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Sample records for future treatment strategies

  1. 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

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

    PubMed

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

    2014-05-01

    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.

  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. Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.

    PubMed

    Davin, Jean-Claude

    2011-03-01

    Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.

  5. Development of early treatment strategies for high-risk myeloma precursor disease in the future.

    PubMed

    Landgren, Ola; Rajkumar, S Vincent

    2011-01-01

    Smoldering myeloma (SMM) is a precursor state of multiple myeloma. It is defined by an M-protein concentration ≥3 g/dL and/or ≥10% clonal bone marrow plasma cells, in the absence of end-organ damage. Based on clinical observations, the natural history of SMM varies greatly, from stable, monoclonal gammopathy of undetermined significance (MGUS)-like disease to highly progressive disease. Using conventional clinical markers, SMM patients can be stratified into clinical risk groups. However, due to considerable molecular heterogeneity, we currently lack reliable markers to predict prognosis for individual SMM patients. Based on the International Myeloma Working Group 2010 guidelines, patients diagnosed with MGUS and SMM should not be treated outside of clinical trials. Overall, treatment trials for MGUS patients are complicated, as these individuals are relatively healthy and the majority has a low life-time risk of progression, especially when other causes of death are taken into account. In contrast to MGUS, early treatment strategies for SMM are particularly attractive, as the rate of progression to multiple myeloma is substantially higher. Until recently, potent drugs with reasonable toxicity profiles have not been available for the development of early multiple myeloma treatment strategies. This review discusses how the integration of novel biological markers and clinical monitoring of SMM could facilitate the development of early treatment strategies for high-risk SMM patients in the future. PMID:21232660

  6. Current and future pharmacological treatment strategies in X-linked adrenoleukodystrophy.

    PubMed

    Berger, Johannes; Pujol, Aurora; Aubourg, Patrick; Forss-Petter, Sonja

    2010-07-01

    Mutations in the ABCD1 gene cause the clinical spectrum of the neurometabolic disorder X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN). Currently, the most efficient therapeutic opportunity for patients with the cerebral form of X-ALD is hematopoietic stem cell transplantation and possibly gene therapy of autologous hematopoietic stem cells. Both treatments, however, are only accessible to a subset of X-ALD patients, mainly because of the lack of markers that can predict the onset of cerebral demyelination. Moreover, for female or male X-ALD patients with AMN, currently only unsatisfying therapeutic opportunities are available. Thus, this review focuses on current and urgently needed future pharmacological therapies. The treatment of adrenal and gonadal insufficiency is well established, whereas applications of immunomodulatory and immunosuppressive drugs have failed to prevent progression of cerebral neuroinflammation. The use of Lorenzo's oil and the inefficacy of lovastatin to normalize very-long-chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed. The latter include pharmacological gene therapy mediated by targeted upregulation of ABCD2, the closest homolog of ABCD1, antioxidative drug treatment, small molecule histone deacetylase inhibitors such as butyrates and valproic acid, and other neuroprotective attempts.

  7. Current and Future Pharmacological Treatment Strategies in X-Linked Adrenoleukodystrophy

    PubMed Central

    Berger, Johannes; Pujol, Aurora; Aubourg, Patrick; Forss-Petter, Sonja

    2010-01-01

    Mutations in the ABCD1 gene cause the clinical spectrum of the neurometabolic disorder X-linked adrenoleukodystrophy/adrenomyeloneuropathy (X-ALD/AMN). Currently, the most efficient therapeutic opportunity for patients with the cerebral form of X-ALD is hematopoietic stem cell transplantation and possibly gene therapy of autologous hematopoietic stem cells. Both treatments, however, are only accessible to a subset of X-ALD patients, mainly because of the lack of markers that can predict the onset of cerebral demyelination. Moreover, for female or male X-ALD patients with AMN, currently only unsatisfying therapeutic opportunities are available. Thus, this review focuses on current and urgently needed future pharmacological therapies. The treatment of adrenal and gonadal insufficiency is well established, whereas applications of immunomodulatory and immunosuppressive drugs have failed to prevent progression of cerebral neuroinflammation. The use of Lorenzo's oil and the inefficacy of lovastatin to normalize very-long-chain fatty acids in clinical trials as well as currently experimental and therefore possible future therapeutic strategies are reviewed. The latter include pharmacological gene therapy mediated by targeted upregulation of ABCD2, the closest homolog of ABCD1, antioxidative drug treatment, small molecule histone deacetylase inhibitors such as butyrates and valproic acid, and other neuroprotective attempts. PMID:20626746

  8. A review of treatment strategies for hydrofluoric acid burns: current status and future prospects.

    PubMed

    Wang, Xingang; Zhang, Yuanhai; Ni, Liangfang; You, Chuangang; Ye, Chunjiang; Jiang, Ruiming; Liu, Liping; Liu, Jia; Han, Chunmao

    2014-12-01

    Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement.

  9. Strategy for treatment of fibrosis in systemic sclerosis: Present and future.

    PubMed

    Yanaba, Koichi

    2016-01-01

    Systemic sclerosis (SSc) is a generalized connective tissue disorder characterized by microvascular damage, autoimmunity, and excessive fibrosis of the skin and various internal organs. Regardless of the recent progress in medicine, no radical therapy for SSc has been developed, and the risk of mortality remains high. Therefore, diagnosis in the early disease stage, risk stratification for the development of serious organ involvement and therapeutic intervention with disease-modifying drugs can reduce the maximum degree of fibrosis, leading to improved long-term survival. Recently, new criteria for very early diagnosis of SSc have been proposed, which are expected to be useful for regularly following up patients with very early SSc, regardless of the absence of skin sclerosis, and for detecting the development of internal organ involvement as early as possible. At present, several immunosuppressants, including methotrexate, corticosteroids and cyclophosphamide, are being used for the treatment of fibrosis. Furthermore, mycophenolate mofetil, i.v. immunoglobulins, B-cell depletion, anti-interleukin-6 receptor antibody, autologous hematopoietic stem cell transplantation, rapamycin, pirfenidone and imatinib mesylate are potential candidates for the treatment of SSc, although their efficacy has not been validated. Moreover, targeting transforming growth factor-1 and its signaling pathway or modulating the imbalance between T-helper 1 and 2 immune responses are also attractive therapeutic options. This review describes recent advances in the strategy for treatment of fibrosis in SSc and future perspectives.

  10. A review of treatment strategies for hydrofluoric acid burns: current status and future prospects.

    PubMed

    Wang, Xingang; Zhang, Yuanhai; Ni, Liangfang; You, Chuangang; Ye, Chunjiang; Jiang, Ruiming; Liu, Liping; Liu, Jia; Han, Chunmao

    2014-12-01

    Hydrofluoric acid (HF), a dangerous inorganic acid, can cause severe corrosive effects and systemic toxicity. HF enters the human body via where it contacts, such as skin and mucosa, alimentary and respiratory tracts, and ocular surfaces. In the recent years, the incidence of HF burn has tended to increase over time. The injury mechanism of HF is associated primarily with the massive absorption of HF and the release of hydrogen ions. Correct diagnosis and timely treatment are especially important for HF burns. The critical procedure to treat HF burn is to prevent on-going HF absorption, and block the progressive destruction caused by fluoride ions. Due to the distinct characteristics of HF burns, the topical treatment, as well as systemic support, has been emphasised. Whereas, management of patients with HF burns remains a great challenge in some situations. To date, there has been no widely accepted protocol for the rescue of HF burns, partly due to the diversity of HF burns. This paper overviews the current status and problems of treatment strategies for HF burns, for the purpose of promoting the future researches and improvement. PMID:24946967

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

    PubMed

    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 function

  12. 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

  13. 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

  14. Human prostate cancer vaccines – proposed mechanisms of action and future combinatorial treatment strategies

    PubMed Central

    Geary, Sean M.; Lemke, Caitlin D.; Lubaroff, David M.; Salem, Aliasger K.

    2015-01-01

    Prostate cancer (PCa) is responsible for the deaths of more than 33,000 American men annually. Once PCa has become metastatic there is no curative treatment. Oncologists worldwide are becoming increasingly convinced that alternative therapies to chemotherapy and radical prostatectomy need to be explored. Cancer vaccines (CaVacs) that promote the cancer patient’s own immune system to develop a tumor-specific cytotoxic T lymphocyte-mediated immune attack have been investigated in clinical trials with modest yet encouraging results. Here we look at the rationale behind different prostate CaVacs and propose key immune events that are likely to contribute to the efficacy of each vaccine. Finally, we prognosticate upon what improvements may be required to generate more effective CaVacs in the future with full consideration of the mechanisms of action. PMID:23399727

  15. 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

  16. Future Directions and Treatment Strategies for Head and Neck Squamous Cell Carcinomas

    PubMed Central

    Wise-Draper, Trisha M.; Draper, David J.; Gutkind, J. Silvio; Molinolo, Alfredo A.; Wikenheiser-Brokamp, Kathryn A.; Wells, Susanne I.

    2012-01-01

    Head and neck cancer is a devastating disease that afflicts many individuals worldwide. Conventional therapies are successful in only a limited subgroup and often leave the patient with disfigurement and long lasting adverse effects on normal physiological functions. The field is in dire need of new therapies. Oncolytic viral as well as targeted therapies have shown some success in other malignancies and are attractive for the treatment of head and neck cancer. Recently, it has been shown that a subset of head and neck cancers is human papillomavirus (HPV) positive and that this subset of cancers is biologically distinct and more sensitive to chemoradiation therapies although the underlying mechanism is unclear. However, chemoresistance remains a general problem. One candidate mediator of therapeutic response, which is of interest for the targeting of both HPV-positive and -negative tumors is the human DEK proto-oncogene. DEK is upregulated in numerous tumors including head and neck cancers regardless of their HPV status. Depletion of DEK in tumor cells in culture results in sensitivity to genotoxic agents, particularly in rapidly proliferating cells. This suggests that tumors with high DEK protein expression may be correlated with poor clinical response to clastogenic therapies. Targeting molecules such as DEK in combination with new and/or conventional therapies, holds promise for novel future therapeutics for head and neck cancer. PMID:22683420

  17. Current and future strategies for the treatment of malignant brain tumors.

    PubMed

    Castro, M G; Cowen, R; Williamson, I K; David, A; Jimenez-Dalmaroni, M J; Yuan, X; Bigliari, A; Williams, J C; Hu, J; Lowenstein, P R

    2003-04-01

    Glioblastoma (GB) is the most common subtype of primary brain tumor in adults. These tumors are highly invasive, very aggressive, and often infiltrate critical neurological areas within the brain. The mean survival time after diagnosis of GB has remained unchanged during the last few decades, in spite of advances in surgical techniques, radiotherapy, and also chemotherapy; patients' survival ranges from 9 to 12 months after initial diagnosis. In the same time frame, with our increasing understanding and knowledge of the physiopathology of several cancers, meaningful advances have been made in the treatment and control of several cancers, such as breast, prostate, and hematopoietic malignancies. Although a number of the genetic lesions present in GB have been elucidated and our understanding of the progressions of this cancer has increased dramatically over the last few years, it has not yet been possible to harness this information towards developing effective cures. In this review, we will focus on the classical ways in which GB is currently being treated, and will introduce a novel therapeutic modality, i.e., gene therapy, which we believe will be used in combination with classical treatment strategies to prolong the life-span of patients and to ultimately be able to control and/or cure these brain tumors. We will discuss the use of several vector systems that are needed to introduce the therapeutic genes within either the tumor mass, if these are not resectable, or the tumor bed, after successful tumor resection. We also discuss different therapeutic modalities that could be exploited using gene therapy, i.e., conditional cytotoxic approach, direct cytotoxicity, immunotherapy, inhibition of angiogenesis, and the use of pro-apoptotic genes. The advantages and disadvantages of each of the current vector systems available to transfer genes into the CNS are also discussed. With the advances in molecular techniques, both towards the elucidation of the physiopathology

  18. 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…

  19. 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

  20. 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

  1. 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.

  2. The future of antihypertensive treatment.

    PubMed

    Israili, Zafar H; Hernández-Hernández, Rafael; Valasco, Manuel

    2007-01-01

    Despite progress in recent years in the prevention, detection, and treatment of high blood pressure (BP), hypertension remains an important public health challenge. Hypertension affects approximately 1 billion individuals worldwide. High BP is associated with an increased risk of mortality and morbidity from stroke, coronary heart disease, congestive heart failure, and end-stage renal disease; it also has a negative impact on the quality of life. Hypertension cannot be eliminated because there are no vaccines to prevent the development of hypertension, but, its incidence can be decreased by reducing the risk factors for its development, which include obesity, high dietary intake of fat and sodium and low intake of potassium, physical inactivity, smoking, and excessive alcohol intake. For established hypertension, efforts are to be directed to control BP by lifestyle modification (LSM). However, if BP cannot be adequately controlled with LSM, then pharmacotherapy can be instituted along with LSM. Normalization of BP reduces cardiovascular risk (for cardiovascular death, myocardial infarction, and cardiac arrest), provides renoprotection (prevention of the onset or slowing of proteinuria and progression of renal dysfunction to end-stage renal disease in patients with hypertension, diabetes mellitus types 1 and 2, and chronic renal disease), and decreases the risk of cerebrovascular events (stroke and cognition impairment), as has been amply demonstrated by a large number of randomized clinical trials. In spite of the availability of more than 75 antihypertensive agents in 9 classes, BP control in the general population is at best inadequate. Therefore, antihypertensive therapy in the future or near future should be directed toward improving BP control in treated hypertensive patients with the available drugs by using the right combinations at optimum doses, individually tailored gene-polymorphism directed therapy, or development of new modalities such as gene therapy

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Strategies for Planning for the Future

    ERIC Educational Resources Information Center

    Holly, L. Neal

    2010-01-01

    This chapter describes strategies that college leaders and faculty can use to develop international collaborations, questions that partners should consider prior to engaging in collaboration, and ways to avoid problems further into the process. It synthesizes the themes within the volume, focusing on the role of motivating factors and assumptions…

  10. New and future strategies to improve asthma control in children.

    PubMed

    Anderson, William C; Szefler, Stanley J

    2015-10-01

    Symptomatic asthma in childhood has lifelong effects on lung function and disease severity, emphasizing the need for improved pediatric asthma control. Control of pediatric risk and impairment domains can be achieved through increased medication adherence or new therapeutic strategies. Developing electronic monitoring device technology with reminders might be a key noninvasive resource to address poor adherence in children and adolescents in a clinical setting. In patients who have persistently poor control despite optimal medication compliance, newly emerging pharmaceuticals, including inhaled therapies and biologics, might be key to their treatment. However, barriers exist to their development in the pediatric population, and insights must be drawn from adult studies, which has its own unique limitations. Biomarkers to direct the use of such potentially expensive therapies to those patients most likely to benefit are imperative. In this review the current literature regarding strategies to improve pediatric asthma control is addressed with the goal of exploring the potential and pitfalls of strategies that might be available in the near future.

  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. 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

  13. 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.

  14. 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

  15. Pharmacological treatment of anxiety disorders: current treatments and future directions.

    PubMed

    Farach, Frank J; Pruitt, Larry D; Jun, Janie J; Jerud, Alissa B; Zoellner, Lori A; Roy-Byrne, Peter P

    2012-12-01

    Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments:the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use.

  16. Pharmacological treatment of anxiety disorders: Current treatments and future directions✩

    PubMed Central

    Farach, Frank J.; Pruitt, Larry D.; Jun, Janie J.; Jerud, Alissa B.; Zoellner, Lori A.; Roy-Byrne, Peter P.

    2012-01-01

    Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments: the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use. PMID:23023162

  17. 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…

  18. 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.

  19. Current and future treatment options for gonorrhoea.

    PubMed

    Ison, Catherine A; Deal, Carolyn; Unemo, Magnus

    2013-12-01

    The delivery of effective antimicrobial therapy is essential for public health control of gonorrhoea, in the absence of a suitable vaccine. The antimicrobial agent chosen should have high efficacy and quality, lack toxicity and give >95% success when given empirically. Guidelines, which are informed by surveillance data, are used to aid clinicians in their choice of appropriate agent. Historically, gonorrhoea treatment has been delivered as a single, directly observed dose but this has resulted in failure of successive antimicrobial agents which have been replaced by a new antimicrobial to which resistance has been rare or non-existing. Following the drift towards decreased susceptibility and treatment failure to the extended spectrum cephalosporins, and the lack of 'new' alternative antimicrobials, the threat of difficult to treat or untreatable gonorrhoea has emerged. The challenge of maintaining gonorrhoea as a treatable infection has resulted in national, regional and global response or action plans. This review discusses different approaches to the future treatment of gonorrhoea including; use of ceftriaxone, the injectable cephalosporin at increased dosage; dual antimicrobial therapy; use of drugs developed for other infections and use of older agents, directed by rapid point of care tests, to susceptible infections. Finally, it is considered whether the time is right to readdress the possibility of developing an effective gonococcal vaccine, given the major advances in our understanding of natural infection, molecular pathogenesis and the revolution in molecular biology techniques.

  20. Current and future treatments of secondary osteoporosis.

    PubMed

    Soriano, Raquel; Herrera, Sabina; Nogués, Xavier; Diez-Perez, Adolfo

    2014-12-01

    Osteoporosis is commonly associated with menopause and ageing. It can, however, also be caused by diseases, lifestyle, genetic diseases, drug therapies and other therapeutic interventions. In cases of secondary osteoporosis, a common rule is the management of the underlying condition. Healthy habits and calcium and vitamin D supplementation are also generally advised. In cases of high risk of fracture, specific antiosteoporosis medications should be prescribed. For most conditions, the available evidence is limited. Special attention should be paid to possible contraindications of drugs used for the treatment of postmenopausal or senile osteoporosis. Bisphosphonates are the most widely used drugs in secondary osteoporosis, and denosumab or teriparatide have been also assessed in some cases. Important research is needed to develop more tailored strategies, specific to the peculiarities of the different types of secondary osteoporosis.

  1. 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

  2. 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.

  3. Primary Sclerosing Cholangitis: Current and Future Management Strategies

    PubMed Central

    Eaton, John E.; Talwalkar, Jayant A.

    2013-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. The etiology of this disorder is unknown and there are no effective medical therapies. PSC is associated with inflammatory bowel disease and an increased risk for hepatobiliary and colorectal malignancies. The aim of this review is to highlight the clinical features and diagnostic approach to patients with suspected PSC, characterize associated comorbidities, review screening strategies for PSC associated malignancies and review contemporary and future therapies. PMID:23682242

  4. Future Treatment of Common Bile Duct Stones.

    PubMed

    Johnson; Hunter

    1997-03-01

    Management options for patients found to have common bile duct stones have expanded as a function of improved instrumentation and radiographic support. Technological advances initially lead to increased costs but eventually result in improved quality for patients. Controversy exists for patients with either soft clinical findings or stones found at the time of laparoscopic cholecystectomy. As laparoscopic common duct exploration becomes more widespread the need for perioperative ERCP will likely decrease; however, this will depend on the experience of the surgeons at a given institution. Common bile duct stones found at the time of laparoscopic cholecystectomy can be approached in a variety of different ways. The most commonly used methods are laparoscopic transcystic common bile duct exploration, laparoscopic choledochotomy with common bile duct exploration, open common bile duct exploration, laparoscopic antegrade sphincterotomy, and postoperative ERCP. In the future, the treatment goal of biliary lithiasis will be to accomplish cholecystectomy and removal of bile duct stones in a single stage. Advances in fiberoptic technology will make transcystic duct exploration more effective, but it is likely that sphincterotomy (antegrade or retrograde) will be used preferentially for the distally impacted stone.

  5. Regenerative treatment strategies in spinal surgery.

    PubMed

    Hegewald, Aldemar Andres; Ringe, Jochen; Sittinger, Michael; Thome, Claudius

    2008-01-01

    Intervertebral disc degeneration is considered a major source of low back pain. Recent advances in regenerative medicine have led to promising new approaches for the biological treatment of disc degeneration. Treatment modalities include the administration of growth factors, the application of autologous or allogenic cells, gene therapy, in situ therapy and the introduction of biomaterials or a combination thereof. Promising experimental results in vitro and in animal studies support the potential feasibility of these treatment modalities in clinical studies. We will review the current literature on regenerative treatment strategies and discuss potential drawbacks as well as opportunities in translating current knowledge into clinical practice. Major obstacles to regenerative treatment strategies might be insufficient nutritional supply, pain mediating factors and functionally impaired donor cells. Therefore, for clinical application, patient selection will be essential. Molecular, cellular and radiological diagnostic tools to evaluate the eligibility of patients for particular treatment strategies need to be developed. In spinal surgery, two approaches are conceivable. Patients operated on lumbar disc herniations often develop back pain due to disc degeneration months to years after surgery. Here, additional regenerative interventions would have a preventive intention, whereas interventions for painful degenerative disc disease as an alternative to spinal fusion or disc arthroplasty would be a curative approach.

  6. Clinical strategies for the treatment of neuroblastoma.

    PubMed

    Niethammer, D; Handgretinger, R

    1995-01-01

    Neuroblastoma is the most common solid extracranial tumour in childhood. In spite of intensive efforts of clinicians and scientists the prognosis for advanced disease is still poor. This paper presents a short review of the state-of-the-art in conventional treatment including surgery, chemotherapy, and radiation. This is followed by a review of the treatment attempts with high dose chemotherapy followed by autologous bone marrow or stem cell transplantation. One of the main problems with this approach is the contaminating tumour cells. Finally the various immunotherapeutic strategies are summarised which are used to remove minimal residual disease. Later, our new approach, combining various treatment modalities, is described.

  7. 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

  8. [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

  9. Therapeutic strategies for the treatment of neuroblastoma.

    PubMed

    Izbicka, Elzbieta; Izbicki, Tadeusz

    2005-12-01

    Neuroblastoma, the most common extracranial solid tumor in children, has a highly heterogeneous clinical presentation and course. Current risk-based therapy is usually effective in patients who have intermediate risk features, however, intensive treatment of advanced neuroblastoma in children over two years of age is far from satisfactory. Current therapeutic approaches include the optimization of pharmacokinetic and pharmacodynamic properties of conventional agents, as well as the development of novel targeted drugs, such as signal transduction and angiogenesis inhibitors, apoptosis/differentiation stimulators and immunotherapeutics. This review provides an overview of current treatment options and future perspectives for the therapy and prevention of neuroblastoma.

  10. [Therapeutics for future treatment of uveitis].

    PubMed

    Deschênes, J

    2000-01-01

    The increased knowledge in immunology and the progresses of pharmacology have improved our treatment of autoimmune diseases. The main anti-inflammatory effects of corticosteroids are an attenuation of the hypersensibility reactions, a sequestration of intravascular lymphocytes and an inhibition of the production of cytokines and eicosanoids. The non-steroidal anti-inflammatory drugs (NSAID's) form another group of medications particularly useful for the treatment of chronic uveitis. Several Cox-2 inhibitory medications are at the moment under clinical investigation and some are commercially available. One of their characteristics is to present less of the most undesirable side effects seen with conventional NSAID's like irritation of the gastro-intestinal tractus and platelets aggregation inhibition. Agents like cyclophosphamide, leukeran, imuran, methotrexate and cyclosporin have been used extensively for the treatment of severe uveitis. Because of its efficacy and safety, methotrexate is the best immunosuppressive agent to be tried for the treatment of chronic uveitis. However, immunosuppressive treatments and corticosteroids have many side effects and are not very selective. To improve our therapeutic arsenal, other treatments are being investigated for the treatment of severe uveitis. Manipulations of cytokines expression by Th1 lymphocytes will be one of then. PMID:10925522

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. The future of osteoporosis treatment - a research update.

    PubMed

    Lippuner, Kurt

    2012-01-01

    Osteoporosis is characterised by a progressive loss of bone mass and microarchitecture which leads to increased fracture risk. Some of the drugs available to date have shown reductions in vertebral and non-vertebral fracture risk. However, in the ageing population of industrialised countries, still more fractures happen today than are avoided, which highlights the large medical need for new treatment options, models, and strategies. Recent insights into bone biology, have led to a better understanding of bone cell functions and crosstalk between osteoblasts, osteoclasts, and osteocytes at the molecular level. In the future, the armamentarium against osteoporotic fractures will likely be enriched by (1.) new bone anabolic substances such as antibodies directed against the endogenous inhibitors of bone formation sclerostin and dickkopf-1, PTH and PTHrp analogues, and possibly calcilytics; (2.) new inhibitors of bone resorption such as cathepsin K inhibitors which may suppress osteoclast function without impairing osteoclast viability and thus maintain bone formation by preserving the osteoclast-osteoblast crosstalk, and denosumab, an already widely available antibody against RANKL which inhibits osteoclast formation, function, and survival; and (3.) new therapeutic strategies based on an extended understanding of the pathophysiology of osteoporosis which may include sequential therapies with two or more bone active substances aimed at optimising the management of bone capital acquired during adolescence and maintained during adulthood in terms of both quantity and quality. Finally, one of the future challenges will be to identify those patients and patient populations expected to benefit the most from a given drug therapy or regimen. The WHO fracture risk assessment tool FRAX® and improved access to bone mineral density measurements by DXA will play a key role in this regard.

  17. Psychotherapy and Psychosocial Treatment: Recent Advances and Future Directions.

    PubMed

    Plakun, Eric M

    2015-09-01

    Psychotherapy and psychosocial treatment have been shown to be effective forms of treatment of a range of individual and complex comorbid disorders. The future role of psychotherapy and psychosocial treatment depends on several factors, including full implementation of mental health parity, correction of underlying false assumptions that shape treatment, payment priorities and research, identification and teaching of common factors or elements shared by effective psychosocial therapies, and adequate teaching of psychotherapy and psychosocial treatment.

  18. 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.

  19. [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

  20. 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

  1. Future pharmacological treatments for substance use disorders

    PubMed Central

    Forray, Ariadna; Sofuoglu, Mehmet

    2014-01-01

    Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted. PMID:23039267

  2. 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.

  3. Future pharmacological treatments for substance use disorders.

    PubMed

    Forray, Ariadna; Sofuoglu, Mehmet

    2014-02-01

    Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted.

  4. Treatment sequencing strategy for hepatic epithelioid haemangioendothelioma

    PubMed Central

    Thomas, Ryan M; Aloia, Thomas A; Truty, Mark J; Tseng, Warren H; Choi, Eugene A; Curley, Steven A; Vauthey, Jean N; Abdalla, Eddie K

    2014-01-01

    Background The biology of hepatic epithelial haemangioendothelioma (HEHE) is variable, lying intermediate to haemangioma and angiosarcoma. Treatments vary owing to the rarity of the disease and frequent misdiagnosis. Methods Between 1989 and 2013, patients retrospectively identified with HEHE from a single academic cancer centre were analysed to evaluate clinicopathological factors and initial treatment regimens associated with survival. Results Fifty patients with confirmed HEHE had a median follow-up of 51 months (range 1–322). There was no difference in 5-year survival between patients presenting with unilateral compared with bilateral hepatic disease (51.4% versus 80.7%, respectively; P = 0.1), localized compared with metastatic disease (69% versus 78.3%, respectively; P = 0.7) or an initial treatment regimen of Surgery, Chemotherapy/Embolization or Observation alone (83.3% versus 71.3% versus 72.4%, respectively; P = 0.9). However, 5-year survival for patients treated with chemotherapy at any point during their disease course was decreased compared with those who did not receive any chemotherapy (43.6% versus 82.9%, respectively; P = 0.02) and was predictive of a decreased overall survival on univariate analysis [HR 3.1 (CI 0.9–10.7), P = 0.02]. Conclusions HEHE frequently follows an indolent course, suggesting that immediate treatment may not be the optimal strategy. Initial observation to assess disease behaviour may better stratify treatment options, reserving surgery for those who remain resectable/transplantable. Prospective cooperative trials or registries may confirm this strategy. PMID:24308564

  5. Anti-GD2 Strategy in the Treatment of Neuroblastoma

    PubMed Central

    Yang, Richard K.; Sondel, Paul M.

    2010-01-01

    The prognosis for advanced neuroblastoma remains poor with high risk of recurrence after consolidation. Therapies based on monoclonal antibodies that specifically target disialoganglioside GD2 on tumor cells are improving treatment results for high-risk neuroblastoma. This article reviews the use of anti-GD2 antibodies either as monotherapy or as part of a larger and more complex treatment approach for advanced neuroblastoma. We review how anti-GD2 antibodies can be combined with other treatments or strategies to enhance their clinical effects. Tumor resistance and other problems that decrease the efficacy of anti-GD2 antibodies are discussed. Future developments in the area of anti-GD2 immunotherapies for neuroblastoma are also addressed. PMID:21037966

  6. 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

  7. Antipsychotics--the future of schizophrenia treatment.

    PubMed

    Beaumont, G

    2000-01-01

    Schizophrenia is a debilitating mental disorder affecting up to five in every thousand people. Although specialist psychiatrists are initially responsible for treating patients suffering from acute schizophrenia, the current structure of mental healthcare in the U.K. puts the onus for the delivery of maintenance therapy of discharged patients on to the general practitioner. It is crucial, therefore, that the general practitioner is aware of all available therapies for the effective, long-term, community-based treatment of patients with schizophrenia. The so-called typical antipsychotics effectively treat the positive but not the negative symptoms of schizophrenia, and up to 40% of patients are nonresponders. These antipsychotics, however, are associated with high levels of extrapyramidal side-effects (EPS), which are the main cause of patient non-compliance and their subsequent relapse and hospital readmission. Clozapine, the first atypical antipsychotic, may cause severe agranulocytosis and patients must undergo regular haematological monitoring, which is both costly and a factor unlikely to foster patient compliance. In contrast, newly developed atypical antipsychotics, such as olanzapine and quetiapine, are not only efficacious in treating the symptoms of schizophrenia, but also give rise to fewer EPS and are generally better tolerated than clozapine. In particular, olanzapine and quetiapine are not associated with severe agranulocytosis. Atypical antipsychotics, therefore, have the potential to enhance patient compliance and thus ease the general practitioner's problems of providing long-term and effective treatment for patients with schizophrenia. PMID:16422033

  8. Future treatment options for human African trypanosomiasis.

    PubMed

    Jones, Amy J; Avery, Vicky M

    2015-01-01

    Over the past 17 years, the number of reported cases of human African trypanosomiasis (HAT) has declined by over 90%, a significant result since the disease was highlighted as a public health problem by the WHO in 1995. However, if the goal of eliminating HAT by 2020 is to be achieved, then new treatments need to be identified and developed. A plethora of compound collections has been screened against Trypanosoma brucei spp, the etiological agents of HAT, resulting in three compounds progressing to clinical development. However, due to the high attrition rates in drug discovery, it is essential that research continues to identify novel molecules. Failure to do so, will result in the absence of molecules in the pipeline to fall back on should the current clinical trials be unsuccessful. This could seriously compromise control efforts to date, resulting in a resurgence in the number of HAT cases.

  9. 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

  10. 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 ...

  11. 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

  12. [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

  13. 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

  14. [Current treatment strategy in malignant pleural effusion].

    PubMed

    Türler, A; Walter, M; Schmitz-Rixen, T

    1996-01-01

    Malignant pleural effusions are a grave consequence of advanced cancer disease. The successful suppression of pleural fluid reaccumulation can make a major contribution to the management and palliative care of patients with disseminated cancer. Many treatment concepts have been reported in the literature. The recommended therapy in malignant pleural effusions consists of intrapleural instillation of a sclerotic agent to produce pleurodesis. Different substances have been used, including tetracyclines, cytostatic agents, fibrin, talc, Corynebacterium parvum, cytokines and others. We reviewed the most frequently used techniques of pleurodesis in order to define the most effective treatment concept. In 15 prospective randomized trials the success rates varied from 13% with bleomycin to 100% with talc or Corynebacterium parvum. Talc was superior to other agents in 6 of 6, Corynebacterium parvum in 3 of 4 and bleomycin or tetracycline only in 3 of 8 studies. Adverse effects were frequently observed with cytostatic agents, but were very rare in the case of talc or fibrin instillation. Comparing the recently published data pleurodesis with talc appears to be the most effective treatment strategy, followed by Corynebacterium parvum, bleomycin and tetracycline. PMID:8686317

  15. Current medical treatment strategies concerning fracture healing.

    PubMed

    Giannotti, Stefano; Bottai, Vanna; Dell'osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-05-01

    The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient's quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research. PMID:24133528

  16. Current medical treatment strategies concerning fracture healing.

    PubMed

    Giannotti, Stefano; Bottai, Vanna; Dell'osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-05-01

    The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient's quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research.

  17. 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

  18. Medical treatments of the future: Between animality and artifice.

    PubMed

    Chapouthier, Georges

    2015-01-01

    Medical treatments are behavioural phenomena developed through acculturation, but dating back to our animal ancestors. Medical treatments, and indeed other cultural phenomena, have been extensively developed in certain human societies, triggering risks that could affect the future of mankind. Excessive modification of the physical animal function of the human body, which has matured harmoniously over millions of years of biological evolution, may change the very nature of the human being. Respect for the animal nature of the human being stands as a key safeguard when considering medical treatments for the future.

  19. IGF-1 Antisense Strategies for Cancer Treatment.

    PubMed

    Pan, Y X; Anthony, D D

    2000-01-01

    The technical approaches to gene therapy for cancer utilize ex vivo and in vivo gene-transfer methodology. This chapter focuses on applicability and use of an ex vivo approach using an IGF-1 antisense RNA strategy of treatment. Insulin-like growth factor 1 (IGF-1) and IGF-2 have pivotal roles in cell proliferation and development (for review, see 1-6). The preponderance of peptide synthesis and activity occur during fetal development, and protein synthesis is downregulated in most mature tissues except for adult liver. Further modulating the activities of these proteins are the levels of their respective cell-surface receptors and ligand-receptor interactions (3,5,6).

  20. Treatment Strategies Targeting Amyloid β-Protein

    PubMed Central

    Schenk, Dale; Basi, Guriqbal S.; Pangalos, Menelas N.

    2012-01-01

    With the advent of the key discovery in the mid-1980s that the amyloid β-protein (Aβ) is the core constituent of the amyloid plaque pathology found in Alzheimer disease (AD), an intensive effort has been underway to attempt to mitigate its role in the hope of treating the disease. This effort fully matured when it was clarified that the Aβ is a normal product of cleavage of the amyloid precursor protein, and well-defined proteases for this process were identified. Further therapeutic options have been developed around the concept of anti-Aβ aggregation inhibitors and the surprising finding that immunization with Aβ itself leads to reduction of pathology in animal models of the disease. Here we review the progress in this field toward the goal of targeting Aβ for treatment and prevention of AD and identify some of the major challenges for the future of this area of medicine. PMID:22951439

  1. Dry eye: diagnosis and current treatment strategies.

    PubMed

    O'Brien, Paul D; Collum, Louis M T

    2004-07-01

    One in four patients attending ophthalmic clinics report symptoms of dry eye, making it one of the most common complaints seen by ophthalmologists. Aqueous-layer deficiency is the most common form of dry eye and is frequently caused by decreased secretion of tears by the lacrimal glands. Evaporative dry eye is often secondary to meibomian gland disease and results in a defective lipid layer. Tear replacement or preservation using artificial tears and/or punctal occlusion are the mainstay of treatment. Newer forms of therapy were designed to modify the underlying disease process. These include the use of topical cyclosporin A, autologous serum, and sodium hyaluronate drops, which suppress underlying inflammation, provide growth factors, and prevent the onset of squamous metaplasia in ocular surface epithelium. Hormonal therapy might have a role in the future of dry eye therapy.

  2. [Present and future strategies for women at risk, or suffering from premature ovarian failure (POF)].

    PubMed

    Gougeon, A

    2012-11-01

    The purpose of this review is to present the strategies for fertility preservation that are currently proposed to patients at risk from premature ovarian failure (POF) due to chemotherapy as well as some future solutions that could allow patients already affected by an IOP to recover their fertility. Today, cryo-preservation of pieces of ovarian cortex followed by orthotopic transplantation as well as in vitro maturation of oocytes (IVM) allow preservation of fertility in patients being to undergo an antitumor treatment. However, although promising results have been obtained, the pregnancy rate remains very low. Improvement of these techniques, but also stimulation of resting follicle activation, in vitro folliculogenesis, and culture of putative oogonia that may be present in the adult ovary, are all future opportunities for patients suffering from an IOP, and are currently the subject of intensive researches.

  3. Current medical treatment strategies concerning fracture healing

    PubMed Central

    Giannotti, Stefano; Bottai, Vanna; Dell’Osso, Giacomo; Pini, Erica; De Paola, Gaia; Bugelli, Giulia; Guido, Giulio

    2013-01-01

    Summary The morbidity and socioeconomic costs associated with bone healing are considerable. A number of fractures are complicated by impaired healing. This is prevalent in certain risk groups such as elderly, osteoporotics, post-menopausal women, and in people with malnutrition. The biologic process of fracture healing is complex and impacted by multiple factors. Some of them, such as the nutritional and health conditions, are patient-dependent, while others depend on the trauma experienced and stability of the fracture. Fracture healing disorders negatively affect the patient’s quality of life and result in high health-care costs, as a second surgery is required to stabilize the fracture and stimulate bone biology. Future biotechnologies that accelerate fracture healing may be useful tools, which might also prevent the onset of these disorders. We list the characteristics of the drugs used for osteoporosis, but we point out in particular the use of strontium ranelate and teriparatide in our clinical practice in elderly patients, especially females, who reported fractures with risk of nonunion. This medical treatment could impaired fracture healing however, most of the evidence is obtained in animal studies and very few studies have been done in humans. Thus one could hypothesize the possibility of a medical treatment both as a preventive and as support to the synthesis. However, no clinical studies are available so far, and such studies are warranted before any conclusions can be drawn. A positive effect of osteoporosis treatments on bone healing is an interesting possibility and merits further clinical research. PMID:24133528

  4. 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…

  5. Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis.

    PubMed

    Al-Shammaa, Hassan-Alaa-Hammed; Li, Yan; Yonemura, Yutaka

    2008-02-28

    This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 mo. With the establishment of several phase II studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase III studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.

  6. Development of treatment strategies for advanced neuroblastoma.

    PubMed

    Hara, Junichi

    2012-06-01

    Neuroblastoma is the most common cancer in childhood. The majority of patients with neuroblastoma are assigned to the high-risk group based on age at diagnosis, stage, histology, MYCN status, and DNA ploidy. Their prognosis remains unsatisfactory; the 5-year event-free survival (EFS) rate is generally 40 %. During the past 20 years, much effort has been made to reinforce chemotherapy, including the introduction of high-dose chemotherapy with autologous stem cell rescue, resulting in a 5-year EFS rate of around 30 %. Subsequently, maintenance therapy aimed at eradicating residual tumors after induction and consolidation therapies was introduced, consisting of differentiation-inducing agents, retinoids, and immunotherapy using anti-GD2 antibodies combined with cytokines. However, such additional treatment provided benefit to only 10-20 % of patients, while the prognosis of about half the patients remains poor. Currently, novel targeted agents are under development. Among them, anaplastic lymphoma kinase (ALK) inhibitors and aurora kinase A inhibitors are promising. ALK somatic mutation or gene amplification predisposing neuroblastoma development occurs in up to 15 % of neuroblastomas. Crizotinib is a dual-specific inhibitor of ALK/Met and inhibits proliferation of neuroblastoma cells harboring R1275Q-mutated ALK or amplified wild-type ALK, but not cells harboring F1174L. Instead, cells with F1174L are sensitive to another small molecule ALK inhibitor, TAE684. Aurora kinase A plays a pivotal role in centrosome maturation and spindle formation during mitosis. MLN8237 (alisertib) is a small molecule inhibitor of aurora kinase A that is currently in early-phase clinical testing. Future treatment will be individually planned, adapting targeted agents based on personal biological tumor characteristics.

  7. 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

  8. 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

  9. 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

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

    PubMed

    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

  11. 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

  12. Cancer treatment strategies targeting sphingolipid metabolism.

    PubMed

    Oskouian, Babak; Saba, Julie D

    2010-01-01

    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.

  13. [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.

  14. 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…

  15. Inventing the Future: Options and Strategies for Educators.

    ERIC Educational Resources Information Center

    Burdin, Joel L.; Nutter, Norma

    A brief overview of Alvin Toffler's "waves" explanation of history (agricultural, industrial, and post-industrial) introduces reflections on future educational practices. While the limitations of the typical American home once made it imperative that education occur in centralized places, societal changes, as well as the development of individual…

  16. Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals

    PubMed Central

    2014-01-01

    Background In Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV. Methods Genotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data. Results The overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3. Conclusions Treatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens

  17. 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

  18. [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

  19. 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.

  20. Current Strategies and Future Directions for Eluding Adenoviral Vector Immunity

    PubMed Central

    Bangari, Dinesh S.; Mittal, Suresh K.

    2006-01-01

    Adenoviral (Ad) vectors can efficiently transduce a broad range of cell types and have been used extensively in preclinical and clinical studies for gene delivery applications. The presence of preexisting Ad immunity in the majority of human population and a rapid development of immune response against the Ad vector backbone following the first inoculation with the vector have impeded clinical use of these vectors. In addition, a number of animal inoculation studies have demonstrated that high systemic doses of Ad vectors invariably lead to initiation of acute inflammatory responses. This is mainly due to activation of innate immunity by vector particles. In general, vector and innate immune responses drastically limit the vector transduction efficiency and the duration of transgene expression. In order to have a predictable response with Ad vectors for gene therapy applications, the above limitations must be overcome. Strategies that are being examined to circumvent these drawbacks of Ad vectors include immunosuppression, immunomodulation, serotype switching, use of targeted Ad vectors, microencapsulation of Ad vectors, use of helper-dependent (HD) Ad vectors, and development of nonhuman Ad vectors. Here we review the current understanding of immune responses to Ad vectors, and recent advances in the strategies for immune evasion to improve the vector transduction efficiency and the duration of transgene expression. Development of novel strategies for targeting specific cell types would further boost the utility of Ad vectors by enhancing the safety, efficacy and duration of transgene expression. PMID:16611043

  1. 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

  2. Strategies for successful esthetic dental treatment.

    PubMed

    Snow, Stephen R

    2007-07-01

    The foundational principles of esthetic smiles reveal the direct influence of individual tooth alignment on dentofacial relationships. The use of clinical photography is an essential means to identify esthetic problems. Smile design provides an opportunity for effective communication to discuss treatment alternatives with the patient in the consultation process. The scope of treatment can be determined, and treatment limitations can be explained. Smile design findings influence preparation design, material selection, and laboratory communication for enhanced predictability and improved treatment success.

  3. 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

  4. Treatment of autoimmune liver disease: current and future therapeutic options

    PubMed Central

    Trivedi, Palak J.

    2013-01-01

    Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice. PMID:23634279

  5. 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.

  6. The Past, Present and Future of Endovascular Aneurysm Treatment.

    PubMed

    Henkes, H; Weber, W

    2015-10-01

    The technology available for the endovascular treatment of intracranial aneurysms is rapidly evolving. Both current and future devices are described. This includes, among others, UNO for parent vessel occlusion, the Medina device for saccular filling, the Comaneci device for remodeling, pCONus for assisted coil occlusion, and WEB and pCANvas for intrasaccular flow disruption. Perspectives of further development such as surface coating for increased radioopacity and decreased thrombogenicity are explained.

  7. Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: Influenza life-cycle and currently available drugs.

    PubMed

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

    2014-09-01

    treatment of influenza are considered in the subsequent review.

  8. 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

  9. 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.

  10. 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.

  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.

  12. 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

  13. 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.…

  14. 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…

  15. 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.…

  16. 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.

  17. 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

  18. Anticipatory Democracy and Citizen Involvement: Strategies for Communication Education for the Future.

    ERIC Educational Resources Information Center

    Flory, Joyce

    This report describes the "anticipatory democracy" movement, which advocates citizen participation and awareness of future problems, and suggests instructional strategies for the field of communication to increase both students' and community members' future-consciousness and involvement in society. Specific topics of concern are the formation of…

  19. Expectations, Fears, and Strategies: Juvenile Offender Thoughts on a Future outside of Incarceration

    ERIC Educational Resources Information Center

    Clinkinbeard, Samantha S.; Zohra, Tusty

    2012-01-01

    The current article explores the possible selves, or future expectations, of 543 incarcerated juvenile offenders in four Western states in the United States. We argue that juveniles who are able to articulate future expectations and fears and generate concrete strategies for achieving their goals have higher levels of motivational capital (i.e.,…

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. Dentinogenesis imperfecta: an early treatment strategy.

    PubMed

    Sapir, S; Shapira, J

    2001-01-01

    Dentinogenesis imperfecta (DI) type 2 is a disease inherited in a simple autosomal dominant mode. As soon as the teeth erupt the parents may notice the problem and look for a pediatric dentist's advice and treatment. Early diagnosis and treatment of DI is recommended, as it may prevent or intercept deterioration of the teeth and occlusion and improve esthetics. The purpose of this article is to present the objectives, treatment options, and problems encountered in the treatment of DI in the early primary dentition. A two-stage treatment of a toddler under general anesthesia is described and discussed. This paper recommends for severe cases of DI two treatment stages performed under general anesthesia. Stage 1 is early (around age 18-20 months) and is directed to covering the incisors with composite restorations and the first primary molars with preformed crowns. Stage 2 (around age 28-30 months) seeks to protect the second primary molars with preformed crowns and cover the canines with composite restorations.

  8. Atrial fibrillation: review of current treatment strategies

    PubMed Central

    Xu, Joshua; Luc, Jessica G. Y.

    2016-01-01

    Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in modern clinical practice, with an estimated prevalence of 1.5–2%. The prevalence of AF is expected to double in the next decades, progressing with age and increasingly becoming a global medical challenge. The first-line treatment for AF is often medical treatment with either rate control or anti-arrhythmic agents for rhythm control, in addition to anti-coagulants such as warfarin for stroke prevention in patient at risk. Catheter ablation has emerged as an alternative for AF treatment, which involves myocardial tissue lesions to disrupt the underlying triggers and substrates for AF. Surgical approaches have also been developed for treatment of AF, particularly for patients requiring concomitant cardiac surgery or those refractory to medical and catheter ablation treatments. Since the introduction of the Cox-Maze III, this procedure has evolved into several modern variations, including the use of alternative energy sources (Cox-Maze IV) such as radiofrequency, cryo-energy and microwave, as well as minimally invasive thoracoscopic epicardial approaches. Another recently introduced technique is the hybrid ablation approach, where in a single setting both epicardial thoracoscopic ablation lesions and endocardial catheter ablation lesions are performed by the cardiothoracic surgeon and cardiologist. There remains controversy surrounding the optimal approach for AF ablation, energy sources, and lesion sets employed. The goal of this article is review the history, classifications, pathophysiology and current treatment options for AF. PMID:27747025

  9. Anti-Angiogenic Therapy: Strategies to Develop Potent VEGFR-2 Tyrosine Kinase Inhibitors and Future Prospect.

    PubMed

    Shi, Leilei; Zhou, Jianfeng; Wu, Jifeng; Shen, Yuemao; Li, Xun

    2016-01-01

    Tumor angiogenesis has always been a major gap for effective cancer therapy. Interruption of aberrant angiogenesis by specific inhibitors targeting receptor tyrosine kinases (RTKs) has been of great interests to medicinal chemists. Among the factors that are involved in tumor angiogenesis, vascular endothelial growth factor receptor-2 (VEGFR-2) is validated as the most closely related factor which can drive angiogenesis through binding with its natural ligand VEGF. The well-validated VEGF-driven VEGFR-2 signaling pathway can stimulate many endothelial responses, including increasing vessel permeability and enhancing endothelial cell proliferation, migration and differentiation. Consequently, circumventing angiogenesis by VEGFR-2 inhibitors represents a promising strategy for counteracting various VEGFR-2-mediated disorders as well as drug resistance. Over the past decades, a considerable number of novel small molecular VEGFR-2 inhibitors have been exploited with diverse chemical scaffolds. Especially, recent frequently launched inhibitors have declared their research values and therapeutic potentials in oncology. Still, the antiangiogenesis based treatment remains an ongoing challenge. In this review, a comprehensive retrospective of newly emerged VEGFR-2 inhibitors have been summarized, with the emphasis on the structure-activity relationship (SAR) investigation, and also binding patterns of representative inhibitors with biotargets. On the basis of all of this information, varied strategies for developing potent VEGFR-2 inhibitors and the future prospect of the clinical application of antiangiogenic inhibitors are discussed hereby.

  10. 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

  11. [Treatment strategies in presumed benign ovarian tumors].

    PubMed

    Bourdel, N; Canis, M

    2013-12-01

    Benign ovarian tumors can be separated in three groups: teratoma, unilocular cyst and endometrioma. Laparoscopy should always be preferred for the surgical approach. Before menopause, conservative treatment should be preferred apart from previous oncologic history (breast and ovary). After menopause, the surgical approach (conservative or radical) should be discussed on case-by-case basis. Concerning teratoma, follow-up is one of the options for small cyst (less than 4 to 6 cm). For larger cyst, surgery seems to be justified but there is no definitive argument for this attitude. Concerning unilocular cyst, hormonal treatment or ultrasound-guided puncture are not recommended. For symptomatic patient, laparoscopic surgery is the gold standard. For asymptomatic patient, there is no definitive argument for systematic surgery. There is no justification for systematic ultrasound follow-up. For cyst larger than 10 cm, the data in the literature are very poor and surgery can be proposed. Concerning endometrioma, there isn't strong data that allows preferring one treatment (surgical, medical, follow-up) over another. Preoperative medical treatment is not recommended. Stripping technique is the gold standard. Hormonal postoperative treatment is recommended (if there is no desire for pregnancy).

  12. 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

  13. 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.

  14. Future treatment and research directions in distal radius fracture.

    PubMed

    Jupiter, Jesse

    2012-05-01

    Whether or not they will have their lives dramatically extended in the next few decades, it is clear that people are living longer, healthier, and more active lives. The two peak incidences of distal radius fractures will remain within the pediatric and geriatric age groups, with the latter experiencing a substantial increase in the coming years. This article attempts to project future developments with regard to epidemiology, risk and prevention, fracture assessment, and treatment of distal radius fractures, and the ever increasing concern for the economic impact of this prevalent injury.

  15. 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

  16. [Treatment strategies of sequelae following burn wound].

    PubMed

    Qiao, L; Huan, J N

    2016-01-01

    Burn patients are facing not only their physical recovery but also some complex problems caused by the injury, including pruritus, sleep disorders, pain, and psychological disorders. These problems may bring about challenges for survivors and burn treatment team members who work with them. The purpose of this paper is to improve the understanding and knowledge of these occult problems for clinicians in this field.

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Weight loss strategies for treatment of obesity.

    PubMed

    Kushner, Robert F

    2014-01-01

    Obesity is one of the most serious and prevalent non-communicable diseases of the 21st century. It is also a patient-centered condition in which affected individuals seek treatment through a variety of commercial, medical and surgical approaches. Considering obesity as a chronic medical disease state helps to frame the concept of using a three-stepped intensification of care approach to weight management. As a foundation, all patients should be counseled on evidence-based lifestyle approaches that include diet, physical activity and behavior change therapies. At the second tier, two new pharmacological agents, phentermine-topiramate and lorcaserin, were approved in 2012 as adjuncts to lifestyle modification. The third step, bariatric surgery, has been demonstrated to be the most effective and long-term treatment for individuals with severe obesity or moderate obesity complicated by comorbid conditions that is not responsive to non-surgical approaches. By using a medical model, clinicians can provide more proactive and effective treatments in assisting their patients with weight loss. PMID:24438739

  4. 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

  5. Nonsurgical mechanical treatment strategies for periodontal disease.

    PubMed

    Apatzidou, Danae A; Kinane, Denis F

    2010-01-01

    The comparison of the efficacy of surgical and nonsurgical procedures revealed that scaling and root planing alone or in combination with flap procedures are effective methods for the treatment of chronic periodontitis. Also, the consistent message is that in treating deep pockets, open-flap debridement results in greater probing pocket depth reduction and clinical attachment gain than nonsurgical modalities. Nonsurgical modalities in shallower pockets consistently involve less post-therapy recession and are clearly recognized as being more conservative. Research is still needed on the clinical benefit of the granulation tissue removal that is a feature of periodontal surgical therapy and, to a lesser extent, occurs through indirect trauma in nonsurgical therapy.

  6. 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

  7. Trigger Finger: Adult and Pediatric Treatment Strategies.

    PubMed

    Giugale, Juan M; Fowler, John R

    2015-10-01

    Trigger fingers are common tendinopathies representing a stenosing flexor tenosynovitis of the fingers. Adult trigger finger can be treated nonsurgically using activity modification, splinting, and/or corticosteroid injections. Surgical treatment options include percutaneous A1 pulley release and open A1 pulley release. Excision of a slip of the flexor digitorum superficialis is reserved for patients with persistent triggering despite A1 release or patients with persistent flexion contracture. Pediatric trigger thumb is treated with open A1 pulley release. Pediatric trigger finger is treated with release of the A1 pulley with excision of a slip or all of the flexor digitorum superficialis if triggering persists. PMID:26410644

  8. 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.

  9. 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…

  10. 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.

  11. 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

  12. [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.

  13. Epigenomics in hematopoietic transplantation: novel treatment strategies.

    PubMed

    Engel, Nicole; Rank, Andreas

    2011-10-01

    Allogeneic hematopoietic stem cell transplantation is a high risk but curative treatment option for leukemia, myelodysplasia and other hematological malignancies. After high dose radio- or chemo-therapy, recipient's hematopoiesis is replaced by a new immunosystem and residual malignant cells are eliminated by the graft-versus-leukemia reaction. The benefit of this immunological effect is limited by the most frequent complication of hematopoietic stem cell transplantation: graft-versus-host disease. In addition to their well-known anti-tumor activity, epigenetic drugs mediate immunotolerance without reducing alloreactivity or even enhance graft-versus-leukemia effect without inducing graft-versus-host disease by regulating cytokine release, increasing the circulating number of regulatory T cells and interacting with natural killer cells. We focus on the use of epigenetic drugs in the allogeneic transplantation setting in relation to their anti-tumor and immunomodulatory potential.

  14. [Current treatment strategies for paediatric burns].

    PubMed

    Küntscher, M V; Hartmann, B

    2006-06-01

    Paediatric burns occupy the third place in the severe accident statistics in Germany after traffic injuries and drowning. The paper reviews current treatment concepts of pre-hospital management, fluid resuscitation and surgical therapy in paediatric burned patients. Specific features in the approximation of the total body surface area burn and indications for transfer of paediatric burn victims to specialized units are discussed. The therapy of severe paediatric burns requires an interdisciplinary team consisting of especially skilled plastic or paediatric surgeons,anaesthetists, psychiatrists or psychologists, specifically trained nurses, physiotherapists and social workers. The rehabilitation process starts basically with admission to the burn unit. A tight cooperation between therapists and the relatives of the paediatric burn victim is needed for psychological recovery and reintegration into society.'The adaptation to the suffered trauma resulting in life-long disability and disfigurement is the main task of psychotherapy.

  15. Cutaneous porphyrias part II: treatment strategies.

    PubMed

    Tintle, Suzanne; Alikhan, Ali; Horner, Mary E; Hand, Jennifer L; Davis, Dawn Marie R

    2014-01-01

    The porphyrias are diverse in pathophysiology, clinical presentation, severity, and prognosis, presenting a diagnostic and therapeutic challenge. Although not easily curable, the dermatological manifestations of these diseases, photosensitivity and associated cutaneous pathology, can be effectively prevented and managed. Sun avoidance is essential, and patient education regarding the irreversibility of photocutaneous damage is a necessary corollary. Beyond preventative measures, the care of fragile, vulnerable skin, and pain management, each of the porphyrias has a limited number of unique additional therapeutic options. Many of the treatments have been published only in small case series or anecdotal reports and do not have well-understood nor proven mechanisms of action. This article presents a comprehensive review of available therapeutic options and long-term management recommendations for the cutaneous porphyrias.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Groin injuries in sport: treatment strategies.

    PubMed

    Lynch, S A; Renström, P A

    1999-08-01

    Groin pain in athletes is a common problem that can result in significant amounts of missed playing time. Many of the problems are related to the musculoskeletal system, but care must be taken not to overlook other more serious and potentially life threatening medical cases of pelvis and groin pain. Stress fractures of the bones of the pelvis occur, particularly after a sudden increase in the intensity of training. Most of these stress fractures will heal with rest, but femoral neck stress fractures can potentially lead to more serious problems, and require closer evaluation and sometimes surgical treatment. Avulsion fractures of the apophyses occur through the relatively weaker growth plate in adolescents. Most of these will heal with a graduated physical therapy programme and do not need surgery. Osteitis pubis is characterised by sclerosis and bony changes about the pubic symphysis. This is a self-limiting disease that can take several months to resolve. Corticosteroid injection can sometimes hasten the rehabilitation process. Sports hernias can cause prolonged groin pain, and provide a difficult diagnostic dilemma. In athletes with prolonged groin pain, with increased pain during valsalva manoeuvres and tenderness along the posterior inguinal wall and external canal, an insidious sports hernia should be considered. In cases of true sports hernia, treatment is by surgical reinforcement of the inguinal wall. Nerve compression can occur to the nerves supplying the groin. In cases that do not respond to desensitisation measures, neurolysis can relieve the pain. Adductor strains are common problems in kicking sports such as soccer. The majority of these are incomplete muscle tendon tears that occur just adjacent to, the musculotendinous junction. Most of these will respond to a graduated stretching and strengthening programme, but these can sometimes take a long time to completely heal. Patience is the key to obtain complete healing, because a return to sports too

  3. Groin injuries in sport: treatment strategies.

    PubMed

    Lynch, S A; Renström, P A

    1999-08-01

    Groin pain in athletes is a common problem that can result in significant amounts of missed playing time. Many of the problems are related to the musculoskeletal system, but care must be taken not to overlook other more serious and potentially life threatening medical cases of pelvis and groin pain. Stress fractures of the bones of the pelvis occur, particularly after a sudden increase in the intensity of training. Most of these stress fractures will heal with rest, but femoral neck stress fractures can potentially lead to more serious problems, and require closer evaluation and sometimes surgical treatment. Avulsion fractures of the apophyses occur through the relatively weaker growth plate in adolescents. Most of these will heal with a graduated physical therapy programme and do not need surgery. Osteitis pubis is characterised by sclerosis and bony changes about the pubic symphysis. This is a self-limiting disease that can take several months to resolve. Corticosteroid injection can sometimes hasten the rehabilitation process. Sports hernias can cause prolonged groin pain, and provide a difficult diagnostic dilemma. In athletes with prolonged groin pain, with increased pain during valsalva manoeuvres and tenderness along the posterior inguinal wall and external canal, an insidious sports hernia should be considered. In cases of true sports hernia, treatment is by surgical reinforcement of the inguinal wall. Nerve compression can occur to the nerves supplying the groin. In cases that do not respond to desensitisation measures, neurolysis can relieve the pain. Adductor strains are common problems in kicking sports such as soccer. The majority of these are incomplete muscle tendon tears that occur just adjacent to, the musculotendinous junction. Most of these will respond to a graduated stretching and strengthening programme, but these can sometimes take a long time to completely heal. Patience is the key to obtain complete healing, because a return to sports too

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 17 CFR 30.7 - Treatment of foreign futures or foreign options secured amount.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 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 commission... options customers denominated as the foreign futures or foreign options secured amount. Such...

  9. Future treatment needs in children, adults and the elderly.

    PubMed

    Holst, D; Schuller, A; Grytten, J

    1997-02-01

    Future treatment needs for dental services are discussed in the perspective of the objective which the services are meant to fulfill. These are, broadly speaking, equal distribution of services and economic efficiency. Within the Nordic countries, the emphasis has been on equity, perhaps less on efficiency. Equity of utilization is best understood as being a situation where patients with equal needs for oral health care receive equal treatment, in terms of both the volume and the quality of the services. The justification for arguing that equality of utilization is the appropriate measure is mainly based on the externality argument: health-care consumption by one person may be the source of utility to another person. According to that view there are two beneficiaries of dental care: the patient who is sick, and the rest of society who care for the sick patient and who derive utility from seeing the patient become healthy. The public dental services for children in the Nordic countries are organized according to the principle of equity of utilization. Equity of access is best understood as being a situation where people with equal needs have equal opportunity to use dental services. It is a supply-side phenomenon; equal access is achieved when patients with the same needs face the same costs of dental-care consumption in terms of both time and money. The oral health situation among children, adults and the elderly is exemplified by national service data and recent studies.

  10. 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.

  11. 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…

  12. Ethical concerns related to developing pharmacogenomic treatment strategies for addiction.

    PubMed

    Shields, Alexandra E

    2011-07-01

    Pharmacogenomics (PGx) research is poised to enable physicians to identify optimally effective treatments for individual substance abusers based on their genetic profiles. This paper addresses ethical issues related to PGx treatment strategies for addiction, focusing especially on the use of race variables in genomics research and ensuring equitable access to novel PGx treatments. Unless the field addresses the ethical challenges posed by these issues, PGx treatment innovations for addiction threaten to exacerbate already dramatic disparities in the burden of drug dependence for minority and other underserved populations.

  13. 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.

  14. Current and potential future drug treatments for osteoporosis.

    PubMed Central

    Patel, S

    1996-01-01

    There has been a major interest in the drug treatment of osteoporosis and an increase in the number of drugs available in most countries. The ideal drug (one which increases or restores bone density and trabecular connectivity) is still not available. However, in patients with relatively preserved trabecular connectivity and moderately reduced bone density, several agents have shown substantial clinical benefit. Oestrogens are still the mainstay of drug treatment, but the risks of breast cancer versus the cardiovascular and skeletal benefits with long term use have to be assessed in the individual. Newer tissue specific oestrogens show some promise in this respect. The bisphosphonates and possibly fluoride are likely to be the major alternatives to oestrogens in the medium term. The newer bisphosphonates, alendronate and in the future risedronate, are likely to supersede etidronate. Calcitriol probably has a limited role, confined to those patients in whom HRT or bisphosphonates are not appropriate. Calcium supplementation, or an increase in dietary intake if deficient, irrespective of which agent is used, is also of benefit. In older patients there is considerable support for using a combination of calcium and vitamin D. Whether combination treatment, for example oestrogens, bisphosphonates, and calcium together, will result in greater efficacy remains to be conclusively shown, but may be an attractive option in younger patients with higher bone turnover. Apart from fluoride, bone formation stimulators are unlikely to have a major role until the next century, although it may be possible to use growth factors as part of an ADFR regimen (A = activate remodelling, D = depress resorption, F = free formation, and R = repeat). This is still an important theoretical approach and needs further work with newer agents to see if increased efficacy can be found. In addition sequential treatment may be necessary in view of the limited time periods over which particular agents

  15. 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

  16. Novel Treatment Strategies for Liver Disease Due to α1-Antitrypsin Deficiency

    PubMed Central

    Maurice, Nicholas; Perlmutter, David H.

    2014-01-01

    Alpha1-antitrypsin (AT) deficiency is the most common genetic cause of liver disease in children and is also a cause of chronic hepatic fibrosis, cirrhosis and hepatocellular carcinoma in adults. Recent advances in understanding how mutant AT molecules accumulate within hepatocytes and cause liver cell injury have led to a novel strategy for chemoprophylaxis of this liver disease. This strategy involves a class of drugs which enhance the intracellular degradation of mutant AT and, because several of these drugs have been used safely in humans for other indications, the strategy can be moved immediately into clinical trials. In this review we will also report on advances that provide a basis for several other strategies that could be used in the future for treatment of the liver disease associated with AT deficiency. PMID:22686209

  17. Optimal antiviral treatment strategies and the effects of resistance.

    PubMed

    Hansen, Elsa; Day, Troy

    2011-04-01

    Recent pandemic planning has highlighted the importance of understanding the effect that widespread antiviral use will have on the emergence and spread of resistance. A number of recent studies have determined that if resistance to antiviral medication can evolve, then deploying treatment at a less than maximum rate often minimizes the outbreak size. This finding, however, involves the assumption that treatment levels remain constant during the entire outbreak. Using optimal control theory, we address the question of optimal antiviral use by considering a large class of time-varying treatment strategies. We prove that, contrary to previous results, it is always optimal to treat at the maximum rate provided that this treatment occurs at the right time. In general the optimal strategy is to wait some fixed amount of time and then to deploy treatment at the maximum rate for the remainder of the outbreak. We derive analytical conditions that characterize this optimal amount of delay. Our results show that it is optimal to start treatment immediately when one of the following conditions holds: (i) immediate treatment can prevent an outbreak, (ii) the initial pool of susceptibles is small, or (iii) when the maximum possible rate of treatment is low, such that there is little de novo emergence of resistant strains. Finally, we use numerical simulations to verify that the results also hold under more general conditions.

  18. 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

  19. 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

  20. 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.

  1. Diagnostic and treatment strategy of Lateral Semicircular Canal Canalolithiasis

    PubMed Central

    Asprella Libonati, G

    2005-01-01

    Summary A new strategy for the diagnosis and treatment both of geo-tropic and apogeotropic Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo is proposed. To this end, a new strategy of approach to Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo is described in order to rapidly highlight both the side and the affected canal. Thus, in the first treatment session, using the so-called “strategy of the minimum stimulus”, a large percentage of cases are successfully treated, with the lowest number of vertigos for the patient. Following a review of the literature, 269 case studies, personally observed over a 4-year period, are described. The diagnostic strategy is performed by a single manoeuvre to determine whether the posterior semicircular canal or the lateral canal is affected. In the latter case, it is possible to highlight the affected sides both of the geotropic and apogeotropic forms. The therapeutic strategy comprises several liberatory manoeuvres, barbecue rotation techniques (Vannucchi-Asprella, Lempert), and Gufoni manoeuvre by continuously monitoring the ampullofugal movement of the otoliths. Almost 98% of cases are successfully treated at the first treatment diagnostic-therapeutic session. This approach to Lateral Semicircular Canal Benign Paroxysmal Positional Vertigo allows a two-fold goal to be achieved, i.e., to effect both diagnosis and treatment at the first examination. Furthermore, thanks to the philosophy of the approach to Benign Paroxysmal Positional Vertigo, called the “Strategy of the minimum stimulus”, patient compliance is very good since a very small number of vertigos are produced, and few neuro-vegetative disorders. PMID:16602326

  2. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies.

    PubMed

    Landgren, Ola

    2013-01-01

    After decades of virtually no progress, multiple myeloma survival has improved significantly in the past 10 years. Indeed, multiple myeloma has perhaps seen more remarkable progress in treatment and patient outcomes than any other cancer during the last decade. Recent data show that multiple myeloma is consistently preceded by a precursor state (monoclonal gammopathy of undetermined significance [MGUS]/smoldering multiple myeloma [SMM]). This observation provides a framework for prospective studies focusing on transformation from precursor disease to multiple myeloma and for the development of treatment strategies targeting "early myeloma." This review discusses current biological insights in MGUS/SMM, provides an update on clinical management, and discusses how the integration of novel biological markers, molecular imaging, and clinical monitoring of MGUS/SMM could facilitate the development of early treatment strategies for high-risk SMM (early myeloma) patients in the future. PMID:24319222

  3. [Modern drug therapy of atrial fibrillation: selection of treatment strategy, antiarrhythmic preparations, and schemes of treatment].

    PubMed

    Kanorskiĭ, S G

    2012-01-01

    This review presents novel literature data on drug treatment of atrial fibrillation. We discuss here choice of strategy of therapy, antiarrhythmic drugs, and algorithms of preventive measures aimed at prevention of recurrences of this arrhythmia.

  4. 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

  5. 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

  6. 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.

  7. Differences in acquired immune deficiency syndrome treatment and evaluation strategies between Chinese and Western Medicine.

    PubMed

    Liu, Zhibin; Li, Xia; Yang, Jiping; Xu, Liran; Guo, Huijun

    2015-12-01

    Complementary and alternative medicine, including Chinese medicine (CM), has been used to treat acquired immune deficiency syndrome (AIDS) foralmost 30 years. We aimed to compare the main differences between AIDS treatment and evaluation strategies between CM and Western Medicine (WM), and analyze advantages and disadvantages. The characteristics of integrative medicine (IM), based on CM and WM, include a patient-centered mode of medicine based on evidence. IM focuses on complex intervention and management with systemic and individual treatment. The evaluation indexes of IM might consist of objective indicators and subjective indexes. IM might be a more valuable method for treating AIDS in the future instead of WM or CM alone.

  8. Monoclonal antibodies-based treatment in gastric cancer: current status and future perspectives.

    PubMed

    Roviello, Giandomenico; Polom, Karol; Petrioli, Roberto; Marano, Luigi; Marrelli, Daniele; Paganini, Giovanni; Savelli, Vinno; Generali, Daniele; De Franco, Lorenzo; Ravelli, Andrea; Roviello, Franco

    2016-01-01

    Gastric cancer (GC) is the second leading cause of cancer-related death, and despite having improved treatment modalities over the last decade, for most patients, only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and the related signaling pathways offers, from the clinical point of view, promising advances for selected groups of patients. In the past, targeted therapies have significantly impacted the treatment strategy of several common solid tumors such as breast, colorectal, and lung cancers. Unfortunately, translational and clinical research shows fewer encouraging targeted treatments with regards to the GC. To date, only two monoclonal antibodies (mAb), named trastuzumab and ramucirumab, are approved for the treatment of advanced GC, suggesting that in GC, maybe more than in other cancers, effective targeted therapy requires patient selection based on precise predictive molecular biomarkers. The aim of this review is to summarize the available data on the clinical advantages offered by the use of mAbs in the treatment of advanced/metastatic GC. Future perspective is also discussed. PMID:26566626

  9. 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

  10. Evaluation of treatment strategies for muscle function in infants with congenital muscular torticollis.

    PubMed

    Ohman, Anna; Mårdbrink, Eva-Lott; Stensby, Jennie; Beckung, Eva

    2011-10-01

    This study focuses on the treatment of the muscle function imbalance and asymmetric head posture for infants with congenital muscular torticollis (CMT). The aim of this study was to compare treatment time for groups with different strategies for muscle function training. The treatment goal was to achieve a symmetric head posture. Thirty-seven infants were randomised to three groups. Group I was treated only with handling strategies. Group II got the same handling strategies but also received specific strength exercises. Group III received the same treatment as group II but was also provided with weekly training by a physiotherapist. Mean age at the start of treatment was 4.5 months of age, range 1-10.5. The possible effect of covariates was also investigated; age at the start of treatment, range of motion (ROM) in rotation of the neck, ROM in lateral flexion of the neck, the muscle function scale (MFS) score, plagiocephaly, and gender were analysed with ANCOVA. Thirty-one treated infants achieved symmetric head posture before the age of 12 months. Mean treatment time (3.5 month) did not differ significantly between the groups. All infants randomised to group I could stay in that group. The MFS score and age at the start of the treatment influenced treatment time (p < 0.05). The treatment time for all groups was similar. Early referral to physical therapy of infants with CMT and muscle function imbalance in lateral righting could shorten treatment time. Studies about natural course and long-term effects of muscular imbalance must be investigated in future research.

  11. Is one technology best? Control strategies to meet current and future regulations

    SciTech Connect

    Altin, C.A.; Bustard, C.J.; Gelfand, P.; Sloat, D.G.; Belba, V.H.

    1994-12-31

    A slide presentation is given that discusses control strategies to meet current and future regulations. Most new regulations will require incremental reductions in specific emissions creating a market for technologies that can be retrofitted to existing systems. Since most metals are associated with particulate matter, improving particle collection will lead to reduced metal emissions and the disposal of sorbents used for capturing vapor phase pollutants, e.g., SO{sub 2} and Hg, can dominate the economics of the process.

  12. 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

  13. 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

  14. 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.

  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. Pharmacokinetic strategies for treatment of drug overdose and addiction

    PubMed Central

    Gorelick, David A

    2012-01-01

    The pharmacokinetic treatment strategy targets the drug molecule itself, aiming to reduce drug concentration at the site of action, thereby minimizing any pharmacodynamic effect. This approach might be useful in the treatment of acute drug toxicity/overdose and in the long-term treatment of addiction. Phase IIa controlled clinical trials with anticocaine and antinicotine vaccines have shown good tolerability and some efficacy, but Phase IIb and III trials have been disappointing because of the failure to generate adequate antibody titers in most participants. Monoclonal antibodies against cocaine, methamphetamine and phencyclidine have shown promise in animal studies, as has enhancing cocaine metabolism with genetic variants of human butyrylcholinesterase, with a bacterial esterase, and with catalytic monoclonal antibodies. Pharmacokinetic treatments offer potential advantages in terms of patient adherence, absence of medication interactions and benefit for patients who cannot take standard medications. PMID:22300100

  17. 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

  18. 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. PMID:27582960

  19. [Treatment strategy for patients with simultaneous cardiac and malignant diseases].

    PubMed

    Osawa, Hisayoshi; Muraki, Satoshi; Sakurada, Taku; Kawaharada, Nobuyoshi; Sasaki, Jun; Araki, Eiji; Nakashima, Shinji

    2014-03-01

    The choice of treatment strategy for patients with simultaneous cardiac and malignant diseases is often debatable. We report 11 patients with simultaneous cardiac and malignant diseases who were hospitalized in our institution over the past 6 years. The patients were 9 males and 2 females with a mean age of 71.9±9.0 years old. There were 7 cases of ischemic heart disease( IHD), and 4 cases of valvular disease. Malignant diseases consisted of 4 cases of colon cancer, 2 cases of pulmonary cancer, 2 cases of hepatic cancer, and 1 case each of sigmoid colon cancer with liver metastasis, gallbladder cancer, and pancreatic cancer. Eight of the 11 cases(73%)were hospitalized because of a symptom associated with cardiac disease, and malignant disease was diagnosed incidentally during examination or treatment. Four of the IHD cases preceded coronary revascularization by off-pump coronary artery bypass grafting (OPCAB) or percutaneous coronary intervention (PCI). Two of the valvular cases and 2 of the IHD cases underwent cardiac surgery after treatment of malignant diseases. In 3 cases, only 1 of the diseases was treated. Seven cases died of malignant diseases at the present. The choice of treatment strategy should be established for patients with simultaneous cardiac and malignant diseases in consideration of the severity of the cardiac disease and the expected prognosis of the malignant disease because there is no standardized method of treatment.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    PubMed

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future.

  8. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies.

    PubMed

    Melzer, N; Meuth, S G

    2014-03-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing-remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future. PMID:24032475

  9. Cognitive-behavioral treatment of depression in men: tailoring treatment and directions for future research.

    PubMed

    Spendelow, Jason S

    2015-03-01

    Depression is a significant public health issue and many researchers have suggested that modifications to conventional cognitive-behavioral therapy (CBT) are required to address infrequent help-seeking in men and counter negative effects of traditional masculinity on therapeutic engagement. This narrative review summarizes recommended alterations to CBT in the areas of therapeutic setting, process, and content. Key themes from this literature include a focus on behavioural interventions, and harmful cognitions that orginate from the traditional male gender stereotype. This literature is marked by limited empirical support for many of the recommended treatment modifications, and several options for future research are outlined.

  10. Strategies and techniques to enhance constructed wetland performance for sustainable wastewater treatment.

    PubMed

    Wu, Haiming; Fan, Jinlin; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan; Liang, Shuang; Hu, Zhen; Liu, Hai

    2015-10-01

    Constructed wetlands (CWs) have been used as an alternative to conventional technologies for wastewater treatment for more than five decades. Recently, the use of various modified CWs to improve treatment performance has also been reported in the literature. However, the available knowledge on various CW technologies considering the intensified and reliable removal of pollutants is still limited. Hence, this paper aims to provide an overview of the current development of CW strategies and techniques for enhanced wastewater treatment. Basic information on configurations and characteristics of different innovations was summarized. Then, overall treatment performance of those systems and their shortcomings were further discussed. Lastly, future perspectives were also identified for specialists to design more effective and sustainable CWs. This information is used to inspire some novel intensifying methodologies, and benefit the successful applications of potential CW technologies. PMID:26268626

  11. Strategies and techniques to enhance constructed wetland performance for sustainable wastewater treatment.

    PubMed

    Wu, Haiming; Fan, Jinlin; Zhang, Jian; Ngo, Huu Hao; Guo, Wenshan; Liang, Shuang; Hu, Zhen; Liu, Hai

    2015-10-01

    Constructed wetlands (CWs) have been used as an alternative to conventional technologies for wastewater treatment for more than five decades. Recently, the use of various modified CWs to improve treatment performance has also been reported in the literature. However, the available knowledge on various CW technologies considering the intensified and reliable removal of pollutants is still limited. Hence, this paper aims to provide an overview of the current development of CW strategies and techniques for enhanced wastewater treatment. Basic information on configurations and characteristics of different innovations was summarized. Then, overall treatment performance of those systems and their shortcomings were further discussed. Lastly, future perspectives were also identified for specialists to design more effective and sustainable CWs. This information is used to inspire some novel intensifying methodologies, and benefit the successful applications of potential CW technologies.

  12. 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

  13. [Lopinavir/ritonavir in new initial antiretroviral treatment strategies].

    PubMed

    Rolón, María José; Figueroa, María Inés; Sued, Omar; Cahn, Pedro

    2014-11-01

    According to evidence from randomized controlled trials and epidemiological data, the antiretroviral treatment (ART) of choice has consisted of the combination of 2 nucleoside analog reverse-transcriptase inhibitors (NRTI) plus 1 non-nucleoside analog reverse-transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) for more than 17 years. There are several unresolved issues, notably the toxocity associated with NRTI, especially thymidine analogs, and the possibility of cross resistance, which may affect subsequent treatment. The development of new antiretroviral drugs with simpler dosing regimens and lower toxicity has led to evaluation of innovative strategies such as dual therapy for initial ART in treatment-naive, with the aim of preventing long-term toxicity and increasing treatment adherence. Despite encouraging results, some combinations have proven unsatisfactory. The strategies with favorable results to date consist of twice-daily lopinavir/ritonavir (LPV/r)-based regimens, those in the PROGRESS (LPV/r + raltegravir) and GARDEL (LPV/r + lamivudine) trials, and the combination of darunavir and raltegravir (NEAT 001 trial), although the latter observed a higher tendency (statistically nonsignificant) to virological failure in the dual combination arm. These trials were based on the use of NRTI-sparing regimens consisting of 2-3 fully- active agents for highly-active ART in treatment-naïve HIV-positive patients. Recent studies provide evidence supporting the use of NRTI-sparing regimens in HIV-infected patients with failure to an initial NNRTI-based ART regimen. The present review will discuss only LPV/r-based innovative strategies in initial ART regimens.

  14. 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

  15. 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…

  16. 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

  17. Cancer-related fatigue: prevalence, assessment and treatment strategies.

    PubMed

    Weis, Joachim

    2011-08-01

    Cancer-related fatigue (CRF) is one of the most common symptoms reported by patients and is defined as the feeling of extraordinary exhaustion associated with a high level of distress, disproportionate to the patients' activity, and is not relieved by sleep or rest. Prevalence rates range from 59 to nearly 100% depending on the clinical status of the cancer. Except for chemotherapy-induced anemia, the mechanisms responsible for CRF are not yet completely understood. Therefore, CRF may be influenced by multiple possible somatic and psychosocial factors. CRF has been shown as either a short-term side effect of adjuvant cancer therapy or a chronic long-term late effect. Compared with other symptoms, such as pain or nausea, CRF is more distressing and often long lasting, with a strong impact on daily living and quality of life. The concept of fatigue has been widely elaborated and operationalized in different dimensions within the last few decades and specific instruments assessing fatigue in cancer populations have been developed. To support patients and alleviate CRF symptoms various treatment strategies are discussed in this article, including information and counseling, enhancement of activities, exercise and sports therapy, psychosocial interventions as well as pharmacological treatment. In most Western countries, treatment of CRF has been identified as a priority for advancing cancer patient care. This article gives an overview of the concept of CRF, its pathogenesis, assessment and treatment strategies. PMID:21831025

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Current Strategies in the Treatment of Scars and Keloids.

    PubMed

    Heppt, Markus V; Breuninger, Helmut; Reinholz, Markus; Feller-Heppt, Gabriele; Ruzicka, Thomas; Gauglitz, Gerd G

    2015-08-01

    Hypertrophic scars (HTSs) and keloids are a major health concern for aesthetic and functional reasons. Despite a plethora of rapidly evolving treatment options and technical advances, the management of pathologic scarring remains difficult. The development of standardized treatment algorithms has been problematic for years due to the lack of sound randomized controlled trials. Expert panels are more and more establishing guidelines to provide an evidence-based framework on a national and international level. This article aims to evaluate the current strategies and upcoming trends in the therapy and prevention of unpleasant scars and keloids from a clinical perspective. There is strong evidence to support a growing role of early combination treatments, particularly the application of 5-fluoruracil adjunct to intralesional steroid injections. Furthermore, the use of fractional ablative laser technologies such as the CO2 laser has recently yielded promising results with respect to aesthetic outcomes and patient satisfaction at tolerable side effects.

  3. [Treatment of cognitive deficits in schizophrenia. Part 2: Pharmacological strategies].

    PubMed

    Roesch-Ely, D; Pfueller, U; Mundt, C; Müller, U; Weisbrod, M

    2010-05-01

    Cognitive deficits in schizophrenia are a clinically relevant symptom dimension and one of the best predictors for functional outcome. Pharmacological treatment of cognitive deficits in schizophrenia is still a challenge. The objective of this article is to present a detailed review of the literature on strategies for the pharmacological treatment of cognitive deficits. It is not clear whether first-generation antipsychotics have a genuine positive influence on cognition. There is only sparse evidence for the positive effect of second-generation antipsychotics on cognitive processes. Furthermore it is not evident that second-generation antipsychotics are more beneficial than first-generation antipsychotics in the treatment of cognitive deficits. The add-on use of substances which directly influence cognitive processes, so-called cognition-enhancing drugs is more promising.

  4. 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

  5. Inclusiveness: a mental health strategy for preventing future mental health problems among adolescents orphaned by AIDS.

    PubMed

    Thupayagale-Tshweneagae, G; Mokomane, Z

    2012-10-01

    The purpose of this paper is to raise an argument that inclusiveness will lessen the pain of losing a parent among adolescents orphaned by AIDS and as a result, prevent future mental health problems that may occur because of inappropriate grieving and maladaptive coping strategies. Participation of adolescents orphaned by AIDS in decisions pertaining to their parents' illnesses and funeral arrangements, for example, may shorten the grieving process and allow for closure. The paper draws data from focus group discussions that were held with 15 adolescents orphaned by AIDS in urban South Africa. The focus group discussions that were structured around four themes: grieving patterns; coping strategies; experience with loss; and expectations. The results of the study demonstrate inclusiveness as an overarching factor in the healing process. The concept is thus a strong recommendation for mental health practice and further study. PMID:22192336

  6. 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

  7. 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

  8. 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

  9. [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

  10. From Bitopic Inhibitors to Multitarget Drugs for the Future Treatment of Alzheimer's Disease.

    PubMed

    Pérez, Daniel I; Martínez, Ana; Gil, Carmen; Campillo, Nuria E

    2015-01-01

    Dementia is one of the main causes of the disease burden in developed regions. According to the World Health Organization (WHO), it will become the world's second leading cause of death by the middle of the century, overtaking cancer. This will have a dramatic impact on medical care, and have important social and economic implications, unless more effective preventive procedures or treatments become available. Alzheimer's disease (AD) is the most common cause of dementia, accounting for approximately 50-75% of all dementias worldwide, followed by vascular dementia, mixed dementia, and Lewy body dementia. Currently, acetylcholinesterase (AChE) inhibitors, such as donepezil, rivastigmine and galantamine are used to treat mild to moderate AD. An alternative therapy for severe AD is memantine, an antagonist of the NMDA-subtype of glutamate receptors. However, these drugs provide only temporary symptom improvement, and do not alter disease progression, except temporarily in some patients. In recent years different approaches have been developed to provide a more effective treatment for AD. These approached include the discovery of emerging targets and new drugs aiming at a single target, but given the complexity of the disease, different targets may need to be engaged simultaneously. New strategies have explored bitopic inhibitors, for example a single drug that acts on different sites of the acetylcholinesterase enzyme to produce at least two different activities, and multitarget drugs that act on multiple therapeutic targets. In this review, we explore the journey from a bitopic inhibitor strategy to multitarget drugs for the future treatment of AD. PMID:26264921

  11. Select a suitable treatment strategy for Crohn's disease: step-up or top-down

    PubMed Central

    Chen, Qian-Qian; Yan, Li; Wan, Jun

    2014-01-01

    Crohn’s Disease (CD) is a chronic immune-mediated disorder with progressive and destructive course. Current guidelines on the treatment strategy still recommend a step-up approach with sequential prescription of corticosteroids and immunosuppressives. However, mounting evidences manifested that top-down therapy with early administration of anti-TNF or combination of immunosuppressives can achieve more rapid and higher rate of mucosal healing and has the potential of modifying the natural course of disease. Therefore, who is suitable to accept and when to start anti-TNF therapy have attracted the attention of gastroenterologists. And what benefit/risk can be expected from the two strategies should be carefully taken into account by clinicians. Age stratification, special patients, disease location and extension, genetic and serologic testing are predictors of disease progression and complication and thus guide a personalized treatment approach in CD. A definition of early CD has been proposed to select an algorithm for treatment of moderate-to-severe CD with a suitable strategy. To date mucosal healing has been widely used, the Lémann score, which assesses the extent and severity of bowel damage at a specific time-point and over time, and is a new disability index for patients with CD, will be considered as a new endpoint for future studies of treatment strategies. Besides medicines of the two strategies, surgery, vaccine, Leukocytapheresis and stem cell therapy are all effective therapeutic approaches which lead to another thinking about what should they be putted in the conditional pyramid. However, we are trying to answer these questions. PMID:26417246

  12. Low-grade oligodendroglioma: current treatments and future hopes.

    PubMed

    Lwin, Zarnie; Gan, Hui K; Mason, Warren P

    2009-11-01

    Current treatment modalities for low-grade gliomas include surgery, radiotherapy and chemotherapy. Management of these ultimately incurable tumors remains controversial, particularly the timing and extent of surgery, and the optimal sequence of radiotherapy and chemotherapy thereafter. Two ongoing Phase III trials should provide definitive answers to some of these controversial issues in the treatment of low-grade gliomas and confirm the impact of molecular predictors of response and outcome. This review will discuss recent progress and topical issues in the treatment of low-grade gliomas.

  13. 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.

  14. [Treatment of hepatitis B virus infection: present and future].

    PubMed

    Planas, Ramón; Morillas, Rosa M

    2008-01-01

    The treatment of chronic hepatitis B virus (HVB) infection constitutes a challenge in spite of the advances in the therapeutic arsenal available. At the moment there are 4 approved antiviral drug groups: interferons, nucleoside analogues (lamivudine, telbivudine), nucleotide analogues (adefovir- dipivoxil) and cyclopents (entecavir), with different antiviral efficacy among them. The primary target of the treatment is a prolonged suppression of viral replication in order to avoid long term complications (cirrhosis, hepatocellular carcinoma) and increase survival. In first place we must decide when to initiate the treatment. Secondly, which is the best therapeutic option based on the demonstrated antiviral effectiveness, profile of security and appearance of resistances. And finally, the duration and modification of the treatment based on the answer to itself. The objective of this article is a practical revision of the present management of the infection by the HVB. PMID:18570812

  15. 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

  16. Drugs for all: the future of global AIDS treatment.

    PubMed

    Biehl, João

    2008-01-01

    I am interested in the arts of government that accompany economic globalization and in the remaking of populations as market segments (specifically therapeutic markets). Using the Brazilian response to AIDS as an ethnographic baseline, I examine the systemic relations between pharmaceutical commerce and public health care and the value systems that underscore global AIDS treatment initiatives. The pharmaceuticalization of governance and citizenship, obviously efficacious in the treatment of AIDS, nonetheless crystallizes new inequalities.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Nanotherapeutic strategies for the treatment of Alzheimer's disease.

    PubMed

    Gu, Xiao; Chen, Hongzhuan; Gao, Xiaoling

    2015-02-01

    Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest unmet medical needs. However, no effective treatment is now available to impede the progression of AD or delay its onset. There are two major challenges for the development of effective therapy for AD. First, the exact cause for AD onset is still unknown. Second, brain drug delivery is significantly hindered by the blood-brain barrier (BBB). In this review, we will summarize the pathological understanding about AD and the related treatments, compare BBB and its effect on brain drug delivery under normal and AD conditions and review the nanotherapeutic strategies that have been developed for AD therapy in recent years. PMID:25690086

  3. [Surgical treatment strategy for flatfoot related with accessory navicular].

    PubMed

    Deng, Yin-shuan; Gao, Qiu-ming; Zhen, Ping; Tang, Kang-lai

    2015-02-01

    Accessory navicular source flatfoot is one of the foot deformity of clinical common disease,its treatment method is more controversial, differences in clinical efficacy of different surgical methods, according to accessory navicular source flatfoot symptoms of surgical treatment,there is no uniform standard, around a pair of accessory navicular excision how to reconstruct the arch produced a series of operation methods, the clinical curative effect of different operative methods produce also different, how to develop the operation strategy, choose operation method, and after acessory navicular excision whether to rebuild posterior tibial tendon, how to rebuild, the problems such as how to rebuild is the research hotspot and difficulty, looking forward to further research.

  4. Implementing treatment strategies for different types of depression.

    PubMed

    McIntyre, Roger S

    2016-02-01

    Diagnosing and treating major depressive disorder (MDD) accurately and efficiently is challenging for many clinicians. Recent additions to the Diagnostic and Statistical Manual of Mental Disorders (DSM) as well as potential moderators of antidepressant response such as pretreatment phenomenological characteristics (eg, body mass index, drug metabolism markers) may help physicians to better stratify patients and make informed decisions on the best course of treatment to obtain remission. The evidence base suggests that combining traditional antidepressant therapy with atypical antipsychotics may increase the chance for remission. Other strategies that may help include switching to another antidepressant as monotherapy or combining lithium, thyroid hormone, or psychotherapy. Moreover, in some cases, a manualized-based psychotherapeutic approach may be an appropriate first-line or alternative treatment avenue for adults with MDD. PMID:26829432

  5. A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis.

    PubMed

    Babokhov, Peter; Sanyaolu, Adekunle O; Oyibo, Wellington A; Fagbenro-Beyioku, Adetayo F; Iriemenam, Nnaemeka C

    2013-07-01

    Despite the recent advances in drug research, finding a safe, effective, and easy to use chemotherapy for human African trypanosomiasis (HAT) remains a challenging task. The four current anti-trypanosomiasis drugs have major disadvantages that limit more widespread use of these drugs in the endemic regions of sub-Saharan Africa. Pentamidine and suramin are limited by their effectiveness against the only first stage of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense, respectively. In addition, melarsoprol and eflornithine (two second stage drugs) each have disadvantages of their own. The former is toxic and has increasing treatment failures while the latter is expensive, laborious to administer, and lacks efficacy against T. b. rhodesiense. Furthermore, melarsoprol's toxicity and decreasing efficacy are glaring problems and phasing out the drug as a frontline treatment against T. b. gambiense is now possible with the emergence of competent, safe combination chemotherapies such as nifurtimox-eflornithine combination treatment (NECT). The future of eflornithine, on the other hand, is more promising. The drug is useful in the context of combination chemotherapy and potential orally administered analogues. Due to the limits of monotherapies, greater emphasis should be placed on the research and development of combination chemotherapies, based on the successful clinical tests with NECT and its current use as a frontline anti-trypanosomiasis treatment. This review discussed the current and future chemotherapy strategies for the treatment of HAT.

  6. 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.

  7. Large-Scale Cooperative Dissemination of Governmental Information in Emergency — An Experiment and Future Strategies

    NASA Astrophysics Data System (ADS)

    Horiba, Katsuhiro; Okawa, Keiko; Murai, Jun

    On the 11th of March, 2011, a massive earthquake hit the northeast region of Japan. The government of Japan needed to publish information regarding the earthquake and its influences. However, their capacity of Web services overflowed. They called the industry and academia for help for providing stable information service to the people. Industry and academia formed a team to answer the call and named themselves the “EQ project”. This paper describes how the EQ Project was organized and operated, and gives analyses of the statistics. An academic organization took the lead in the EQ Project. Ten organizations which consisted of commercial IT industry and academics specialized in Internet technology, were participating in the EQ Project and they structured the three clusters based on their relationships and technological approach. In WIDE Cluster, one of three clusters in the structure of EQ, the peak number of file accesses per day was over 90 thousand, the mobile browsers was 3.4% and foreign languages (translated contents) were referred 35%. We have also discussed the future information distribution strategies in emergency situation based on the experiences of the EQ Project, and proposed nine suggestions to the MEXT as a future strategy.

  8. 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

  9. 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

  10. 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

  11. 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.

  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. 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

  15. Advances in Risk Classification and Treatment Strategies for Neuroblastoma

    PubMed Central

    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.

    2015-01-01

    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

  16. 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.

  17. Current treatment of medulloblastoma: recent advances and future challenges.

    PubMed

    Rood, Brian R; Macdonald, Tobey J; Packer, Roger J

    2004-10-01

    Medulloblastoma (MB) is the most common malignant brain tumor of childhood, yet it makes up only 1% of adult brain tumors. MB is uniquely sensitive to chemotherapy and radiation, but successful surgical resection continues to be an important component of therapeutic success. Progress in the treatment of MB has occurred in multiple areas from improved neurosurgical techniques, refined dosing and delivery of radiation, and optimized chemotherapy. Tumors are currently risk-stratified as average risk or high risk depending on clinical factors such as age, extent of resection, and presence of metastases. Molecular biology is beginning to improve upon clinical prognostication and may soon provide the means to accurately predict response to therapy. Treatment for average-risk MB has achieved a level of success that allows efforts to be focused on the limitation of adverse treatment effects. Therapy for high-risk and relapsed MB has been positively affected by the advent of high-dose chemotherapy with stem cell rescue. In addition, molecular targets are being elucidated and new therapeutic agents are being tested for safety and efficacy. Treatment for this disease has evolved a great deal over the preceding decades, but a great deal of work remains to be done to effect reliable cures while reducing long-term sequelae of therapy.

  18. Current and future treatments for Alzheimer’s disease

    PubMed Central

    Papageorgiou, Sokratis G.

    2013-01-01

    Alzheimer’s dementia (AD) is increasingly being recognized as one of the most important medical and social problems in older people in industrialized and non-industrialized nations. To date, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance. Three cholinesterase inhibitors (CIs) are currently available and have been approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist. Treatments capable of stopping or at least effectively modifying the course of AD, referred to as ‘disease-modifying’ drugs, are still under extensive research. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review we discuss current symptomatic treatments and new potential disease-modifying therapies for AD that are currently being studied in phase I–III trials. PMID:23277790

  19. 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…

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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

  6. 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).

  7. Drug treatment of depression in the 2000s: An overview of achievements in the last 10 years and future possibilities.

    PubMed

    Baghai, Thomas C; Volz, Hans-Peter; Möller, Hans-Jürgen

    2006-01-01

    During the past 10 years our knowledge about the pharmacotherapy of depression has been consolidated, and a variety of very interesting new compounds launched onto the market. The pipeline of the pharmaceutical industry is still filled with an assortment of new developments and very promising new approaches towards the pharmacotherapy of depressive disorders. Future pharmacological treatments of depression will not only enhance serotonergic and noradrenergic neurotransmission: other systems, such as the melatonergic receptor system and the hypothalamus-pituitary-adrenal axis, are also the targets of newly developed and upcoming substances with putative antidepressant effects. The main advantages of the currently available newer pharmacotherapeutic options are the broadening of the spectrum of possible antidepressant treatments, which is of particular importance for the growing number of patients suffering from difficult-to-treat depression, and a far better tolerability profile in comparison to older compounds such as tricyclic antidepressants. Unresolved issues are the unacceptably high rate of non-responsiveness during antidepressant treatment, a latency of sometimes several weeks until clinical improvement and remission can be achieved, and a variety of possible side effects also present during treatment with modern compounds. This review mainly presents the development of antidepressant pharmacotherapies during the past 10 years, together with pharmacokinetic and pharmacodynamic information and a comparison of different pharmacological treatment principles evaluated in randomized controlled clinical trials. In addition, new pharmacological strategies that are not yet available on the market and strategies currently under development are reviewed in detail. The study of new treatment options is of major importance to provide better strategies for the clinical management of depression in the future, and is thus also of great socio-economic importance.

  8. 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

  9. Angina pectoris: current therapy and future treatment options.

    PubMed

    Parikh, Raj; Kadowitz, Philip J

    2014-02-01

    Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, roughly half a million new cases of angina per year. Chest pain, while having many etiologies, is generally considered to be most lethal when related to a cardiac cause. In this review, the authors outline the current medical and surgical therapies that are used in the management of angina. Highlights of the various clinical trials that have assisted in the investigation of these therapies are summarized also. Then, the authors provide a focused review of the novel therapy options for angina that are currently being explored. From new medical treatments to revised surgical techniques to the discovery of stem cell therapy, many innovative options are being investigated for the treatment of angina.

  10. Vanadium salts and the future treatment of diabetes.

    PubMed

    Shechter, Y; Shisheva, A

    1993-03-01

    Until the discovery of insulin by Banting and Best in 1922, diabetes had a high mortality rate. Since then regular administration of the drug has brought it under control. Nevertheless it is not an ideal drug, in that it has to be injected and because of the incidence of insulin resistance. There is, therefore, a need for alternative forms of treatment and in recent years interest has centred on the possibilities of vanadium salts.

  11. 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

  12. Current and Future Treatment of Hypertension in the SPRINT Era.

    PubMed

    Phillips, Robert A

    2015-01-01

    Based on the SPRINT trial, it is highly likely that new SPRINT-era guidelines will establish a blood pressure (BP) goal of < 130/80 mm Hg for those aged 50 or older who are at high risk for a cardiovascular event. In this group, SPRINT demonstrated that assignment to an intensive-treatment systolic BP (SBP) goal of < 120 mm Hg significantly reduced cardiovascular events and mortality compared to those assigned to a standard-treatment SPB goal of < 140 mm Hg. This review critically assesses current hypertension guidelines and presents predictions for SPRINT-era guidelines in the elderly, African Americans, and patients with uncomplicated essential hypertension, diabetes, chronic kidney disease, cardiovascular disease, and coronary artery disease. Specific attention is paid to BP goals and preferred pharmacological antihypertensive therapy in these populations, and an algorithm that incorporates the SPRINT trial results is presented. Inhibitors of the renin-angiotensin-aldosterone system as well as calcium channel blockers are universally accepted as first-line therapy in uncomplicated hypertension, but controversy exists over the role of thiazide diuretics and beta blockers. This review also discusses a physiologically and outcomes-based approach to combination therapy for treatment of hypertension.

  13. 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.

  14. Nuclear Energy - Hydrogen Production - Fuel Cell: A Road Towards Future China's Sustainable Energy Strategy

    SciTech Connect

    Zhiwei Zhou

    2006-07-01

    Sustainable development of Chinese economy in 21. century will mainly rely on self-supply of clean energy with indigenous natural resources. The burden of current coal-dominant energy mix and the environmental stress due to energy consumptions has led nuclear power to be an indispensable choice for further expanding electricity generation capacity in China and for reducing greenhouse effect gases emission. The application of nuclear energy in producing substitutive fuels for road transportation vehicles will also be of importance in future China's sustainable energy strategy. This paper illustrates the current status of China's energy supply and the energy demand required for establishing a harmonic and prosperous society in China. In fact China's energy market faces following three major challenges, namely (1) gaps between energy supply and demand; (2) low efficiency in energy utilization, and (3) severe environmental pollution. This study emphasizes that China should implement sustainable energy development policy and pay great attention to the construction of energy saving recycle economy. Based on current forecast, the nuclear energy development in China will encounter a high-speed track. The demand for crude oil will reach 400-450 million tons in 2020 in which Chinese indigenous production will remain 180 million tons. The increase of the expected crude oil will be about 150 million tons on the basis of 117 million tons of imported oil in 2004 with the time span of 15 years. This demand increase of crude oil certainly will influence China's energy supply security and to find the substitution will be a big challenge to Chinese energy industry. This study illustrates an analysis of the market demands to future hydrogen economy of China. Based on current status of technology development of HTGR in China, this study describes a road of hydrogen production with nuclear energy. The possible technology choices in relation to a number of types of nuclear reactors are

  15. 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

  16. Alloy Design Strategies and Future Trends in High-Entropy Alloys

    NASA Astrophysics Data System (ADS)

    Yeh, Jien-Wei

    2013-12-01

    High-entropy alloys (HEAs) are newly emerging advanced materials. In contrast to conventional alloys, HEAs contain multiple principal elements, often five or more in equimolar or near-equimolar ratios. The basic principle behind HEAs is that solid-solution phases are relatively stabilized by their significantly high entropy of mixing compared to intermetallic compounds, especially at high temperatures. This makes them feasibly synthesized, processed, analyzed, and manipulated, and as well provides many opportunities for us. There are huge numbers of possible compositions and combinations of properties in the HEA field. Wise alloy design strategies for suitable compositions and processes to fit the requirements for either academic studies or industrial applications thus become especially important. In this article, four core effects were emphasized, several misconceptions on HEAs were clarified, and several routes for future HEA research and development were suggested.

  17. 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

  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. 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

  20. New immunotherapeutic strategies for the treatment of neuroblastoma.

    PubMed

    Croce, Michela; Corrias, Maria Valeria; Rigo, Valentina; Ferrini, Silvano

    2015-01-01

    The prognosis of high-risk neuroblastoma (NB) is still poor, in spite of aggressive multimodal treatment. Recently, adjuvant immunotherapy with anti-GD2 antibodies combined with IL-2 or GM-CSF has been shown to improve survival. Several other immunotherapy strategies proved efficacy in preclinical models of NB, including different types of vaccines, adoptive cell therapies and combined approaches. The remarkable differences in the immunobiology of syngeneic models and human NB may, at least in part, limit the translation of preclinical therapies to a clinical setting. Nonetheless, several preliminary evidences suggest that new antibodies, cancer vaccines and adoptive transfer of lymphocytes, genetically engineered to acquire NB specificity, may result in clinical benefit, and clinical studies are currently ongoing.

  1. 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

  2. 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.

  3. 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

  4. [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

  5. [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.

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

    PubMed

    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.

  8. 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

  9. Adult nephrotic syndrome: non-specific strategies for treatment.

    PubMed

    Charlesworth, John A; Gracey, David M; Pussell, Bruce A

    2008-02-01

    Irrespective of aetiology, the nephrotic syndrome presents a range of potentially serious complications. These include thrombo-embolism, infection and hyperlipidaemia. Despite the prevalence of the nephrotic state among renal patients, there has been little prospective analysis of the therapeutic approach to these potentially life-threatening events even though their pathogenesis has been examined in some detail. Most of these complications are more prevalent once the albumin concentration falls below 20 g/L and it is recognized that restoration of serum albumin significantly diminishes their frequency. However, this may be difficult to achieve, especially in adults. The problems of thrombo-embolism and infection are of immediate concern but, in persistent cases, the additional issues of hyperlipidaemia and loss of bone density also require consideration for therapy. Thus, in addition to specific attempts to reduce proteinuria, it is recommended that high-risk nephrotic patients receive anticoagulation, pneumococcal vaccination and lipid lowering therapy. Strategies for the preservation of bone density should also be considered, particularly in patients who receive high-dose corticosteroids. Among a range of non-specific treatments for proteinuria, angiotensin-converting enzyme inhibitors appear best in terms of efficacy and safety. Prospective trials are required to clarify the longitudinal impact of these generic strategies on the protection of the persistently nephrotic patient.

  10. 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

  11. 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

  12. 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.

  13. 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

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

    PubMed

    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.

  15. 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

  16. Nanocomposite-Based Photodynamic Therapy Strategies for Deep Tumor Treatment.

    PubMed

    Hu, Jun; Tang, Yong'an; Elmenoufy, Ahmed H; Xu, Huibi; Cheng, Zhen; Yang, Xiangliang

    2015-11-25

    Photodynamic therapy (PDT), as an emerging clinically approved modality, has been used for treatment of various cancer diseases. Conventional PDT strategies are mainly focused on superficial lesions because the wavelength of illumination light of most clinically approved photosensitizers (PSs) is located in the UV/VIS range that possesses limited tissue penetration ability, leading to ineffective therapeutic response for deep-seated tumors. The combination of PDT and nanotechnology is becoming a promising approach to fight against deep tumors. Here, the rapid development of new PDT modalities based on various smartly designed nanocomposites integrating with conventionally used PSs for deep tumor treatments is introduced. Until now many types of multifunctional nanoparticles have been studied, and according to the source of excitation energy they can be classified into three major groups: near infrared (NIR) light excited nanomaterials, X-ray excited scintillating/afterglow nanoparticles, and internal light emission excited nanocarriers. The in vitro and in vivo applications of these newly developed PDT modalities are further summarized here, which highlights their potential use as promising nano-agents for deep tumor therapy. PMID:26398119

  17. 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

  18. Polycystic ovary syndrome in adolescents: current and future treatment options.

    PubMed

    Mastorakos, George; Lambrinoudaki, Irene; Creatsas, George

    2006-01-01

    contraceptives. Independently of medical treatment, restoration and maintenance of bodyweight within normal range is of paramount importance.

  19. 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.

  20. Current strategies for the treatment of hereditary tyrosinemia type I.

    PubMed

    Ashorn, Merja; Pitkänen, Sari; Salo, Matti K; Heikinheimo, Markku

    2006-01-01

    Hereditary tyrosinemia type I (HT-I) is the most common of the three known diseases caused by defects in tyrosine metabolism. This type of tyrosinemia is caused by a mutation in the gene coding for fumarylacetoacetate hydrolase; several mutations in this gene have been identified. The main clinical features of HT-I are caused by hepatic involvement and renal tubular dysfunction. Dietary intervention with restriction of phenylalanine and tyrosine together with supportive measures can ameliorate the symptoms, but given the high risk for hepatocellular carcinoma, a cure for these patients has so far been possible only with liver transplantation. Pharmacologic treatment with nitisinone, a peroral inhibitor of the tyrosine catabolic pathway, offers an improved means of treatment for patients with HT-I. However, longer follow-up periods are needed to establish the role of this drug in ultimately protecting patients from end-stage organ involvement and hepatocellular carcinoma. Experimental work in mice has provided some promise for the future management of tyrosinemia with gene therapy.

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. Behcet's Disease: New Concepts in Cardiovascular Involvements and Future Direction for Treatment

    PubMed Central

    Owlia, M. B.; Mehrpoor, G.

    2012-01-01

    Behcet's disease (BD) is the only systemic vasculitis involving both arteries and vein in any sizes. It frequently encounters in rheumatology clinics. It has some major morbidities and even fatal outcomes in some cases. The aim of this paper is to analyze the main concepts on pathophysiology and treatment options in BD, focusing on cardiovascular aspects, thrombosis, and potential future treatment. PMID:22530146

  7. Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges.

    PubMed

    Pfister, Bryan J; Gordon, Tessa; Loverde, Joseph R; Kochar, Arshneel S; Mackinnon, Susan E; Cullen, D Kacy

    2011-01-01

    Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.

  8. 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

  9. 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

  10. 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

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

    PubMed

    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.

  12. Strategies for Reforestation under Uncertain Future Climates: Guidelines for Alberta, Canada

    PubMed Central

    Gray, Laura K.; Hamann, Andreas

    2011-01-01

    Background Commercial forestry programs normally use locally collected seed for reforestation under the assumption that tree populations are optimally adapted to local environments. However, in western Canada this assumption is no longer valid because of climate trends that have occurred over the last several decades. The objective of this study is to show how we can arrive at reforestation recommendations with alternative species and genotypes that are viable under a majority of climate change scenarios. Methodology/Principal Findings In a case study for commercially important tree species of Alberta, we use an ecosystem-based bioclimate envelope modeling approach for western North America to project habitat for locally adapted populations of tree species using multi-model climate projections for the 2020s, 2050s and 2080s. We find that genotypes of species that are adapted to drier climatic conditions will be the preferred planting stock over much of the boreal forest that is commercially managed. Interestingly, no alternative species that are currently not present in Alberta can be recommended with any confidence. Finally, we observe large uncertainties in projections of suitable habitat that make reforestation planning beyond the 2050s difficult for most species. Conclusion/Significance More than 50,000 hectares of forests are commercially planted every year in Alberta. Choosing alternative planting stock, suitable for expected future climates, could therefore offer an effective climate change adaptation strategy at little additional cost. Habitat projections for locally adapted tree populations under observed climate change conform well to projections for the 2020s, which suggests that it is a safe strategy to change current reforestation practices and adapt to new climatic realities through assisted migration prescriptions. PMID:21853061

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Chiral High-Speed Counter-Current Chromatography: Future Strategies for Chiral Selector Development.

    PubMed

    Ma, Ying; Ito, Yoichiro

    2014-01-01

    In conventional high-performance liquid chromatography, chiral separations are performed by chiral column with a chiral selector (CS) chemically boned to the solid support. In contrast, high-speed counter-current chromatography (HSCCC) performs chiral separations by dissolving CS in the liquid stationary phase. During the past two decades, several CSs were developed to successfully carry out chiral HSCCC which include N-dodecanoyl-L-proline-3,5-dimethylanilide, β-cyclodextrin derivatives, vancomycin, cinchona alkaloid derivatives, cellulose and amylose derivatives, tartaric acid derivatives, etc. Compared to HPLC which uses over hundred different kinds of CSs, the number of CSs effectively used in HSCCC is limited to several compounds. This may be due to the violent molecular movement of CS dissolved in the liquid stationary phase which reduces chiral selectivity based on steric affinity. Future development strategy of CS for HSCC proposed here is to suppress the molecular movement of the CS in the liquid stationary phase by the following three ways: 1) using viscous stationary phase such as aqueous-aqueous polymer phase system; 2) attaching a long hydrophobic chain to the asymmetric carbon, or 3) chemically bonding CS onto hydrophobic small particles such as carbon nanotubes, gold colloidal particles, and submicron silica particles.

  20. Chiral High-Speed Counter-Current Chromatography: Future Strategies for Chiral Selector Development

    PubMed Central

    Ma, Ying; Ito, Yoichiro

    2014-01-01

    In conventional high-performance liquid chromatography, chiral separations are performed by chiral column with a chiral selector (CS) chemically boned to the solid support. In contrast, high-speed counter-current chromatography (HSCCC) performs chiral separations by dissolving CS in the liquid stationary phase. During the past two decades, several CSs were developed to successfully carry out chiral HSCCC which include N-dodecanoyl-L-proline-3,5-dimethylanilide, β-cyclodextrin derivatives, vancomycin, cinchona alkaloid derivatives, cellulose and amylose derivatives, tartaric acid derivatives, etc. Compared to HPLC which uses over hundred different kinds of CSs, the number of CSs effectively used in HSCCC is limited to several compounds. This may be due to the violent molecular movement of CS dissolved in the liquid stationary phase which reduces chiral selectivity based on steric affinity. Future development strategy of CS for HSCC proposed here is to suppress the molecular movement of the CS in the liquid stationary phase by the following three ways: 1) using viscous stationary phase such as aqueous-aqueous polymer phase system; 2) attaching a long hydrophobic chain to the asymmetric carbon, or 3) chemically bonding CS onto hydrophobic small particles such as carbon nanotubes, gold colloidal particles, and submicron silica particles. PMID:24611132

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. Direct Traumatic Carotid Cavernous Fistula: Angiographic Classification and Treatment Strategies

    PubMed Central

    Chi, Cuong Tran; Nguyen, Dang; Duc, Vo Tan; Chau, Huynh Hong; Son, Vo Tan

    2014-01-01

    Summary We report our experience in treatment of traumatic direct carotid cavernous fistula (CCF) via endovascular intervention. We hereof recommend an additional classification system for type A CCF and suggest respective treatment strategies. Only type A CCF patients (Barrow's classification) would be recruited for the study. Based on the angiographic characteristics of the CCF, we classified type A CCF into three subtypes including small size, medium size and large size fistula depending on whether there was presence of the anterior carotid artery (ACA) and/or middle carotid artery (MCA). Angiograms with opacification of both ACA and MCA were categorized as small size fistula. Angiograms with opacification of either ACA or MCA were categorized as medium size fistula and those without opacification of neither ACA nor MCA were classified as large size fiatula. After the confirm angiogram, endovascular embolization would be performed impromptu using detachable balloon, coils or both. All cases were followed up for complication and effect after the embolization. A total of 172 direct traumatic CCF patients were enrolled. The small size fistula was accountant for 12.8% (22 cases), medium size 35.5% (61 cases) and large size fistula accountant for 51.7% (89 cases). The successful rate of fistula occlusion under endovascular embolization was 94% with preservation of the carotid artery in 70%. For the treatment of each subtype, a total of 21/22 cases of the small size fistulas were successfully treated using coils alone. The other single case of small fistula was defaulted. Most of the medium and large size fistulas were cured using detachable balloons. When the fistula sealing could not be obtained using detachable balloon, coils were added to affirm the embolization of the cavernous sinus via venous access. There were about 2.9% of patient experienced direct carotid artery puncture and 0.6% puncture after carotid artery cut-down exposure. About 30% of cases

  9. 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

  10. [DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

    PubMed

    Mikhaĭlova, M V; Zubarovskiĭ, I N; Osipenko, S K

    2015-01-01

    The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

  11. 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

  12. 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.

  13. Optimal Treatment Strategies in the Context of ‘Treatment for Prevention’ against HIV-1 in Resource-Poor Settings

    PubMed Central

    Duwal, Sulav; Winkelmann, Stefanie; Schütte, Christof; von Kleist, Max

    2015-01-01

    An estimated 2.7 million new HIV-1 infections occurred in 2010. `Treatment-for-prevention’ may strongly prevent HIV-1 transmission. The basic idea is that immediate treatment initiation rapidly decreases virus burden, which reduces the number of transmittable viruses and thereby the probability of infection. However, HIV inevitably develops drug resistance, which leads to virus rebound and nullifies the effect of `treatment-for-prevention’ for the time it remains unrecognized. While timely conducted treatment changes may avert periods of viral rebound, necessary treatment options and diagnostics may be lacking in resource-constrained settings. Within this work, we provide a mathematical platform for comparing different treatment paradigms that can be applied to many medical phenomena. We use this platform to optimize two distinct approaches for the treatment of HIV-1: (i) a diagnostic-guided treatment strategy, based on infrequent and patient-specific diagnostic schedules and (ii) a pro-active strategy that allows treatment adaptation prior to diagnostic ascertainment. Both strategies are compared to current clinical protocols (standard of care and the HPTN052 protocol) in terms of patient health, economic means and reduction in HIV-1 onward transmission exemplarily for South Africa. All therapeutic strategies are assessed using a coarse-grained stochastic model of within-host HIV dynamics and pseudo-codes for solving the respective optimal control problems are provided. Our mathematical model suggests that both optimal strategies (i)-(ii) perform better than the current clinical protocols and no treatment in terms of economic means, life prolongation and reduction of HIV-transmission. The optimal diagnostic-guided strategy suggests rare diagnostics and performs similar to the optimal pro-active strategy. Our results suggest that ‘treatment-for-prevention’ may be further improved using either of the two analyzed treatment paradigms. PMID:25927964

  14. Strategies to improve water productivity in a water-stressed future

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As water shortages become more commonplace, strategies to increase crop water productivity are increasingly sought by producers. Common strategies include increasing irrigation application efficiency, changing irrigation application methods, improving irrigation scheduling, using sensing systems to ...

  15. 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

  16. 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

  17. 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

  18. Current and future strategies for relapsed neuroblastoma: challenges on the road to precision therapy.

    PubMed

    Morgenstern, Daniel A; Baruchel, Sylvain; Irwin, Meredith S

    2013-07-01

    More than half of the patients with high-risk neuroblastoma (NB) will relapse despite intensive multimodal therapy, with an additional 10% to 20% refractory to induction chemotherapy. Management of these patients is challenging, given disease heterogeneity, resistance, and organ toxicity including poor hematological reserve. This review will discuss the current treatment options and consider novel therapies on the horizon. Cytotoxic chemotherapy regimens for relapse and refractory NB typically center on the use of the camptothecins, topotecan and irinotecan, in combination with agents such as cyclophosphamide and temozolomide, with objective responses but poor long-term survival. I-meta-iodobenzylguanidine therapy is also effective for relapsed patients with meta-iodobenzylguanidine-avid disease, with objective responses in a third of cases. Immunotherapy with anti-GD2 has recently been incorporated into upfront therapy, but its role in the relapse setting remains uncertain, especially for patients with bulky disease. Future cell-based immunotherapies and other approaches may be able to overcome this limitation. Finally, many novel molecularly targeted agents are in development, some of which show specific promise for NB. Successful incorporation of these agents will require combinations with conventional cytotoxic chemotherapies, as well as the development of predictive biomarkers, to ultimately personalize approaches to patients with "targetable" molecular abnormalities.

  19. 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

  20. Transrectal high-intensity focused ultrasound for the treatment of prostate cancer: Past, present, and future

    PubMed Central

    Mearini, Luigi; Porena, Massimo

    2010-01-01

    Upon a review of recently published articles on high-intensity focused ultrasound (HIFU) in the treatment of prostate cancer, we evaluated the current status of HIFU as a primary treatment option for localized prostate cancer and its use as salvage therapy when radiation failed. We also briefly discuss current issues in indications, definition of response, and finally the future of HIFU development. PMID:20535278

  1. Constructing evidence-based treatment strategies using methods from computer science

    PubMed Central

    Pineau, Joelle; Bellemare, Marc G.; Rush, A. John; Ghizaru, Adrian; Murphy, Susan A.

    2007-01-01

    This paper details a new methodology, instance–based reinforcement learning, for constructing adaptive treatment strategies from randomized trials. Adaptive treatment strategies are operationalized clinical guidelines which recommend the next best treatment for an individual based on his/her personal characteristics and response to earlier treatments. The instance-based reinforcement learning methodology comes from the computer science literature, where it was developed to optimize sequences of actions in an evolving, time varying system. When applied in the context of treatment design, this method provides the means to evaluate both the therapeutic and diagnostic effects of treatments in constructing an adaptive treatment strategy. The methodology is illustrated with data from the STAR*D trial, a multi-step randomized study of treatment alternatives for individuals with treatment-resistant major depressive disorder. PMID:17320311

  2. Constructing evidence-based treatment strategies using methods from computer science.

    PubMed

    Pineau, Joelle; Bellemare, Marc G; Rush, A John; Ghizaru, Adrian; Murphy, Susan A

    2007-05-01

    This paper details a new methodology, instance-based reinforcement learning, for constructing adaptive treatment strategies from randomized trials. Adaptive treatment strategies are operationalized clinical guidelines which recommend the next best treatment for an individual based on his/her personal characteristics and response to earlier treatments. The instance-based reinforcement learning methodology comes from the computer science literature, where it was developed to optimize sequences of actions in an evolving, time varying system. When applied in the context of treatment design, this method provides the means to evaluate both the therapeutic and diagnostic effects of treatments in constructing an adaptive treatment strategy. The methodology is illustrated with data from the STAR*D trial, a multi-step randomized study of treatment alternatives for individuals with treatment-resistant major depressive disorder.

  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. 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...

  5. 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

  6. 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…

  7. 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

  8. 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.

  9. 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

  10. Treatment strategies for the infertile polycystic ovary syndrome patient.

    PubMed

    Tannus, Samer; Burke, Yechiel Z; Kol, Shahar

    2015-11-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Infertility is a prevalent presenting feature of PCOS, and approximately 75% of these women suffer infertility due to anovulation. Lifestyle modification is considered the first-line treatment and is associated with improved endocrine profile. Clomiphene citrate (CC) should be considered as the first line pharmacologic therapy for ovulation induction. In women who are CC resistant, second-line treatment should be considered, as adding metformin, laparoscopic ovarian drilling or treatment with gonadotropins. In CC treatment failure, Letrozole could be an alternative or treatment with gonadotropins. IVF is considered the third-line treatment; the 'short', antagonist-based protocol is the preferred option for PCOS patients, as it is associated with lower risk of developing ovarian hyperstimulation syndrome (specifically by using a gonadotropin--releasing hormone agonist as ovulation trigger), but with comparable outcomes as the long protocol.

  11. 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

  12. Emotional exposure in the treatment of substance use disorders: conceptual model, evidence, and future directions.

    PubMed

    Otto, Michael W; Powers, Mark B; Fischmann, Diana

    2005-09-01

    In this article, we review research on the nature and treatment of panic disorder, and apply these findings to a discussion of the role of internal cue exposure in the treatment of substance use disorders (SUDs). Two features of panic treatment were used as a model for interventions for SUDs: exposure to internal (interoceptive) cues rather than reliance on external (environmental) exposure alone, and use of cue exposure to try to inoculate individuals against future maladaptive patterns. Specifically, we emphasized the role of exposure to internal, largely emotional cues, as a way to enhance resilience to cues for relapse in individuals with SUDs. Hypothesized moderators and mediators of this treatment approach were discussed, as were similarities between this research agenda and an increasing focus on the role of emotional acceptance/tolerance in cognitive-behavioral treatments.

  13. Michael Pressley's Contributions to the History and Future of Strategies Research

    ERIC Educational Resources Information Center

    Harris, Karen R.; Alexander, Patricia; Graham, Steve

    2008-01-01

    The history of strategies research during the past quarter century has been a story of significant conceptualizations and reconceptualizations regarding the nature, development, and teaching of cognitive and metacognitive strategies. Theoretical models, empirical research, and discussions contributed by Michael Pressley have been central to…

  14. 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

  15. 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

  16. 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.

  17. Cognitive dissonance in behavior therapy: some basic treatment strategies.

    PubMed

    Jensen, R E

    1979-04-01

    As the behavioral model becomes liberalized and more encompassing very different frameworks may offer treatment resources. Several treatment techniques derived from cognitive-dissonance theory are discussed in the context of relevant theoretical postulates. Most of the techniques may be applied as needed regardless of the orientation of the practitioner.

  18. Therapeutic strategies for Parkinson's disease: the ancient meets the future--traditional Chinese herbal medicine, electroacupuncture, gene therapy and stem cells.

    PubMed

    Wang, Xuan; Liang, Xi-Bin; Li, Feng-Qiao; Zhou, Hui-Fang; Liu, Xian-Yu; Wang, Jian-Jun; Wang, Xiao-Min

    2008-10-01

    In China, it has been estimated that there are more than 2.0 million people suffering from Parkinson's disease, which is currently becoming one of the most common chronic neurodegenerative disorders during recent years. For many years, scientists have struggled to find new therapeutic approaches for this disease. Since 1994, our research group led by Drs. Ji-Sheng Han and Xiao-Min Wang of Neuroscience Research Institute, Peking University has developed several prospective treatment strategies for the disease. These studies cover the traditional Chinese medicine-herbal formula or acupuncture, and modern technologies such as gene therapy or stem cell replacement therapy, and have achieved some original results. It hopes that these data may be beneficial for the research development and for the future clinical utility for treatment of Parkinson's disease.

  19. 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.

  20. 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

  1. 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

  2. Comprehensive strategies for the prevention and control of diabetes and cardiovascular diseases in Africa: future directions.

    PubMed

    Muna, Walinjom F T

    2013-01-01

    The countries of the Sub Saharan African region have insufficient resources and healthcare systems that are poorly adapted to cope with the longstanding burden associated with communicable diseases and the ongoing HIV/AIDS pandemic. In addition, the rising burden of non-communicable diseases, including diabetes, cardiovascular diseases, and their risk factors, poses additional challenges. These countries need to urgently develop strategies to address these challenges of disease prevention and control. These strategies will require a new vision and more relevant and 'suitable' vocabulary in dealing with healthcare design, planning and implementation (using a cross-sectorial approach). Lessons learnt from the past (e.g. primary health care) in sub-Saharan Africa and other regions of the world may equally prove useful in developing strategies for the prevention and control of non-communicable diseases. Any potential strategy must emphasize the crucial role of economic, social, and environmental health determinants as well as the use of appropriate health technology.

  3. 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)

  4. Genetic strategies for the treatment of sickle cell anaemia.

    PubMed

    Mansilla-Soto, Jorge; Rivière, Isabelle; Sadelain, Michel

    2011-09-01

    Sickle cell anaemia is a severe inherited blood disorder for which there is presently no curative therapy other than allogeneic haematopoietic stem cell (HSC) transplantation. This therapeutic option, however, is not available to most patients because of the lack of a matched related donor. Different genetic strategies aiming to treat the anaemia and prevent sickling are under investigation. They include strategies to transfer a regulated globin gene in autologous HSCs-the most developed approach, which is about to undergo clinical evaluation-, and strategies to either restore endogenous HBG expression, repair or eliminate HBB(S) mutant transcripts, or correct the sickle mutation in HSCs or induced pluripotent stem cells. Their common ultimate goals are to afford therapeutic levels of HbA or HbF in the erythroid progeny of autologous HSCs (sufficient to prevent pathological sickling) and engraft the genetically modified HSCs with minimal short-term toxicity (primarily caused by the conditioning regimen) and long-term toxicity (primarily caused by genotoxicity). We discuss here the status of application of these technologies, outlining recent advances and the hurdles that lay ahead.

  5. Renal denervation for treatment of cardiac arrhythmias: state of the art and future directions.

    PubMed

    Kosiuk, Jedrzej; Hilbert, Sebastian; Pokushalov, Evgeny; Hindricks, Gerhard; Steinberg, Jonathan S; Bollmann, Andreas

    2015-02-01

    It has now been more than a quarter of a century since modulation of the sympathetic nervous system was proposed for the treatment of cardiac arrhythmias of different origins. But it has also been some time since some of the early surgical attempts have been abandoned. With the development of ablation techniques, however, new approaches and targets have been recently introduced that have revolutionized our way of thinking about sympathetic modulation. Renal nerve ablation technology is now being successfully used for the treatment of resistant hypertension, but the indication spectrum might broaden and new therapeutic options might arise in the near future. This review focuses on the possible impact of renal sympathetic system modulation on cardiac arrhythmias, the current evidence supporting this approach, and the ongoing trials of this method in electrophysiological laboratories. We will discuss the potential roles that sympathetic modulation may play in the future.

  6. 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

  7. Future Prospects for the Treatment of Graves' Hyperthyroidism and Eye Disease.

    PubMed

    Neumann, S; Place, R F; Krieger, C C; Gershengorn, M C

    2015-09-01

    Although there are adequate therapies for Graves' hyperthyroidism, mild to moderate Graves' orbitopathy (GO) is usually treated symptomatically whereas definitive therapy is reserved for severe, vision-threatening GO. Importantly, none of the treatment regimens for Graves' disease used today are directed at the pathogenesis of the disease. Herein, we review some aspects of what is known about the pathogenesis of these 2 major components of Graves' disease, specifically the apparent important roles of the TSH and IGF-1 receptors, and thereafter describe future therapeutic approaches directed at these receptors. We propose that targeting these receptors will yield effective and better tolerated treatments for Graves' disease, especially for GO.

  8. 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…

  9. [Strategies for First-Line Treatment of mCRPC].

    PubMed

    Miller, K; Gschwend, J; Wolff, J-M

    2016-09-01

    At present, abiraterone acetate and enzalutamide are the most commonly used substances in the first-line treatment of asymptomatic or mildly symptomatic metastatic castration-resistant prostate carcinoma (mCRPC). Since the relevant pivotal trials have demonstrated comparable clinical efficacy for both substances, further factors should be considered for the choice of treatment. As mCRPC patients usually receive several lines of treatment, different adaptation and resistance mechanisms leading to treatment failure could be important. This is indicated by daily routine observations and some initial clinical studies on resistance and different sequences of therapy. However, until the clinical relevance has been confirmed, it is mostly adverse events and comorbidities that are taken into account for the choice of first-line therapy. Also potential interactions with comedications and patient preferences should be considered. In the first-line treatment of mCRPC, ongoing discussions not only centre around the choice of medication for first-line mCRPC therapy, but also around the point in time they are started. For abiraterone acetate, for example, there is confirmed evidence that patients may benefit from early use within the approved indication. If the clinical importance of the different resistance mechanisms and differences in efficacy of various sequences could be confirmed, this would be a strong argument for therapy decisions and should therefore be further analysed in prospective clinical studies. PMID:27680191

  10. 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 ...

  11. Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.

    PubMed

    Stine, Jonathan G; Lewis, James H

    2016-01-01

    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

  12. 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

  13. 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

  14. 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.

  15. European perspective on multiple myeloma treatment strategies: update following recent congresses.

    PubMed

    Ludwig, Heinz; Avet-Loiseau, Hervé; Bladé, Joan; Boccadoro, Mario; Cavenagh, Jamie; Cavo, Michele; Davies, Faith; de la Rubia, Javier; Delimpasi, Sosana; Dimopoulos, Meletios; Drach, Johannes; Einsele, Hermann; Facon, Thierry; Goldschmidt, Hartmut; Hess, Urs; Mellqvist, Ulf-Henrik; Moreau, Philippe; San-Miguel, Jesús; Sondergeld, Pia; Sonneveld, Pieter; Udvardy, Miklos; Palumbo, Antonio

    2012-01-01

    The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies.

  16. 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…

  17. Takotsubo Syndrome-Scientific Basis for Current Treatment Strategies.

    PubMed

    Omerovic, Elmir

    2016-10-01

    Takotsubo syndrome (TS) is characterized by severe reversible left ventricular (LV) wall motion abnormality in the absence of explanatory coronary lesion. Despite an increasing number of patients diagnosed with TS worldwide, there are no randomized clinical trials. In mild cases, no treatment or a short course of limited anticoagulation therapy may be sufficient. Positive inotropic and vasodilating agents should be avoided. In severe cases with refractory cardiogenic shock, early treatment with mechanical support using venoarterial extracorporeal membrane oxygenation or a LV assist device should be considered. PMID:27638027

  18. 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

  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. 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

  1. 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

  2. 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.

  3. 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)

  4. 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...

  5. 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.

  6. New Treatment Strategies for Alcohol-Induced Heart Damage

    PubMed Central

    Fernández-Solà, Joaquim; Planavila Porta, Ana

    2016-01-01

    High-dose alcohol misuse induces multiple noxious cardiac effects, including myocyte hypertrophy and necrosis, interstitial fibrosis, decreased ventricular contraction and ventricle enlargement. These effects produce diastolic and systolic ventricular dysfunction leading to congestive heart failure, arrhythmias and an increased death rate. There are multiple, dose-dependent, synchronic and synergistic mechanisms of alcohol-induced cardiac damage. Ethanol alters membrane permeability and composition, interferes with receptors and intracellular transients, induces oxidative, metabolic and energy damage, decreases protein synthesis, excitation-contraction coupling and increases cell apoptosis. In addition, ethanol decreases myocyte protective and repair mechanisms and their regeneration. Although there are diverse different strategies to directly target alcohol-induced heart damage, they are partially effective, and can only be used as support medication in a multidisciplinary approach. Alcohol abstinence is the preferred goal, but control drinking is useful in alcohol-addicted subjects not able to abstain. Correction of nutrition, ionic and vitamin deficiencies and control of alcohol-related systemic organ damage are compulsory. Recently, several growth factors (myostatin, IGF-1, leptin, ghrelin, miRNA, and ROCK inhibitors) and new cardiomyokines such as FGF21 have been described to regulate cardiac plasticity and decrease cardiac damage, improving cardiac repair mechanisms, and they are promising agents in this field. New potential therapeutic targets aim to control oxidative damage, myocyte hypertrophy, interstitial fibrosis and persistent apoptosis In addition, stem-cell therapy may improve myocyte regeneration. However, these strategies are not yet approved for clinical use. PMID:27690014

  7. Female fertility preservation strategies: cryopreservation and ovarian tissue in vitro culture, current state of the art and future perspectives.

    PubMed

    Filatov, M A; Khramova, Y V; Kiseleva, M V; Malinova, I V; Komarova, E V; Semenova, M L

    2016-10-01

    In the present review, the main strategies of female fertility preservation are covered. Procedures of fertility preservation are necessary for women who suffer from diseases whose treatment requires the use of aggressive therapies, such as chemotherapy and radiotherapy. These kinds of therapy negatively influence the health of gametes and their progenitors. The most commonly used method of female fertility preservation is ovarian tissue cryopreservation, followed by the retransplantation of thawed tissue. Another approach to female fertility preservation that has been actively developed lately is the ovarian tissue in vitro culture. The principal methods, advantages and drawbacks of these two strategies are discussed in this article.

  8. [Treatment Strategies for Septic Arthritis of the Sternoclavicular Joint].

    PubMed

    Kuhtin, O; Schmidt-Rohlfing, B; Dittrich, M; Lampl, L; Hohls, M; Haas, V

    2015-10-01

    Septic arthritis of the sternoclavicular joint (SCJ) is a relatively rare disease. Due to serious complications including mediastinitis and generalised sepsis early diagnosis and rapid onset of treatment are mandatory. The disease often affects immunocompromised patients, diabetics, or patients with other infectious diseases. The therapeutic options range from administration of antibiotics to extended surgery including reconstructive procedures. Apart from rare situations where conservative treatment with antibiotics is sufficient, joint resection followed by plastic surgical procedures are required. We present a retrospective analysis with data from two hospitals. From January 2008 to December 2012 23 patients with radiographically confirmed septic arthritis of various aetiology were included. Fourteen (60.8 %) male, nine (39.2 %) female patients with an average age of 60.3 ± 14.2 years (range: 23-88 years) with septic arthritis of the SCJ were treated. Seven (30.4 %) patients suffered from Diabetes mellitus, nine (39.1 %) had underlying diseases with a compromised immune system. In 14 (60.8 %) out of 23 patients a bacterial focus was detected. Only six (26 %) patients suffered from confined septic arthritis of the SCG, in 17 (73,9 %) patients osteomyelitis of the adjacent sternum, and the clavicle was present. In addition, 15 (65.2 %) patients already suffered from mediastinitis at the time of diagnosis, eight (35 %) patients even from septicaemia. In conclusion, septic arthritis requires an active surgical treatment. Limited incision of the joint and debridement alone is only successful at early stages of the disease. The treatment concept has to include the local joint and bone resection as well as complications like mediastinitis. After successful treatment of the infection, the defect of the chest wall requires secondary reconstructive surgery using a pedicled pectoralis muscle flap.

  9. 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

  10. 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.

  11. 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

  12. 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)

  13. Pacesetting Schools Share Successful Strategies to Prepare Students for the Future. Best Practices Newsletter

    ERIC Educational Resources Information Center

    Southern Regional Education Board (SREB), 2013

    2013-01-01

    Pacesetting high schools, middle grades schools and technology centers have changed classroom and other practices to prepare students to meet postsecondary requirements and rising workplace needs. The strategies include raising expectations, project-based learning, guidance and advisement, improving students' reading and writing skills,…

  14. 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…

  15. The Behavior Chain Interruption Strategy: A Review of Research and Discussion of Future Directions.

    ERIC Educational Resources Information Center

    Carter, Mark; Grunsell, Julie

    2001-01-01

    A review of 10 studies that utilize the behavior chain interruption strategy (BCIS) to teach communication skills to individuals with severe disabilities found that BCIS has been successfully applied to individuals across a wide range of ages and levels of disability, including learners with multiple disabilities. Generalization concerns are…

  16. 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…

  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. 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…

  19. 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

  20. Treatment of impulse control disorders in Parkinson's disease: Practical considerations and future directions.

    PubMed

    Ramirez-Zamora, Adolfo; Gee, Lucy; Boyd, James; Biller, José

    2016-01-01

    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

  1. Medical treatment of obesity: the past, the present and the future.

    PubMed

    Bray, George A

    2014-08-01

    Medications for the treatment of obesity began to appear in the late 19th and early 20th century. Amphetamine-addiction led to the search for similar drugs without addictive properties. Four sympathomimetic drugs currently approved in the US arose from this search, but may not be approved elsewhere. When noradrenergic drugs were combined with serotonergic drugs, additional weight loss was induced. At present there are three drugs (orlistat, phentermine/topiramate and lorcaserin) approved for long-term use and four sympathomimetic drugs approved by the US FDA for short-term treatment of obesity. Leptin produced in fat cells and glucagon-like peptide-1, a gastrointestinal hormone, provide a new molecular basis for treatment of obesity. New classes of agents acting on the melanocortin system in the brain or mimicking GLP-1 have been tried with variable success. Combination therapy can substantially increase weight loss; a promising approach for the future. PMID:25194183

  2. 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

  3. Juvenile dermatomyositis: new insights and new treatment strategies

    PubMed Central

    Martin, Neil; Li, Charles K.

    2012-01-01

    Juvenile dermatomyositis (JDM) is a rare but complex and potentially life-threatening autoimmune disease of childhood, primarily affecting proximal muscles and skin. Although the cause of JDM remains unknown it is clear that genetic and environmental influences play a role in the aetiology. In contrast to adults with dermatomyositis, children with JDM are more likely to have complications that are thought to indicate a vasculopathic process, such as severe skin disease, with ulceration or calcinosis, gut vasculopathy or central nervous system disease. New treatments are much needed and are becoming available and being tested through international multicentre trials. This review will focus on recent insights into pathogenesis, the assessment of the disease in children and the modern approach to its treatment. PMID:22870494

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. [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

  10. 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

  11. Future clinical uses of neurophysiological biomarkers to predict and monitor treatment response for schizophrenia.

    PubMed

    Light, Gregory A; Swerdlow, Neal R

    2015-05-01

    Advances in psychiatric neuroscience have transformed our understanding of impaired and spared brain functions in psychotic illnesses. Despite substantial progress, few (if any) laboratory tests have graduated to clinics to inform diagnoses, guide treatments, and monitor treatment response. Providers must rely on careful behavioral observation and interview techniques to make inferences about patients' inner experiences and then secondary deductions about impacted neural systems. Development of more effective treatments has also been hindered by a lack of translational quantitative biomarkers that can span the brain-behavior treatment knowledge gap. Here, we describe an example of a simple, low-cost, and translatable electroencephalography (EEG) measure that offers promise for improving our understanding and treatment of psychotic illnesses: mismatch negativity (MMN). MMN is sensitive to and/or predicts response to some pharmacologic and nonpharmacologic interventions and accounts for substantial portions of variance in clinical, cognitive, and psychosocial functioning in schizophrenia (SZ). This measure has recently been validated for use in large-scale multisite clinical studies of SZ. Finally, MMN greatly improves our ability to forecast which individuals at high clinical risk actually develop a psychotic illness. These attributes suggest that MMN can contribute to personalized biomarker-guided treatment strategies aimed at ameliorating or even preventing the onset of psychosis. PMID:25752648

  12. Pharmacological treatment of schizophrenia: a critical review of the pharmacology and clinical effects of current and future therapeutic agents.

    PubMed

    Miyamoto, S; Miyake, N; Jarskog, L F; Fleischhacker, W W; Lieberman, J A

    2012-12-01

    Since the introduction of chlorpromazine and throughout the development of the new-generation antipsychotic drugs (APDs) beginning with clozapine, the D(2) receptor has been the target for the development of APDs. Pharmacologic actions to reduce neurotransmission through the D(2) receptor have been the only proven therapeutic mechanism for psychoses. A number of novel non-D(2) mechanisms of action of APDs have been explored over the past 40 years but none has definitively been proven effective. At the same time, the effectiveness of treatments and range of outcomes for patients are far from satisfactory. The relative success of antipsychotics in treating positive symptoms is limited by the fact that a substantial number of patients are refractory to current medications and by their lack of efficacy for negative and cognitive symptoms, which often determine the level of functional impairment. In addition, while the newer antipsychotics produce fewer motor side effects, safety and tolerability concerns about weight gain and endocrinopathies have emerged. Consequently, there is an urgent need for more effective and better-tolerated antipsychotic agents, and to identify new molecular targets and develop mechanistically novel compounds that can address the various symptom dimensions of schizophrenia. In recent years, a variety of new experimental pharmacological approaches have emerged, including compounds acting on targets other than the dopamine D(2) receptor. However, there is still an ongoing debate as to whether drugs selective for singe molecular targets (that is, 'magic bullets') or drugs selectively non-selective for several molecular targets (that is, 'magic shotguns', 'multifunctional drugs' or 'intramolecular polypharmacy') will lead to more effective new medications for schizophrenia. In this context, current and future drug development strategies can be seen to fall into three categories: (1) refinement of precedented mechanisms of action to provide drugs

  13. Estimating the Impact of Expanding Treatment Coverage and Allocation Strategies for Chronic Hepatitis C in a Direct Antiviral Agent Era.

    PubMed

    Poovorawan, Kittiyod; Pan-Ngum, Wirichada; White, Lisa J; Soonthornworasiri, Ngamphol; Wilairatana, Polrat; Wasitthankasem, Rujipat; Tangkijvanich, Pisit; Poovorawan, Yong

    2016-01-01

    Hepatitis C virus (HCV) infection is an important worldwide public health problem, and most of the global HCV burden is in low- to middle-income countries. This study aimed to estimate the future burden of chronic hepatitis C (CHC) and the impact of public health policies using novel antiviral agents in Thailand. A mathematical model of CHC transmission dynamics was constructed to examine the disease burden over the next 20 years using different treatment strategies. We compared and evaluated the current treatment (PEGylated interferon and ribavirin) with new treatments using novel direct-acting antiviral agents among various treatment policies. Thailand's CHC prevalence was estimated to decrease 1.09%-0.19% in 2015-2035. Expanding treatment coverage (i.e., a five-fold increment in treatment accessibility) was estimated to decrease cumulative deaths (33,007 deaths avoided, 25.5% reduction) from CHC-related decompensated cirrhosis and hepatocellular carcinoma (HCC). The yearly incidence of HCC-associated HCV was estimated to decrease from 2,305 to 1,877 cases yearly with expanding treatment coverage. A generalized treatment scenario (i.e., an equal proportional distribution of available treatment to individuals at all disease stages according to the number of cases at each stage) was predicted to further reduce death from HCC (9,170 deaths avoided, 11.3% reduction) and the annual incidence of HCC (i.e., a further decrease from 1,877 to 1,168 cases yearly, 37.7% reduction), but cumulative deaths were predicted to increase (by 3,626 deaths, 3.7% increase). Based on the extensive coverage scenario and the generalized treatment scenario, we estimated near-zero death from decompensated cirrhosis in 2031. In conclusion, CHC-related morbidity and mortality in Thailand are estimated to decrease dramatically over the next 20 years. Treatment coverage and allocation strategies are important factors that affect the future burden of CHC in resource-limited countries like

  14. Estimating the Impact of Expanding Treatment Coverage and Allocation Strategies for Chronic Hepatitis C in a Direct Antiviral Agent Era

    PubMed Central

    Poovorawan, Kittiyod; Pan-ngum, Wirichada; White, Lisa J.; Soonthornworasiri, Ngamphol; Wilairatana, Polrat; Wasitthankasem, Rujipat; Tangkijvanich, Pisit; Poovorawan, Yong

    2016-01-01

    Hepatitis C virus (HCV) infection is an important worldwide public health problem, and most of the global HCV burden is in low- to middle-income countries. This study aimed to estimate the future burden of chronic hepatitis C (CHC) and the impact of public health policies using novel antiviral agents in Thailand. A mathematical model of CHC transmission dynamics was constructed to examine the disease burden over the next 20 years using different treatment strategies. We compared and evaluated the current treatment (PEGylated interferon and ribavirin) with new treatments using novel direct-acting antiviral agents among various treatment policies. Thailand’s CHC prevalence was estimated to decrease 1.09%–0.19% in 2015–2035. Expanding treatment coverage (i.e., a five-fold increment in treatment accessibility) was estimated to decrease cumulative deaths (33,007 deaths avoided, 25.5% reduction) from CHC-related decompensated cirrhosis and hepatocellular carcinoma (HCC). The yearly incidence of HCC-associated HCV was estimated to decrease from 2,305 to 1,877 cases yearly with expanding treatment coverage. A generalized treatment scenario (i.e., an equal proportional distribution of available treatment to individuals at all disease stages according to the number of cases at each stage) was predicted to further reduce death from HCC (9,170 deaths avoided, 11.3% reduction) and the annual incidence of HCC (i.e., a further decrease from 1,877 to 1,168 cases yearly, 37.7% reduction), but cumulative deaths were predicted to increase (by 3,626 deaths, 3.7% increase). Based on the extensive coverage scenario and the generalized treatment scenario, we estimated near-zero death from decompensated cirrhosis in 2031. In conclusion, CHC-related morbidity and mortality in Thailand are estimated to decrease dramatically over the next 20 years. Treatment coverage and allocation strategies are important factors that affect the future burden of CHC in resource-limited countries like

  15. 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

  16. Changing needs for appropriate excreta disposal and small wastewater treatment methodologies or The future technology of small wastewater treatment systems.

    PubMed

    Randall, C W

    2003-01-01

    Recent developments will strongly influence the design and utilization of small wastewater treatment systems in the future, e.g. population increases in non-sewered rural areas and developing countries; increasing impairment of surface water quality; the construction of occupied high-rise buildings in metropolitan areas; the development of planned but somewhat isolated communities, growing shortages of water that mandate reuse of wastewaters. It is well known that there is a very strong linkage between wastewater disposal methods in rural areas and developing countries and the general health of the population. These problems could be greatly reduced or prevented by the utilization of well known excreta disposal and small wastewater treatment system technologies, but the development of more innovative on-site systems is needed. It is expected that future environmental and public health pressures in developed countries will require increasingly stringent effluent limitations for small and on-site wastewater disposal systems, based primarily on nutrient discharges. Both on-site and small-scale technologies are available for the more stringent requirements, but innovative and more economical designs are needed for wide-spread acceptance. Water reuse should be a consideration for the designs of these systems. Implementation and utilization of well known technologies are needed, but the obstacles are often more social and political than economical.

  17. Current Grid Generation Strategies and Future Requirements in Hypersonic Vehicle Design, Analysis and Testing

    NASA Technical Reports Server (NTRS)

    Papadopoulos, Periklis; Venkatapathy, Ethiraj; Prabhu, Dinesh; Loomis, Mark P.; Olynick, Dave; Arnold, James O. (Technical Monitor)

    1998-01-01

    Recent advances in computational power enable computational fluid dynamic modeling of increasingly complex configurations. A review of grid generation methodologies implemented in support of the computational work performed for the X-38 and X-33 are presented. In strategizing topological constructs and blocking structures factors considered are the geometric configuration, optimal grid size, numerical algorithms, accuracy requirements, physics of the problem at hand, computational expense, and the available computer hardware. Also addressed are grid refinement strategies, the effects of wall spacing, and convergence. The significance of grid is demonstrated through a comparison of computational and experimental results of the aeroheating environment experienced by the X-38 vehicle. Special topics on grid generation strategies are also addressed to model control surface deflections, and material mapping.

  18. [Strategies for safety assessment of genetically modified crops: current and future development].

    PubMed

    Zhuo, Qin; Yang, Xiao-guang

    2005-03-01

    Gene recombinant technologies supply agriculture product with great vitality. But the risk of genetically modified crops cannot be ignored. The international organizations such as WHO, FAO and OECD have reached common agreement: the safety of transgenic crops should be thoroughly evaluated based on "substantial equivalence"principle. The relevant strategies including: substantial equivalent analysis, toxic tests, protein allergenic study, nutritional assessment, etc. With the development of new technologies, the approaches of genomic, proteomics, metabolomics would be applied to detect the unintended effects. The EU recently adopted legislation on the cultivation GM crops requiring the post market surveillance for any unanticipated adverse effects in the long term. In conclusion, the strategies of the safety assessment of GM crop are very strict and likely development.

  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. 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.

  1. Beyond Exposure for Posttraumatic Stress Disorder (PTSD) Symptoms: Broad-Spectrum PTSD Treatment Strategies

    ERIC Educational Resources Information Center

    Lombardo, Thomas W.; Gray, Matt J.

    2005-01-01

    Although cases of posttraumatic stress disorder (PTSD) with comorbid disorders are common, the first generation of PTSD treatment approaches, including exposure and cognitive-behavioral therapy, generally ignore symptoms beyond those specific to PTSD. Optimum PTSD treatment outcome requires more comprehensive strategies, and the development and…

  2. The past, present and future in scaffold-based tendon treatments.

    PubMed

    Lomas, A J; Ryan, C N M; Sorushanova, A; Shologu, N; Sideri, A I; Tsioli, V; Fthenakis, G C; Tzora, A; Skoufos, I; Quinlan, L R; O'Laighin, G; Mullen, A M; Kelly, J L; Kearns, S; Biggs, M; Pandit, A; Zeugolis, D I

    2015-04-01

    Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained release of therapeutics/biologics; and the ability to positively interact with the host to promote repair and regeneration. Herein, we critically discuss current therapies and emerging technologies that aim to transform tendon treatments in the years to come.

  3. The past, present and future in scaffold-based tendon treatments.

    PubMed

    Lomas, A J; Ryan, C N M; Sorushanova, A; Shologu, N; Sideri, A I; Tsioli, V; Fthenakis, G C; Tzora, A; Skoufos, I; Quinlan, L R; O'Laighin, G; Mullen, A M; Kelly, J L; Kearns, S; Biggs, M; Pandit, A; Zeugolis, D I

    2015-04-01

    Tendon injuries represent a significant clinical burden on healthcare systems worldwide. As the human population ages and the life expectancy increases, tendon injuries will become more prevalent, especially among young individuals with long life ahead of them. Advancements in engineering, chemistry and biology have made available an array of three-dimensional scaffold-based intervention strategies, natural or synthetic in origin. Further, functionalisation strategies, based on biophysical, biochemical and biological cues, offer control over cellular functions; localisation and sustained release of therapeutics/biologics; and the ability to positively interact with the host to promote repair and regeneration. Herein, we critically discuss current therapies and emerging technologies that aim to transform tendon treatments in the years to come. PMID:25499820

  4. Treatment of Metastatic Colorectal Cancer: Standard of Care and Future Perspectives.

    PubMed

    Holch, Julian; Stintzing, Sebastian; Heinemann, Volker

    2016-06-01

    Palliative chemotherapy for metastatic colorectal cancer has undergone substantial changes in recent years. The implementation of modern biologicals in the treatment has substantially improved overall survival up to 30 months. With the increasing number of therapeutic options, the question of optimal treatment sequence arises, which is addressed in current studies like FIRE 4 or STRATEGIC-1. Furthermore, clinical and molecular biomarkers to predict efficacy and tolerability are urgently needed. Today, the detection of activating RAS mutations is the only validated biomarker which precludes patients from anti-EGFR treatment. The detection of BRAF mutation V600E is associated with a very poor prognosis corresponding to a survival of 9-12 months. Prospective trials evaluating an optimal approach to this subgroup are still missing. First results from strategies targeting the aberrant signal transduction are promising and require further validation. Despite the advances so far, life expectancy unfortunately continues to be limited in the majority of patients with metastatic colorectal cancer. New strategies are needed to improve the prognosis. To this end, the identification of Her2/neu as a potential target and first experiences with checkpoint inhibition in patients with mismatch repair-deficient tumors are promising and also require further validation. PMID:27493945

  5. 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.

  6. 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

  7. 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

  8. Principles and Current Strategies for Targeting Autophagy for Cancer Treatment

    PubMed Central

    Amaravadi, Ravi K.; Lippincott-Schwartz, Jennifer; Yin, Xiao-Ming; Weiss, William A.; Takebe, Naoko; Timmer, William; DiPaola, Robert S.; Lotze, Michael T.; White, Eileen

    2010-01-01

    Autophagy is an evolutionarily conserved, intracellular self-defense mechanism where organelles and proteins are sequestered into autophagic vesicles (AVs) that are subsequently degraded through fusion with lysosomes. Cells thereby prevent the toxic accumulation of damaged or unnecessary components, but also recycle these components to sustain metabolic homoeostasis. Heightened autophagy is a mechanism of resistance for cancer cells faced with metabolic and therapeutic stress, revealing opportunities for exploitation as a therapeutic target in cancer. We summarize recent developments in the field of autophagy and cancer, and build upon the results presented at the Cancer Therapeutics and Evaluation Program (CTEP) Early Drug Development meeting in March, 2010. Herein, we describe our current understanding of the core components of the autophagy machinery, the functional relevance of autophagy within the tumor microenvironment and outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy and immunotherapy. Finally, we describe ongoing clinical trials involving HCQ as a first generation autophagy inhibitor, as well as strategies for the development of novel, more potent and specific inhibitors of autophagy. PMID:21325294

  9. 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

  10. Banking or Bankrupting: Strategies for Sustaining the Economic Future of Public Cord Blood Banks

    PubMed Central

    Magalon, Jeremy; Maiers, Martin; Kurtzberg, Joanne; Navarrete, Cristina; Rubinstein, Pablo; Brown, Colin; Schramm, Catherine; Larghero, Jérome; Katsahian, Sandrine; Chabannon, Christian; Picard, Christophe; Platz, Alexander; Schmidt, Alexander; Katz, Gregory

    2015-01-01

    Background Cord blood is an important source of stem cells. However, nearly 90% of public cord blood banks have declared that they are struggling to maintain their financial sustainability and avoid bankruptcy. The objective of this study is to evaluate how characteristics of cord blood units influence their utilization, then use this information to model the economic viability and therapeutic value of different banking strategies. Methods Retrospective analysis of cord blood data registered between January 1st, 2009 and December 31st, 2011 in Bone Marrow Donor Worldwide. Data were collected from four public banks in France, Germany and the USA. Samples were eligible for inclusion in the analysis if data on cord blood and maternal HLA typing and biological characteristics after processing were available (total nucleated and CD34+ cell counts). 9,396 banked cord blood units were analyzed, of which 5,815 were Caucasian in origin. A multivariate logistic regression model assessed the influence of three parameters on the CBU utilization rate: ethnic background, total nucleated and CD34+ cell counts. From this model, we elaborated a Utilization Score reflecting the probability of transplantation for each cord blood unit. We stratified three Utilization Score thresholds representing four different banking strategies, from the least selective (scenario A) to the most selective (scenario D). We measured the cost-effectiveness ratio for each strategy by comparing performance in terms of number of transplanted cord blood units and level of financial deficit. Results When comparing inputs and outputs over three years, Scenario A represented the most extreme case as it delivered the highest therapeutic value for patients (284 CBUs transplanted) along with the highest financial deficit (USD 5.89 million). We found that scenario C resulted in 219 CBUs transplanted with a limited deficit (USD 0.98 million) that charities and public health could realistically finance over the long

  11. Treatment of the benign inverted nipple: A systematic review and recommendations for future therapy.

    PubMed

    Hernandez Yenty, Q M; Jurgens, W J F M; van Zuijlen, P P M; de Vet, H C W; Verhaegen, P D H M

    2016-10-01

    The inverted nipple is a frequently encountered problem which can cause difficulties with breastfeeding, sexuality, and aesthetic dissatisfaction. Up to now, no consensus exists on a preferred treatment method. We performed a systematic review to identify the best treatment method for correction of benign inverted nipples. Treatment techniques were subdivided in the categories lactiferous duct preserving and lactiferous duct damaging. A systematic review was performed using the PRISMA statement. Inclusion criteria were: female patients with congenital or acquired inverted nipples, a minimum sample size of 10 nipples, and studies reporting recurrence of inversion with a minimum follow-up of six months. Exclusion criteria were nipple inversion caused by malignancy. Thirteen studies met the inclusion criteria which all had a level of evidence IV. No non-invasive treatment techniques were identified. In the duct preserving category eight studies were included with a recurrence rate of 0.6% (2/350) versus 9.9% (16/161) in the duct damaging category (n = 5). Other outcome parameters were not systematically reported in all studies. Because of a small number of low quality studies with heterogeneous interventions and outcomes a meta-analysis could not be performed and no preferred treatment method was identified. Based on the available data there is no statistical evidence that duct damaging treatment is superior to duct preserving treatment. We recommend that the first method of choice should be a duct preserving treatment method. In the future, more studies of better methodological quality are required and recommendations were made on how these could be conducted. PMID:27476082

  12. Dizziness in the older adult, Part 1. Evaluation and general treatment strategies.

    PubMed

    Eaton, Deborah A; Roland, Peter S

    2003-04-01

    Dizziness is one of the most common complaints among patients age 50 and older who present to primary care physicians. The evaluation of dizziness is challenging due to the wide range of diagnostic possibilities, including four symptom categories each with multiple potential underlying causes. Although each cause has specific treatment options, general management strategies can be applied to all patients presenting with dizziness. These strategies include use of medications to control acute vestibular and autonomic symptoms as well as vestibular rehabilitation exercises. Difficult cases that do not respond to treatment efforts should be referred to an otolaryngologist for further evaluation and treatment. PMID:12708153

  13. Using ecological forecasting of future vegetation transition and fire frequency change in the Sierra Nevada to assess fire management strategies

    NASA Astrophysics Data System (ADS)

    Thorne, J. H.; Schwartz, M. W.; Holguin, A. J.; Moritz, M.; Batllori, E.; Folger, K.; Nydick, K.

    2013-12-01

    strong upslope shifting of open grassland, chaparral and hardwood types, which may be initiated by increased fire frequencies, particularly where fires have not recently burned within normal fire recurrence interval departures (FRID). An evaluation of four fire management strategies (business as usual; resist change; foster orderly change; protect vital resources) across four combinations of future climate and fire frequency found that no single management strategy was uniformly successful in protecting critical resources across the range of future conditions examined. This limitation is somewhat driven by current management constraints on the amount of management available to resource managers, which suggests management will need to use a triage approach to application of proactive fire management strategies, wherein MOC landscape projections can be used in decision support.

  14. The treatment strategies of autoimmune disease may need a different approach from conventional protocol: A review

    PubMed Central

    Chandrashekara, S.

    2012-01-01

    Autoimmune disease (AD) is one of the emerging noncommunicable diseases. Remission is a possibility in AD, but current treatment strategies are not able to achieve this. We have well-established protocols for infections, oncology, metabolic diseases, and transplantation which are often used as models for the management of AD. Studies and observations suggest that in contrast to diseases used as a role model, AD has wide variability, different causative and pathogenic process, which is highly dynamic, making the current treatment strategies to fall short of expected complete remission. In this brief review, it is attempted to highlight the current understanding of AD and the probable gaps in the treatment strategies. Few hypothetical suggestions to modify the treatment protocols are presented. PMID:23248391

  15. Physical Exercise for the Treatment of Neuropsychiatric Disturbances in Alzheimer's Dementia: Possible Mechanisms, Current Evidence and Future Directions.

    PubMed

    Matura, Silke; Carvalho, André F; Alves, Gilberto S; Pantel, Johannes

    2016-01-01

    Behavioral and psychological symptoms of dementia (BPSD), also known as neuropsychiatric or non-cognitive symptoms are common and often distressing features of Alzheimer's Dementia. BPSD significantly increase patient suffering, early institutionalization and caregiver's burden. The clinical management of BPSD is dominated by a pharmacological approach, although these medications often come with serious adverse side-effects. There are only few nonpharmacological treatment strategies for BPSD. A substantial amount of intervention studies that have investigated non-pharmacological treatment options for BPSD have focused on physical exercise. Although these studies are very heterogeneous in terms of type and severity of dementia, as well as type and duration of the exercise intervention, the overall picture shows a positive effect of physical exercise in alleviating BPSD. There is evidence that numerous mechanisms contribute to the positive effect of physical exercise on BPSD. No attempt has been undertaken so far to give an overview of the existing knowledge regarding these mechanisms. Therefore, the current review aims to integrate the existing evidence on psychological and neurobiological mechanisms that contribute to the beneficial effects of physical exercise in ameliorating BPSD in Alzheimer's dementia. A discussion of psychological mechanisms such as improved sleep and stress reduction will be followed by a discussion of neurobiological mechanisms including the exercise induced change in neurotransmitter concentrations, increased synthesis of neurotrophins and immune activation. The review closes with recommendations for future research to overcome the shortcomings of existing studies and broaden the current knowledge on the positive effects of physical exercise on BPSD.

  16. Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering

    PubMed Central

    Fernández-Robredo, P.; Sancho, A.; Johnen, S.; Recalde, S.; Gama, N.; Thumann, G.; Groll, J.; García-Layana, A.

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

  17. Current treatment limitations in age-related macular degeneration and future approaches based on cell therapy and tissue engineering.

    PubMed

    Fernández-Robredo, P; Sancho, A; Johnen, S; Recalde, S; Gama, N; Thumann, G; Groll, J; García-Layana, A

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. PMID:24672707

  18. Macrolide-resistant Streptococcus pyogenes: prevalence and treatment strategies.

    PubMed

    Silva-Costa, Catarina; Friães, Ana; Ramirez, Mario; Melo-Cristino, Jose

    2015-05-01

    Although penicillin remains the first-choice treatment for Streptococcus pyogenes infection, macrolides are important alternatives for allergic patients and lincosamides are recommended together with β-lactams in invasive infections. S. pyogenes may exhibit macrolide resistance because of active efflux (mef genes) or target modification (erm genes), the latter conferring cross resistance to lincosamides and streptogramin B. Worldwide, resistance is restricted to a limited number of genetic lineages, despite resistance genes being encoded on mobile genetic elements. For reasons that are not completely clear, resistance and the associated phenotypes are highly variable across countries. Although resistance remains high in several countries, particularly in Asia, an overall decreasing trend of resistance has been noted in recent years, mostly in Europe. This decrease is not always accompanied by declines in macrolide consumption, suggesting significant roles of other factors in determining the dynamics of macrolide-resistant clones. Continued surveillance is needed to obtain further insights into the forces governing macrolide resistance in S. pyogenes.

  19. Human Papillomavirus (HPV)-associated Oral Cancers and Treatment Strategies.

    PubMed

    Sathish, N; Wang, X; Yuan, Y

    2014-07-01

    Human papillomavirus (HPV) is known to be associated with several types of human cancer, including cervical, vulvar, vaginal, penile, anal, and head-and-neck cancers. Among these cancers, HPV-associated head-and-neck cancers, inclusive of oropharyngeal squamous cell carcinoma (OSCC) and oral cavity squamous cell carcinomas (OCSCC), have recently risen dramatically in men under 50 years old. Within 20 years, the percentage of HPV-positive OSCC in total OSCC went from less than 20% to more than 70% in the United States and some European countries. This article reviews the incidence trend and pathogenesis of HPV-associated head-and-neck cancers as well as current treatment modalities for the disease.

  20. Development of treatment strategies to combat Ebola and Marburg viruses.

    PubMed

    Paragas, Jason; Geisbert, Thomas W

    2006-02-01

    Ebola and Marburg viruses are emerging/re-emerging pathogens that pose a significant threat to human health. These naturally occurring viral infections frequently cause a lethal hemorrhagic fever in humans and nonhuman primates. The disastrous consequences of infection with these viruses have been pursued as potential biological weapons. To date, there are no therapeutic options available for the prophylaxis or treatment of infected individuals. The recognition that Ebola and Marburg viruses may be exploited as biological weapons has resulted in major efforts to develop modalities to counter infection. In this review, select technologies and approaches will be highlighted as part of the critical path for the development of therapeutics to ameliorate the invariably devastating outcomes of human filoviral infections.

  1. 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

  2. Novel Strategies in the Treatment of Pulmonary Arterial Hypertension.

    PubMed

    Madonna, Rosalinda; Cocco, Nino

    2016-01-01

    Pulmonary arterial hypertension (PAH) is a pathophysiological condition characterized by increased pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury. Recent studies confirmed the key role of endothelin (ET)-1 in the vasoconstriction and remodeling of pulmonary microcirculation during PAH. In responders patients, classical treatments for PAH are prostanoids, phosphodiesterase (PDE)-5 inhibitors and endothelin receptor antagonists (ERAs), which target prostaglandin I2, nitric oxide and endothelin pathways, respectively. Randomised, placebo-controlled trials have shown that ERAs improves haemodynamic parameters of the pulmonary circulation, functional capacity and clinical outcome in patients affected by PAH. Here, we will review the definition, classification and pathophysiology of PH. Furthermore, we will provide an up-to-date overview of currently recommended diagnostic and therapeutic work-up in PAH. PMID:26201488

  3. 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

  4. Review of Pharmacological Treatment in Mood Disorders and Future Directions for Drug Development

    PubMed Central

    Li, Xiaohua; Frye, Mark A; Shelton, Richard C

    2012-01-01

    After a series of serendipitous discoveries of pharmacological treatments for mania and depression several decades ago, relatively little progress has been made for novel hypothesis-driven drug development in mood disorders. Multifactorial etiologies of, and lack of a full understanding of, the core neurobiology of these conditions clearly have contributed to these development challenges. There are, however, relatively novel targets that have raised opportunities for progress in the field, such as glutamate and cholinergic receptor modulators, circadian regulators, and enzyme inhibitors, for alternative treatment. This review will discuss these promising new treatments in mood disorders, the underlying mechanisms of action, and critical issues of their clinical application. For these new treatments to be successful in clinical practice, it is also important to design innovative clinical trials that identify the specific actions of new drugs, and, ideally, to develop biomarkers for monitoring individualized treatment response. It is predicted that future drug development will identify new agents targeting the molecular mechanisms involved in the pathophysiology of mood disorders. PMID:21900884

  5. Minimally invasive mapping guided surgical treatment of atrial fibrillation. Utopia or near future?

    PubMed

    van Brakel, Thomas J; Bolotin, Gil; Allessie, M A; Maessen, Jos G

    2006-01-01

    Isolation of the pulmonary veins has been used as surgical treatment for atrial fibrillation (AF) from the early 90s, as it was incorporated in the Maze procedure. With the evidence that triggers form this area can induce AF, the Maze III procedure has been adapted and modified towards a single lesion around the pulmonary veins for the treatment of paroxysmal and chronic AF in some centers. New ablation techniques with a diversity of energy sources further paved the way for less invasive procedures. Minimal invasive techniques to prevent major surgery may potentially make the treatment available for a patient population that do not have to undergo cardiac surgery for other reasons. Besides these technical developments, high density mapping can be used to identify the AF substrate in the individual patient and optimization of the treatment by local substrate guided ablation. This review aims to summarize the robotic and thoracoscopic techniques to isolate the pulmonary veins. Furthermore, it is discussed why pulmonary veins isolation may be effective in patients with chronic AF, and whether there is a role for mapping guided minimal invasive surgical treatment of AF in the near future.

  6. 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

  7. Intracranial growing teratoma syndrome: clinical characteristics and treatment strategy.

    PubMed

    Kim, Chae-Yong; Choi, Jung-Won; Lee, Ji Yeon; Kim, Seung-Ki; Wang, Kyu-Chang; Park, Sung-Hye; Choe, Gheeyoung; Ahn, Hyo Seop; Kim, Il-Han; Cho, Byung-Kyu

    2011-01-01

    This study evaluated the clinical and radiological characteristics, as well as the treatment outcomes, for the rare phenomenon known as intracranial growing teratoma syndrome (iGTS). One hundred seventy patients diagnosed with intracranial germ cell tumours (GCT) between 1997 and 2008 were enrolled in this retrospective analysis. Thorough reviews of medical records, brain magnetic resonance images (MRI), pathological findings and tumour markers [alpha-fetoprotein (αFP) and beta-human chorionic gonadotropin (βHCG)] were performed to identify the incidence of iGTS cases and to clarify their clinical characteristics. Eleven out of the 170 intracranial GCT patients (6.5%) were identified as having iGTS. All instances of iGTS originated from non-germinomatous GCT (NGGCT), with incidence rate of 21% (11/52). Six iGTS cases developed from mixed GCTs, four from immature teratomas (ITs) and one from yolk sac tumour. All 11 iGTS patients showed honeycomb-shaped multi-cystic growth patterns on MRI, which is a typical characteristic of iGTS. Surgical excision was performed in all patients, and complete excision was possible in nine patients. Eight of them are alive with no evidence of recurrence; however, two patients who had residual masses died owing to progression of iGTS. Early recognition and suspicion of iGTS, during or after adjuvant therapy of NGGCT, is crucial to ensure that surgical intervention can be performed in a timely manner. Early radical excision may be the treatment of choice for better iGTS prognosis. PMID:20532955

  8. 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

  9. [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

  10. Limitations of Neuroendoscopic Treatment for Pediatric Hydrocephalus and Considerations from Future Perspectives

    PubMed Central

    NISHIYAMA, Kenichi; YOSHIMURA, Junichi; FUJII, Yukihiko

    2015-01-01

    Neuroendoscopy has become common in the field of pediatric neurosurgery. As an alternative procedure to cerebrospinal fluid shunt, endoscopic third ventriculostomy has been the routine surgical treatment for obstructive hydrocephalus. However, the indication is still debatable in infantile periods. The predictors of late failure and how to manage are still unknown. Recently, the remarkable results of endoscopic choroid plexus coagulation in combination with third ventriculostomy, reported from experiences in Africa, present puzzling complexity. The current data on the role of neuroendoscopic surgery for pediatric hydrocephalus is reported with discussion of its limitations and future perspectives, in this review. PMID:26226979

  11. Emerging Technologies in the Treatment of Anorexia Nervosa and Ethics: Sufferers' Accounts of Treatment Strategies and Authenticity.

    PubMed

    Coman, Alina

    2014-09-01

    New neural models for anorexia nervosa (AN) are emerging as a result of increased research on the neurobiology of AN, and these offer a rationale for the development of new treatment technologies such as neuromodulation. The emergence of such treatment technologies raises new ethical questions; however these have been little discussed for AN. In this article, I take an empirical approach and explore how young women who suffer from AN perceive treatment technologies in light of the concept of authenticity. Interview data showed that participants in this study did not seem to unconditionally adhere to treatment modalities that only imply laborious self-work, such as therapy. The data also showed that they were willing to accept new treatment possibilities such as pharmacological or brain-directed treatment strategies, which they view as having potential instrumental value in coping with certain symptoms of the illness. However, such modalities can pose threats to patients' authenticity, especially with regard to self-discovery. I argue that, in a context where there is an increased interest in brain-directed treatment strategies for AN, studies should continue to explore the ethical and psychological impact of such treatment technologies on individuals.

  12. Reflectance spectroscopy in planetary science: Review and strategy for the future

    NASA Technical Reports Server (NTRS)

    Mccord, Thomas B. (Editor)

    1987-01-01

    Reflectance spectroscopy is a remote sensing technique used to study the surfaces and atmospheres of solar system bodies. It provides first-order information on the presence and amounts of certain ions, molecules, and minerals on a surface or in an atmosphere. Reflectance spectroscopy has become one of the most important investigations conducted on most current and planned NASA Solar System Exploration Program space missions. This book reviews the field of reflectance spectroscopy, including information on the scientific technique, contributions, present conditions, and future directions and needs.

  13. Optical treatment strategies to slow myopia progression: effects of the visual extent of the optical treatment zone.

    PubMed

    Smith, Earl L

    2013-09-01

    In order to develop effective optical treatment strategies for myopia, it is important to understand how visual experience influences refractive development. Beginning with the discovery of the phenomenon of form deprivation myopia, research involving many animal species has demonstrated that refractive development is regulated by visual feedback. In particular, animal studies have shown that optically imposed myopic defocus slows axial elongation, that the effects of vision are dominated by local retinal mechanisms, and that peripheral vision can dominate central refractive development. In this review, the results obtained from clinical trials of traditional optical treatment strategies employed in efforts to slow myopia progression in children are interpreted in light of the results from animal studies and are compared to the emerging results from preliminary clinical studies of optical treatment strategies that manipulate the effective focus of the peripheral retina. Overall, the results suggest that imposed myopic defocus can slow myopia progression in children and that the effectiveness of an optical treatment strategy in reducing myopia progression is influenced by the extent of the visual field that is manipulated. PMID:23290590

  14. Osteoarthritis: an overview of the disease and its treatment strategies.

    PubMed

    Sarzi-Puttini, Piercarlo; Cimmino, Marco A; Scarpa, Raffaele; Caporali, Roberto; Parazzini, Fabio; Zaninelli, Augusto; Atzeni, Fabiola; Canesi, Bianca

    2005-08-01

    Osteoarthritis (OA) is currently defined by the American College of Rheumatology as a "heterogeneous group of conditions that leads to joint symptoms and signs which are associated with defective integrity of articular cartilage, in addition to related changes in the underlying bone at the joint margins." Its prevalence after the age of 65 years is about 60% in men and 70% in women. The etiology of OA is multifactorial, with inflammatory, metabolic, and mechanical causes. A number of environmental risk factors, such as obesity, occupation, and trauma, may initiate various pathological pathways. OA indicates the degeneration of articular cartilage together with changes in subchondral bone and mild intraarticular inflammation. The principal treatment objectives are to control pain adequately, improve function, and reduce disability. Acetaminophen is frequently used for symptomatic OA with mild to moderate pain. Nonsteroidal antiinflammatory drugs (NSAIDs) are more effective in the case of moderate-severe pain, but they have an increased risk of serious upper gastrointestinal adverse events. The newer cyclooxygenase COX-2 specific inhibitors (Coxibs) are as efficacious as traditional NSAIDs and have a better gastrointestinal safety profile. Other compounds (eg, chondroitin sulfate, diacerein, glucosamine sulfate) have a symptomatic effect that is slower and less than that of NSAIDs. The structure-modifying effects of drugs are currently being evaluated, and both glucosamine sulfate and diacerein have been shown in some trials to have a beneficial structural effect. Nonpharmacological interventions are frequently and widely used in the management of OA patients, but there is little evidence that they are effective: the best studied and most successful nonpharmacological interventions are patient education, self-management, and exercise. There is some evidence for the pain-relieving efficacy of thermotherapy and transcutaneous electrical nerve stimulation (TENS) but not

  15. 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

  16. New therapeutic approaches for treatment-resistant schizophrenia: a look to the future.

    PubMed

    Miyamoto, Seiya; Jarskog, L Fredrik; Fleischhacker, W Wolfgang

    2014-11-01

    Schizophrenia for many patients is a lifelong mental disorder with significant consequences on most functional domains. One fifth to one third of patients with schizophrenia experience persistent psychotic symptoms despite adequate trials of antipsychotic treatment, and are considered to have treatment-resistant schizophrenia (TRS). Clozapine is the only medication to demonstrate efficacy for psychotic symptoms in such patients. However, clozapine is not effective in 40%-70% of patients with TRS and it has significant limitations in terms of potentially life-threatening side effects and the associated monitoring. Accordingly, a number of pharmacological and non-pharmacological biological approaches for clozapine-resistant TRS have emerged. This article provides a brief updated critical review of recent therapeutic strategies for TRS, particularly for clozapine-resistant TRS, which include pharmacotherapy, electroconvulsive therapy, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation.

  17. Development of Laser Beam Transmission Strategies for Future Ground-to-Space Optical Communications

    NASA Technical Reports Server (NTRS)

    Wilson, Keith E.; Kovalik, Joseph M.; Biswas, Abhijit; Roberts, William T.

    2007-01-01

    Optical communications is a key technology to meet the bandwidth expansion required in the global information grid. High bandwidth bi-directional links between sub-orbital platforms and ground and space terminals can provide a seamless interconnectivity for rapid return of critical data to analysts. The JPL Optical Communications Telescope Laboratory (OCTL) is located in Wrightwood California at an altitude of 2.2.km. This 200 sq-m facility houses a state-of- the-art 1-m telescope and is used to develop operational strategies for ground-to-space laser beam propagation that include safe beam transmission through navigable air space, adaptive optics correction and multi-beam scintillation mitigation, and line of sight optical attenuation monitoring. JPL has received authorization from international satellite owners to transmit laser beams to more than twenty retro-reflecting satellites. This paper presents recent progress in the development of these operational strategies tested by narrow laser beam transmissions from the OCTL to retro-reflecting satellites. We present experimental results and compare our measurements with predicted performance for a variety of atmospheric conditions.

  18. Strategies for engaging with future radiation protection professionals: a public outreach case study.

    PubMed

    Cole, P; Gornall, B T; Wood, M D; Whitcher, R; Bannon, A; Bloomer, S; Fear, J; Hale, H; Humphries, J; Hunak, S; Jones, C; Matthewman, C; Matthews, A; Slater, S; Stephens, C; Stewart, J

    2015-12-01

    It is evident that there is a nuclear skills shortage within the UK, and logically it can be assumed that the shortfall extends to the radiation protection arena. Plans for nuclear new-build and the decommissioning of existing nuclear sites will require many more people with radiological knowledge and practical competencies. This converts to a nuclear industry requirement in the order of 1000 new recruits per year over at least the next ten years, mainly as new apprentices and graduates. At the same time, the strong demand for persons with radiation protection know-how in the non-nuclear and health care sectors is unlikely to diminish. The task of filling this skills gap is a significant one and it will require a determined effort from many UK stakeholders. The Society for Radiological Protection (SRP) has adopted a strategy in recent years to help address this skills gap. The aim is to engage the interest of secondary school students in the science of radiation and inspire them to follow a career in radiation protection. This paper presents the reasoning behind this strategy and, in an 'outreach case study', describes the establishment of the annual SRP Schools Event. This event is becoming an important addition to the national efforts aimed at increasing the numbers of skilled UK radiation protection professionals over the forthcoming decades. PMID:26444019

  19. 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.

  20. Insights into pathophysiology of punding reveal possible treatment strategies.

    PubMed

    Fasano, A; Petrovic, I

    2010-06-01

    Punding is a stereotyped behavior characterized by an intense fascination with a complex, excessive, nongoal oriented, repetitive activity. Men tend to repetitively tinker with technical equipment such as radio sets, clocks, watches and car engines, the parts of which may be analyzed, arranged, sorted and cataloged but rarely put back together. Women, in contrast, incessantly sort through their handbags, tidy continuously, brush their hair or polish their nails. Punders are normally aware of the inapposite and obtuse nature of the behavior; however, despite the consequent self-injury, they do not stop such behavior. The most common causes of punding are dopaminergic replacement therapy in patients affected by Parkinson's disease (PD) and cocaine and amphetamine use in addicts. The vast majority of information about punding comes from PD cases. A critical review of these cases shows that almost all afflicted patients (90%) were on treatment with drugs acting mainly on dopamine receptors D1 and D2, whereas only three cases were reported in association with selective D2 and D3 agonists. Epidemiological considerations and available data from animal models suggest that punding, drug-induced stereotypies, addiction and dyskinesias all share a common pathophysiological process. Punding may be related to plastic changes in the ventral and dorsal striatal structures, including the nucleus accumbens, and linked to psychomotor stimulation and reward mechanisms. Possible management guidelines are proposed. PMID:20489735

  1. 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.

  2. [The treatment of intra-stent restenosis. The current situation and future outlook].

    PubMed

    Gómez-Hospital, J A; Cequier, A; Fernández-Nofrerías, E; Mauri, J; García del Blanco, B; Iráculis, E; Jara, F; Esplugas, E

    1999-12-01

    In-stent restenosis is an increasing problem due to the frequent use of coronary stent as a form of percutaneous revascularization. The global incidence is near to 28%, and it is well document that a neointimal hyperplasia is its principal mechanism. The most commonly related factors for its appearance are diabetes mellitus, a longer length of the original lesion, a smaller diameter of the reference vessel, the left anterior descending artery location and a smaller luminal diameter at the end of the procedure. Due to a different long term evolution in-stent restenosis has been classified as focal or diffuse, according to the length of the restenotic lesion (focal < 10 mm and diffuse > or = 10 mm). Some strategies have been proven for its treatment, but no randomized-controlled trials have been published comparing these different treatments. In focal in-stent restenosis the practice of a conventional balloon angioplasty is associated with high initial clinical success with a favourable long term evolution (target lesion revascularization between 11-15%). But on the contrary, in diffuse in-stent restenosis, in spite of a high initial success rate, an elevated target lesion revascularization has been detected at the follow-up (up to 43%). Other proved such as atherectomy or excimer laser are associated with a significant procedural non-Q-wave infarction (near to 9%) and a long term target lesion revascularization during follow-up (23-31%). The implantation of an additional stent has been performed with low procedural complications and with a long term target lesion revascularization near to 27%. Patients treated with intracoronary radiation as a complementary technique seem to have a better long term evolution than those having had the other strategies alone. In conclusion, in-stent-restenosis is a new and progressively more frequent problem, requiring complex treatment and of which as been established. Comparative controlled studies need to be performed in order to

  3. Comparison of microhabitats and foraging strategies between the captive-born Zhangxiang and wild giant pandas: implications for future reintroduction.

    PubMed

    Lei, Miaowen; Yuan, Shibin; Yang, Zisong; Hong, Mingsheng; Yang, Xuyu; Gu, Xiaodong; Huang, Feng; Zhang, Zejun

    2015-10-01

    The female giant panda Zhangxiang (pedigree number 826) was born on August 20, 2011 in Wolong Nature Reserve, China. On November 6, 2013, Zhangxiang was transported into the acclimatization enclosure in the Liziping Nature Reserve. Before Zhangxiang left the enclosure into the wild, we conducted the first study to compare microhabitats and foraging strategies between Zhangxiang in the enclosure and giant pandas in the wild. Compared with the latter, microhabitats of Zhangxiang in the enclosure are characteristic of gentler slope, more trees, higher canopy, smaller tree DBH, and lower density of living bamboos. Diet composition and foraging behaviors significantly differed between Zhangxiang and wild giant pandas, perhaps reflecting the combined consequence of environmental conditions (e.g., bamboo species) and individual status (e.g., age, mastication ability, etc.). The difference in microhabitats and foraging strategies between Zhangxiang and wild giant pandas implied that after being released into the natural habitat in the reserve, Zhangxiang will have to adapt to the environmental conditions once again. For future reintroduction, the enclosure can be extended to the Bashania spanostachya forest in the reserve, and captive giant pandas for release can thus normally transit into the wild without human intervention during acclimatization period. For other acclimatization enclosures to be constructed in the future, ecological environment inside, including topography, forests, and bamboos as well, should as possible as can match the habitat that the giant panda to-be-reinforced populations inhabit. PMID:26003090

  4. Comparison of microhabitats and foraging strategies between the captive-born Zhangxiang and wild giant pandas: implications for future reintroduction.

    PubMed

    Lei, Miaowen; Yuan, Shibin; Yang, Zisong; Hong, Mingsheng; Yang, Xuyu; Gu, Xiaodong; Huang, Feng; Zhang, Zejun

    2015-10-01

    The female giant panda Zhangxiang (pedigree number 826) was born on August 20, 2011 in Wolong Nature Reserve, China. On November 6, 2013, Zhangxiang was transported into the acclimatization enclosure in the Liziping Nature Reserve. Before Zhangxiang left the enclosure into the wild, we conducted the first study to compare microhabitats and foraging strategies between Zhangxiang in the enclosure and giant pandas in the wild. Compared with the latter, microhabitats of Zhangxiang in the enclosure are characteristic of gentler slope, more trees, higher canopy, smaller tree DBH, and lower density of living bamboos. Diet composition and foraging behaviors significantly differed between Zhangxiang and wild giant pandas, perhaps reflecting the combined consequence of environmental conditions (e.g., bamboo species) and individual status (e.g., age, mastication ability, etc.). The difference in microhabitats and foraging strategies between Zhangxiang and wild giant pandas implied that after being released into the natural habitat in the reserve, Zhangxiang will have to adapt to the environmental conditions once again. For future reintroduction, the enclosure can be extended to the Bashania spanostachya forest in the reserve, and captive giant pandas for release can thus normally transit into the wild without human intervention during acclimatization period. For other acclimatization enclosures to be constructed in the future, ecological environment inside, including topography, forests, and bamboos as well, should as possible as can match the habitat that the giant panda to-be-reinforced populations inhabit.

  5. Future therapeutic directions for factor Xa inhibition in the prophylaxis and treatment of thrombotic disorders.

    PubMed

    Turpie, Alexander G G

    2003-11-15

    The targeted mechanism of factor Xa inhibition has been studied extensively, initially as prophylaxis for venous thromboembolism (VTE) in the orthopedic surgical setting. Future therapeutic directions for selective factor Xa inhibition in the management of other thrombotic diseases are discussed. Thromboembolic diseases can occur in the venous or arterial sides of the circulatory system. Factor Xa inhibition is a targeted approach to anticoagulation that resulted from significant advances in our understanding of the coagulation cascade. The factor Xa inhibitor fondaparinux has been studied extensively in the orthopedic surgical setting for the prophylaxis of VTE. Current investigations that are under way or completed evaluate the efficacy and safety of fondaparinux for the management of various thrombotic diseases. The future development of fondaparinux resides primarily in three therapeutic areas: prevention of VTE, treatment of VTE, and treatment of acute coronary syndromes. For the prevention of VTE, fondaparinux has been studied as extended prophylaxis following hip fracture surgery (PENTHIFRA Plus), for use in high-risk abdominal surgical patients (PEGASUS and APOLLO), and for use in medical patients (ARTEMIS). Studies evaluating fondaparinux for the treatment of VTE are part of the large MATISSE clinical program (MATISSE DVT and MATISSE PE). Fondaparinux was investigated in phase 2 studies for the treatment of acute coronary syndromes, including acute ST-segment myocardial infarction (PENTALYSE) and unstable angina (PENTUA). Encouraging data from these trials are the basis for phase 3 programs in this area (MICHELANGELO). The orthopedic prophylactic and nonorthopedic clinical programs for fondaparinux in the management of thrombosis support the concept that targeted inhibition of coagulation is an effective advance in antithrombotic therapy. PMID:14650863

  6. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.

    PubMed

    Unemo, Magnus

    2015-08-21

    Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed

  7. Current and future antimicrobial treatment of gonorrhoea - the rapidly evolving Neisseria gonorrhoeae continues to challenge.

    PubMed

    Unemo, Magnus

    2015-01-01

    Neisseria gonorrhoeae has developed antimicrobial resistance (AMR) to all drugs previously and currently recommended for empirical monotherapy of gonorrhoea. In vitro resistance, including high-level, to the last option ceftriaxone and sporadic failures to treat pharyngeal gonorrhoea with ceftriaxone have emerged. In response, empirical dual antimicrobial therapy (ceftriaxone 250-1000 mg plus azithromycin 1-2 g) has been introduced in several particularly high-income regions or countries. These treatment regimens appear currently effective and should be considered in all settings where local quality assured AMR data do not support other therapeutic options. However, the dual antimicrobial regimens, implemented in limited geographic regions, will not entirely prevent resistance emergence and, unfortunately, most likely it is only a matter of when, and not if, treatment failures with also these dual antimicrobial regimens will emerge. Accordingly, novel affordable antimicrobials for monotherapy or at least inclusion in new dual treatment regimens, which might need to be considered for all newly developed antimicrobials, are essential. Several of the recently developed antimicrobials deserve increased attention for potential future treatment of gonorrhoea. In vitro activity studies examining collections of geographically, temporally and genetically diverse gonococcal isolates, including multidrug-resistant strains particularly with resistance to ceftriaxone and azithromycin, are important. Furthermore, understanding of effects and biological fitness of current and emerging (in vitro induced/selected and in vivo emerged) genetic resistance mechanisms for these antimicrobials, prediction of resistance emergence, time-kill curve analysis to evaluate antibacterial activity, appropriate mice experiments, and correlates between genetic and phenotypic laboratory parameters, and clinical treatment outcomes, would also be valuable. Subsequently, appropriately designed

  8. Bipolar disorder in the postpartum period: management strategies and future directions.

    PubMed

    Pope, Carley J; Sharma, Verinder; Mazmanian, Dwight

    2014-07-01

    Bipolar I and II disorder are chronic and severe psychiatric illnesses that affect many women. Furthermore, women are at increased risk for mood episodes during the postpartum period compared with non-postpartum periods. Unfortunately, identification of clinically significant depressive or (hypo)manic episodes can be challenging. Delays in detection, as well as misdiagnosis, put women at risk of many negative consequences, such as symptom exacerbation and treatment refractoriness. Early and accurate detection of bipolar I or II disorder in the postpartum period is critical to improve prognosis. At this time, limited recommendations can be made due to a paucity of research. Further research on postpartum bipolar I or II disorder focusing on its identification, consequences and treatment is urgently needed to allow for empirically informed clinical decision-making. PMID:25259898

  9. Strategies and Innovative Approaches for the Future of Space Weather Forecasting

    NASA Astrophysics Data System (ADS)

    Hoeksema, J. T.

    2012-12-01

    The real and potential impacts of space weather have been well documented, yet neither the required research and operations programs, nor the data, modeling and analysis infrastructure necessary to develop and sustain a reliable space weather forecasting capability for a society are in place. The recently published decadal survey "Solar and Space Physics: A Science for a Technological Society" presents a vision for the coming decade and calls for a renewed national commitment to a comprehensive program in space weather and climatology. New resources are imperative. Particularly in the current fiscal environment, implementing a responsible strategy to address these needs will require broad participation across agencies and innovative approaches to make the most of existing resources, capitalize on current knowledge, span gaps in capabilities and observations, and focus resources on overcoming immediate roadblocks.

  10. Targeting mitochondria: strategies, innovations and challenges: The future of medicine will come through mitochondria.

    PubMed

    Edeas, Marvin; Weissig, Volkmar

    2013-09-01

    Mitochondrial dysfunction has been associated with the aging process and a large variety of human disorders, such as cardiovascular and neurodegenerative diseases, cancer, migraine, infertility, kidney and liver diseases, toxicity of drugs and many more. It is well recognized that the physiological role of mitochondria widely exceeds that of solely being the biochemical power plant of our cells. Over the recent years, mitochondria have become an interesting target for drug therapy, and the research field aimed at "targeting mitochondria" is active and expanding as witnessed by this already third edition of the world congress on targeting mitochondria. It is becoming a necessity and an urge to know why and how to target mitochondria with bioactive molecules and drugs in order to treat and prevent mitochondria-based pathologies and chronic diseases. This special issue covers a variety of new strategies and innovations as well as clinical applications in mitochondrial medicine.

  11. Emerging concepts on drug resistance in bladder cancer: Implications for future strategies.

    PubMed

    Massari, Francesco; Santoni, Matteo; Ciccarese, Chiara; Brunelli, Matteo; Conti, Alessandro; Santini, Daniele; Montironi, Rodolfo; Cascinu, Stefano; Tortora, Giampaolo

    2015-10-01

    The combination chemotherapies with methotrexate plus vinblastine, doxorubicin and cisplatin (MVAC or CMV regimens) or gemcitabine plus cisplatin represent the standard as first-line therapy for patients with metastatic urothelial cancer. In Europe, vinflunine is an option for second-line therapy for patients progressed during first-line or perioperative platinum-containing regimen. Alternative regimens containing taxanes and/or gemcitabine may be valuated case by case. Furthermore, carboplatin should be considered in patients unfit for cisplatin both in the first and second-line setting. Based on these findings, a better comprehension of the mechanisms underlying the development of drug resistance in patients with bladder cancer will represent a major step forward in optimizing patients' outcome. This article reviews the current knowledge of the mechanisms and emerging strategies to overcome resistance in patients with advanced urothelial cancer.

  12. [Bilingual teaching in stomatological education in China: problems and future strategies].

    PubMed

    Zheng, Jia-Wei; Cao, Xia; Xu, Yuan-Jin; Zhang, Jian-Zhong; Feng, Xi-Ping; Guo, Lian; Zhang, Zhi-Yuan

    2010-02-01

    Bilingual teaching has been used for several years in many Colleges of Stomatology in China, but there are still some problems be solved in textbooks, training of teachers, methods of teaching, etc. This paper discusses the purpose, manners, problems and strategies of bilingual teaching in stomatology. We believe that the specialties of stomatology and the situations of China should be considered in conducting bilingual teaching. The purposes of bilingual teaching are to use English and/or Chinese to teach basic and clinical knowledge and skill in Stomatology, and enhance the English ability of the students as well. To achieve the purposes and improve the quality of bilingual teaching, a well-organized textbook and adequate qualified teachers are demanded, modern teaching medias and methods should be adopted, and a rational teaching quality evaluation system should be established and fulfilled. PMID:20300706

  13. [Bilingual teaching in stomatological education in China: problems and future strategies].

    PubMed

    Zheng, Jia-Wei; Cao, Xia; Xu, Yuan-Jin; Zhang, Jian-Zhong; Feng, Xi-Ping; Guo, Lian; Zhang, Zhi-Yuan

    2010-02-01

    Bilingual teaching has been used for several years in many Colleges of Stomatology in China, but there are still some problems be solved in textbooks, training of teachers, methods of teaching, etc. This paper discusses the purpose, manners, problems and strategies of bilingual teaching in stomatology. We believe that the specialties of stomatology and the situations of China should be considered in conducting bilingual teaching. The purposes of bilingual teaching are to use English and/or Chinese to teach basic and clinical knowledge and skill in Stomatology, and enhance the English ability of the students as well. To achieve the purposes and improve the quality of bilingual teaching, a well-organized textbook and adequate qualified teachers are demanded, modern teaching medias and methods should be adopted, and a rational teaching quality evaluation system should be established and fulfilled.

  14. High resolution digital soil mapping as a future instrument for developing sustainable landuse strategies

    NASA Astrophysics Data System (ADS)

    Gries, Philipp; Funke, Lisa-Marie; Baumann, Frank; Schmidt, Karsten; Behrens, Thorsten; Scholten, Thomas

    2016-04-01

    Climate change, increase in population and intensification of land use pose a great challenge for sustainable handling of soils. Intelligent landuse systems are able to minimize and/or avoid soil erosion and loss of soil fertility. A successful application of such systems requires area-wide soil information with high resolution. Containing three consecutive steps, the project INE-2-H („innovative sustainable landuse") at the University of Tuebingen is about creating high-resolution soil information using Digital Soil Mapping (DSM) techniques to develop sustainable landuse strategies. Input data includes soil data from fieldwork (texture and carbon content), the official digital soil and geological map (1:50.000) as well as a wide selection of local, complex and combined terrain parameters. First, soil maps have been created using the DSM approach and Random Forest (RF). Due to high resolution (10x10 m pixels), those maps show a more detailed spatial variability of soil information compared to the official maps used. Root mean square errors (RMSE) of the modelled maps vary from 2.11 % to 6.87 % and the coefficients of determination (R²) go from 0.42 to 0.68. Second, soil erosion potentials have been estimated according to the Universal Soil Loss Equation (USLE). Long-term average annual soil loss ranges from 0.56 to 24.23 [t/ha/a]. Third, combining high-resolution erosion potentials with expert-knowledge of local farmers will result in a landuse system adapted to local conditions. This system will include sustainable strategies reducing soil erosion and conserving soil fertility.

  15. [Addressing intimate partner violence in substance-abuse treatment programmes: a challenge for the future].

    PubMed

    Fernández-Montalvo, Javier; López-Goñi, José Javier

    2011-01-01

    There is a close relationship between substance abuse (alcohol and other drugs) and intimate partner violence. Studies carried out with male offenders and with addicted patients show a high comorbidity rate between these two phenomena. However, few batterer intervention programmes have been implemented to date in the field of drug addiction. This paper proposes, first, the need to detect cases of intimate partner violence that are camouflaged beneath a drug problem. Thus, it is important to determine the prevalence rate of intimate partner aggressors among users of drug-addiction treatment programmes, as well as identifying the specific characteristics of these patients. Second, once aggressors are identified, it would be possible to develop specific programmes for the simultaneous treatment of the two problems (addiction and intimate partner violence). Some studies have already been carried with joint treatments for addiction and intimate partner violence. The results obtained are encouraging, and show that intervention programs with addictions can be a useful framework for applying also, where necessary, specific treatments for those addicted patients with an associated problem of intimate partner violence. Finally, implications for clinical practice and future research in this field are discussed.

  16. IL-6 inhibitors for treatment of rheumatoid arthritis: past, present, and future.

    PubMed

    Kim, Go Woon; Lee, Na Ra; Pi, Ryo Han; Lim, Yee Seul; Lee, Yu Mi; Lee, Jong Min; Jeong, Hye Seung; Chung, Sung Hyun

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by polyarthritis. Numerous agents with varying mechanisms are used in the treatment of RA, including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and some biological agents. Studies to uncover the cause of RA have recently ended up scrutinizing the importance of pro-inflammatory cytokine such as tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the pathogenesis of RA. TNF-α inhibitors are increasingly used to treat RA patients who are non-responsive to conventional anti-arthritis drugs. Despite its effectiveness in a large patient population, up to two thirds of RA patients are found to be partially responsive to anti-TNF therapy. Therefore, agents targeting IL-6 such as tocilizumab (TCZ) attracted significant attention as a promising agent in RA treatment. In this article, we review the mechanism of anti-IL-6 in the treatment of RA, provide the key efficacy and safety data from clinical trials of approved anti-IL-6, TCZ, as well as six candidate IL-6 blockers including sarilumab, ALX-0061, sirukumab, MEDI5117, clazakizumab, and olokizumab, and their future perspectives in the treatment of RA.

  17. [Addressing intimate partner violence in substance-abuse treatment programmes: a challenge for the future].

    PubMed

    Fernández-Montalvo, Javier; López-Goñi, José Javier

    2011-01-01

    There is a close relationship between substance abuse (alcohol and other drugs) and intimate partner violence. Studies carried out with male offenders and with addicted patients show a high comorbidity rate between these two phenomena. However, few batterer intervention programmes have been implemented to date in the field of drug addiction. This paper proposes, first, the need to detect cases of intimate partner violence that are camouflaged beneath a drug problem. Thus, it is important to determine the prevalence rate of intimate partner aggressors among users of drug-addiction treatment programmes, as well as identifying the specific characteristics of these patients. Second, once aggressors are identified, it would be possible to develop specific programmes for the simultaneous treatment of the two problems (addiction and intimate partner violence). Some studies have already been carried with joint treatments for addiction and intimate partner violence. The results obtained are encouraging, and show that intervention programs with addictions can be a useful framework for applying also, where necessary, specific treatments for those addicted patients with an associated problem of intimate partner violence. Finally, implications for clinical practice and future research in this field are discussed. PMID:21503558

  18. Current adjuvant treatment modalities for gastric cancer: From history to the future

    PubMed Central

    Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

    2016-01-01

    The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

  19. Long-Term Instrumentation, Information, and Control Systems (II&C) Modernization Future Vision and Strategy

    SciTech Connect

    Kenneth Thomas

    2012-02-01

    Life extension beyond 60 years for the U.S operating nuclear fleet requires that instrumentation and control (I&C) systems be upgraded to address aging and reliability concerns. It is impractical for the legacy systems based on 1970's vintage technology operate over this extended time period. Indeed, utilities have successfully engaged in such replacements when dictated by these operational concerns. However, the replacements have been approached in a like-for-like manner, meaning that they do not take advantage of the inherent capabilities of digital technology to improve business functions. And so, the improvement in I&C system performance has not translated to bottom-line performance improvement for the fleet. Therefore, wide-scale modernization of the legacy I&C systems could prove to be cost-prohibitive unless the technology is implemented in a manner to enable significant business innovation as a means of off-setting the cost of upgrades. A Future Vision of a transformed nuclear plant operating model based on an integrated digital environment has been developed as part of the Advanced Instrumentation, Information, and Control (II&C) research pathway, under the Light Water Reactor (LWR) Sustainability Program. This is a research and development program sponsored by the U.S. Department of Energy (DOE), performed in close collaboration with the nuclear utility industry, to provide the technical foundations for licensing and managing the long-term, safe and economical operation of current nuclear power plants. DOE's program focus is on longer-term and higher-risk/reward research that contributes to the national policy objectives of energy security and environmental security . The Advanced II&C research pathway is being conducted by the Idaho National Laboratory (INL). The Future Vision is based on a digital architecture that encompasses all aspects of plant operations and support, integrating plant systems, plant work processes, and plant workers in a seamless

  20. Long-Term Instrumentation, Information, and Control Systems (II&C) Modernization Future Vision and Strategy

    SciTech Connect

    Kenneth Thomas; Bruce Hallbert

    2013-02-01

    Life extension beyond 60 years for the U.S operating nuclear fleet requires that instrumentation and control (I&C) systems be upgraded to address aging and reliability concerns. It is impractical for the legacy systems based on 1970’s vintage technology operate over this extended time period. Indeed, utilities have successfully engaged in such replacements when dictated by these operational concerns. However, the replacements have been approached in a like-for-like manner, meaning that they do not take advantage of the inherent capabilities of digital technology to improve business functions. And so, the improvement in I&C system performance has not translated to bottom-line performance improvement for the fleet. Therefore, wide-scale modernization of the legacy I&C systems could prove to be cost-prohibitive unless the technology is implemented in a manner to enable significant business innovation as a means of off-setting the cost of upgrades. A Future Vision of a transformed nuclear plant operating model based on an integrated digital environment has been developed as part of the Advanced Instrumentation, Information, and Control (II&C) research pathway, under the Light Water Reactor (LWR) Sustainability Program. This is a research and development program sponsored by the U.S. Department of Energy (DOE), performed in close collaboration with the nuclear utility industry, to provide the technical foundations for licensing and managing the long-term, safe and economical operation of current nuclear power plants. DOE’s program focus is on longer-term and higher-risk/reward research that contributes to the national policy objectives of energy security and environmental security . The Advanced II&C research pathway is being conducted by the Idaho National Laboratory (INL). The Future Vision is based on a digital architecture that encompasses all aspects of plant operations and support, integrating plant systems, plant work processes, and plant workers in a

  1. Strategies for a Creative Future with Computer Science, Quality Design and Communicability

    NASA Astrophysics Data System (ADS)

    Cipolla Ficarra, Francisco V.; Villarreal, Maria

    In the current work is presented the importance of the two-way triad between computer science, design and communicability. It is demonstrated how the principles of quality of software engineering are not universal since they are disappearing inside university training. Besides, a short analysis of the term "creativity" males apparent the existence of plagiarism as a human factor that damages the future of communicability applied to the on-line and off-line contents of the open software. A set of measures and guidelines are presented so that the triad works again correctly in the next years to foster the qualitative design of the interactive systems on-line and/or off-line.

  2. Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine.

    PubMed

    Ramanathan, Babu; Poh, Chit Laa; Kirk, Kristin; McBride, William John Hannan; Aaskov, John; Grollo, Lara

    2016-01-01

    Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine. PMID:27223692

  3. Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine

    PubMed Central

    Poh, Chit Laa; Kirk, Kristin; McBride, William John Hannan; Aaskov, John; Grollo, Lara

    2016-01-01

    Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques. A multi-step computational approach predicted six antigenic regions within the E protein of DENV-2 that concur with the 6 epitopes identified by the combined ELISA and epitope extraction approach. The selected peptides representing B-cell epitopes were attached to a known dengue T-helper epitope and evaluated for their vaccine potency. Immunization of mice revealed two novel synthetic vaccine constructs that elicited good humoral immune responses and produced cross-reactive neutralising antibodies against DENV-1, 2 and 3. The findings indicate new directions for epitope mapping and contribute towards the future development of multi-epitope based synthetic peptide vaccine. PMID:27223692

  4. Effectiveness and Tradeoffs between Portfolios of Adaptation Strategies Addressing Future Climate and Socioeconomic Uncertainties in California's Central Valley

    NASA Astrophysics Data System (ADS)

    Tansey, M. K.; Van Lienden, B.; Das, T.; Munevar, A.; Young, C. A.; Flores-Lopez, F.; Huntington, J. L.

    2013-12-01

    The Central Valley of California is one of the major agricultural areas in the United States. The Central Valley Project (CVP) is operated by the Bureau of Reclamation to serve multiple purposes including generating approximately 4.3 million gigawatt hours of hydropower and providing, on average, 5 million acre-feet of water per year to irrigate approximately 3 million acres of land in the Sacramento, San Joaquin, and Tulare Lake basins, 600,000 acre-feet per year of water for urban users, and 800,000 acre-feet of annual supplies for environmental purposes. The development of effective adaptation and mitigation strategies requires assessing multiple risks including potential climate changes as well as uncertainties in future socioeconomic conditions. In this study, a scenario-based analytical approach was employed by combining three potential 21st century socioeconomic futures with six representative climate and sea level change projections developed using a transient hybrid delta ensemble method from an archive of 112 bias corrected spatially downscaled CMIP3 global climate model simulations to form 18 future socioeconomic-climate scenarios. To better simulate the effects of climate changes on agricultural water demands, analyses of historical agricultural meteorological station records were employed to develop estimates of future changes in solar radiation and atmospheric humidity from the GCM simulated temperature and precipitation. Projected changes in atmospheric carbon dioxide were computed directly by weighting SRES emissions scenarios included in each representative climate projection. These results were used as inputs to a calibrated crop water use, growth and yield model to simulate the effects of climate changes on the evapotranspiration and yields of major crops grown in the Central Valley. Existing hydrologic, reservoir operations, water quality, hydropower, greenhouse gas (GHG) emissions and both urban and agricultural economic models were integrated

  5. The epilepsy treatment gap in developing countries: a systematic review of the magnitude, causes and intervention strategies

    PubMed Central

    Mbuba, Caroline K.; Ngugi, Anthony K.; Newton, Charles R.; Carter, Julie A.

    2013-01-01

    In many developing countries, people with epilepsy do not receive appropriate treatment for their condition, a phenomenon called the treatment gap (TG). We carried out a systematic review to investigate the magnitude, causes and intervention strategies to improve outcomes in developing countries. We systematically searched MEDLINE, EMBASE and PsycINFO databases, supplemented by a hand search of references in the key papers. The degree of heterogeneity and a pooled TG estimate were determined using meta-analysis techniques. The estimates were further stratified by continent and location of study (urban, rural). Twenty-seven studies met the inclusion criteria: twelve from Africa, nine from Asia and six from Latin America. We observed a high degree of heterogeneity and inconsistency between studies. The overall estimate of the TG was 56/100 (95% CI: 31.1-100.0). The variation in estimates could possibly be explained by non-uniform TG estimation methods and the diverse study populations, among other factors. The TG was mainly attributed to inadequate skilled manpower, cost of treatment, cultural beliefs and unavailability of anti-epileptic drugs (AEDs). These factors have been addressed using different intervention strategies for instance education and supply of AEDs. Future research should estimate the TG coherently and develop sustainable interventions that will address the causes. PMID:18557778

  6. Treatment strategy: Role of enfuvirtide in managing treatment-limiting side effects.

    PubMed

    Tsoukas, Christos

    2007-01-01

    Side effects can limit the options available to physicians for the treatment of HIV infection. Management of these side effects is essential, to avoid cessation of treatment. The entry inhibitor enfuvirtide can be useful as one of three active agents in an HIV treatment regimen as a way to both reduce treatment-limiting side effects and provide an efficacious agent for viral control. In the present case, the patient had a problematic and lengthy treatment history, with numerous concomitant conditions. His latest regimen, which includes an agent in a new drug class (enfuvirtide), has maintained HIV suppression while minimizing toxicity.

  7. Inspiring the undergraduate soil students for a future effective public outreach role: Success strategies and approaches.

    NASA Astrophysics Data System (ADS)

    Al-Ismaily, Said; Al-Maktoumi, Ali; Kacimov, Anvar

    2015-04-01

    Undergraduates, majoring in soil sciences (SS), have a broad holistic role because SS integrates several intertwined geo-environmental/ecological and socio-economical aspects. Consequently, students have to learn how the information, advice, practices and expertise, pertinent to food security, water shortage, hydropedology, among others amalgamate through SS . Hence, university SS-programs should incorporate public outreach activities. We present experience at Sultan Qaboos University (SQU) in Oman on how to develop an effective public outreach program that can be implemented by undergraduate students. Our strategy has three components : (i) offering a course Soil and Water Tour (SWAE 4110) of hydropedology nature that integrates field, laboratory-work, and presentation-extension activities; the course is research-oriented and designed to provide opportunities for students to practice their metacognitive abilities and critical thinking; the course is offered by the Department of Soils, Water & Agricultural Engineering (SWAE), (ii) Training and involving the undergraduates in planning and conducting enjoyable, interactive, and effective workshops for school pupils; a training workshop on "Soils" was conducted for pupils (a total 300 participants, grades 7-9) and teachers aiming to unveil the secrets and the role of soil in ecosystems; workshop was organized by the SWAE Students Society (iii) Guiding the undergraduates on the best practice for raising funds for their outreach activities (e.g. the undergraduates secured funds for the workshop on "Soils", which was sponsored by Muscat Municipality, a governmental agency, and several private companies such as HMR Consultants, Metal Engineering L.L.C and Bauer Nimr LLC); SS students were mentored in submission of research proposals to the national research agency (e.g. FURAP program of The Research Council, TRC, WWW.trc.gov.om). The three components were evaluated quantitatively and qualitatively using fixed-response and

  8. Optimal strategy for controlling the spread of Plasmodium Knowlesi malaria: Treatment and culling

    NASA Astrophysics Data System (ADS)

    Abdullahi, Mohammed Baba; Hasan, Yahya Abu; Abdullah, Farah Aini

    2015-05-01

    Plasmodium Knowlesi malaria is a parasitic mosquito-borne disease caused by a eukaryotic protist of genus Plasmodium Knowlesi transmitted by mosquito, Anopheles leucosphyrus to human and macaques. We developed and analyzed a deterministic Mathematical model for the transmission of Plasmodium Knowlesi malaria in human and macaques. The optimal control theory is applied to investigate optimal strategies for controlling the spread of Plasmodium Knowlesi malaria using treatment and culling as control strategies. The conditions for optimal control of the Plasmodium Knowlesi malaria are derived using Pontryagin's Maximum Principle. Finally, numerical simulations suggested that the combination of the control strategies is the best way to control the disease in any community.

  9. Can genotype be used to tailor treatment of obesity? State of the art and guidelines for future studies and applications.

    PubMed

    Corella, D; Ordovás, J M

    2013-09-01

    Current treatments for losing weight based mainly on diet and exercise are, in general, unsuccessful. So, as an alternative to the general strategy of one-size-fits-all, a more individualized approach is proposed through the so-called Personalised Medicine in which genotype data are used to personalize treatment and to optimize the results. This paper examines the current situation of the evidence on the influence of the genotype in modulating the association between diet or exercise on obesity and weight-related measures. Most of these studies are observational studies, as there are far fewer experimental ones assessing short-term weight-loss or its long-term maintenance. Many more studies are therefore required for that purpose. Having reviewed the results of the studies undertaken to date, we can say that huge progress has been made in identifying polymorphisms in genes related with obesity and that there is a great consistency of the influence of the FTO gene on the same, while for other variants, there is less consistency. Moreover, the results on gene-diet and gene-physical activity interactions in determining obesity phenotypes are very heterogeneous, so an important recommendation is to standardize the methodology for undertaking these studies. Furthermore, an important lack of replication has been observed suggesting undetected higher-level interactions and/or experimental caveats. Therefore, the current evidence level of applying genotype data to obesity treatment is at its early stages. Nevertheless, future prospects are encouraging and to make this come true, several guidelines are proposed for carrying out new studies on applications in clinical practice. PMID:24126543

  10. Can genotype be used to tailor treatment of obesity? State of the art and guidelines for future studies and applications.

    PubMed

    Corella, D; Ordovás, J M

    2013-09-01

    Current treatments for losing weight based mainly on diet and exercise are, in general, unsuccessful. So, as an alternative to the general strategy of one-size-fits-all, a more individualized approach is proposed through the so-called Personalised Medicine in which genotype data are used to personalize treatment and to optimize the results. This paper examines the current situation of the evidence on the influence of the genotype in modulating the association between diet or exercise on obesity and weight-related measures. Most of these studies are observational studies, as there are far fewer experimental ones assessing short-term weight-loss or its long-term maintenance. Many more studies are therefore required for that purpose. Having reviewed the results of the studies undertaken to date, we can say that huge progress has been made in identifying polymorphisms in genes related with obesity and that there is a great consistency of the influence of the FTO gene on the same, while for other variants, there is less consistency. Moreover, the results on gene-diet and gene-physical activity interactions in determining obesity phenotypes are very heterogeneous, so an important recommendation is to standardize the methodology for undertaking these studies. Furthermore, an important lack of replication has been observed suggesting undetected higher-level interactions and/or experimental caveats. Therefore, the current evidence level of applying genotype data to obesity treatment is at its early stages. Nevertheless, future prospects are encouraging and to make this come true, several guidelines are proposed for carrying out new studies on applications in clinical practice.

  11. Breaking the Ice: Strategies for Future European Research in the Polar Oceans - The AURORA BOREALIS Concept

    NASA Astrophysics Data System (ADS)

    Lembke-Jene, L.; Biebow, N.; Wolff-Boenisch, B.; Thiede, J.; European Research Icebreaker Consortium

    2011-12-01

    tackle problems of high societal relevance beyond the scope of individual disciplines. It is planned to use part of the berthing capacity of AURORA BOREALIS for dedicated university education and teaching programmes in order to give future polar scientists the best training facilities available and enable a vital international exchange between educational centres. This aims at helping to vertically structure the new generation of young and well-trained students and playing a key role in the construction of an efficient research and innovation environment for future collaboration in polar research

  12. Neoadjuvant strategies for triple negative breast cancer: 'state-of-the-art' and future perspectives.

    PubMed

    Carbognin, Luisa; Furlanetto, Jenny; Vicentini, Cecilia; Nortilli, Rolando; Pilotto, Sara; Brunelli, Matteo; Pellini, Francesca; Pollini, Giovanni Paolo; Bria, Emilio; Tortora, Giampaolo

    2015-01-01

    Neoadjuvant therapy for triple negative breast cancer (TNBC) has recently generated growing interest given the more aggressive biologic characteristics of such subtype and the lack of approved targeted therapies. Systemic chemotherapy represents the mainstay of treatment for TNBC. Although neoadjuvant chemotherapy has consistently demonstrated higher response rates for TNBC compared to non-TNBC, and the pathological complete response predicts long-term outcome, most patient display residual disease with a higher risk of relapse. In order to improve the outcome of TNBC new chemotherapic combinations, including platinum agents, and different targeted agents such as antiangiogenetics, poly-ADP ribose polymerase (PARP) inhibitors and other small molecule inhibitors are being evaluated in neoadjuvant setting. Currently, the research is ongoing to further characterize TNBC from a phenotypical and molecular perspective, in order to identify potential new target agents and to individualize the treatment. In this regard, the neoadjuvant setting may represent the best potential scenario to assess the activity and the sensitivity of novel agents.

  13. Second-generation prophylactic HPV vaccines: current options and future strategies for vaccines development.

    PubMed

    Fruscalzo, Arrigo; Londero, Ambrogio P; Bertozzi, Serena; Lellè, Ralf J

    2016-02-01

    Two vaccines focused on the prevention of HPV-related diseases have been introduced in the last decade, the quadrivalent vaccine Gardasil and the bivalent vaccine Cervarix. They are targeted to prevent precancerous and cancerous lesions not only of the cervix, but also of the vulva, vagina, anal and head-neck region. Furthermore, the protection of the quadrivalent vaccine Gardasil includes also genital warts and recurrent respiratory Papillomatosis, two benign conditions with high socio-economic impact. Although their efficacy in reducing the burden of HPV-related pathologies has been already documented, second-generation HPV vaccines are being developed in order to overcome major limitations, above all the cost of production, distribution and acceptance, thus promoting an easier access to vaccination, especially in developing countries. Recently a new multivalent VLP vaccine active against nine HPV subtypes, called Gardasil 9 (Merck & Co., Inc., Whitehouse Station, NJ, USA), has been approved, showing promising preliminary results. In this article, we outline the strategies adopted for second-generation HPV vaccine engineering, the latest HPV vaccines available at this time, as well as those currently in development.

  14. Bone-cartilage interface crosstalk in osteoarthritis: potential pathways and future therapeutic strategies.

    PubMed

    Yuan, X L; Meng, H Y; Wang, Y C; Peng, J; Guo, Q Y; Wang, A Y; Lu, S B

    2014-08-01

    Currently, osteoarthritis (OA) is considered a disease of the entire joint, which is not simply a process of wear and tear but rather abnormal remodelling and joint failure of an organ. The bone-cartilage interface is therefore a functioning synergistic unit, with a close physical association between subchondral bone and cartilage suggesting the existence of biochemical and molecular crosstalk across the OA interface. The crosstalk at the bone-cartilage interface may be elevated in OA in vivo and in vitro. Increased vascularisation and formation of microcracks associated with abnormal bone remodelling in joints during OA facilitate molecular transport from cartilage to bone and vice versa. Recent reports suggest that several critical signalling pathways and biological factors are key regulators and activate cellular and molecular processes in crosstalk among joint compartments. Therapeutic interventions including angiogenesis inhibitors, agonists/antagonists of molecules and drugs targeting bone remodelling are potential candidates for this interaction. This review summarised the premise for the presence of crosstalk in bone-cartilage interface as well as the current knowledge of the major signalling pathways and molecular interactions that regulate OA progression. A better understanding of crosstalk in bone-cartilage interface may lead to development of more effective strategies for treating OA patients.

  15. Analogs and the BHP Risk Reduction Strategy for Future Spaceflight Missions

    NASA Technical Reports Server (NTRS)

    Whitmire, Sandra; Leveton, Lauren

    2011-01-01

    In preparation for future exploration missions to distant destinations (e.g., Moon, Near Earth Objects (NEO), and Mars), the NASA Human Research Program s (HRP) Behavioral Health and Performance Element (BHP) conducts and supports research to address four human health risks: Risk of Behavioral Conditions; Risk of Psychiatric Conditions; Risk of Performance Decrements Due to Inadequate Cooperation, Coordination, Communication, and Psychosocial Adaptation within a Team; and Risk of Performance Errors due to Sleep Loss, Fatigue, Circadian Desynchronization, and Work Overload (HRP Science Management Plan, 2008). BHP Research, in collaboration with internal and external research investigators, as well as subject matter experts within NASA operations including flight surgeons, astronauts, and mission planners and others within the Mission Operations Directorate (MOD), identifies knowledge and technology gaps within each Risk. BHP Research subsequently manages and conducts research tasks to address and close the gaps, either through risk assessment and quantification, or the development of countermeasures and monitoring technologies. The resulting deliverables, in many instances, also support current Medical Operations and/or Mission Operations for the International Space Station (ISS).

  16. [Professional error and nursing ethics: from past consideration to future strategy].

    PubMed

    Germini, Francesco; Lattarulo, Pio

    2008-01-01

    In 1960, the National Federation IPASVI emanated its first ethical code which does not deal at all with the prevention of error or how to behave in the case this does happen, with the exception of point 6, which recommends scrupulously respecting the therapy prescribed and encouraging patients to trust the physicians and the other health workers. The second ethical code was dated 1977. In this eighteen year interval the hospital organization had been deeply modified and this new layout of the Code reflected some remarkable changes of thought but no precise reference to the matter of error management. In the 1999 version of the code the radical changes in the profession are reflected and formally recognized by the law (42/1999) and by society acting as a reference for the regulation of the nursing profession and referring to one of the most ancient principles of medicine, the "primum non nocere". It is important to remember that an ethical code derives from professional considerations, applied to the context of "here and now". Some strategic considerations for the future regarding the important role of risk prevention and management of errors (which do, unfortunately, occur) are therefore expressed.

  17. The future of spaceborne altimetry. Oceans and climate change: A long-term strategy

    NASA Technical Reports Server (NTRS)

    Koblinsky, C. J. (Editor); Gaspar, P. (Editor); Lagerloef, G. (Editor)

    1992-01-01

    The ocean circulation and polar ice sheet volumes provide important memory and control functions in the global climate. Their long term variations are unknown and need to be understood before meaningful appraisals of climate change can be made. Satellite altimetry is the only method for providing global information on the ocean circulation and ice sheet volume. A robust altimeter measurement program is planned which will initiate global observations of the ocean circulation and polar ice sheets. In order to provide useful data about the climate, these measurements must be continued with unbroken coverage into the next century. Herein, past results of the role of the ocean in the climate system is summarized, near term goals are outlined, and requirements and options are presented for future altimeter missions. There are three basic scientific objectives for the program: ocean circulation; polar ice sheets; and mean sea level change. The greatest scientific benefit will be achieved with a series of dedicated high precision altimeter spacecraft, for which the choice of orbit parameters and system accuracy are unencumbered by requirements of companion instruments.

  18. Epidemiology of dengue in Nepal: History of incidence, current prevalence and strategies for future control.

    PubMed

    Subedi, Dinesh; Taylor-Robinson, Andrew W

    2016-03-01

    Dengue is now established as one of the most important arboviral infections. As the epidemic continues unabated globally, this Aedes mosquito-transmitted pathogen is considered a major re-emerging tropical disease and significant public health concern. Four well-established distinct serotypes of dengue virus, with a fifth one recently proposed, are responsible for causing a spectrum of clinical symptoms in humans ranging from mild fever to severe haemorrhagic manifestations. Indigenous cases of dengue were first recognised in Nepal, a Himalayan country bordered by India and China, just a decade ago in a cluster of tropical and subtropical areas. Subsequently, the range of infection has extended all over the country and now comprises not only low lying regions, but also hilly locations including the capital city Kathmandu. The two major epidemics to date, in 2010 and 2013, have demonstrated the capacity of infection outbreaks to be explosive and challenging to currently available disease control measures. There is a pressing need to undertake effective vector surveillance studies supported by provision of well-equipped diagnostic virology laboratories. However, sincere efforts are being made to map the nationwide prevalence and understand the epidemiology of dengue infection. Yet, the precise burden of dengue in Nepal remains unknown, since most reports are confined to economically affluent areas and do not account for regions of relative social deprivation in which disease is more likely to occur. This review presents a current overview of dengue in Nepal and discusses future prospects for control of this debilitating disease in the country.

  19. Antibiotic Treatment for First Episode of Acute Otitis Media Is Not Associated with Future Recurrences

    PubMed Central

    te Molder, Marthe; de Hoog, Marieke L. A.; Uiterwaal, Cuno S. P. M.; van der Ent, Cornelis K.; Smit, Henriette A.; Schilder, Anne G. M.; Damoiseaux, Roger A. M. J.; Venekamp, Roderick P.

    2016-01-01

    Objective Antibiotic treatment of acute otitis media (AOM) has been suggested to increase the risk of future AOM episodes by causing unfavorable shifts in microbial flora. Because current evidence on this topic is inconclusive and long-term follow-up data are scarce, we wanted to estimate the effect of antibiotic treatment for a first AOM episode occurring during infancy on AOM recurrences and AOM-related health care utilization later in life. Methods We obtained demographic information and risk factors from data of the Wheezing Illnesses Study Leidsche Rijn, a prospective birth cohort study in which all healthy newborns born in Leidsche Rijn (between 2001 and 2012), The Netherlands, were enrolled. These data were linked to children’s primary care electronic health records up to the age of four. Children with at least one family physician-diagnosed AOM episode before the age of two were included in analyses. The exposure of interest was the prescription of oral antibiotics (yes vs no) for a child’s first AOM episode before the age of two years. Results 848 children were included in analyses and 512 (60%) children were prescribed antibiotics for their first AOM episode. Antibiotic treatment was not associated with an increased risk of total AOM recurrences (adjusted rate ratio: 0.94, 95% CI: 0.78–1.13), recurrent AOM (≥3 episodes in 6 months or ≥4 in one year; adjusted risk ratio: 0.79, 95% CI: 0.57–1.11), or with increased AOM-related health care utilization during children’s first four years of life. Conclusions Oral antibiotic treatment of a first AOM episode occurring during infancy does not affect the number of AOM recurrences and AOM-related health care utilization later in life. This information can be used when weighing the pros and cons of various AOM treatment options. PMID:27632355

  20. Chronic Hepatitis C Virus Infection: A Review of Current Direct-Acting Antiviral Treatment Strategies

    PubMed Central

    Zhang, Johnathan; Nguyen, Douglas; Hu, Ke-Qin

    2016-01-01

    Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents. PMID:27293521