaluation of Product Algorithm Strategies for the Future Lightning Imager on MTG

    NASA Astrophysics Data System (ADS)

    Finke, U.; Grandell, J.

    2014-12-01

    The future European geostationary Meteosat Third Generation (MTG) will carry a lightning observation instrument - the Lightning Imager (LI), which will observe lightning in thunderstorm for the whole visible Earth disk with high temporal and spatial resolution. Its data will be of great benefit for nowcasting of lightning thread and severe weather, as well as for applications in lightning physics, chemistry and climatology. Primary data output of the instrument are the 'lightning events' corresponding to triggered pixels of the detector matrix. These primary data are processed into a set of products: hierarchically organized point data - groups and flashes, and various products of data accumulated over time and space bins. The algorithm strategies for generation of these level-2 products are evaluated in this contribution.The clustering of the lightning event data consists of two steps: i) pixel events are clustered in a group representing the optical pulse, and ii) the groups are clustered in a flash representing the lightning flash. The algorithm strategies for clustering are discussed and evaluated for the various algorithm parameters. The distance function and linkage criteria are formulated in time and space. For groups the criterion is immediate adjacency in time and space. For flashes the gap to the nearest neighbor in time and space have to be lower a threshold value. Examples and statistics of the application of the clustering algorithms are presented for LIS data and for proxy data.The second group of products accumulate the lightning point data in time (30s) and space (2km) intervals. The planned products are the accumulated flash number, flash area and flash radiance. All these products are created on a per flash bases using the pixel set for each flash. They are calculated on a grid which correspond cloud imager (FCI) grid on the same platform. The accumulated products represent an snapshot picture of the current lightning activity, valuable in

  6. China's coastal wetlands: conservation history, implementation efforts, existing issues and strategies for future improvement.

    PubMed

    Sun, Zhigao; Sun, Wenguang; Tong, Chuan; Zeng, Congsheng; Yu, Xiang; Mou, Xiaojie

    2015-06-01

    concerted efforts at all levels. The major strategies for future improvement of China's coastal wetland conservation include: exploring effective measures in response to major threaten factors; improving the conservation and compensation system for coastal wetlands; strengthening coastal wetland legislation and management; increasing funds for coastal wetland conservation and research; and strengthening coastal wetland education and international cooperation. PMID:25771079

  7. Targeted photodynamic therapy--a promising strategy of tumor treatment.

    PubMed

    Bugaj, Andrzej M

    2011-07-01

    Targeted therapy is a new promising therapeutic strategy, created to overcome growing problems of contemporary medicine, such as drug toxicity and drug resistance. An emerging modality of this approach is targeted photodynamic therapy (TPDT) with the main aim of improving delivery of photosensitizer to cancer tissue and at the same time enhancing specificity and efficiency of PDT. Depending on the mechanism of targeting, we can divide the strategies of TPDT into "passive", "active" and "activatable", where in the latter case the photosensitizer is activated only in the target tissue. In this review, contemporary strategies of TPDT are described, including new innovative concepts, such as targeting assisted by peptides and aptamers, multifunctional nanoplatforms with navigation by magnetic field or "photodynamic molecular beacons" activatable by enzymes and nucleic acid. The imperative of introducing a new paradigm of PDT, focused on the concepts of heterogeneity and dynamic state of tumor, is also called for. PMID:21547329

  8. The neurobiology of emotion–cognition interactions: fundamental questions and strategies for future research

    PubMed Central

    Okon-Singer, Hadas; Hendler, Talma; Pessoa, Luiz; Shackman, Alexander J.

    2015-01-01

    Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the ‘emotional’ and the ‘cognitive’ brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of ‘the emotional brain’ and ‘the cognitive brain’ are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders. PMID:25774129

  9. The neurobiology of emotion-cognition interactions: fundamental questions and strategies for future research.

    PubMed

    Okon-Singer, Hadas; Hendler, Talma; Pessoa, Luiz; Shackman, Alexander J

    2015-01-01

    Recent years have witnessed the emergence of powerful new tools for assaying the brain and a remarkable acceleration of research focused on the interplay of emotion and cognition. This work has begun to yield new insights into fundamental questions about the nature of the mind and important clues about the origins of mental illness. In particular, this research demonstrates that stress, anxiety, and other kinds of emotion can profoundly influence key elements of cognition, including selective attention, working memory, and cognitive control. Often, this influence persists beyond the duration of transient emotional challenges, partially reflecting the slower molecular dynamics of catecholamine and hormonal neurochemistry. In turn, circuits involved in attention, executive control, and working memory contribute to the regulation of emotion. The distinction between the 'emotional' and the 'cognitive' brain is fuzzy and context-dependent. Indeed, there is compelling evidence that brain territories and psychological processes commonly associated with cognition, such as the dorsolateral prefrontal cortex and working memory, play a central role in emotion. Furthermore, putatively emotional and cognitive regions influence one another via a complex web of connections in ways that jointly contribute to adaptive and maladaptive behavior. This work demonstrates that emotion and cognition are deeply interwoven in the fabric of the brain, suggesting that widely held beliefs about the key constituents of 'the emotional brain' and 'the cognitive brain' are fundamentally flawed. We conclude by outlining several strategies for enhancing future research. Developing a deeper understanding of the emotional-cognitive brain is important, not just for understanding the mind but also for elucidating the root causes of its disorders. PMID:25774129

  10. Novel Strategies for Immunotherapy in Multiple Myeloma: Previous Experience and Future Directions

    PubMed Central

    Danylesko, Ivetta; Beider, Katia; Shimoni, Avichai; Nagler, Arnon

    2012-01-01

    Multiple myeloma (MM) is a life-threatening haematological malignancy for which standard therapy is inadequate. Autologous stem cell transplantation is a relatively effective treatment, but residual malignant sites may cause relapse. Allogeneic transplantation may result in durable responses due to antitumour immunity mediated by donor lymphocytes. However, morbidity and mortality related to graft-versus-host disease remain a challenge. Recent advances in understanding the interaction between the immune system of the patient and the malignant cells are influencing the design of clinically more efficient study protocols for MM. Cellular immunotherapy using specific antigen-presenting cells (APCs), to overcome aspects of immune incompetence in MM patients, has received great attention, and numerous clinical trials have evaluated the potential for dendritic cell (DC) vaccines as a novel immunotherapeutic approach. This paper will summarize the data investigating aspects of immunity concerning MM, immunotherapy for patients with MM, and strategies, on the way, to target the plasma cell more selectively. We also include the MM antigens and their specific antibodies that are of potential use for MM humoral immunotherapy, because they have demonstrated the most promising preclinical results. PMID:22649466

  11. Targeting cell death signaling in colorectal cancer: Current strategies and future perspectives

    PubMed Central

    Koehler, Bruno Christian; Jäger, Dirk; Schulze-Bergkamen, Henning

    2014-01-01

    The evasion from controlled cell death induction has been considered as one of the hallmarks of cancer cells. Defects in cell death signaling are a fundamental phenomenon in colorectal cancer. Nearly any non-invasive cancer treatment finally aims to induce cell death. However, apoptosis resistance is the major cause for insufficient therapeutic success and disease relapse in gastrointestinal oncology. Various compounds have been developed and evaluated with the aim to meet with this obstacle by triggering cell death in cancer cells. The aim of this review is to illustrate current approaches and future directions in targeting cell death signaling in colorectal cancer. The complex signaling network of apoptosis will be demonstrated and the “druggability” of targets will be identified. In detail, proteins regulating mitochondrial cell death in colorectal cancer, such as Bcl-2 and survivin, will be discussed with respect to potential therapeutic exploitation. Death receptor signaling and targeting in colorectal cancer will be outlined. Encouraging clinical trials including cell death based targeted therapies for colorectal cancer are under way and will be demonstrated. Our conceptual understanding of cell death in cancer is rapidly emerging and new types of controlled cellular death have been identified. To meet this progress in cell death research, the implication of autophagy and necroptosis for colorectal carcinogenesis and therapeutic approaches will also be depicted. The main focus of this topic highlight will be on the revelation of the complex cell death concepts in colorectal cancer and the bridging from basic research to clinical use. PMID:24587670

  12. Improving Outcomes in Resectable Gastric Cancer: A Review of Current and Future Strategies.

    PubMed

    Chan, Bryan A; Jang, Raymond W; Wong, Rebecca K S; Swallow, Carol J; Darling, Gail E; Elimova, Elena

    2016-07-01

    Gastric cancer is a highly fatal malignancy, and surgery alone often does not provide a cure, even for relatively early stages of disease. Various approaches have been adopted around the world to improve surgical outcomes; however, there currently is no global consensus with regard to the extent of surgery or the timing and choice of chemotherapy and radiation. Here we review the evidence supporting current approaches to resectable gastric cancer, including discussion of the optimal extent of surgery and lymphadenectomy, adjuvant chemotherapy, postoperative chemotherapy with chemoradiation, and perioperative chemotherapy. Additionally, we discuss novel approaches, including intensified chemotherapy (in neoadjuvant, perioperative, and adjuvant settings), pre- and postoperative chemoradiation in combination with chemotherapy, and the role of biologics and targeted therapy. Finally, we examine the promise of molecular subtyping and potential biomarkers for improved patient selection. Upcoming and future trials should help answer questions regarding the optimal sequencing and choice of treatments, in order to further improve survival and move us towards ultimately curing more patients with resectable gastric cancer. PMID:27422110

  13. Hepatitis C virus infection treatment: An era of game changer direct acting antivirals and novel treatment strategies.

    PubMed

    Shahid, Imran; ALMalki, Waleed Hassan; Hafeez, Muhammad Hassan; Hassan, Sajida

    2016-08-01

    Chronic hepatitis C virus infection and associated liver diseases represent a major health care burden all over the world. The current standard of care, i.e. peginterferon-alfa (PEG-IFNα) plus ribavirin (RBV) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. The approval of first and second generation HCV protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals (DAAs) against different HCV genotypes and establishes a new standard of care for chronically infected HCV genotypes 1 patients. Similarly, next generation protease inhibitors and HCV RNA polymerase inhibitors have shown better pharmacokinetics and pharmacodynamics in terms of broader HCV genotypes coverage, better safety profile, fewer drug interactions and possible once daily administration than first generation direct acting antivirals. The testing of adenovirus-based vector vaccines, which escalates the innate and acquired immune responses against the most conserved regions of the HCV genome in chimpanzees and humans, may be a promising therapeutic approach against HCV infection in coming future. This review article presents up-to-date knowledge and recent developments in HCV therapeutics, insights the shortcomings of current HCV therapies and key lessons from the therapeutic potential of improved anti-HCV treatment strategies. PMID:25373616

  14. Tau-targeted treatment strategies in Alzheimer's disease.

    PubMed

    Götz, Jürgen; Ittner, Arne; Ittner, Lars M

    2012-03-01

    With populations ageing worldwide, the need for treating and preventing diseases associated with high age is pertinent. Alzheimer's disease (AD) is reaching epidemic proportions, yet the currently available therapies are limited to a symptomatic relief, without halting the degenerative process that characterizes the AD brain. As in AD cholinergic neurons are lost at high numbers, the initial strategies were limited to the development of acetylcholinesterase inhibitors, and more recently the NMDA receptor antagonist memantine, in counteracting excitotoxicity. With the identification of the protein tau in intracellular neurofibrillary tangles and of the peptide amyloid-β (Aβ) in extracellular amyloid plaques in the AD brain, and a better understanding of their role in disease, newer strategies are emerging, which aim at either preventing their formation and deposition or at accelerating their clearance. Interestingly, what is well established to combat viral diseases in peripheral organs - vaccination - seems to work for the brain as well. Accordingly, immunization strategies targeting Aβ show efficacy in mice and to some degree also in humans. Even more surprising is the finding in mice that immunization strategies targeting tau, a protein that forms aggregates in nerve cells, ameliorates the tau-associated pathology. We are reviewing the literature and discuss what can be expected regarding the translation into clinical practice and how the findings can be extended to other neurodegenerative diseases with protein aggregation in brain. PMID:22044248

  15. Tank waste remediation system optimized processing strategy with an altered treatment scheme

    SciTech Connect

    Slaathaug, E.J.

    1996-03-01

    This report provides an alternative strategy evolved from the current Hanford Site Tank Waste Remediation System (TWRS) programmatic baseline for accomplishing the treatment and disposal of the Hanford Site tank wastes. This optimized processing strategy with an altered treatment scheme performs the major elements of the TWRS Program, but modifies the deployment of selected treatment technologies to reduce the program cost. The present program for development of waste retrieval, pretreatment, and vitrification technologies continues, but the optimized processing strategy reuses a single facility to accomplish the separations/low-activity waste (LAW) vitrification and the high-level waste (HLW) vitrification processes sequentially, thereby eliminating the need for a separate HLW vitrification facility.

  16. Muscle wasting in end-stage renal disease promulgates premature death: established, emerging and potential novel treatment strategies.

    PubMed

    Stenvinkel, Peter; Carrero, Juan Jesus; von Walden, Ferdinand; Ikizler, T Alp; Nader, Gustavo A

    2016-07-01

    Muscle wasting (or sarcopenia) is a common feature of the uremic phenotype and predisposes this vulnerable patient population to increased risk of comorbid complications, poor quality of life, frailty and premature death. The old age of dialysis patients is in addition a likely contributor to loss of muscle mass. As recent evidence suggests that assessment of muscle strength (i.e. function) is a better predictor of outcome and comorbidities than muscle mass, this opens new screening, assessment and therapeutic opportunities. Among established treatment strategies, the benefit of resistance exercise and endurance training are increasingly recognized among nephrologists as being effective and should be promoted in sedentary chronic kidney disease patients. Testosterone and growth hormone replacement appear as the most promising among emerging treatments strategies for muscle wasting. As treatment of muscle wasting is difficult and seldom successful in this often old, frail, sedentary and exercise-hesitant patient group, novel treatment strategies are urgently needed. In this review, we summarize recent studies on stimulation of mitochondrial biogenesis, myogenic stem (satellite) cells and manipulation of transforming growth factor family members, all of which hold promise for more effective therapies to target muscle mass loss and function in the future. PMID:25910496

  17. Current Strategies for the Treatment of Aneurysmal Bone Cysts.

    PubMed

    Tsagozis, Panagiotis; Brosjö, Otte

    2015-12-28

    Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient. PMID:26793296

  18. Current Strategies for the Treatment of Aneurysmal Bone Cysts

    PubMed Central

    Brosjö, Otte

    2015-01-01

    Aneurysmal bone cysts are benign bone tumors that usually present in childhood and early adulthood. They usually manifest as expansile osteolytic lesions with a varying potential to be locally aggressive. Since their first description in 1942, a variety of treatment methods has been proposed. Traditionally, these tumors were treated with open surgery. Either intralesional surgical procedures or en bloc excisions have been described. Furthermore, a variety of chemical or physical adjuvants has been utilized in order to reduce the risk for local recurrence after excision. Currently, there is a shift to more minimally invasive procedures in order to avoid the complications of open surgical excision. Good results have been reported during percutaneous surgery, or the use of embolization. Recently, sclerotherapy has emerged as a promising treatment, showing effective consolidation of the lesions and functional results that appear to be superior to the ones of open surgery. Lastly, non-invasive treatment, such as pharmaceutical intervention with denosumab or bisphosphonates has been reported to be effective in the management of the disease. Radiotherapy has also been shown to confer good local control, either alone or in conjunction to other treatment modalities, but is associated with serious adverse effects. Here, we review the current literature on the methods of treatment of aneurysmal bone cysts. The indication for each type of treatment along reported outcome of the intervention, as well as potential complications are systematically presented. Our review aims to increase awareness of the different treatment modalities and facilitate decision-making regarding each individual patient. PMID:26793296

  19. Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis

    PubMed Central

    2013-01-01

    Background A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. Methods A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Results Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and

  20. Arthrogryposis: an update on clinical aspects, etiology, and treatment strategies

    PubMed Central

    Feluś, Jarosław

    2016-01-01

    Arthrogryposes – multiple joint contractures – are a clinically and etiologically heterogeneous class of diseases, where accurate diagnosis, recognition of the underlying pathology and classification are of key importance for the prognosis as well as for selection of appropriate management. This treatment remains challenging and optimally in arthrogrypotic patients should be carried out by a team of specialists familiar with all aspects of arthrogryposis pathology and treatment modalities: rehabilitation, orthotics and surgery. In this comprehensive review article, based on literature and clinical experience, the authors present an update on current knowledge on etiology, classifications and treatment options for skeletal deformations possible in arthrogryposis. PMID:26925114

  1. New treatment strategies against hepatitis C viral infection

    PubMed Central

    Bilodeau, Marc; Lamarre, Daniel

    2006-01-01

    Treatment of hepatitis C virus infection is currently based on a combination of pegylated interferon and ribavirin. Because efficacy of this therapy remains suboptimal and side effects sometimes problematic, major efforts have been put forward by scientists and the pharmaceutical industry to develop alternative treatments for this chronic infection. Over the past few years, clinical studies performed with some of these new agents have been presented at major international meetings. The present paper aims to review the rationale underlying the development of these new forms of treatment as well as the current available data concerning their clinical efficacy. PMID:17111056

  2. Sex biased spatial strategies relying on the integration of multimodal cues in a rat model of schizophrenia: impairment in predicting future context?

    PubMed

    Bertholet, Léa; Meunier, Cécile; Preissmann, Delphine; Schenk, Françoise

    2014-04-01

    Male and female Wistar rats were treated postnatally (PND 5-16) with BSO (l-buthionine-(S,R)-sulfoximine) to provide a rat model of schizophrenia based on transient glutathione deficit. In the watermaze, BSO-treated male rats perform very efficiently in conditions where a diversity of visual information is continuously available during orientation trajectories [1]. Our hypothesis is that the treatment impairs proactive strategies anticipating future sensory information, while supporting a tight visual adjustment on memorized snapshots, i.e. compensatory reactive strategies. To test this hypothesis, BSO rats' performance was assessed in two conditions using an 8-arm radial maze task: a semi-transparent maze with no available view on the environment from maze centre [2], and a modified 2-parallel maze known to induce a neglect of the parallel pair in normal rats [3-5]. Male rats, but not females, were affected by the BSO treatment. In the semi-transparent maze, BSO males expressed a higher error rate, especially in completing the maze after an interruption. In the 2-parallel maze shape, BSO males, unlike controls, expressed no neglect of the parallel arms. This second result was in accord with a reactive strategy using accurate memory images of the contextual environment instead of a representation based on integrating relative directions. These results are coherent with a treatment-induced deficit in proactive decision strategy based on multimodal cognitive maps, compensated by accurate reactive adaptations based on the memory of local configurations. Control females did not express an efficient proactive capacity in the semi-transparent maze, neither did they show the significant neglect of the parallel arms, which might have masked the BSO induced effect. Their reduced sensitivity to BSO treatment is discussed with regard to a sex biased basal cognitive style. PMID:24406722

  3. Future Directions in Etiologic, Prevention, and Treatment Research for Eating Disorders

    ERIC Educational Resources Information Center

    Stice, Eric; South, Kelsey; Shaw, Heather

    2012-01-01

    Significant advances have occurred regarding the understanding of etiologic processes that give rise to eating disorders and the design and evaluation of efficacious prevention programs and treatment interventions. Herein we offer suggestions regarding potentially fruitful directions for future research in these areas. We suggest it would be…

  4. Fetal Alcohol Spectrum Disorders: Experimental Treatments and Strategies for Intervention

    PubMed Central

    Idrus, Nirelia M.; Thomas, Jennifer D.

    2011-01-01

    Despite the known damaging effects of prenatal alcohol exposure, women continue to drink during pregnancy, creating a need for effective interventions and treatments for fetal alcohol spectrum disorders (FASD). Experimental models can be useful in identifying potential treatments, and this article describes the spectrum of experimental therapeutics that currently are being investigated, including pharmacological, nutritional, and environmental/behavioral interventions. Some treatments target the underlying mechanisms that contribute to alcohol-induced damage, protecting against alcohol’s teratogenic effects, whereas other treatments may enhance central nervous system plasticity either during alcohol exposure or long after alcohol exposure has ceased. The insights gained to date from experimental models offer several candidates for attenuating the deficits associated with FASD. PMID:23580044

  5. Psychosocial treatments for negative symptoms in schizophrenia: Current practices and future directions

    PubMed Central

    Elis, Ori; Caponigro, Janelle M.; Kring, Ann M.

    2014-01-01

    Schizophrenia can be a chronic and debilitating psychiatric disorder. Though advancements have been made in the psychosocial treatment of some symptoms of schizophrenia, people with schizophrenia often continue to experience some level of symptoms, particularly negative symptoms, throughout their lives. Because negative symptoms are associated with poor functioning and quality of life, the treatment of negative symptoms is a high priority for intervention development. However, current psychosocial treatments primarily focus on the reduction of positive symptoms with comparatively few studies investigating the efficacy of psychosocial treatments for negative symptoms. In this article, we review and evaluate the existing literature on three categories of psychosocial treatments – cognitive behavioral therapy (CBT), social skills training (SST), and combined treatment interventions – and their impact on the negative symptoms of schizophrenia. Of the interventions reviewed, CBT and SST appear to have the most empirical support, with some evidence suggesting that CBT is associated with maintenance of negative symptom improvement beyond six months after treatment. It remains unclear if a combined treatment approach provides improvements above and beyond those associated with each individual treatment modality. Although psychosocial treatments show promise for the treatment of negative symptoms, there are many unanswered questions about how best to intervene. We conclude with a general discussion of these unanswered questions, future directions and methodological considerations, and suggestions for the further development of negative symptom interventions. PMID:23988452

  6. Treatment strategies for radioactive iodine-refractory differentiated thyroid cancer

    PubMed Central

    2014-01-01

    Until recently, no truly effective treatment options have existed for patients with radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), a serious disease with poor prognosis. In November 2013, the targeted multikinase inhibitor, sorafenib, was approved for use in these patients based on substantially improved progression-free survival compared with placebo. A number of other targeted agents, including lenvatinib, are being investigated in phase II and phase III trials. With the advent of these new treatment options, practitioners are faced with making important decisions in determining which patients are candidates for systemic treatment and the optimal timing for treatment initiation. Since patients may remain asymptomatic for a protracted period of time, tumor size and growth rate are the primary considerations for making these choices. Proactive management of side effects is also critical in optimizing the effectiveness of treatment. Here we review targeted systemic agents that are either in use or are under investigation for RAI-refractory DTC and provide recommendations on the rationale for initiating systemic treatment and on managing adverse events. Four illustrative case studies are provided. PMID:25364392

  7. Role of yoga in the treatment of neurotic disorders: current status and future directions.

    PubMed

    Grover, P; Varma, V K; Pershad, D; Verma, S K

    1994-10-01

    A large number of studies have consistently demonstrated the potential of yoga, not only in the treatment of psychiatric and psychosomatic disorder but also in promoting positive physical and mental health. This paper reviews various studies on the treatment of neurosis with techniques derived from yoga. A few lacunae have been identified and possible directions for future research are outlined. It is hoped that research along these lines will develop a standardized method of yoga therapy which can be utilized and integrated within the existing methods of treatment of neurotic disorders. PMID:21743694

  8. Towards a Strategy for Future Projects in High-Energy Physics (European Perspective)

    NASA Astrophysics Data System (ADS)

    Engelen, J.

    2006-07-01

    This write-up is a very brief `telegram style' summary of a much more extensive talk delivered at the Conference. The subject of the talk is of current topical interest, in particular because the CERN Council has installed a Strategy Group with the mandate to formulate a strategy for European high energy physics. The recommendations of the Strategy Group will be discussed during a special session of CERN Council in Lisbon, Portugal, on July 14 2006.

  9. Insights Into Severe Form of Dwarfism Could Lead to New Treatment Strategies

    MedlinePlus

    ... Could Lead to New Treatment Strategies Observations of mice engineered to carry a mutation that causes a ... to 1 month of age are shown for mice engineered to have PSACH (on right) compared to ...

  10. Strategies for the cost effective treatment of Oak Ridge legacy wastes

    SciTech Connect

    Compere, A.L.; Griffith, W.L.; Huxtable, W.P.; Wilson, D.F.

    1998-03-01

    Research and development treatment strategies for treatment or elimination of several Oak Ridge plant liquid, solid, and legacy wastes are detailed in this report. Treatment strategies for volumetrically contaminated nickel; enriched uranium-contaminated alkali metal fluorides; uranium-contaminated aluminum compressor blades; large, mercury-contaminated lithium isotope separations equipment; lithium process chlorine gas streams; high-concentration aluminum nitrate wastes, and high-volume, low-level nitrate wastes are discussed. Research needed to support engineering development of treatment processes is detailed.

  11. Coping Strategies in Bulimia Nervosa Treatment: Impact on Outcome in Group Cognitive-Behavioral Therapy

    ERIC Educational Resources Information Center

    Binford, Roslyn B.; Mussell, Melissa Pederson; Crosby, Ross D.; Peterson, Carol B.; Crow, Scott J.; Mitchell, James E.

    2005-01-01

    This study's purpose was to examine the extent to which participants (N = 143) receiving cognitive-behavioral therapy for bulimia nervosa (BN) reported implementing therapeutic strategies to abstain from BN behaviors, and to assess whether use of specific strategies predicts outcome at treatment end and 1-and 6-month follow-up. Frequency of…

  12. Strategies for managing aortoiliac occlusions: access, treatment and outcomes

    PubMed Central

    Clair, Daniel G; Beach, Jocelyn M

    2015-01-01

    Treatment of severe aortoiliac disease has dramatically evolved from a dependence on open aortobifemoral grafting to hybrid and endovascular only approaches. Open surgery has been the gold standard treatment of severe aortoiliac disease with excellent patency rates, but with increased length of stay and major complications. In contrast, endovascular interventions can successfully treat almost any lesion with decreased risk, compared to open surgery. Although primary patency rates remain inferior, secondary endovascular interventions are often minor procedures resulting in comparable long-term outcomes. The risks of renal insufficiency, embolization and access complications are not insignificant; however, most can be prevented or managed without significant clinical consequence. Endovascular therapies should be considered a first-line treatment option for all patients with aortoiliac disease, especially those with high-risk cardiovascular comorbidities. PMID:25907618

  13. Mechanical valve obstruction: Review of diagnostic and treatment strategies

    PubMed Central

    Salamon, Jason; Munoz-Mendoza, Jerson; Liebelt, Jared J; Taub, Cynthia C

    2015-01-01

    Prosthetic valve obstruction (PVO) is a rare but feared complication of mechanical valve replacement. Diagnostic evaluation should focus on differentiating prosthetic valve thrombosis (PVT) from pannus formation, as their treatment options differ. History of sub-optimal anti-coagulation and post-op time course to development of PVO are useful clinical characteristics in differentiating thrombus from pannus formation. Treatment of PVT is influenced by the patient’s symptoms, valve location, degree of obstruction and thrombus size and may include thrombolysis or surgical intervention. Alternatively, pannus formation requires surgical intervention. The purpose of this article is to review the pathophysiology, epidemiology, diagnostic approach and treatment options for aortic and mitral valve PVO. PMID:26730292

  14. Behavioral activation: a strategy to enhance treatment response.

    PubMed

    Sudak, Donna M; Majeed, Muhammad H; Youngman, Branden

    2014-07-01

    Behavioral activation is an empirically validated treatment for depression pioneered in 1973 by Ferster, based on B.F. Skinner's behavioral principles. After publication of Beck's work on cognitive therapy, the boundaries of behavioral and cognitive therapies were blurred and the two now overlap substantially. Behavioral activation is also used as a stand-alone treatment and can also be effective in conjunction with antidepressant medication. Case conceptualization in behavioral activation entails an assessment of the behaviors that the patient has stopped that produce pleasure or are of importance, as well as behaviors essential to self-care. Activity monitoring, which provides treatment targets and leads to the case conceptualization in behavioral activation, consists of using charts, forms, or other prompts to track the relationship between activities and other variables (e.g., mood, enjoyment). That technique is also used to target rumination, procrastination, and avoidance and may also be helpful for patients with psychosis. PMID:25036582

  15. Treatment strategies for advanced hormone receptor-positive and human epidermal growth factor 2-negative breast cancer: the role of treatment order.

    PubMed

    Perez, Edith A

    2016-01-01

    Although survival rates among patients with breast cancer have improved in recent years, those diagnosed with advanced disease with distant metastasis face a 5-year survival rate of less than 25%, making the management of these patients an area still in significant need of continued research. Selecting the optimal treatment order from among the variety of currently available therapy options presents a relevant challenge for medical oncologists. With the understanding that the majority of patients with breast cancer and those who succumb to this disease have HR-positive disease, this review will focus on treatment options and treatment order in patients with HR-positive advanced breast cancer. While endocrine therapy is considered the preferred treatment for first-line therapy in HR-positive/HER2-negative breast cancer, selection of the specific agent depends on the menopausal status of the patient. Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is also recommended as first-line treatment in patients with ER-positive/HER2-negative disease. In patients with endocrine therapy-resistant disease, specific strategies include sequencing of other antiestrogen receptor agents, or agents that target other molecular pathways. Future treatment strategies for patients with primary or secondary resistance to endocrine therapy for advanced disease are discussed. These strategies include first-line therapy with high-dose fulvestrant or everolimus (in combination with exemestane or letrozole or with other endocrine therapies), use of the PI3K inhibitors (e.g., buparlisib, alpelisib, pictilisib, taselisib), entinostat, CDK 4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib), and novel selective estrogen receptor degradation agents that may enhance the targeting of acquired mutations in the ESR1 gene. PMID:26830312

  16. Minimising time to treatment: targeted strategies to minimise time to thrombolysis for acute ischaemic stroke.

    PubMed

    Tai, Y J; Yan, B

    2013-11-01

    Time to thrombolysis is a critical determinant of favourable outcomes in acute ischaemic stroke. It is not infrequent that patient outcomes are compromised due to out-of-hospital and in-hospital time delays. On the other hand, time delays could be minimised through the identification of barriers and the implementation of targeted solutions. This review outlines the different strategies in minimising treatment delays and offers recommendations. Literature search in PubMed, Medline and EBSCO Host was conducted to identify studies that are relevant to reduction of time to treatment from January 1995 to December 2012. Strategies to reduce time to thrombolysis are categorised into pre-hospital strategies, in-hospital strategies and post-treatment decision strategies. Proposed pre-hospital strategies include public education on stroke symptoms awareness, prioritising stroke by emergency medical services, increasing ease of access to medical records, pre-hospital notification, and mobile computed tomography scanning. In-hospital strategies include a streamlined code stroke system, computed tomography scanner co-location with emergency department, 24/7 availability of stroke physicians, point-of-care laboratory testing and access to expert neuroimaging interpretation. Post-decision strategies include increasing availability of intravenous thrombolysis and simplification of informed consent procurement. Time to thrombolysis delays is multifactorial. Effective reduction of time delays for acute ischaemic stroke requires the correct identification of and targeted strategies to overcome time barriers. PMID:23734983

  17. Antidepressant Use During Pregnancy: Current Controversies and Treatment Strategies

    PubMed Central

    Payne, Jennifer L.; Meltzer-Brody, Samantha

    2009-01-01

    The treatment of depression during pregnancy is both a common and complex clinical challenge. The decision to expose the fetus to antidepressant medication during pregnancy must be weighed against the risks of untreated maternal depression to both mother and fetus. Maternal depression during pregnancy has been associated with increased rates of preterm birth and maternal substance use. The safety of antidepressant use during pregnancy appears to be largely reassuring but there remain two areas of controversy including neonatal withdrawal syndrome and primary pulmonary hypertension of the newborn (PPHN). Individualized treatment recommendations based on the patient's history are essential in order to optimize outcomes. PMID:19661762

  18. Strategies for Training Counselors in Evidence-Based Treatments

    PubMed Central

    Martino, Steve

    2010-01-01

    Evidence-based treatments (EBTs) for substance abuse and dependence have demonstrated superiority over treatment as usual when applied with strict fidelity in controlled clinical trials. Effective counselor training is critical if substance abuse programs are to realize these interventions’ full potential to enhance client outcomes in community practice. Although few empirical evaluations of training in EBTs have been conducted to date, the existing data warrant tentative conclusions concerning the appropriate roles and effectiveness of workshops, clinical supervision, distance learning, and blended learning. Among several outstanding research issues are questions of benchmarks for counselors’ performance in training and the relationships between such performance and clients’ substance abuse outcomes. PMID:22002451

  19. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  20. A Bridge to the Future. Australia's National Strategy for Vocational Education and Training 1998-2003.

    ERIC Educational Resources Information Center

    Australian National Training Authority, Brisbane.

    The National Strategy for Vocational Education and Training 1998-2003 expresses the collective commitment by Australian governments, in partnership with Australian industry, to vocational education and training. The strategy includes the following mission: to ensure that the skills of the Australian labor force are sufficient to support…

  1. Antigen-specific tolerogenic and immunomodulatory strategies for the treatment of autoimmune arthritis

    PubMed Central

    Satpute, Shailesh R.; Durai, Malarvizhi; Moudgil, Kamal D.

    2008-01-01

    Objectives To review various antigen-specific tolerogenic and immunomodulatory approaches for arthritis in animal models and patients in regard to their efficacy, mechanisms of action and limitations. Methods We reviewed the published literature in Medline (PubMed) on the induction of antigen-specific tolerance and its effect on autoimmune arthritis, as well as the recent work on B cell-mediated tolerance from our laboratory. The prominent key words used in different combinations included arthritis, autoimmunity, immunotherapy, innate immunity, tolerance, treatment, and rheumatoid arthritis (RA). Although this search spanned the years 1975 to 2007, the majority of the short-listed articles belonged to the period 1990 to 2007. The relevant primary as well as cross-referenced articles were then collected from links within PubMed and reviewed. Results Antigen-specific tolerance has been successful in the prevention and/or treatment of arthritis in animal models. The administration of soluble native antigen or an altered peptide ligand intravenously, orally, or nasally, and the delivery of the DNA encoding a particular antigen by gene therapy have been the mainstay of immunomodulation. Recently, the methods for in vitro-expansion of CD4+CD25+ regulatory T cells have been optimized. Furthermore, interleukin-17 has emerged as a promising new therapeutic target in arthritis. However, in RA patients, non-antigen-specific therapeutic approaches have been much more successful than antigen-specific tolerogenic regimens. Conclusion An antigen-specific treatment against autoimmune arthritis is still elusive. However, insights into newly emerging mechanisms of disease pathogenesis provide hope for the development of effective and safe immunotherapeutic strategies in the near future. PMID:18177689

  2. Using AQUACROP to model the impacts of future climates on crop production and possible adaptation strategies in Sardinia and Tunisia

    NASA Astrophysics Data System (ADS)

    Bird, Neil; Benabdallah, Sihem; Gouda, Nadine; Hummel, Franz; La Jeunesse, Isabelle; Meyer, Swen; Soddu, Antonino; Woess-Gallasch, Susanne

    2014-05-01

    A work package in the FP-7 funded CLIMB Project - Climate Induced Changes on the Hydrology of Mediterranean Basins Reducing Uncertainty and Quantifying Risk through an Integrated Monitoring and Modeling System had the goal of assessing socioeconomic vulnerability in two super-sites in future climates (2040-2070). The work package had deliverables to describe of agricultural adaptation measures appropriate to each site under future water availability scenarios and assess the risk of income losses due to water shortages in agriculture. The FAO model AQUACROP was used to estimate losses of agricultural productivity and indicate possible adaptation strategies. The presentation will focus on two interesting crops which show extreme vulnerability to expected changes in climate; irrigated lettuce in Sardinia and irrigated tomatoes in Tunisia. Modelling methodology, results and possible adaptation strategies will be presented.

  3. Control strategies for effective robot assisted gait rehabilitation: the state of art and future prospects.

    PubMed

    Cao, Jinghui; Xie, Sheng Quan; Das, Raj; Zhu, Guo L

    2014-12-01

    A large number of gait rehabilitation robots, together with a variety of control strategies, have been developed and evaluated during the last decade. Initially, control strategies applied to rehabilitation robots were adapted from those applied to traditional industrial robots. However, these strategies cannot optimise effectiveness of gait rehabilitation. As a result, researchers have been investigating control strategies tailored for the needs of rehabilitation. Among these control strategies, assisted-as-needed (AAN) control is one of the most popular research topics in this field. AAN training strategies have gained the theoretical and practical evidence based backup from motor learning principles and clinical studies. Various approaches to AAN training have been proposed and investigated by research groups all around the world. This article presents a review on control algorithms of gait rehabilitation robots to summarise related knowledge and investigate potential trends of development. There are existing review papers on control strategies of rehabilitation robots. The review by Marchal-Crespo and Reinkensmeyer (2009) had a broad cover of control strategies of all kinds of rehabilitation robots. Hussain et al. (2011) had specifically focused on treadmill gait training robots and covered a limited number of control implementations on them. This review article encompasses more detailed information on control strategies for robot assisted gait rehabilitation, but is not limited to treadmill based training. It also investigates the potential to further develop assist-as-needed gait training based on assessments of patients' ability. In this paper, control strategies are generally divided into the trajectory tracking control and AAN control. The review covers these two basic categories, as well as other control algorithm and technologies derived from them, such as biofeedback control. Assessments on human gait ability are also included to investigate how to

  4. Strategies for the reduction of Legionella in biological treatment systems.

    PubMed

    Nogueira, R; Utecht, K-U; Exner, M; Verstraete, W; Rosenwinkel, K-H

    2016-01-01

    A community-wide outbreak of Legionnaire's disease occurred in Warstein, Germany, in August 2013. The epidemic strain, Legionella pneumophila Serogruppe 1, was isolated from an industrial wastewater stream entering the municipal wastewater treatment plant (WWTP) in Wartein, the WWTP itself, the river Wäster and air/water samples from an industrial cooling system 3 km downstream of the WWTP. The present study investigated the effect of physical-chemical disinfection methods on the reduction of the concentration of Legionella in the biological treatment and in the treated effluent entering the river Wäster. Additionally, to gain insight into the factors that promote the growth of Legionella in biological systems, growth experiments were made with different substrates and temperatures. The dosage rates of silver micro-particles, hydrogen peroxide, chlorine dioxide and ozone and pH stress to the activated sludge were not able to decrease the number of culturable Legionella spp. in the effluent. Nevertheless, the UV treatment of secondary treated effluent reduced Legionella spp. on average by 1.6-3.4 log units. Laboratory-scale experiments and full-scale measurements suggested that the aerobic treatment of warm wastewater (30-35 °C) rich in organic nitrogen (protein) is a possible source of Legionella infection. PMID:27533856

  5. Four treatment strategies for complex regional pain syndrome type 1.

    PubMed

    Lee, Sang Ki; Yang, Dae Suk; Lee, Jae Won; Choy, Won Sik

    2012-06-01

    Complex regional pain syndrome (CRPS) poses a dilemma for many clinicians due to its unknown etiology and largely unsuccessful treatment modalities. The purpose of this study was to compare the clinical results of 4 treatment modalities for CRPS type 1. A total of 59 patients were divided into 4 groups based on treatment modality: group A, an oral nonsteroidal anti-inflammatory drug (NSAID) (n=10); group B, oral gabapentin (n=12); group C, intravenous (IV) 10% mannitol and steroid (n=11); group D, a combination of IV 20% mannitol and steroid with oral gabapentin (n=26). The patients remained under medical supervision after discharge and were evaluated either once a month or once every 2 months until final follow-up at a mean of 8 months. Patients in group A showed improvement in pain level, finger range of motion, swelling, and grip strength, without statistical significance (P=.076, P=.062, P=.312, and P=.804, respectively). Patients in group B showed significant improvement in pain level (P<.001), and patients in group C showed improvement in pain, finger range of motion, and swelling (P=.127), which rendered functional impairment unchanged. In comparison, patients in group D showed recovery of grip strength and improvement in pain level, finger range of motion, and (P<.001, P=.016, P=.031, and P=.047, respectively). Based on these results, a protocol including a combination of IV 20% mannitol and steroid with oral gabapentin is an acceptable and effective treatment for CRPS type 1. PMID:22691654

  6. Anti-inflammatory strategies in the treatment of schizophrenia.

    PubMed

    Andrade, Chittaranjan

    2016-01-01

    Schizophrenia is a major mental illness with a lifetime prevalence of about 1%. Antipsychotic drugs, with a primary mechanism of action that involves dopamine receptor blockade, are the mainstay in the treatment of the disorder. However, despite optimum antipsychotic treatment, few patients return to pre-morbid levels; the treatment deficit includes refractory positive symptoms, negative symptoms, mood impairments, cognitive impairments, social impairments, and/or a variety of medication-related adverse effects, including extrapyramidal symptoms, metabolic disturbances, hyperprolactinemia, and others. To address these, antipsychotic treatment has been augmented with psychosocial interventions, cognitive rehabilitation, different kinds of electrical and magnetic brain stimulation, and a large range of drugs from the neuropsychiatric as well as, surprise, the general medical pharmacopeia. The pleomorphic pathophysiology of schizophrenia includes abnormalities in immunological and inflammatory pathways, and so it is not surprising that anti-inflammatory drugs have also been trialed as augmentation agents in schizophrenia. This article critically examines the outcomes after augmentation with conventional anti-inflammatory interventions; results from randomized controlled trials do not encourage the use of either aspirin (1000 mg/day) or celecoxib (400 mg/day), both of which have been studied for this indication during the past decade and a half. PMID:26427750

  7. VETERINARY PHARMACEUTICALS: POTENTIAL ENVIRONMENTAL IMPACT AND TREATMENT STRATEGIES

    EPA Science Inventory

    In the late 1970s it was recognized that there were increasing occurrences of antibiotic-resistant organisms in Europe and the US. Even in the early stages, concerns were raised that large-scale treatment of farm animals for infectious disease as well as growth enhancement may be...

  8. Current Treatment Strategies for Castration-Resistant Prostate Cancer

    PubMed Central

    Kim, Sun Il

    2011-01-01

    Prostate cancer is the most common cancer in men in United States and the fifth most common cancer in men in Korea. Although the majority of patients with metastatic prostate cancer initially respond to androgen deprivation therapy, almost all patients will eventually progress to develop castration-resistant prostate cancer (CRPC). Treatment options for CRPC remain limited. Prostate cancer was considered unresponsive to chemotherapy until the mid-1990s, when mitoxantrone combined with prednisone was shown to play a role in the palliative treatment of patients with CRPC. In 2004, two large randomized clinical trials demonstrated for the first time a small but significant survival advantage of docetaxel-based chemotherapy compared with mitoxantrone in patients with metastatic CRPC. Recently, cabazitaxel was shown to improve survival in patients with metastatic CRPC who progressed after docetaxel-based chemotherapy. Sipuleucel-T was also demonstrated to improve overall survival in patients with asymptomatic or minimally symptomatic metastatic CRPC. Along with mitoxantrone and docetaxel, cabazitaxel and sipuleucel-T are now approved for use in metastatic CRPC by the US Food and Drug Administration. There have been multiple early-phase clinical trials of various agents for the treatment of CRPC, and some are in phase III development. This review focuses on the key clinical trials of various treatment options of CRPC currently in use and under investigation. PMID:21461278

  9. Self-Injurious Behavior: Characteristics and Innovative Treatment Strategies

    ERIC Educational Resources Information Center

    Dykes, Michelle; Specian, Victoria; Nelson, Meredith; Gray, Neal

    2006-01-01

    Self-injurious behavior is the intentional harming of one's own body. Little attention has been given to SIB in the past, particularly in terms of innovative treatment approaches. Adolescents are at a particularly high-risk for developing this ineffectual coping mechanism. School counselors are in a unique position to aid in the identification of…

  10. Rational-Emotive Therapy with Children and Adolescents: Treatment Strategies.

    ERIC Educational Resources Information Center

    Bernard, Michael E.

    1990-01-01

    Presents rational-emotive therapy (RET) conceptualization of childhood disorders, discussing interaction of child temperament and parenting styles. Discusses RET child treatment goals, which involve modification of negative and inappropriate childhood emotions. Illustrates particular RET cognitive change methods (philosophical disputation;…

  11. Orgasm During Intercourse: A Treatment Strategy for Women

    ERIC Educational Resources Information Center

    Zeiss, Antonette M.; And Others

    1977-01-01

    A six-step treatment program for women who are inorgasmic during intercourse is described. Teaches women to associate orgasms brought on by manual clitoral stimulation with arousing thoughts about intercourse and vaginal containment of a dildo. Learning is generalized to vaginal containment of the partner's penis and thrusting movements. (Author)

  12. Contrasting water strategies of two Mediterranean shrubs of limited distribution: uncertain future under a drier climate.

    PubMed

    Lázaro-Nogal, Ana; Forner, Alicia; Traveset, Anna; Valladares, Fernando

    2013-12-01

    Plants have evolved different strategies to cope with drought, involving alternative ecophysiologies and different levels of plasticity. These strategies are critical for species of limited distribution, which are especially vulnerable to the current rates of rapid environmental change. The aim of this study was to assess the water strategy of two species with limited distribution, Cneorum tricoccon L. and Rhamnus ludovici-salvatoris Chodat., and evaluate their interpopulation variability along an aridity gradient to estimate their vulnerability to a drier climate. We measured different ecophysiological traits influenced by drought--stomatal conductance, maximum photochemical efficiency of photosynthesis II, carbon isotope ratio and chlorophyll concentration--in two climatically contrasting years, before and during summer drought. Both species were vulnerable to drought at the aridity limit of the gradient, but showed contrasting water strategies: while C. tricoccon was consistent in its water conservation strategy across the aridity gradient, R. ludovici-salvatoris was not, displaying higher and more variable stomatal conductances and being able to increase water-use efficiency at the most xeric sites. Changes in length and intensity of drought events may favor one species' strategy to the detriment of the other: C. tricoccon is more vulnerable to chronic and prolonged droughts, whereas short but acute droughts might have a stronger effect on R. ludovici-salvatoris. In those communities where these two species coexist, such different strategies might lead to changes in community structure under climate change scenarios, with unknown cascade effects on ecosystem functioning. PMID:24319030

  13. Impact of three empirical tuberculosis treatment strategies for people initiating antiretroviral therapy

    PubMed Central

    Van Rie, Annelies; Westreich, Daniel; Sanne, Ian

    2016-01-01

    Background Early mortality in people initiating antiretroviral treatment (ART) in Africa remains high. Empiric TB treatment strategies aim to reduce early mortality by initiating TB treatment in individuals without clinical suspicion of TB who are at high-risk of death from undiagnosed TB. Methods Using data from 16,913 individuals starting ART under programmatic conditions, we simulated the impact of three empiric treatment strategies on mortality and incident TB: two randomized clinical trials (REMEMBER and PrOMPT) and a pragmatic approach. The main analysis assumed that 50% of early deaths and 100% of incident TB is averted in those eligible and ignored outcomes in those lost to follow up. Results The increase in individuals eligible for TB treatment under empirical TB treatment strategies ranged from 4.4% to 31.4% as compared to those started on clinical or mycobacteriological grounds. The proportion of deaths averted by empiric treatment strategies ranged from 5.5% to 25.4%. The proportion of incident TB cases averted ranged from 10.9% to 57.3%. The proportion receiving any TB treatment during the first six months of ART increased from the observed 24.0% to an estimated 27.5%, 40.4% and 51.3% under the PrOMPT, REMEMBER and pragmatic approach, respectively. Conclusion The impact of empiric TB treatment strategies depends greatly on the eligibility criteria chosen. The additional strain placed on TB treatment facilities and the relatively limited impact of some empirical TB strategies raise the question whether the benefits will outweigh the risks at population level. PMID:25299868

  14. Treatment Strategy after Incomplete Endoscopic Resection of Early Gastric Cancer

    PubMed Central

    Kim, Sang Gyun

    2016-01-01

    Endoscopic resection of early gastric cancer is defined as incomplete when tumor cells are found at the resection margin upon histopathological examination. However, a tumor-positive resection margin does not always indicate residual tumor; it can also be caused by tissue contraction during fixation, by the cautery effect during endoscopic resection, or by incorrect histopathological mapping. Cases of highly suspicious residual tumor require additional endoscopic or surgical resection. For inoperable patients, argon plasma coagulation can be used as an alternative endoscopic treatment. Immediately after the incomplete resection or residual tumor has been confirmed by the pathologist, clinicians should also decide upon any additional treatment to be carried out during the follow-up period. PMID:27435699

  15. Treatment Strategy after Incomplete Endoscopic Resection of Early Gastric Cancer.

    PubMed

    Kim, Sang Gyun

    2016-07-01

    Endoscopic resection of early gastric cancer is defined as incomplete when tumor cells are found at the resection margin upon histopathological examination. However, a tumor-positive resection margin does not always indicate residual tumor; it can also be caused by tissue contraction during fixation, by the cautery effect during endoscopic resection, or by incorrect histopathological mapping. Cases of highly suspicious residual tumor require additional endoscopic or surgical resection. For inoperable patients, argon plasma coagulation can be used as an alternative endoscopic treatment. Immediately after the incomplete resection or residual tumor has been confirmed by the pathologist, clinicians should also decide upon any additional treatment to be carried out during the follow-up period. PMID:27435699

  16. The neurovascular unit and combination treatment strategies for stroke

    PubMed Central

    Zhang, Li; Zhang, Zhang Gang; Chopp, Michael

    2012-01-01

    Tissue plasminogen activator (tPA) administered within 4.5 hours of symptom onset restores cerebral blood flow and promotes neurological recovery of stroke patients. However, the narrow therapeutic time window and the risk of intracerebral hemorrhage after tPA treatment pose major hurdles to its clinical usage. In light of the failures of neuroprotective therapies in clinical trials, emerging concepts suggest that neuroprotection alone without restoration of tissue perfusion and vascular integrity may not be adequate for treatment of acute stroke. Here we review evidence of the use of adjuvant pharmacological agents to extend the therapeutic window for tPA via targeting the neurovascular unit and the underlying mechanisms of the combination therapy in experimental stroke. PMID:22595494

  17. Nanomedicine strategies for treatment of secondary spinal cord injury

    PubMed Central

    White-Schenk, Désirée; Shi, Riyi; Leary, James F

    2015-01-01

    Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly. Unfortunately, the delivery of effective therapeutics is quite limited. Due to the inefficient delivery of therapeutic drugs, nanoparticles have become a major field of exploration for medical applications. Based on their material properties, they can help treat disease by delivering drugs to specific tissues, enhancing detection methods, or a mixture of both. Incorporating nanomedicine into the treatment of neuronal injury and disease would likely push nanomedicine into a new light. This review highlights the various pathological issues involved in secondary spinal cord injury, current treatment options, and the improvements that could be made using a nanomedical approach. PMID:25673988

  18. Alcoholic liver disease. Treatment strategies for the potentially reversible stages.

    PubMed

    Hill, D B; Kugelmas, M

    1998-04-01

    Even modest alcohol ingestion can increase the risk of steatosis, and long-term, excessive consumption can lead to alcoholic hepatitis and eventually cirrhosis. Most patients with clinically significant alcoholic liver disease have histologic findings typical of all three conditions. The only clearly beneficial treatment is abstinence from alcohol. Abstinence in combination with proper nutrition and general supportive care is state of the art. Steatosis is reversible upon withdrawal of alcohol, but alcoholic hepatitis can persist even with abstinence and may progress to cirrhosis. Corticosteroid therapy may reduce short-term mortality rates in patients with moderate or severe alcoholic hepatitis who have hepatic encephalopathy but no evidence of infection or gastrointestinal bleeding. Treatment with colchicine may decrease the risk of cirrhosis; however, once cirrhosis has developed, the liver damage is irreversible. The prognosis is improved with abstinence, but complications (e.g., ascites, gastrointestinal bleeding) often occur. Liver transplantation may be considered in patients with severe complications. PMID:9553600

  19. Leachate pre-treatment strategies before recirculation in landfill bioreactors.

    PubMed

    Vigneron, V; Bouchez, T; Bureau, C; Mailly, N; Mazeas, L; Duquennoi, C; Audic, J M; Hébé, L; Bernet, N

    2005-01-01

    Nitrified leachate recirculation represents a promising strategy for a more sustainable landfill management. Our objective was to determine the reactions involved in nitrate reduction in municipal solid waste batch biodegradation tests. Anaerobic digestion of waste in the three control reactors showed a good reproducibility. In two test reactors, nitrate was added at various moments of the waste degradation process. We observed that: (1) H2S concentration controlled the nitrate reduction pathway: above a certain threshold of H2S, dissimilatory nitrate reduction to ammonium (DNRA) replaced denitrification. (2) N2O/N2 ratio varied with the organic carbon concentration: the lower the easily biodegradable carbon concentration, the higher the N2O/N2 ratio. (3) N2 was consumed after denitrification. The possibility of a nitrogen fixation reaction in the presence of NH4 is discussed. Nitrified leachate recirculation during acidogenesis should be avoided because of higher H2S production which could induce DNRA. PMID:16180441

  20. Overactive bladder: strategies to ensure treatment compliance and adherence

    PubMed Central

    Dhaliwal, Prabhpreet; Wagg, Adrian

    2016-01-01

    Overactive bladder is a common, debilitating condition for many patients who may benefit from pharmacological management of their condition. However, adherence to medication in this condition is markedly worse than other chronic medical conditions. This review explores what is known about persistence and the factors which influence medication adherence for overactive bladder, those factors that might be modifiable to improve adherence, and the measures the health care provider can take to optimize adherence to therapy and thereby improve treatment outcomes. PMID:27350744

  1. [Prevention and treatment strategy for burn wound sepsis in children].

    PubMed

    Niu, Xihua; Li, Xiaoling

    2016-02-01

    Wound sepsis is one of the main causes of death in patients with severe burn and trauma. The high incidence of burn wound sepsis in children is attributed to their imperfect immune system function, poor resistance against infection, and the weakened skin barrier function after burn. The key to reduce the mortality of pediatric patients with burn wound sepsis is to enhance the understanding of its etiology, epidemiology, pathogenesis, and diagnostic criteria, in order to improve its early diagnosis and treatment. PMID:26902271

  2. New and improved strategies for the treatment of gout

    PubMed Central

    Dubchak, Natalie; Falasca, Gerald F

    2010-01-01

    The Western world appears to be in the midst of the third great gout epidemic of all time. In this century, gout is increasing in prevalence despite an increased understanding of its risk factors and pathophysiology, and the availability of reasonably effective treatment. The main cultural factors responsible for this appear to be diet, obesity, ethanol use and medications. Excess fructose consumption is a newly recognized modifiable risk factor. The debate has been renewed concerning hyperuricemia as an independent risk factor for renal insufficiency and cardiovascular disease. Prevention is still rooted in lifestyle choices. Existing treatments have proven to be unsatisfactory in many patients with comorbidities. New treatments are available today and on the horizon for tomorrow, which offer a better quality of life for gout sufferers. These include febuxostat, a nonpurine inhibitor of xanthine oxidase with a potentially better combination of efficacy and safety than allopurinol, and investigational inhibitors of URAT-1, an anion exchanger in the proximal tubule that is critical for uric acid homeostasis. New abortive treatments include interleukin-1 antagonists that can cut short the acute attack in 1 to 2 days in persons who cannot take nonsteroidal anti-inflammatory drugs, colchicine or corticosteroids. Lastly, newer formulations of uricase have the ability to dissolve destructive tophi over weeks or months in patients who cannot use currently available hypouricemic agents. Diagnostically, ultrasound and magnetic resonance imaging offer advanced ways to diagnose gout noninvasively, and just as importantly, a way to follow the progress of tophus dissolution. The close association of hyperuricemia with metabolic syndrome, hypertension and renal insufficiency ensures that nephrologists will see increasing numbers of gout-afflicted patients. PMID:21694941

  3. [The modern strategies for the treatment of allergic rhinitis].

    PubMed

    Nosulya, E V; Kim, I A

    2016-01-01

    The present literature review had the objective to analyze the published data concerning the effectiveness of intranasal administration of antihistamine preparations and intranasal glucocorticoids for the treatment of allergic rhinitis. Special emphasis is placed on the clinical significance and the further prospects for the application of a fixed combination of these medications including azelastineplusmometasonefuroateas the first choice therapy of moderately severe and severe manifestations of allergic rhinitis. PMID:27213663

  4. Spontaneous fractures of the mandible concept & treatment strategy

    PubMed Central

    Marcussen, Mette

    2016-01-01

    Background Spontaneous fractures of the mandible dispose a surgical challenge in comparisons to fractures caused by trauma due to several complicating factors. Additionally: controversies exist concerning the terminology of the field. Material and Methods We conducted a retrospective study of all patients with mandibular fractures, with exclusion of fractures of the coronoid process and the alveolar process, treated at the Department of Oral and Maxillofacial Surgery, Aalborg University Hospital, Denmark between February 2003 and February 2013. Data collected from the medical records included sex, age, cause of fracture, site of fracture, and treatment. Results We identified 517 patients with 684 mandible fractures. Twenty-five of these were spontaneous fractures and 659 fractures were of traumatic origin. Condylar fractures rarely occur spontaneously, but constitute the majority of the traumatic fractures. Excluding these fractures from the analysis, we found a non-surgical approach in 14 of 24 (58%) of the spontaneous fractures and 110 of 376 (29%) of the traumatic fractures. This was statistically significant. Conclusions We found a statistical significant difference in favor of non-surgical approach in spontaneous fractures and we discussed the treatment challenges of these fractures. We addressed the terminological controversies regarding pathological fractures, and suggested the term spontaneous fractures denoting a fracture occurring during normal jaw function being either pathological or non-pathological. Key words:Mandibular fractures, spontaneous fractures, pathological fractures, traumatic fractures, treatment. PMID:26636905

  5. Treatment strategy in schizophrenia combined with eating disorder.

    PubMed

    Dadić-Hero, Elizabeta; Ružić, Klementina; Grahovac, Tanja; Valković, Toni; Petranović, Duška

    2011-03-01

    Like any other patient, a schizophrenic patient can get a physical illness, too. As such patients tend to ignore reality and neglect themselves and are stigmatized by society, due to which their physical symptomatology is often ignored, physical illness can remain undetected. If the schizophrenic patient is observed and adequate care is provided by the family, family doctor and a psychiatrist, it is possible to recognize the physical illness and intervene promptly. We are presenting a case of a female patient who has been treated for schizophrenia for a number of years. The treatment was mostly ambulatory (i.e. the patient was hospitalized twice) and consisted of first-generation antipsychotics. During the past two years, for reasons unknown, the patient stopped taking regular meals and as a result lost significant body weight, became apathetic and withdrawn, started avoiding social contacts and neglected personal hygiene. She reportedly took the psychopharmaca regularly, but rarely attended psychiatric follow-up consultations. Due to substantial weight loss and hypotonia, correction of antipsychotic was made and internist treatment administered. The choice of olanzapine was not an accidental one. We decided to take advantage of its side effect for the treatment of an anorectic syndrome. Interdisciplinary cooperation proved to be a justified decision. PMID:21448107

  6. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status

    PubMed Central

    Thon, Niklas; Kreth, Simone; Kreth, Friedrich-Wilhelm

    2013-01-01

    The identification of molecular genetic biomarkers considerably increased our current understanding of glioma genesis, prognostic evaluation, and treatment planning. In glioblastoma, the most malignant intrinsic brain tumor entity in adults, the promoter methylation status of the gene encoding for the repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) indicates increased efficacy of current standard of care, which is concomitant and adjuvant chemoradiotherapy with the alkylating agent temozolomide. In the elderly, MGMT promoter methylation status has recently been introduced to be a predictive biomarker that can be used for stratification of treatment regimes. This review gives a short summery of epidemiological, clinical, diagnostic, and treatment aspects of patients who are currently diagnosed with glioblastoma. The most important molecular genetic markers and epigenetic alterations in glioblastoma are summarized. Special focus is given to the physiological function of DNA methylation–in particular, of the MGMT gene promoter, its clinical relevance, technical aspects of status assessment, its correlation with MGMT mRNA and protein expressions, and its place within the management cascade of glioblastoma patients. PMID:24109190

  7. Exchange of futures for physicals offers several hedging strategies for volatile markets

    SciTech Connect

    Kane, G.J.; Scott, D.C.

    1989-01-23

    Exchange of futures for physicals (EFP), as applied to the Nymex energy complex, is in its simplest form, a mechanism for pricing a contract for physicals made basis a futures price, or exchanging a futures position (either long or short) for a similar position in the physical market. The level at which the futures are exchanged becomes the reference price used to establish the final flat price for the physical transaction. In most cases, EFPs are used to manage price risk, and at the same time, establish contractual commitments in the cash market with terms and conditions that are tailored to the needs of industry participants. Hence, EFPs nominally combine the making or taking of delivery of petroleum products against Nymex futures positions, but they are primarily used by the industry to hedge transactions and fix prices for cash deals. Most future markets are used primarily by commercial participants to hedge exposure to changing prices. Some future markets have no mechanism for the actual delivery of the physical commodity; settlement is made in cash. In most markets where there is a physical delivery, most positions are unwound before the delivery date. Likewise, actual delivery under Nymex energy contracts constitutes a small percentage of the total number of contracts traded.

  8. Monoclonal antibodies in the treatment of multiple myeloma: current status and future perspectives

    PubMed Central

    Lonial, S; Durie, B; Palumbo, A; San-Miguel, J

    2016-01-01

    The treatment landscape for patients with multiple myeloma (MM) is constantly evolving. Over the past decade, the introduction of novel agents such as proteasome inhibitors and immunomodulatory drugs has led to notable changes in therapeutic strategy, and improvements in survival, yet MM remains incurable in the vast majority of cases. More recently, a targeted approach to MM treatment has emerged, using monoclonal antibodies (mAbs) to target antigens expressed on the surface of MM cells. MAbs tested to date kill MM cells via the host's immune system and/or by promoting apoptosis, and appear to have generally improved tolerability compared with currently available treatments. Due to their distinct mode of action, mAbs are promising both for patients who have exhausted current regimens, and as part of first-line treatments in newly diagnosed patients. This review examines the recent developments in mAb-based therapy for MM, primarily focused on those agents in ongoing clinical testing. PMID:26265184

  9. Improving Treatment Adherence in Bipolar Disorder: A Review of Current Psychosocial Treatment Efficacy and Recommendations for Future Treatment Development

    ERIC Educational Resources Information Center

    Gaudiano, Brandon A.; Weinstock, Lauren M.; Miller, Ivan W.

    2008-01-01

    Treatment adherence is a frequent problem in bipolar disorder, with research showing that more than 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at…

  10. Treatment Strategies of Adult Primary Focal Segmental Glomerulosclerosis: A Systematic Review Focusing on the Last Two Decades

    PubMed Central

    Beer, Arno; Mayer, Gert

    2016-01-01

    Adult primary focal segmental glomerulosclerosis (FSGS) remains a therapeutic challenge for the treating physician. With the advent of novel immunosuppressive measures, our arsenal of therapeutic options increased considerably. The aim of this review was to summarize reports published over the last two decades which reported on treatment outcome. Most reports included patients with a steroid-resistant (SR) disease course, yet the cohort with the highest unmet need, since persistent nephrotic range proteinuria is associated with a poor renal prognosis and portends a high risk of developing end-stage renal disease. While in first-line treatment, steroid treatment remains the recommended standard with an overall remission rate of 50% and higher, optimal treatment strategies for steroid-dependent/multirelapsing (SD/MR) and SR patients have to be defined. In both entities, calcineurin inhibitors showed good efficacy, while mycophenolate mofetil was less effective in SR cases compared to those with SD/MR. The same was true for rituximab, a monoclonal antibody targeting B-cells. In resistant cases, addition of extracorporeal treatment options or treatment with alkylating agents may be considered. To shape the future for treatment of FSGS, international collaborations to conduct larger clinical trials are needed to identify potential novel efficacious immunosuppressive or immunomodulatory therapies. PMID:27144166

  11. The Future of Nematology: Integration of New and Improved Management Strategies

    PubMed Central

    Roberts, Philip A.

    1993-01-01

    The potential for managing plant-parasitic nenlatodes by combining two or more control strategies in an integrated program is examined. Advantages of this approach include the use of partially effective strategies and protection of highly effective ones vulnerable from nematode adaptation or environmental risk. Strategies can be combined sequentially from season to season or applied simultaneously. Programs that have several strategies available but that are limited in the true integration of control components are used as examples of current management procedures and the potential for their improvement. These include potato cyst nematodes in northern Europe, soybean cyst nematode in North Carolina, and root-knot nematodes on vegetable and field crops in California. A simplified model of the impact of component strategies on the nematode damage function indicates the potential for combining control measures with different efficacies to give acceptable nematode population reduction and crop protection. The likelihood for additive, synergistic, or antagonistic effects from combining strategies is considered with respect to the biological target and component compatibility. PMID:19279784

  12. Integrated health promotion strategies: a contribution to tackling current and future health challenges.

    PubMed

    Jackson, Suzanne F; Perkins, Fran; Khandor, Erika; Cordwell, Lauren; Hamann, Stephen; Buasai, Supakorn

    2006-12-01

    This paper was presented as a technical background paper at the WHO sixth Global Conference on Health Promotion in Bangkok Thailand, August 2005. It describes what we know about the effectiveness of four of the Ottawa Charter health promotion strategies from eight reviews that have been conducted since 1999. The six lessons are that (i) the investment in building healthy public policy is a key strategy; (ii) supportive environments need to be created at the individual, social and structural levels; (iii) the effectiveness of strengthening community action is unclear and more research and evidence is required; (iv) personal skills development must be combined with other strategies to be effective; (v) interventions employing multiple strategies and actions at multiple levels are most effective; (vi) certain actions are central to effectiveness, such as intersectoral action and interorganizational partnerships at all levels, community engagement and participation in planning and decision-making, creating healthy settings (particularly focusing on schools, communities, workplaces and municipalities), political commitment, funding and infrastructure and awareness of the socio-environmental context. In addition, four case studies at the international, national, regional and local levels are described as illustrations of combinations of the key points described earlier. The paper concludes that the four Ottawa Charter strategies have been effective in addressing many of the issues faced in the late 20th century and that these strategies have relevance for the 21st century if they are integrated with one another and with the other actions described in this paper. PMID:17307960

  13. Immunomodulators for the treatment of Crohn's disease in adults: optimal use and prospects for future drug treatments.

    PubMed

    Allen, Patrick B; Peyrin-Biroulet, Laurent

    2016-07-01

    Crohn's disease (CD) requires treatment beyond symptoms by enabling and maintaining mucosal healing and therefore clinical remission. However, with the increasing use of biologics there have been safety concerns and there is a significant cost implication with the early use of biologics. Therefore, it is imperative that patients with severe/complicated disease or poor prognostic factors are treated with an aggressive strategy while all remaining patients should be treated in a step-up strategy. The potential for disease modification with thiopurines and methotrexate is debated in CD when they are used as a monotherapy. In this review we discuss existing and newer therapies that have recently been developed for CD. We will also provide an algorithm for current management of adult CD patients in routine clinical practice. PMID:26900725

  14. Antifungal agents for onychomycosis: new treatment strategies to improve safety.

    PubMed

    Zane, Lee T; Chanda, Sanjay; Coronado, Dina; Del Rosso, James

    2016-01-01

    Onychomycosis is a common and difficult-to-treat fungal infection of the nail unit that gradually leads to dystrophic changes of the nail plate and nail bed. If untreated, infection progresses and may lead to discomfort, reduced quality of life, and risk of complications in patients with comorbid conditions (eg, diabetes, human immunodeficiency virus, peripheral vascular disease). Onychomycosis treatments are designed to eradicate causative pathogens (most commonly Trichophyton rubrum and Trichophyton mentagrophytes), restore healthy nails, and prevent recurrence or spread of infection. Given the deep-seated nature of most cases of onychomycosis, an effective antifungal agent needs to achieve and maintain sufficient drug concentrations throughout the nail unit for the duration of healthy nail in-growth. Oral antifungal drugs are the most effective available therapy and are generally well tolerated, but may be limited by safety concerns and the potential for drug-drug interactions (DDIs). Thus, treating physicians and pharmacists must be cognizant of a patient's current medications; indeed, it may not be feasible to treat onychomycosis in patients with diabetes, heart disease, or depression because of the risk for DDIs. Current topical therapy is not associated with risk of DDIs. Tavaborole and efinaconazole, two recently approved topical agents, have demonstrated good nail penetration and high negative culture rates in clinical trials of patients with onychomycosis. This article provides the treating physician and pharmacist with information on the safety and effectiveness of current oral (allylamine, azole) and topical (ciclopirox, efinaconazole, tavaborole) treatment to aid in making informed treatment decisions based on the unique characteristics (medication history, comorbidities, nature of onychomycosis) of each patient. PMID:27136621

  15. Lessons from Environmental Education: Developing Strategies for Public Consultation with the Georgia Basin Futures Project.

    ERIC Educational Resources Information Center

    Moore, Janet

    2002-01-01

    Describes an interdisciplinary project involving university researchers, community groups, and industry partners in a collaborative dialogue about sustainability. Focuses on the Georgia Basin Futures Project. (Contains 20 references.) (DDR)

  16. Second-line treatment of metastatic gastric cancer: Current options and future directions

    PubMed Central

    Kanagavel, Dheepak; Fedyanin, Mikhail; Tryakin, Alexey; Tjulandin, Sergei

    2015-01-01

    Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed. PMID:26556991

  17. Semantic Feature Analysis: Incorporating Typicality Treatment and Mediating Strategy Training to Promote Generalization

    ERIC Educational Resources Information Center

    Wambaugh, Julie L.; Mauszycki, Shannon; Cameron, Rosalea; Wright, Sandra; Nessler, Christina

    2013-01-01

    Purpose: This investigation was designed to examine the generalization effects of semantic treatment for word retrieval deficits in people with aphasia. Semantic feature analysis (SFA; Boyle & Coelho, 1995), typicality treatment (Kiran & Thompson, 2003), and mediating strategy training were combined to maximize potential generalization effects.…

  18. Recommended treatment strategies for patients with excessive daytime sleepiness.

    PubMed

    Rosenberg, Russell P

    2015-10-01

    Excessive daytime sleepiness (EDS) is a common and bothersome phenomenon. It can be associated with insufficient sleep syndrome, narcolepsy, idiopathic hypersomnia, obstructive sleep apnea, shift work disorder, Kleine-Levin syndrome, or Parkinson's disease. Once the underlying cause of the excessive sleepiness is determined, clinicians must select the most appropriate behavioral and pharmacologic interventions to reduce daytime sleepiness, alleviate other symptoms, improve functioning, and ensure the safety of patients and those around them. Patient history, adverse effects, and efficacy in specific conditions should be considered in pharmacologic treatment options for patients with EDS. PMID:26528660

  19. Impetigo and scabies - Disease burden and modern treatment strategies.

    PubMed

    Yeoh, Daniel K; Bowen, Asha C; Carapetis, Jonathan R

    2016-07-01

    Impetigo and scabies both present different challenges in resource-limited compared with industrialised settings. Severe complications of these skin infections are common in resource-limited settings, where the burden of disease is highest. The microbiology, risk factors for disease, diagnostic approaches and availability and suitability of therapies also vary according to setting. Taking this into account we aim to summarise recent data on the epidemiology of impetigo and scabies and describe the current evidence around approaches to individual and community based treatment. PMID:27180311

  20. Current Approaches, Challenges and Future Directions for Monitoring Treatment Response in Prostate Cancer

    PubMed Central

    Wallace, T.J.; Torre, T.; Grob, M.; Yu, J.; Avital, I.; Brücher, BLDM; Stojadinovic, A.; Man, Y.G.

    2014-01-01

    Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright. PMID:24396494

  1. Current surgical treatment strategies for hepatocellular carcinoma in North America.

    PubMed

    Khan, Adeel S; Fowler, Kathryn J; Chapman, William C

    2014-11-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor that often occurs in the setting of chronic liver disease. Many patients do not initially manifest any symptoms of HCC and present late when cure with surgical resection or transplantation is no longer possible. For this reason, patients at high risk for developing HCC are subjected to frequent screening processes. The surgical management of HCC is complex and requires an inter-disciplinary approach. Hepatic resection is the treatment of choice for HCC in patients without cirrhosis and is indicated in some patients with early cirrhosis (Child-Pugh A). Liver transplantation has emerged in the past decade as the standard of care for patients with cirrhosis and HCC meeting Milan criteria and in select patients with HCC beyond Milan criteria. Loco-regional therapy with transarterial chemoembolization, transarterial embolization, radiofrequency ablation and other similar local treatments can be used as neo-adjuvant therapy to downstage HCC to within Milan criteria or as a bridge to transplantation in patients on transplant wait list. PMID:25386049

  2. Therapeutic Strategies for the Treatment of Severe Cushing's Syndrome.

    PubMed

    Alexandraki, Krystallenia I; Grossman, Ashley B

    2016-03-01

    Severe Cushing's syndrome presents an acute emergency and is defined by massively elevated random serum cortisol [more than 36 μg/dL (1000 nmol/L)] at any time or a 24-h urinary free cortisol more than fourfold the upper limit of normal and/or severe hypokalaemia (<3.0 mmol/L), along with the recent onset of one or more of the following: sepsis, opportunistic infection, intractable hypokalaemia, uncontrolled hypertension, heart failure, gastrointestinal haemorrhage, glucocorticoid-induced acute psychosis, progressive debilitating myopathy, thromboembolism or uncontrolled hyperglycaemia and ketocacidosis. Treatment focuses on the management of the severe metabolic disturbances followed by rapid resolution of the hypercortisolaemia, and subsequent confirmation of the cause. Emergency lowering of the elevated serum cortisol is most rapidly achieved with oral metyrapone and/or ketoconazole; if parenteral therapy is required then intravenous etomidate is rapidly effective in almost all cases, but all measures require careful supervision. The optimal order and combination of drugs to treat severe hypercortisolaemia-mostly in the context of ectopic ACTH-secreting syndrome, adrenocortical carcinoma or an ACTH-secreting pituitary adenoma (mainly macroadenomas)-is not yet established. Combination therapy may be useful not only to rapidly control cortisol excess but also to lower individual drug dosages and consequently the possibility of adverse effects. If medical treatments fail, bilateral adrenalectomy should be performed in the shortest possible time span to prevent the debilitating complications of uncontrolled hypercortisolaemia. PMID:26833215

  3. New Strategies in the Treatment of Multiple Myeloma

    PubMed Central

    Munshi, Nikhil C.; Anderson, Kenneth C.

    2014-01-01

    Multiple myeloma (MM) is the second most common hematologic malignancy affecting terminally differentiated plasma cells. Although high-dose chemotherapy and autologous stem cell transplantation improved survival in younger patients, the natural history of MM has been changed with the availability of five new agents approved in last 10 years (thalidomide, bortezomib, lenalidomide, liposomal doxorubicin and carfilzomib). Despite this significant improvement in overall outcome, MM remains incurable in majority of patients prompting continued search for additional therapeutic options. Extensive molecular and genomic characterization of MM cells in its bone marrow milieu, which affects myeloma cell growth and survival, has provided number of novel drugable targets and pathways. Perturbation of protein catabolism at multiple levels has become an important target in MM. Similarly with improvements in monoclonal antibody generation and vaccine development along with identification of number of cell surface and cellular targets have led to development of various strategies including antibodies and antibody-drug conjugates which are under investigation both preclinically as well as in early clinical studies. We propose that eventually, molecularly-informed multi-agent combination therapies will be required to eliminate the MM cell clone for a long-term disease control. PMID:23515406

  4. Pharmacological treatments and strategies for reducing oral and intestinal acetaldehyde.

    PubMed

    Salaspuro, Ville

    2007-01-01

    Strong epidemiological, genetic and biochemical evidence indicates that local acetaldehyde exposure is a major factor behind gastrointestinal cancers especially associated with alcohol drinking and smoking. Thus, reducing the exposure to carcinogenic acetaldehyde either by decreasing the production or by eliminating acetaldehyde locally might offer a preventive strategy against acetaldehyde-induced gastrointestinal cancers. Thiol products, such as the amino acid cysteine, are known to be able to protect against acetaldehyde toxicity. Cysteine is able to bind acetaldehyde efficiently by forming a stable thiazolidine-carboxylic acid compound. Special cysteine preparations (such as lozenge and chewing gum) have already been developed to bind smoking and alcohol drinking derived acetaldehyde from the oral cavity. Most importantly, these type of drug formulations offer a novel method for intervention studies aimed to resolve the eventual role of acetaldehyde in the pathogenesis of upper digestive tract cancers. Acetaldehyde exposure could also be influenced by modifying the acetaldehyde producing microbiota. With regard to the upper digestive tract, acetaldehyde production from ingested ethanol could be significantly reduced by using an antiseptic mouthwash, chlorhexidine. In the large intestine acetaldehyde production could be markedly decreased either by reducing the Gram-negative microbes by ciprofloxacin antibiotic or by lowering the intraluminal pH by lactulose. PMID:17590993

  5. Pulmonary alveolar proteinosis. Clinical manifestations and optimal treatment strategies.

    PubMed

    Venkateshiah, Saiprakash B; Thomassen, Mary Jane; Kavuru, Mani S

    2004-01-01

    Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of surfactant phospholipids and proteins within the lung alveoli. Important advances have been made over the past 8 years in our understanding of this disease, offering new directions for research and patient care. First, genetically altered mice that are homozygous for a disrupted granulocyte-macrophage colony-stimulating factor (GM-CSF) gene developed a lung lesion with histologic resemblance to PAP. The surfactant is thought to be catabolized or cleared mostly by alveolar macrophages, this process being dependent on GM-CSF. Second, a neutralizing autoantibody against GM-CSF was found in serum and bronchoalveolar lavage fluid of patients with idiopathic PAP but not in healthy controls, thereby raising the suspicion that human PAP may be an autoimmune disease. The relationship between the antibody and disease pathogenesis remains unclear but data suggest that the GM-CSF antibody may have a potential role as a diagnostic test. No specific therapy exists for PAP. Sequential whole lung lavage is the standard of care. Exogenous therapy with GM-CSF may improve the lung disease in some patients with PAP but this therapy is still experimental. Interventions directed at treating a relative GM-CSF deficiency by administration of GM-CSF or lowering the antibody level (i.e. by plasmapheresis or immunosuppression) may hold promise as future therapy for this rare disease. PMID:15350160

  6. Therapeutic Strategies for the Treatment of Alcoholic Hepatitis.

    PubMed

    Singal, Ashwani K; Shah, Vijay H

    2016-02-01

    Acute alcoholic hepatitis is a unique clinical syndrome among patients with chronic and active heavy alcohol use. Presenting with acute or chronic liver failure, a severe episode has a potential for 30 to 40% mortality at 1 month from presentation, if not recognized and left untreated. Alcoholic hepatitis patients need supportive therapy for abstinence and nutritional supplementation for those patients with markedly reduced caloric intake. Results of the recently published STOPAH (Steroids or Pentoxifylline for Alcoholic Hepatitis) Study showed only a benefit of corticosteroids on short-term mortality without any benefit of pentoxifylline. Neither of these two drugs impacts medium- and long-term mortality, which is mainly driven by abstinence from alcohol. With the emerging data on the benefits of liver transplantation, liver transplantation could be an important salvage option for a very highly select group of AH patients. More data are needed on the use of liver transplantation in AH as the basis for deriving protocols for selecting cases and for posttransplant management. Currently, many clinical trials are examining the efficacy and safety of new or repurposed compounds in severe AH. These drugs are targeted at various pathways in the pathogenesis of AH: the gut-liver axis, the inflammatory cascade, and liver injury. With increasing interest of researchers and clinicians, supported by funding from the National Institute on Alcohol Abuse and Alcoholism, the future seems promising for the development of effective and safe pharmacological interventions for severe AH. PMID:26870933

  7. Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.

    PubMed

    Stine, Jonathan G; Lewis, James H

    2016-04-01

    While the pace of discovery of new agents, mechanisms and risk factors involved in drug-induced liver injury (DILI) remains brisk, advances in the treatment of acute DILI seems slow by comparison. In general, the key to treating suspected DILI is to stop using the drug prior to developing irreversible liver failure. However, predicting when to stop is an inexact science, and commonly used ALT monitoring is an ineffective strategy outside of clinical trials. The only specific antidote for acute DILI remains N-acetylcysteine (NAC) for acetaminophen poisoning, although NAC is proving to be beneficial in some cases of non-acetaminophen DILI in adults. Corticosteroids can be effective for DILI associated with autoimmune or systemic hypersensitivity features. Ursodeoxycholic acid, silymarin and glycyrrhizin have been used to treat DILI for decades, but success remains anecdotal. Bile acid washout regimens using cholestyramine appear to be more evidenced based, in particular for leflunomide toxicity. For drug-induced acute liver failure, the use of liver support systems is still investigational in the United States and emergency liver transplant remains limited by its availability. Primary prevention appears to be the key to avoiding DILI and the need for acute treatment. Pharmacogenomics, including human leukocyte antigen genotyping and the discovery of specific DILI biomarkers offers significant promise for the future. This article describes and summarizes the numerous and diverse treatment and prevention modalities that are currently available to manage DILI. PMID:26633044

  8. Effects of Urban Heat Island Mitigation Strategies on Current and Future Meteorology of Atlanta, Georgia

    NASA Astrophysics Data System (ADS)

    Crosson, W. L.; Lapenta, W. M.; Griggs, L.; Kenna, G.; Johnson, H.; Dembek, S.

    2004-05-01

    The characterization of land use/land cover is an integral component of an ongoing air quality modeling project focused on evaluating strategies for reducing the Urban Heat Island (UHI) and improving air quality in Atlanta, Georgia. The `UHI mitigation strategies' applied in this project involve `Cool Communities' principles of high albedo pavement and roofing as well as increased urban tree canopy. These strategies have been developed based on input from local stakeholders and represent conditions that are attainable assuming broad-based support from local government and the community. In order to evaluate the impact of these strategies on urban meteorology (principally near-surface air temperature) and ultimately on air quality, mesoscale model simulations have been performed for the Atlanta region based on land use for 1999 and projected to 2030 using the Spatial Growth Model assuming `Business as Usual' development. Significant land use change associated with continuing urban sprawl is expected from now until 2030. Model simulations based on identical synoptic forcing were performed to evaluate the effects of local land use change on local and regional meteorology. For the 2030 case, results from `Business as Usual' and `UHI mitigation strategies' simulations will be compared. The impacts of higher urban albedo and increased tree cover will be examined separately and in combination.

  9. Transoral treatment strategies for head and neck tumors

    PubMed Central

    Arens, Christoph

    2012-01-01

    The introduction of transoral endoscopic surgery has initiated a fundamental change in the treatment of head and neck cancer. The endoscopic approach minimizes the intraoperative trauma. Due to the lower burden for the patient and the savings potential these methods have gained wide acceptance. These transoral accesses routes allow experienced surgeons to reduce the morbidity of surgical resection with no deterioration of oncologic results. This suggests a further extension of the indication spectrum and a high growth potential for these techniques and equipment in the coming years. For selected patients with selected tumors the minimally invasive transoral surgery offers improved oncological and functional results. In the present paper, different surgical access routes are presented and their indications discussed. PMID:23320057

  10. Alternative pharmacological strategies for adult ADHD treatment: a systematic review.

    PubMed

    Buoli, Massimiliano; Serati, Marta; Cahn, Wiepke

    2016-01-01

    Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder. PMID:26693882

  11. Current strategies for treatment of relapsed/refractory multiple myeloma.

    PubMed

    Laubach, Jacob P; Voorhees, Peter M; Hassoun, Hani; Jakubowiak, Andrzej; Lonial, Sagar; Richardson, Paul G

    2014-02-01

    In spite of significant advances in the management of multiple myeloma (MM), the disease remains incurable and nearly all patients ultimately relapse and require salvage chemotherapy. As such, relapsed and relapsed-refractory MM remains a critical area of research pertaining to biological mechanisms of progression and chemotherapy resistance, as well as to the development of new pharmacologic agents and immunologic approaches for the disease. The immunomodulatory agents and proteasome inhibitors represent the cornerstone of treatment in this setting, with combination regimens incorporating these drugs demonstrating encouraging rates and duration of response, including the newer agents, pomalidomide and carfilzomib. In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat. PMID:24471924

  12. Mechanism and Treatment Strategy of Osteoporosis after Transplantation.

    PubMed

    Song, Lei; Xie, Xu-Biao; Peng, Long-Kai; Yu, Shao-Jie; Peng, Ya-Ting

    2015-01-01

    Osteoporosis (OP) has emerged as a frequent and devastating complication of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressants on bone remodeling and bone quality. Many factors contribute to the pathogenesis of OP in transplanted patients. Many mechanisms of OP have been deeply approached. Drugs for OP can be generally divided into "bone resorption inhibitors" and "bone formation accelerators," the former hindering bone resorption by osteoclasts and the latter increasing bone formation by osteoblasts. Currently, bisphosphonates, which are bone resorption inhibitors drugs, are more commonly used clinically than others. Using the signaling pathway or implantation bone marrow stem cell provides a novel direction for the treatment of OP, especially OP after transplantation. This review addresses the mechanism of OP and its correlation with organ transplantation, lists prevention and management of bone loss in the transplant recipient, and discusses the recipients of different age and gender. PMID:26273295

  13. [The lazy eye - contemporary strategies of amblyopia treatment].

    PubMed

    Sturm, V

    2011-02-16

    Amblyopia is a condition of decreased monocular or binocular visual acuity caused by form deprivation or abnormal binocular interaction. Amblyopia is the most common cause of monocular vision loss in children with a prevalence of 2 to 5%. During the last decade, several prospective randomized studies have influenced our clinical management. Based on these studies, optimum refractive correction should be prescribed first. However, most patients will need additional occlusion therapy which is still considered the «gold standard» of amblyopia management. Now much lower doses have been shown to be effective. In moderate amblyopia, penalization with atropine is as effective as patching. New treatment modalities including perceptual learning, pharmacotherapy with levodopa and citicholine or transcranial magnetic stimulation have not yet been widely accepted. PMID:21328237

  14. Understanding the neuroinflammatory response following concussion to develop treatment strategies

    PubMed Central

    Patterson, Zachary R.; Holahan, Matthew R.

    2012-01-01

    Mild traumatic brain injuries (mTBI) have been associated with long-term cognitive deficits relating to trauma-induced neurodegeneration. These long-term deficits include impaired memory and attention, changes in executive function, emotional instability, and sensorimotor deficits. Furthermore, individuals with concussions show a high co-morbidity with a host of psychiatric illnesses (e.g., depression, anxiety, addiction) and dementia. The neurological damage seen in mTBI patients is the result of the impact forces and mechanical injury, followed by a delayed neuroimmune response that can last hours, days, and even months after the injury. As part of the neuroimmune response, a cascade of pro- and anti-inflammatory cytokines are released and can be detected at the site of injury as well as subcortical, and often contralateral, regions. It has been suggested that the delayed neuroinflammatory response to concussions is more damaging then the initial impact itself. However, evidence exists for favorable consequences of cytokine production following traumatic brain injuries as well. In some cases, treatments that reduce the inflammatory response will also hinder the brain's intrinsic repair mechanisms. At present, there is no evidence-based pharmacological treatment for concussions in humans. The ability to treat concussions with drug therapy requires an in-depth understanding of the pathophysiological and neuroinflammatory changes that accompany concussive injuries. The use of neurotrophic factors [e.g., nerve growth factor (NGF)] and anti-inflammatory agents as an adjunct for the management of post-concussion symptomology will be explored in this review. PMID:23248582

  15. Treatment strategies for osteoarthritis patients with pain and hypertension.

    PubMed

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-08-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  16. Treatment Strategies for Osteoarthritis Patients with Pain and Hypertension

    PubMed Central

    Verdecchia, Paolo; Angeli, Fabio; Mazzotta, Giovanni; Martire, Paola; Garofoli, Marta; Gentile, Giorgio; Reboldi, Gianpaolo

    2010-01-01

    Out of 100 patients with osteoarthritis (OA), almost 40 have a concomitant diagnosis of hypertension. Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors may trigger a rise in blood pressure (BP), which is more marked in patients with established hypertension. NSAIDs and COX-2 inhibitors attenuate the antihypertensive effect of several antihypertensive agents. Frequent BP controls are needed in treated hypertensive patients who are concomitantly receiving NSAIDs or COX-2 inhibitors because even a small increase in BP may be associated with an important rise in the risk of major cardiovascular complications. In meta-analyses, an increase in systolic BP of 5mmHg was associated with a 25% higher risk of cardiovascular events. These data have been confirmed in randomized studies with rofecoxib and celecoxib, where a modest increase in BP was associated with a significantly higher risk of cardiovascular disease. There is emerging evidence that the COX-inhibiting nitric oxide donator (CINOD) class is promising in the treatment of patients with OA. Naproxcinod, the first CINOD investigated in clinical trials, is composed of the traditional NSAID naproxen covalently bound to the nitric oxide (NO)-donating moiety butanediol mono-nitrate (BDMN). The molecule has the potential to provide a sustained release of NO. In clinical studies, naproxcinod prevented the BP rise in normotensive and hypertensive patients observed with naproxen. The BP benefit of naproxcinod over naproxen was greater in patients concomitantly receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. These investigational data suggest that naproxcinod is a valuable alternative to NSAIDs and COX-2 inhibitors for treatment of OA patients. PMID:22870450

  17. AN EFFICIENT TREATMENT STRATEGY FOR HISTOTRIPSY BY REMOVING CAVITATION MEMORY

    PubMed Central

    Wang, Tzu-Yin; Xu, Zhen; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.

    2012-01-01

    Cavitation memory effects occur when remnants of cavitation bubbles (nuclei) persist in the host medium and act as seeds for subsequent events. In pulsed cavitational ultrasound therapy, or histotripsy, this effect may cause cavitation to repeatedly occur at these seeded locations within a target volume, producing inhomogeneous tissue fractionation or requiring an excess number of pulses to completely homogenize the target volume. We hypothesized that by removing the cavitation memory, i.e., the persistent nuclei, the cavitation bubbles could be induced at random locations in response to each pulse; therefore, complete disruption of a tissue volume may be achieved with fewer pulses. To test the hypothesis, the cavitation memory was passively removed by increasing the intervals between successive pulses, Δt, from 2, 10, 20, 50 and 100, to 200 ms. Histotripsy treatments were performed in red blood cell tissue phantoms and ex vivo livers using 1-MHz ultrasound pulses of 10 cycles at P−/P+ pressure of 21/59 MPa. The phantom study allowed for direct visualization of the cavitation patterns and the lesion development process in real time using high-speed photography; the ex vivo tissue study provided validation of the memory effect in real tissues. Results of the phantom study showed an exponential decrease in the correlation coefficient between cavitation patterns in successive pulses from 0.5 ± 0.1 to 0.1 ± 0.1 as Δt increased from 2–200 ms; correspondingly, the lesion was completely fractionated with significantly fewer pulses for longer Δts. In the tissue study, given the same number of therapy pulses, complete and homogeneous tissue fractionation with well-defined lesion boundaries was achieved only for Δt ≥ 100 ms. These results indicated that the removal of the cavitation memory resulted in more efficient treatments and homogeneous lesions. PMID:22402025

  18. [Acute necrotizing pancreatitis--diagnostic and treatment strategy].

    PubMed

    Madzhov, R; Georgiev, K; Arnaudov, P; Radev, R; Bankov, P

    2003-01-01

    Despite of the current achievements of medicine, the mortality of necrotizing pancreatitis (NP) is still too high--up to 35-40% and stands as a serious diagnostic and treatment problem. The results of treatment of 148 patients, admitted in the clinic with diagnosis NP, 95 males and 53 females, are discussed. The ratio between patients with acute oedematic and acute NP is 81.1% to 18.9%. According to the hystopatology findings, the results are as follows: pancreatic necrosis--128 patients, peripancreatic necrosis--42 patients, retropancreatic necrosis--29 patients, phlegmonous cholecystitis--31 patients. For the exact diagnostic estimation of the development and prognosis of NP, we are based on: Clinic symptomatology, biochemical constellations (the prognostic scale of Ranson), ultrasonography, CT, ERCP, ES, laparoscopy (48 pts), and laparoscopic drainage (34 pts) of the abdominal cavity with one or two drains, in order to decrease the intoxication and manage intraperitoneal irrigation with antibiotics and enzymes. The operative intervations consists of a thorough exploration, broad necrectomy combined with lavage and large drainage. COLD (controlled open lesser sac drainage) has been performed at 34 cases. In 31 pts cholecystectomy and choledochotomy with T-tube drainage of d. choledochus (Kehr drainage) was performed. Reoperations have been made at 34 pts (22.9%); in 11 of them--2 operative revisions have been carried out, in 3 cases--three, and in 3 cases--4 operative revisions were performed. The total postoperative death rate was 21.6% (32 patients). The most common postoperative complications were as follows: pulmonary complications at 11 cases, pleural effusions--9 pts, intraabdominal abscesses--6 patients, postnecrotic pseudocysts--9 cases, pancreatic fistulas--6 cases, fistulas of the colon--2 pts, bleeding--4 patients. PMID:15584453

  19. Probiotic as a Novel Treatment Strategy Against Liver Disease

    PubMed Central

    Imani Fooladi, Abbas Ali; Mahmoodzadeh Hosseini, Hamideh; Nourani, Mohammad Reza; Khani, Soghra; Alavian, Seyed Moayed

    2013-01-01

    Context A symbiotic relationship between the liver and intestinal tract enables the healthy status of both organs. Microflora resident in intestinal lumen plays a significant role in hepatocytes function. Alterations to the type and amount of microorganisms that live in the intestinal tract can result in serious and harmful liver dysfunctions such as cirrhosis, nonalcoholic fatty liver disease, alcoholic liver disease, and hepatic encephalopathy. An increased number of pathogens, especially enterobacteriaceae, enterococci, and streptococci species causes the elevation of intestinal permeability and bacterial translocation. The presence of high levels of lipopolysaccharide (LPS) and bacterial substances in the blood result in a portal hypertension and ensuing hepatocytes damage. Several methods including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens. Compared to prebiotic and antibiotic therapy, probiotics strains are a safer and less expensive therapy. Probiotics are "live microorganisms (according to the FAO/WHO) which when administered in adequate amounts confer a health benefit on the host”. Evidence Acquisitions Data from numerous preclinical and clinical trials allows for control of the flora bacteria quantity, decreases in compounds derived from bacteria, and lowers proinflammatory production such as TNF-α, IL-6 and IFN-γ via down-regulation of the nuclear factor kappa B (NF-κ B). Results On the other hand, probiotic can reduce the urease activity of bacterial microflora. Furthermore, probiotic decreases fecal pH value and reduces ammonia adsorption. In addition, the serum level of liver enzymes and other substances synthesized by the liver are modulated subsequent to probiotic consumption. Conclusions According to our knowledge, Probiotic therapy as a safe, inexpensive and a noninvasive strategy can reduce pathophysiological symptoms and improve different types of liver diseases without side

  20. [Novel treatment strategies for refractory patients with obsessive-compulsive disorder].

    PubMed

    Nakamae, Takashi

    2013-01-01

    Although selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT) are first-line treatments for obsessive-compulsive disorder (OCD), response rates to these therapies are 40-60%. There may be many treatment-refractory patients who do not respond to several SSRIs and intensive CBT treatment. The current treatment guidelines suggest various strategies for treatment-refractory cases, but there is no established evidence for most of them. Augmentation therapies with antipsychotics and glutamate modulator drugs have yielded some supporting evidence. When all drugs and CBT are ineffective, non-pharmacological treatment including deep brain stimulation (DBS) should be applied. However, it is necessary to establish criteria for treatment-refractory patients and standardize conventional treatment before neuromodulation treatment is applied in Japan. PMID:24228478

  1. Tailored treatment strategies: a new approach for modern management of atrial fibrillation.

    PubMed

    Van Gelder, I C; Hobbelt, A H; Marcos, E G; Schotten, U; Cappato, R; Lewalter, T; Schwieler, J; Rienstra, M; Boriani, G

    2016-05-01

    Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options. PMID:26991684

  2. A global logrank test for adaptive treatment strategies based on observational studies.

    PubMed

    Li, Zhiguo; Valenstein, Marcia; Pfeiffer, Paul; Ganoczy, Dara

    2014-02-28

    In studying adaptive treatment strategies, a natural question that is of paramount interest is whether there is any significant difference among all possible treatment strategies. When the outcome variable of interest is time-to-event, we propose an inverse probability weighted logrank test for testing the equivalence of a fixed set of pre-specified adaptive treatment strategies based on data from an observational study. The weights take into account both the possible selection bias in an observational study and the fact that the same subject may be consistent with more than one treatment strategy. The asymptotic distribution of the weighted logrank statistic under the null hypothesis is obtained. We show that, in an observational study where the treatment selection probabilities need to be estimated, the estimation of these probabilities does not have an effect on the asymptotic distribution of the weighted logrank statistic, as long as the estimation of the parameters in the models for these probabilities is n-consistent. Finite sample performance of the test is assessed via a simulation study. We also show in the simulation that the test can be pretty robust to misspecification of the models for the probabilities of treatment selection. The method is applied to analyze data on antidepressant adherence time from an observational database maintained at the Department of Veterans Affairs' Serious Mental Illness Treatment Research and Evaluation Center. PMID:24108518

  3. The opportunity and strategy for quality and health-system improvement now and in the future.

    PubMed

    Sherar, Michael; Maley, Oonagh

    2015-01-01

    Since 2004, Cancer Care Ontario (CCO) has played a leadership role in linking funding to quality of care, and in using evidence and administrative and clinical data to drive performance and quality improvement. This article describes how CCO has used its cancer and renal health system strategies to establish an environment of continuous health system improvement. The article also describes how CCO's Corporate Strategy is driving organizational improvement: evolving CCO's capacity and capability to drive quality and value across healthcare settings, and its ability to advance broader health system transformation in support of cancer and renal patients. PMID:25562136

  4. Multimodal treatment for stage IVA thymoma: a proposable strategy.

    PubMed

    Rena, Ottavio; Mineo, Tommaso Claudio; Casadio, Caterina

    2012-04-01

    A retrospective review of a series of consecutive patients was carried out to evaluate the feasibility and the efficacy of a multimodal treatment in the management of stage IVA thymoma at first diagnosis. From 1998 to 2008, 18 patients affected by stage IVA thymoma underwent neoadjuvant chemotherapy, surgery and subsequent mediastinal radiation therapy. There were 10 males and 8 females, mean age 54.5 years (range 29-68). Not specific symptoms were present in 12 cases and thymus-related syndromes were reported in 4. Histological subtypes were 1 AB, 2 B1, 4 B2, 7 B3, 1 mixed B1-B2, 1 mixed B1-B3 and 2 mixed B2-B3 thymomas. Neoadjuvant chemotherapy (4 courses of cisplatin-based chemotherapy) was well tolerated in all cases. Those patients demonstrating clinical response at restaging (16/18) received surgical resection: "en-bloc" thymoma, residual thymic tissue and tumour involved organs resection was carried out together with the pleural implants removal. Complete macroscopic resection was achieved 10/16 patients (64%). Postoperative mortality and morbidity were null and 24%, respectively. Adjuvant radiation therapy consisted of 45-54 Gy administered by a 6 MV linear accelerator to the whole mediastinum and previous tumour bed. Mean follow-up was 82±33 months (range 31-143); overall survival was 85% and 53% at 5- and 10-years. Disease-related survival of the entire cohort was 100% and 58% at 5- and 10-years, whereas freedom from relapse survival for patients submitted to complete resection was 58% and 42% at 5- and 10-years. Disease-related survival when complete and not complete resection were considered were 100% and 52% and 72% and 0% at 5- and 10-years respectively (p=0.048). Multimodal management based on induction chemotherapy, subsequent surgery and postoperative mediastinal radiation allows a good complete resection rate and it is demonstrated to be a safe and effective treatment to warrant a good long-term survival in stage IVA thymoma patients. PMID

  5. Endovascular strategies for treatment of embolizing thoracoabdominal aortic lesions

    PubMed Central

    Jeyabalan, Geetha; Wallace, Justin R.; Chaer, Rabih Antoine; Leers, Steven A.; Marone, Luke Keith; Makaroun, Michel S.

    2014-01-01

    -up. The 1-year mortality rate was 25%. Conclusions Endovascular coverage of atheroembolic sources in the aorta is feasible and is safe and effective in properly selected patients. It does not appear to worsen renal function when performed with the use of specific technical strategies. PMID:24433783

  6. Current knowledge and future research directions in treatment-related second primary malignancies

    PubMed Central

    Morton, Lindsay M.; Swerdlow, Anthony J.; Schaapveld, Michael; Ramadan, Safaa; Hodgson, David C.; Radford, John; van Leeuwen, Flora E.

    2014-01-01

    Currently, 17–19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk. In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer. Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose–volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening. PMID:26217162

  7. Secondary Low-Level Waste Treatment Strategy Analysis

    SciTech Connect

    D.M. LaRue

    1999-05-25

    The objective of this analysis is to identify and review potential options for processing and disposing of the secondary low-level waste (LLW) that will be generated through operation of the Monitored Geologic Repository (MGR). An estimate of annual secondary LLW is generated utilizing the mechanism established in ''Secondary Waste Treatment Analysis'' (Reference 8.1) and ''Secondary Low-Level Waste Generation Rate Analysis'' (Reference 8.5). The secondary LLW quantities are based on the spent fuel and high-level waste (HLW) arrival schedule as defined in the ''Controlled Design Assumptions Document'' (CDA) (Reference 8.6). This analysis presents estimates of the quantities of LLW in its various forms. A review of applicable laws, codes, and standards is discussed, and a synopsis of those applicable laws, codes, and standards and their impacts on potential processing and disposal options is presented. The analysis identifies viable processing/disposal options in light of the existing laws, codes, and standards, and then evaluates these options in regard to: (1) Process and equipment requirements; (2) LLW disposal volumes; and (3) Facility requirements.

  8. Genetic heterogeneity in Alzheimer disease and implications for treatment strategies.

    PubMed

    Ringman, John M; Goate, Alison; Masters, Colin L; Cairns, Nigel J; Danek, Adrian; Graff-Radford, Neill; Ghetti, Bernardino; Morris, John C

    2014-11-01

    Since the original publication describing the illness in 1907, the genetic understanding of Alzheimer's disease (AD) has advanced such that it is now clear that it is a genetically heterogeneous condition, the subtypes of which may not uniformly respond to a given intervention. It is therefore critical to characterize the clinical and preclinical stages of AD subtypes, including the rare autosomal dominant forms caused by known mutations in the PSEN1, APP, and PSEN2 genes that are being studied in the Dominantly Inherited Alzheimer Network study and its associated secondary prevention trial. Similar efforts are occurring in an extended Colombian family with a PSEN1 mutation, in APOE ε4 homozygotes, and in Down syndrome. Despite commonalities in the mechanisms producing the AD phenotype, there are also differences that reflect specific genetic origins. Treatment modalities should be chosen and trials designed with these differences in mind. Ideally, the varying pathological cascades involved in the different subtypes of AD should be defined so that both areas of overlap and of distinct differences can be taken into account. At the very least, clinical trials should determine the influence of known genetic factors in post hoc analyses. PMID:25217249

  9. Adenomyosis: new knowledge is generating new treatment strategies.

    PubMed

    Benagiano, Giuseppe; Brosens, Ivo; Carrara, Sabina

    2009-05-01

    In the early days, all mucosal invasions of abdominal organs were considered to be one pathological condition of uncertain origin, termed adenomyoma. It was only in the 1920s that endometriosis and adenomyosis were clearly separated and it took approximately 80 years to put forward a new theory reunifying their pathogenesis. Today, identification of adenomyosis is carried out exclusively through vaginal ultrasonography and MRI. These techniques have made a careful evaluation of a distinct anatomical structure and the inner myometrial layers underlying the endometrium, termed the junctional zone, possible. Adenomyosis is characterized by a homogeneous thickening of this portion of the myometrium. When this hyperplasia is associated to an alteration of spiral arterioles' angiogenesis, then both adenomyosis and endometriosis may develop. Evidence is being accumulated that pre-eclampsia, fetal growth restriction and premature delivery may be linked, together representing a new, major obstetrical syndrome characterized by a modified uterine environment around the time of nidation. A dozen different medical or surgical techniques are utilized for the treatment of adenomyosis and novel approaches are being tested. These include use of inhibitors of angiogenesis that have been shown to cause reduced neo-angiogenesis, a significant modification of gene expression and a decrease in the percentage of active lesions. Encouraging results have also been obtained with the levonorgestrel-releasing intrauterine system. PMID:19392615

  10. [Treatment Strategy for Gastric Carcinoma with Lymphoid Stroma].

    PubMed

    Kobayashi, Ryosuke; Takiguchi, Nobuhiro; Nabeya, Yoshihiro; Ikeda, Atsushi; Souda, Hiroaki; Kainuma, Osamu; Tonooka, Toru; Imanishi, Shunsuke; Arimitsu, Hidehito; Chibana, Tomofumi; Ishige, Fumitaka; Sasaki, Kosuke; Yamamoto, Hiroshi

    2015-11-01

    Gastric carcinoma with lymphoid stroma (GCLS) is a histological type with severe lymphocytic infiltration. GCLS is very rare and few cases have been reported. We examined the clinical features, problems of preoperative diagnosis, and treatment of 14 cases (1.8%) that were diagnosed as GCLS out of 790 gastric cancers surgically resected in our hospital. The mean age was 69 years. Six, 8, and 0 cases were located in the upper, middle, and lower fields of the stomach, respectively, and 8, 1, 4, and 1 cases were macroscopically 0-Ⅱc, 0-Ⅰ, type 2, and type 3, respectively. The depth of invasion was M, SM1, SM2, MP, and SS in 0, 0, 9, 3, and 2 cases, respectively. There were 12 cases(86%)with infection by Epstein-Barr virus, and just 1 case with lymph node metastasis. All cases have had no evidence of recurrence. There were no cases that were diagnosed as GCLS before surgery. GCLS is recognized as having a more favorable prognosis compared with other types of gastric carcinoma, so an aggressive surgery might achieve good outcomes. However, preoperative diagnosis is very difficult and there is a compelling need for new techniques or criteria for diagnosis of GCLS. PMID:26805251

  11. The past, present, and future of DARPA's investment strategy in smart materials

    NASA Astrophysics Data System (ADS)

    Wax, S. G.; Fischer, G. M.; Sands, R. R.

    2003-12-01

    The Defense Advanced Research Projects Agency (DARPA) smart materials research programs past, present, and future are reviewed in this article. Several articles have been written about the history of smart materials at DARPA;1 4 therefore, discussions of past efforts are limited and present and future work is emphasized. More importantly, this article presents the authors’ vision of what is next in the smart materials arena, for it is their belief that the journey to truly smart materials and structures has really just begun.

  12. Combining Pharmacological and Psychological Treatments for Binge Eating Disorder: Current Status, Limitations, and Future Directions.

    PubMed

    Grilo, Carlos M; Reas, Deborah L; Mitchell, James E

    2016-06-01

    Binge eating disorder (BED) is characterized by recurrent binge eating and marked distress about binge eating without the extreme compensatory behaviors for weight control that characterize other eating disorders. BED is prevalent, associated strongly with obesity, and is associated with heightened levels of psychological, psychiatric, and medical concerns. This article provides an overview of randomized controlled treatments for combined psychological and pharmacological treatment of BED to inform current clinical practice and future treatment research. In contrast to the prevalence and significance of BED, to date, limited research has been performed on combining psychological and pharmacological treatments for BED to enhance outcomes. Our review here found that combining certain medications with cognitive behavioral therapy (CBT) or behavioral weight loss (BWL) interventions produces superior outcomes to pharmacotherapy only but does not substantially improve outcomes achieved with CBT/BWL only. One medication (orlistat) has improved weight losses with CBT/BWL albeit minimally, and only one medication (topiramate) has enhanced reductions achieved with CBT in both binge eating and weight. Implications for future research are discussed. PMID:27086316

  13. Pharmacological Treatment of Obesity in Children and Adolescents: Present and Future

    PubMed Central

    Iughetti, Lorenzo; China, Mariachiara; Berri, Rossella; Predieri, Barbara

    2011-01-01

    The prevalence of overweight and obesity is increasing in children and adolescents worldwide raising the question on the approach to this condition because of the potential morbidity, mortality, and economic tolls. Dietetic and behavioral treatments alone have only limited success; consequently, discussion on strategies for treating childhood and adolescent obesity has been promoted. Considering that our knowledge on the physiological systems regulating food intake and body weight is considerably increased, many studies have underlined the scientific and clinical relevance of potential treatments based on management of peripheral or central neuropeptides signals by drugs. In this paper, we analyze the data on the currently approved obesity pharmacological treatment suggesting the new potential drugs. PMID:21197151

  14. Treatment of impulse control disorders in Parkinson's disease: Practical considerations and future directions.

    PubMed

    Ramirez-Zamora, Adolfo; Gee, Lucy; Boyd, James; Biller, José

    2016-04-01

    Impulse control disorders (ICDs) including compulsive gambling, buying, sexual behaviors, and eating occur relatively frequently in Parkinson disease (PD) with at least one ICD identified in 14% of PD patients in a large, multicenter, observational study. ICDs behaviors range widely in severity but can lead to catastrophic consequences, including financial ruin, divorce, loss of employment, and increased health risks. The main risk factor for ICDs in PD is the use of Dopamine agonists (DAs) and discontinuation of the offending agent is considered first line treatment. However, many patients do not tolerate this intervention as consequence of increased motor and psychiatric disability or appearance of DA withdrawal syndrome. In this article, we review current management strategies and emerging new interventions for treatment of ICDs in PD. Pharmacological treatment should be individualized based on patient's unique neuropsychiatric profile, social support, medical comorbidities, tolerability and motor symptoms. PMID:26923084

  15. The Superintendent of the Future: Strategy & Action for Achieving Academic Excellence.

    ERIC Educational Resources Information Center

    Spillane, Robert R., Ed.; Regnier, Paul, Ed.

    As public education undergoes profound changes, school superintendents must join the dialogue surrounding this evolution in schools. Strategies for doing this are presented here. The book focuses on connecting the practical with the intellectual in ways that will make sense to people who are daily inundated with practical problems. It supports the…

  16. Needed Capabilities and Development Strategies for Future Information Professionals: A Malaysian Perspective.

    ERIC Educational Resources Information Center

    Rehman, Saijad Ur; Baker, Ahmad Bakeri Abu; Majid, Sheheen

    1998-01-01

    Discusses results of a survey of professional leadership of library and information organizations in Malaysia that was conducted to gather perceptions about the trends in the field during the next 10 years, the extent of preparedness of entry-level professionals, and strategies for improving education and development programs. (Author/LRW)

  17. Educating for Digital Futures: What the Learning Strategies of Digital Media Professionals Can Teach Higher Education

    ERIC Educational Resources Information Center

    Bridgstock, Ruth

    2016-01-01

    This article explores how universities might engage more effectively with the imperative to develop students' twenty-first century skills for the information society, by examining learning challenges and professional learning strategies of successful digital media professionals. The findings of qualitative interviews with professionals from…

  18. Total Leaders: Applying the Best Future-Focused Change Strategies to Education.

    ERIC Educational Resources Information Center

    Schwahn, Charles J.; Spady, William G.

    This book focuses on education management and the change strategies needed to guide education in the upcoming years. It is intended for those who are responsible for selecting, supervising, developing, or evaluating people in leadership positions or who want to analyze their leadership performance and plan for further professional growth. The text…

  19. Jobs for the Future: Strategies in a New Framework. Alternatives for the 1980's, No. 13.

    ERIC Educational Resources Information Center

    Baily, Martin Neil; And Others

    This volume consists of four articles dealing with strategies for combatting unemployment in the 1980s. In the first article, entitled "The Problem of Unemployment in the United States," Martin Neil Baily examines the nature of unemployment, the inflation trade-off and the natural rate of unemployment, indicators of structural change, and sources…

  20. Learning Strategies in Enterprises: Empirical Findings, Implications and Perspectives for the Immediate Future

    ERIC Educational Resources Information Center

    Brandi, Ulrik; Iannone, Rosa Lisa

    2016-01-01

    The article examines learning strategies at the enterprise level, conceptualising them into three main dimensions: learning systems and incentives, connecting to the affective dimension of learning which behavioural learning addresses effectively; skills' development, chiefly addressing the cognitive dimension of learning to which cognitive and…