WorldWideScience

Sample records for therapeutic strategy comparison

  1. Therapeutic strategies in pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Leonello eFuso

    2011-04-01

    Full Text Available Pulmonary hypertension (PH is a life-threatening condition characterized by elevated pulmonary arterial pressure. It is clinically classified into five groups: patients in the first group are considered to have pulmonary arterial hypertension (PAH whereas patients of the other groups have PH that is due to cardiopulmonary or other systemic diseases. The management of patients with PH has advanced rapidly over the last decade and the introduction of specific treatments especially for PAH has lead to an improved outcome. However, despite the progress in the treatment, the functional limitation and the survival of these patients remain unsatisfactory and there is no cure for PAH. Therefore the search for an ideal therapy still goes on. At present, two levels of treatment can be identified: primary and specific therapy. Primary therapy is directed at the underlying cause of the PH. It also includes a supportive therapy consisting in oxygen supplementation, diuretics, and anticoagulation which should be considered in all patients with PH. Specific therapy is directed at the PH itself and includes treatment with vasodilatators such as calcium channel blockers and with vasodilatator and pathogenetic drugs such as prostanoids, endothelin receptor antagonists and phosphodiesterase type-5 inhibitors. These drugs act in several pathogenetic mechanisms of the PH and are specific for PAH although they might be used also in the other groups of PH. Finally, atrial septostomy and lung transplantation are reserved for patients refractory to medical therapy. Different therapeutic approaches can be considered in the management of patients with PH. Therapy can be established on the basis of both the clinical classification and the functional class. It is also possible to adopt a goal-oriented therapy in which the timing of treatment escalation is determined by inadequate response to known prognostic indicators.

  2. [Therapeutic strategies against myasthenia gravis].

    Science.gov (United States)

    Utsugisawa, Kimiaki; Nagane, Yuriko

    2013-05-01

    Many patients with myasthenia gravis (MG) still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of oral corticosteroids, since full remission is not common. Our analysis demonstrated that disease severity, oral corticosteroids, and depressive state are the major factors negatively associated with QOL, and that QOL of MM status patients taking CSR and is a target of treatment. In order to achieve early MM or better status with prednisolne strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved status using low-dose oral corticosteroids and calcineurin inhibitors.

  3. A Comparison of Short- and Long-Term Therapeutic Outcomes of Infliximab- versus Tacrolimus-Based Strategies for Steroid-Refractory Ulcerative Colitis

    Directory of Open Access Journals (Sweden)

    Katsuya Endo

    2016-01-01

    Full Text Available Background/Aims. Antitumor necrosis factor antibodies and calcineurin inhibitors have shown good therapeutic efficacy for steroid-refractory ulcerative colitis (UC. Although some studies have compared the efficacy of infliximab (IFX and cyclosporin A, there are no published studies comparing IFX and tacrolimus (Tac. This study aimed to compare therapeutic efficacies between IFX- and Tac-based strategies for steroid-refractory UC. Methods. Between July 2009 and August 2013, 95 patients with steroid-refractory UC received either IFX (n=48 or Tac (n=47 in our hospital. In the IFX group, the patients continued to receive maintenance treatment with IFX. In the Tac group, patients discontinued Tac treatment up to 3 months and subsequently received thiopurine. We retrospectively compared the therapeutic outcomes between the groups. Results. There was no significant difference in the colectomy-free rate, clinical remission rate, and clinical response rate at 2 months between the groups. However, relapse-free survival was significantly higher in the IFX group than in the Tac group (p<0.001; log-rank test. The proportions of serious adverse events did not differ between the groups. Conclusion. The findings of our study showed that IFX and Tac have similar short-term therapeutic efficacy for steroid-refractory UC. Maintenance treatment with IFX, however, yields better long-term outcomes than Tac-thiopurine bridging treatment.

  4. [Therapeutic strategy for different types of epicanthus].

    Science.gov (United States)

    Gaofeng, Li; Jun, Tan; Zihan, Wu; Wei, Ding; Huawei, Ouyang; Fan, Zhang; Mingcan, Luo

    2015-11-01

    To explore the reasonable therapeutic strategy for different types of epicanthus. Patients with epicanthus were classificated according to the shape, extent and inner canthal distance and treated with different methods appropriately. Modified asymmetric Z plasty with two curve method was used in lower eyelid type epicanthus, inner canthus type epicanthus and severe upper eyelid type epicanthus. Moderate upper epicanthus underwent '-' shape method. Mild Upper epicanthus in two conditions which underwent nasal augumentation and double eyelid formation with normal inner canthal distance need no correction surgery. The other mild epicanthus underwent '-' shape method. A total of 66 cases underwent the classification and the appropriate treatment. All wounds healed well. During 3 to 12 months follow-up period, all epicanthus were corrected completely with natural contour and unconspicuous scars. All patients were satisfied with the results. Classification of epicanthus hosed on the shape, extent and inner canthal distance and correction with appropriate methods is a reasonable therapeutic strategy.

  5. Therapeutic strategies to improve control of hypertension.

    Science.gov (United States)

    Armario, Pedro; Waeber, Bernard

    2013-03-01

    Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

  6. Colorectal cancer: diagnostic and therapeutic strategies

    International Nuclear Information System (INIS)

    Vaillant, J.C.

    1996-01-01

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

  7. Hydrogels for central nervous system therapeutic strategies.

    Science.gov (United States)

    Russo, Teresa; Tunesi, Marta; Giordano, Carmen; Gloria, Antonio; Ambrosio, Luigi

    2015-12-01

    The central nervous system shows a limited regenerative capacity, and injuries or diseases, such as those in the spinal, brain and retina, are a great problem since current therapies seem to be unable to achieve good results in terms of significant functional recovery. Different promising therapies have been suggested, the aim being to restore at least some of the lost functions. The current review deals with the use of hydrogels in developing advanced devices for central nervous system therapeutic strategies. Several approaches, involving cell-based therapy, delivery of bioactive molecules and nanoparticle-based drug delivery, will be first reviewed. Finally, some examples of injectable hydrogels for the delivery of bioactive molecules in central nervous system will be reported, and the key features as well as the basic principles in designing multifunctional devices will be described. © IMechE 2015.

  8. Therapeutic Symptomatic Strategies in the Parasomnias.

    Science.gov (United States)

    Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

    2018-06-05

    The purpose of this review was to discuss the currently available pharmacologic and non-pharmacologic treatment options for parasomnias. Recent pathophysiological findings about sleep structure in parasomnias helped understanding several drug mechanisms of action. Serotoninergic theory accounts for the effect of serotoninergic drugs. Study about spectral analysis of sleep showed the effect of clonazepam on spectral bands. Cannabinoids proved to be effective in some of parasomnias, as in many other neurological disorders. A series of therapeutic strategies were analyzed and compared. Benzodiazepines, antidepressant drugs, and L-5-hydroxytryptophan may be beneficial in DOA. SSRI and topiramate are effective in SRED. RBD responds to clonazepam, melatonin, and to a lesser extent to dopaminergic and anticholinergic agents. Prazosin and cannabinoids are effective in nightmare disorder. Sleep paralysis may respond to antidepressant agents. Tricyclic antidepressant may be effective in sleep-related hallucinations and exploding head syndrome. Sleep enuresis may be successfully treated with desmopressin, anticholinergic drugs, and imipramine.

  9. [Type 2 diabetes: what therapeutic strategy?].

    Science.gov (United States)

    Grimaldi, A; Hartemann-Heurtier, A

    2001-02-17

    GOAL OF TREATMENT: Prevention of diabetic micro and macroangiopathy is the goal of treatment in type 2 diabetes mellitus. A well-controlled glucose level is the key to prevention of microangiopathy; there is no threshold level. Antihypertensive treatment, with the goal of blood pressure below 130/80 mmHg is also beneficial in preventing aggravation of microangiopathy. For macroangiopathy, prevention is based in priority on treatment of other risk factors for cardiovascular disease; the threshold level for drug treatment and the therapeutic objective are those defined for secondary prevention in non-diabetic patients, i.e. blood pressure below 140/80 mmHg and LDL cholesterol under 1.30 g/l. The beneficial effect of lower glucose levels on preventing macrovascular risk was not formally demonstrated by the UKPDS, probably because the difference between the control and the treatment group HbA1c levels was minimal, 0.9 points. REVISITING STRATEGY: It is thus time to revisit the preventive strategy for type 2 diabetes mellitus, i.e. step-by-step increments, as currently proposed for worsening glucose levels. Metformine should be prescribed if the HbA1c is above normal in order to achieve the demonstrated benefit in prevention of microangiopathy and in the hope, motivated by pathophysiology data, of preventing insulin failure. Slow-release insulin at bedtime should be added to the oral hypoglycemiants if fasting glucose exceeds 1.60 or 1.80 g/l, even if the HbA1c remains below 8%. NEW HYPOGLYCEMIANTS: The role of these new agents in this more "aggressive" strategy remains to be defined. Glinides will have to demonstrate their superiority over sulfamides (fewer episodes of hypoglycemia with comparable efficacy) to justify their high cost. Glitazones will have to demonstrate a beneficial effect in second intention combination with metformine on cardiovascular morbidity mortality in type 2 diabetes patients with a metabolic insulin-resistance syndrome and visceral obesity

  10. Investigation of therapeutic strategy for acute empyema

    International Nuclear Information System (INIS)

    Mochinaga, Koji; Akamine, Shinji; Muraoka, Masashi; Morino, Shigeyuki

    2011-01-01

    Recently, it has been reported that video-assisted thoracoscopic chest drainage is a useful treatment for acute empyema, but its indication has not been clarified. We retrospectively reviewed acute empyema patients by dividing them into 3 groups: operation group (7 patients), drainage group (6 patients), and antibiotic treatment group (9 patients), and then we evaluated the therapeutic strategy by examining the radiological findings, drainage period, and hospital stay. In the antibiotic treatment group, the ratio of pleural effusion on chest radiograph was under 1/4 in all patients. There were 5 patients who showed multilocular findings on chest CT, and all patients underwent an operation. Regarding the drainage period, the operation group showed a significantly shorter period than the drainage group. Concerning the hospital stay, the drainage group showed a significantly longer stay than the other 2 groups. The ratio of pleural effusion on chest radiograph was under 1/4, giving an indication for antibiotic treatment. With multilocular findings on CT, an indication for surgery is needed. Patients requiring drainage, which necessitates a long hospital stay, should be advised to consider surgery. (author)

  11. Towards new therapeutic strategies in chondrosarcoma

    NARCIS (Netherlands)

    Schrage, Yvonne Maria

    2009-01-01

    This thesis presents the identification of new targets for therapeutic treatment of chondrosarcoma, tumours that are highly insensitive to conventional chemo- and radiation thearapy. A relatively new array technique to identify active kinases in chondrosarcoma cell cultures was used, which

  12. Therapeutic Strategy for Chronic Headache in Children

    Directory of Open Access Journals (Sweden)

    H.O. Lezhenko

    2016-05-01

    Full Text Available The therapeutic efficacy of a combined homeopathic preparation Cefavora, which consists of alcoholic extracts of Ginkgo biloba, hawthorn (Crataegus and white mistletoe (Viscum album, has been studied in the treatment of chronic tension-type headache in children. It has been shown that alongside with elimination of headache manifestations, the use of homeopathic medicine has contributed to the normalization of adaptive mechanisms of autonomic regulation in children indicating its high therapeutic efficacy.

  13. Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

    Science.gov (United States)

    Ito, Masaoki; Miyata, Yoshihiro; Hirano, Shoko; Kimura, Shingo; Irisuna, Fumiko; Ikeda, Kyoko; Kushitani, Kei; Tsutani, Yasuhiro; Ueda, Daisuke; Tsubokawa, Norifumi; Takeshima, Yukio; Okada, Morihito

    2017-12-12

    Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

  14. Delta hedging strategies comparison

    DEFF Research Database (Denmark)

    De Giovanni, Domenico; Ortobelli, S.; Rachev, S.T.

    2008-01-01

    In this paper we implement dynamic delta hedging strategies based on several option pricing models. We analyze different subordinated option pricing models and we examine delta hedging costs using ex-post daily prices of S&P 500. Furthermore, we compare the performance of each subordinated model...

  15. Inflammatory bowel disease: potential therapeutic strategies

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Bregenholt, S

    1997-01-01

    This review deals with potential and possibly primary therapeutics that, through insight into the inflammatory cascade, result in more rational treatment principles replacing the classical therapy of inflammatory bowel disease (IBD), i.e. Crohn's disease (CD) and ulcerative colitis (UC). These ne...

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

    CSIR Research Space (South Africa)

    Manoto, Sello L

    2017-10-01

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

  17. Myasthenia gravis: subgroup classification and therapeutic strategies.

    Science.gov (United States)

    Gilhus, Nils Erik; Verschuuren, Jan J

    2015-10-01

    Myasthenia gravis is an autoimmune disease that is characterised by muscle weakness and fatigue, is B-cell mediated, and is associated with antibodies directed against the acetylcholine receptor, muscle-specific kinase (MUSK), lipoprotein-related protein 4 (LRP4), or agrin in the postsynaptic membrane at the neuromuscular junction. Patients with myasthenia gravis should be classified into subgroups to help with therapeutic decisions and prognosis. Subgroups based on serum antibodies and clinical features include early-onset, late-onset, thymoma, MUSK, LRP4, antibody-negative, and ocular forms of myasthenia gravis. Agrin-associated myasthenia gravis might emerge as a new entity. The prognosis is good with optimum symptomatic, immunosuppressive, and supportive treatment. Pyridostigmine is the preferred symptomatic treatment, and for patients who do not adequately respond to symptomatic therapy, corticosteroids, azathioprine, and thymectomy are first-line immunosuppressive treatments. Additional immunomodulatory drugs are emerging, but therapeutic decisions are hampered by the scarcity of controlled studies. Long-term drug treatment is essential for most patients and must be tailored to the particular form of myasthenia gravis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Therapeutic Strategies for Hereditary Kidney Cancer.

    Science.gov (United States)

    Sidana, Abhinav; Srinivasan, Ramaprasad

    2016-08-01

    The study of hereditary forms of kidney cancer has vastly increased our understanding of metabolic and genetic pathways involved in the development of both inherited and sporadic kidney cancers. The recognition that diverse molecular events drive different forms of kidney cancers has led to the preclinical and clinical development of specific pathway-directed strategies tailored to treat distinct subgroups of kidney cancer. Here, we describe the molecular mechanisms underlying the pathogenesis of several different types of hereditary renal cancers, review their clinical characteristics, and summarize the treatment strategies for the management of these cancers.

  19. Biliary parasites: diagnostic and therapeutic strategies.

    Science.gov (United States)

    Khandelwal, Niraj; Shaw, Joanna; Jain, Mamta K

    2008-04-01

    Parasitic infections of the biliary tract are a common cause of biliary obstruction in endemic areas. This article focuses on primary biliary parasites: Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, Dicrocoelium dendriticum, Fasciola hepatica, and Fasciola gigantica. Tropical and subtropical countries have the highest incidence and prevalence of these infections. Diagnosis is made primarily through direct microscopic examination of eggs in the stool, duodenal, or bile contents. Radiologic imaging may show intrahepatic ductal dilatation, whereas endoscopic retrograde cholangiopancreatography can be used diagnostically and therapeutically. However, oral treatment is inexpensive and effective for most of these parasites and can prevent untoward consequences. Primary and alternative treatments are available and are reviewed in this article.

  20. [Premenstrual dysphoric disorder: diagnosis and therapeutic strategy].

    Science.gov (United States)

    Bianchi-Demicheli, F

    2006-02-08

    Prementrual dysphoric disorder (PMDD) is considered to be a very severe form of the premenstrual syndrome (PMS) that occurs regularly in the last week of the luteal phase of the cycle and begin to remit after the onset of follicular phase and is absent in the week postmenses. What sets PMDD apart from PMS is its severity and its dominant psychiatric symptoms. PMDD includes depression, anxiety, tension, irritability and moodiness. Moreover, women with PMDD find that it has a very disruptive effect on their everyday lives. Although, many treatments have been used for PMDD over the years, PMDD remains difficult to be cured. Until recently, only few of these treatments were evaluated in carefully designed research studies and even fewer were shown to be effective. Here, we discuss the different therapeutic options for PMDD.

  1. Therapeutic strategies in the treatment of periodontitis

    Directory of Open Access Journals (Sweden)

    Liljana Bogdanovska

    2012-04-01

    Full Text Available Periodontitis is a chronic inflammatory process which affects the tooth - supporting structures of the teeth. The disease is initiated by subgingival periopathogenic bacteria in susceptible periodontal sites. The host immune response towards periodontal pathogens helps to sustain periodontal disease and eventual alveolar bone loss. Although scaling and root planing is the standard treatment modality for periodontitis, it suffers from several drawbacks such as the inability to reach the base of deep pockets and doesn’t arrest migration of periodontal pathogens from other sites in the oral cavity. In order to overcome the limitations of scaling and root planning, adjunctive chemotherapeutics and host modulatory agents to the treatment are used. These therapeutic agents show substantial beneficial effects when compared to scaling and root planning alone. This review will cover an update on chemotherapeutic and past and future host immune modulatory agents used adjunctively to treat and manage periodontal diseases.

  2. [The place of a new drug in the therapeutic strategy].

    Science.gov (United States)

    Castaigne, A; Goehrs, J M; Ravoire, S

    A therapeutic strategy is a hierarchical set of appropriate measures to provide an answer to a pathological state. A drug is a part of this set (together with the diagnosis, the environment and the other medicinal interventions or not). A new drug's place in a therapeutic strategy can be evaluated according to one or several referential(s) when it (or they) exist, referentials which express the state of knowledge before launch of the new drug. The drug's profile (indication or contraindication, etc.), at the point when the marketing authorization is given, is purely theoretical. One must evaluate the real place of the drug under its real conditions of use (pragmatic trials, observable surveys). A new drugs' place in a therapeutic strategy can only be evaluated in the course of time unless a therapeutic revolution occurs.

  3. Ebola virus (EBOV) infection: Therapeutic strategies.

    Science.gov (United States)

    De Clercq, Erik

    2015-01-01

    Within less than a year after its epidemic started (in December 2013) in Guinea, Ebola virus (EBOV), a member of the filoviridae, has spread over a number of West-African countries (Guinea, Sierra Leone and Liberia) and gained allures that have been unprecedented except by human immunodeficiency virus (HIV). Although EBOV is highly contagious and transmitted by direct contact with body fluids, it could be counteracted by the adequate chemoprophylactic and -therapeutic interventions: vaccines, antibodies, siRNAs (small interfering RNAs), interferons and chemical substances, i.e. neplanocin A derivatives (i.e. 3-deazaneplanocin A), BCX4430, favipiravir (T-705), endoplasmic reticulum (ER) α-glucosidase inhibitors and a variety of compounds that have been found to inhibit EBOV infection blocking viral entry or by a mode of action that still has to be resolved. Much has to be learned from the mechanism of action of the compounds active against VSV (vesicular stomatitis virus), a virus belonging to the rhabdoviridae, that in its mode of replication could be exemplary for the replication of filoviridae. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Therapeutic Strategies and Intellectualism in On Anger by Seneca

    Directory of Open Access Journals (Sweden)

    Rodrigo Sebastián Braicovich

    2015-08-01

    Full Text Available I try to show that a the treatise On Anger by Seneca includes not one but two therapeutic strategies designed to avoid anger and that b the second of these strategies –which has been neglected in the secondary literature– presents unsolvable problems when we contrast it with the Stoic theory of action, which is rooted in intellectualist premises.

  5. Endovascular therapeutic strategies in ruptured intracranial aneurysms

    International Nuclear Information System (INIS)

    Machi, Paolo; Lobotesis, Kyriakos; Vendrell, Jean Francoise; Riquelme, Carlos; Eker, Omer; Costalat, Vincent; Bonafe, Alain

    2013-01-01

    The aim of the present study was to evaluate endovascular techniques used currently which were not available at the time of ISAT inclusion period, such as balloon remodelling and flow-divertion, in order to assess whether these new technologies have improved the endovascular approach outcomes. We present a review of articles, published in major journals, with the aim to evaluate the efficacy and the safety of coiling with balloon remodelling for the treatment of ruptured aneurysms in comparison to coiling performed without such coadjutant techniques. Furthermore, we reviewed publications reporting on the treatment of ruptured aneurysms in the acute phase with the one of the most recent technologies available nowadays: the flow diverting stent. Looking at the recent literature the results regarding ruptured aneurysms treated with balloon assisted coiling (BAC) have shown an improvement in terms of anatomical results and morbi-mortality rates. Case series of ruptured middle cerebral artery (MCA) aneurysms treated by EVT report results similar to those obtained by surgical clipping. Several articles recently report encouraging results in treating ruptured dissecting and blister aneurysms with flow diverters. Questions regarding the best treatment available for ruptured aneurysms are yet to be answered. Hence there is a need for a subsequent trial aiming to answer these unresolved issues

  6. [Innovative therapeutic strategies for intravesical drug administration].

    Science.gov (United States)

    Moch, C; Salmon, D; Rome, P; Marginean, R; Pivot, C; Colombel, M; Pirot, F

    2013-05-01

    Perspectives for innovative pharmaceutical molecules and intravesical administration of pharmacological agents are presented in the present review carried out from a recent literature. This review of the literature was built by using the PubMed and ScienceDirect databases running 20keywords revealing 34publications between 1983 and 2012. The number of referenced articles on ScienceDirect has increased in recent years, highlighting the interest of scientists for intravesical drug administration and the relevance of innovating drug delivery systems. Different modalities of intravesical administration using physical (e.g., iontophoresis, electroporation) or chemical techniques (e.g., enzyme, solvent, nanoparticles, liposomes, hydrogels) based on novel formulation methods are reported. Finally, the development of biopharmaceuticals (e.g., bacillus Calmette-Guérin, interferon α) and gene therapies is also presented and analyzed in this review. The present review exhibits new development in the pipeline for emerging intravesical drug administration strategies. Knowledge of all these therapies allows practitioners to propose a specific and tailored treatment to each patient with limiting systemic side effects. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Novel therapeutic strategies against AIDS progression based on the ...

    African Journals Online (AJOL)

    Novel therapeutic strategies against AIDS progression based on the pathogenic effects of HIV-1 and V pr Proteins. Ahmed A Azad. Abstract. No Abstract. Discovery and Innovation Vol. 17, 2005: 52-60. Full Text: EMAIL FULL TEXT EMAIL FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. Article Metrics.

  8. Therapeutic and prevention strategies against human enterovirus 71 infection

    Science.gov (United States)

    Kok, Chee Choy

    2015-01-01

    Human enterovirus 71 (HEV71) is the cause of hand, foot and mouth disease and associated neurological complications in children under five years of age. There has been an increase in HEV71 epidemic activity throughout the Asia-Pacific region in the past decade, and it is predicted to replace poliovirus as the extant neurotropic enterovirus of highest global public health significance. To date there is no effective antiviral treatment and no vaccine is available to prevent HEV71 infection. The increase in prevalence, virulence and geographic spread of HEV71 infection over the past decade provides increasing incentive for the development of new therapeutic and prevention strategies against this emerging viral infection. The current review focuses on the potential, advantages and disadvantages of these strategies. Since the explosion of outbreaks leading to large epidemics in China, research in natural therapeutic products has identified several groups of compounds with anti-HEV71 activities. Concurrently, the search for effective synthetic antivirals has produced promising results. Other therapeutic strategies including immunotherapy and the use of oligonucleotides have also been explored. A sound prevention strategy is crucial in order to control the spread of HEV71. To this end the ultimate goal is the rapid development, regulatory approval and widespread implementation of a safe and effective vaccine. The various forms of HEV71 vaccine designs are highlighted in this review. Given the rapid progress of research in this area, eradication of the virus is likely to be achieved. PMID:25964873

  9. Cell-based therapeutic strategies for multiple sclerosis

    DEFF Research Database (Denmark)

    Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C

    2017-01-01

    and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities......, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved...

  10. A Brief Overview of Tauopathy: Causes, Consequences, and Therapeutic Strategies.

    Science.gov (United States)

    Orr, Miranda E; Sullivan, A Campbell; Frost, Bess

    2017-07-01

    There are currently no disease-modifying therapies for the treatment of tauopathies, a group of progressive neurodegenerative disorders that are pathologically defined by the presence of tau protein aggregates in the brain. Current challenges for the treatment of tauopathies include the inability to diagnose early and to confidently discriminate between distinct tauopathies in patients, alongside an incomplete understanding of the cellular mechanisms involved in pathogenic tau-induced neuronal death and dysfunction. In this review, we describe current diagnostic and therapeutic strategies, known drivers of pathogenic tau formation, recent contributions to our current mechanistic understanding of how pathogenic tau induces neuronal death, and potential diagnostic and therapeutic approaches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

    Science.gov (United States)

    Vinay, Dass S; Ryan, Elizabeth P; Pawelec, Graham; Talib, Wamidh H; Stagg, John; Elkord, Eyad; Lichtor, Terry; Decker, William K; Whelan, Richard L; Kumara, H M C Shantha; Signori, Emanuela; Honoki, Kanya; Georgakilas, Alexandros G; Amin, Amr; Helferich, William G; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Keith, W Nicol; Bilsland, Alan; Bhakta, Dipita; Halicka, Dorota; Fujii, Hiromasa; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan; Choi, Beom K; Kwon, Byoung S

    2015-12-01

    Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system. Immune editing is one of the key aspects why tumors evade surveillance causing the tumors to lie dormant in patients for years through "equilibrium" and "senescence" before re-emerging. In addition, tumors exploit several immunological processes such as targeting the regulatory T cell function or their secretions, antigen presentation, modifying the production of immune suppressive mediators, tolerance and immune deviation. Besides these, tumor heterogeneity and metastasis also play a critical role in tumor growth. A number of potential targets like promoting Th1, NK cell, γδ T cell responses, inhibiting Treg functionality, induction of IL-12, use of drugs including phytochemicals have been designed to counter tumor progression with much success. Some natural agents and phytochemicals merit further study. For example, use of certain key polysaccharide components from mushrooms and plants have shown to possess therapeutic impact on tumor-imposed genetic instability, anti-growth signaling, replicative immortality, dysregulated metabolism etc. In this review, we will discuss the advances made toward understanding the basis of cancer immune evasion and summarize the efficacy of various therapeutic measures and targets that have been developed or are being investigated to enhance tumor rejection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Therapeutic targeting strategies using endogenous cells and proteins.

    Science.gov (United States)

    Parayath, Neha N; Amiji, Mansoor M

    2017-07-28

    Targeted drug delivery has become extremely important in enhancing efficacy and reducing the toxicity of therapeutics in the treatment of various disease conditions. Current approaches include passive targeting, which relies on naturally occurring differences between healthy and diseased tissues, and active targeting, which utilizes various ligands that can recognize targets expressed preferentially at the diseased site. Clinical translation of these mechanisms faces many challenges including the immunogenic and toxic effects of these non-natural systems. Thus, use of endogenous targeting systems is increasingly gaining momentum. This review is focused on strategies for employing endogenous moieties, which could serve as safe and efficient carriers for targeted drug delivery. The first part of the review involves cells and cellular components as endogenous carriers for therapeutics in multiple disease states, while the second part discusses the use of endogenous plasma components as endogenous carriers. Further understanding of the biological tropism with cells and proteins and the newer generation of delivery strategies that exploits these endogenous approaches promises to provide better solutions for site-specific delivery and could further facilitate clinical translations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Strategy Use and Strategy Choice in Fraction Magnitude Comparison

    Science.gov (United States)

    Fazio, Lisa K.; DeWolf, Melissa; Siegler, Robert S.

    2016-01-01

    We examined, on a trial-by-trial basis, fraction magnitude comparison strategies of adults with more and less mathematical knowledge. College students with high mathematical proficiency used a large variety of strategies that were well tailored to the characteristics of the problems and that were guaranteed to yield correct performance if executed…

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

    Science.gov (United States)

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

    2017-01-01

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

  15. Antioxidants as a Potential Preventive and Therapeutic Strategy for Cadmium.

    Science.gov (United States)

    Brzóska, Malgorzata M; Borowska, Sylwia; Tomczyk, Michal

    2016-01-01

    Epidemiological studies provide a growing number of evidences that chronic exposure to relatively low levels of cadmium (Cd), nowadays taking place in industrialized countries, may cause health hazard. Thus, growing interest has been focused on effective ways of protection from adverse effects of exposure to this heavy metal. Because numerous effects to Cd's toxic action result from its prooxidative properties, it seems reasonable that special attention should be directed to agents that can prevent or reduce this metal-induced oxidative stress and its consequences in tissues, organs and systems at risk of toxicity, including liver, kidneys, testes, ears, eyes, cardiovascular system and nervous system as well as bone tissue. This review discusses a wide range of natural (plant and animal origin) and synthetic antioxidants together with many plant extracts (e.g. black and green tea, Aronia melanocarpa, Allium sativum, Allium cepa, Ocimum sanctum, Phoenix dactylifera, Physalis peruviana, Zingiber officinale) that have been shown to prevent from Cd toxicity. Moreover, some attention has been focused on the fact that substances not possessing antioxidative potential may also prevent Cd-induced oxidative stress and its consequences. So far, most of the data on the protective effects of the natural and synthetic antioxidants and plant extracts come from studies in animals' models; however, numerous of them seem to be promising preventive/therapeutic strategies for Cd toxicity in humans. Further investigation of prophylactic and therapeutic use of antioxidants in populations exposed to Cd environmentally and occupationally is warranted, given that therapeutically effective chelation therapy for this toxic metal is currently lacking.

  16. Therapeutic strategies based on glucagon-like peptide 1

    DEFF Research Database (Denmark)

    Deacon, Carolyn F

    2004-01-01

    of factors influencing its metabolic stability and pharmacokinetic/pharmacodynamic profile, have therefore been the focus of intense research in both academia and the pharmaceutical industry. Such strategies include DPP-IV-resistant GLP-1 analogs and selective enzyme inhibitors to prevent in vivo degradation...... excursions. Furthermore, via its ability to enhance satiety, GLP-1 reduces food intake, thereby limiting weight gain, and may even cause weight loss. Taken together, these actions give GLP-1 a unique profile, considered highly desirable for an antidiabetic agent, particularly since the glucose dependency...... of its antihyperglycemic effects should minimize any risk of severe hypoglycemia. However, its pharmacokinetic/pharmacodynamic profile is such that native GLP-1 is not therapeutically useful. Thus, while GLP-1 is most effective when administered continuously, single subcutaneous injections have short...

  17. Emerging Therapeutic Strategies for Targeting Chronic Myeloid Leukemia Stem Cells

    Directory of Open Access Journals (Sweden)

    Ahmad Hamad

    2013-01-01

    Full Text Available Chronic myeloid leukemia (CML is a clonal myeloproliferative disorder. Current targeted therapies designed to inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein have made a significant breakthrough in the treatment of CML patients. However, CML remains a chronic disease that a patient must manage for life. Although tyrosine kinase inhibitors (TKI therapy has completely transformed the prognosis of CML, it has made the therapeutic management more complex. The interruption of TKI treatment results in early disease progression because it does not eliminate quiescent CML stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML to achieve a permanent cure, and to allow TKI interruption. This review summarizes recent research done on alternative targeted therapies with a particular focus on some important signaling pathways (such as Alox5, Hedgehog, Wnt/b-catenin, autophagy, and PML that have the potential to target CML stem cells and potentially provide cure for CML.

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

    Science.gov (United States)

    2015-01-01

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

  19. Music as a Therapeutic Assistant: Strategy to Reduce Work Stress

    Directory of Open Access Journals (Sweden)

    Dereck Sena de Lima

    2017-02-01

    Full Text Available Objective: to understand the influence of music as a therapeutic assistant in reducing work stress of nursing professionals in a basic health unit. Method: it is an exploratory and descriptive research with a quantitative approach, developed with 9 nursing professionals from UBS Integrated Nova Esperança in João Pessoa, Paraíba. Data collection began after approval of the Research Ethics Committee of the Health Sciences Center of the Federal University of Paraíba, nº. 0508/16, CAAE: 58741916.6.0000.5188. Results: we identified that 33.3% of nursing professionals presented signs of stress, of the 33.3% who presented stress, 100% demonstrated to be in the resistance phase, 100% of the nursing professionals evaluated the musical strategy in a positive way. Conclusion: the musical strategy received extremely positive evaluations by the participants of the research, about 100% of professionals said that listening to music can reduce work stress.

  20. Therapeutic strategies for spinal muscular atrophy: SMN and beyond

    Directory of Open Access Journals (Sweden)

    Melissa Bowerman

    2017-08-01

    Full Text Available Spinal muscular atrophy (SMA is a devastating neuromuscular disorder characterized by loss of motor neurons and muscle atrophy, generally presenting in childhood. SMA is caused by low levels of the survival motor neuron protein (SMN due to inactivating mutations in the encoding gene SMN1. A second duplicated gene, SMN2, produces very little but sufficient functional protein for survival. Therapeutic strategies to increase SMN are in clinical trials, and the first SMN2-directed antisense oligonucleotide (ASO therapy has recently been licensed. However, several factors suggest that complementary strategies may be needed for the long-term maintenance of neuromuscular and other functions in SMA patients. Pre-clinical SMA models demonstrate that the requirement for SMN protein is highest when the structural connections of the neuromuscular system are being established, from late fetal life throughout infancy. Augmenting SMN may not address the slow neurodegenerative process underlying progressive functional decline beyond childhood in less severe types of SMA. Furthermore, individuals receiving SMN-based treatments may be vulnerable to delayed symptoms if rescue of the neuromuscular system is incomplete. Finally, a large number of older patients living with SMA do not fulfill the present criteria for inclusion in gene therapy and ASO clinical trials, and may not benefit from SMN-inducing treatments. Therefore, a comprehensive whole-lifespan approach to SMA therapy is required that includes both SMN-dependent and SMN-independent strategies that treat the CNS and periphery. Here, we review the range of non-SMN pathways implicated in SMA pathophysiology and discuss how various model systems can serve as valuable tools for SMA drug discovery.

  1. Targeting mitochondrial respiration as a therapeutic strategy for cervical cancer.

    Science.gov (United States)

    Tian, Shenglan; Chen, Heng; Tan, Wei

    2018-05-23

    Targeting mitochondrial respiration has been documented as an effective therapeutic strategy in cancer. However, the impact of mitochondrial respiration inhibition on cervical cancer cells are not well elucidated. Using a panel of cervical cancer cell lines, we show that an existing drug atovaquone is active against the cervical cancer cells with high profiling of mitochondrial biogenesis. Atovaquone inhibited proliferation and induced apoptosis with varying efficacy among cervical cancer cell lines regardless of HPV infection, cellular origin and their sensitivity to paclitaxel. We further demonstrated that atovaquone acts on cervical cancer cells via inhibiting mitochondrial respiration. In particular, atovaquone specifically inhibited mitochondrial complex III but not I, II or IV activity, leading to respiration inhibition and energy crisis. Importantly, we found that the different sensitivity of cervical cancer cell lines to atovaquone were due to their differential level of mitochondrial biogenesis and dependency to mitochondrial respiration. In addition, we demonstrated that the in vitro observations were translatable to in vivo cervical cancer xenograft mouse model. Our findings suggest that the mitochondrial biogenesis varies among patients with cervical cancer. Our work also suggests that atovaquone is a useful addition to cervical cancer treatment, particularly to those with high dependency on mitochondrial respiration. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Cell-based therapeutic strategies for multiple sclerosis.

    Science.gov (United States)

    Scolding, Neil J; Pasquini, Marcelo; Reingold, Stephen C; Cohen, Jeffrey A

    2017-11-01

    The availability of multiple disease-modifying medications with regulatory approval to treat multiple sclerosis illustrates the substantial progress made in therapy of the disease. However, all are only partially effective in preventing inflammatory tissue damage in the central nervous system and none directly promotes repair. Cell-based therapies, including immunoablation followed by autologous haematopoietic stem cell transplantation, mesenchymal and related stem cell transplantation, pharmacologic manipulation of endogenous stem cells to enhance their reparative capabilities, and transplantation of oligodendrocyte progenitor cells, have generated substantial interest as novel therapeutic strategies for immune modulation, neuroprotection, or repair of the damaged central nervous system in multiple sclerosis. Each approach has potential advantages but also safety concerns and unresolved questions. Moreover, clinical trials of cell-based therapies present several unique methodological and ethical issues. We summarize here the status of cell-based therapies to treat multiple sclerosis and make consensus recommendations for future research and clinical trials. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

  3. Gut microbiota role in irritable bowel syndrome: New therapeutic strategies.

    Science.gov (United States)

    Distrutti, Eleonora; Monaldi, Lorenzo; Ricci, Patrizia; Fiorucci, Stefano

    2016-02-21

    In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome (IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial (Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful (Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.

  4. Patent documentation - comparison of two MT strategies

    DEFF Research Database (Denmark)

    Offersgaard, Lene; Povlsen, Claus

    2007-01-01

    This paper focuses on two matters: A comparison of how two different MT strategies manage translating the text type of patent documentation and a survey of what is needed to transform a MT research prototype system to a translation application for patent texts. The two MT strategies is represented....... The distinctive text type of patents pose special demands for machine translation and these aspects are discussed based on linguistic observations with focus on the users point of view. Two main demands are automatic pre processing of the documents and implementation of a module which in a flexible and user......-friendly manner offers the opportunity to extend the lexical coverage of the system. These demands and the comparison of the two MT strategies are discussed on the basis of proofread patents....

  5. Retinopathy of Prematurity: Therapeutic Strategies Based on Pathophysiology.

    Science.gov (United States)

    Cayabyab, Rowena; Ramanathan, Rangasamy

    2016-01-01

    retinal detachment. Long-term complications such as refractory errors, recurrence of ROP and risk of retinal detachment require continued follow-up with an ophthalmologist through adolescence and beyond. Optimal nutrition including adequate intake of omega-3 polyunsaturated fatty acids and decreasing infection/inflammation to promote normal vascularization are important strategies. Screening guidelines for ROP based on local incidence of ROP in different regions of the world are very important. Oxygen therapy is clearly a modifiable risk factor to decrease ROP that needs further study. Understanding the two phases of ROP will help to identify appropriate therapeutic strategies and improve visual outcomes in many preterm infants globally. © 2016 S. Karger AG, Basel.

  6. Therapeutic strategies in an animal model of neurodegeneration

    NARCIS (Netherlands)

    Borre, Y.E.

    2013-01-01

    Neurodegenerative diseases have complex and multifactorial etiologies, creating an enormous burden on society without an effective treatment. This thesis utilized olfactory bulbectomized rats to investigate therapeutic approaches to neurodegenerative disorders. Removal of the olfactory bulbs, leads

  7. COMPARISON OF TWO STRUCTURE AND MOTION STRATEGIES

    Directory of Open Access Journals (Sweden)

    R. Roncella

    2012-09-01

    Full Text Available Automatic orientation of image sequences in close range photogrammetry is becoming more and more important, not least to maintain a degree of competitiveness with other survey techniques, such as laser scanning. The objective of this paper is to compare two Structure from Motion (SFM strategies. The previous strategy has been used at our Department for some years already in a wide range of projects and is based on the Harris operator and the fundamental matrix plus the trifocal tensor estimation to filter out the outliers. While it has in most cases performed satisfactorily, the percentage of accepted matches is generally smaller than expected; sometimes this leads to failure of the successful estimation of the trifocal tensor. The second one has only recently been implemented and is still under testing; it is based on the SURF operator and the 5-point relative orientation algorithm. The paper will show a comparison between the two strategies on a series of test cases.

  8. Indications of hematopoietic stem cell transplantations and therapeutic strategies of accidental irradiations

    International Nuclear Information System (INIS)

    2003-01-01

    Produced by a group of experts, this document first discusses the issue of accidental irradiations in terms of medical management. They notably outline the peculiar characteristics of these irradiations with respect to therapeutic irradiations. They agreed on general principles regarding casualty sorting criteria and process, and their medical treatment (systematic hematopoiesis stimulation, allogeneic transplantation of hematopoietic stem cells). They discuss some practical aspects of these issues: casualty sorting within a therapeutic perspective (actions to be performed within 48 hours), therapeutic strategies (support therapy, use of cytokines, and therapy by hematopoietic stem cell transplant). They state a set of recommendations regarding the taking into care and diagnosis, therapeutic strategies, research perspectives, and teaching

  9. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    OpenAIRE

    Thomas L. Chenevert; Charles R. Meyer; Bradford A. Moffat; Alnawaz Rehemtulla; Suresh K. Mukherji; Stephen S. Gebarski; Douglas J. Quint; Patricia L. Robertson; Theodore S. Lawrence; Larry Junck; Jeremy M. G. Taylor; Timothy D. Johnson; Qian Dong; Karin M. Muraszko; James A. Brunberg

    2002-01-01

    The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular ...

  10. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

    Science.gov (United States)

    Barage, Sagar H; Sonawane, Kailas D

    2015-08-01

    Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Novel Therapeutic Strategy for the Prevention of Bone Fractures

    Science.gov (United States)

    2015-02-01

    therapeutic potential for improving muscle function in older adults , perhaps leading to the prevention of falls and fractures. Body Aim 1 (months 1-12...directly to postural instability, which in turn increases the risk for falls , and falls are the main etiolog ical factor inmore than 90% of bone...vitamin D supplementation (Girgis et al., 2013) may improve muscle strength and/or neuromuscular control and proprioception, perhaps reducing fall risk

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. Conclusion: imaging in strategy of endocrine diagnosis and therapeutics

    International Nuclear Information System (INIS)

    Mornex, R.

    1995-01-01

    Images in medicine have to help the doctor in a diagnostic or therapeutic aim. The choice must be made in function of pathology or organ as known (it is not necessary to ask for a computed tomography where we know that only an echography can give the answer to the question we ask ), the criteria must stay the best performance for the cheapest price, but the quality of interpretation is a more important thing. It is important to avoid a lot of examinations which do not give better informations but are heavy to endure for the patients. In conclusion, the aim of this kind of proceedings is to assure to the patients who come confidently to us, the best service at the less constraints price without forgetting that a conclusion depends on a given methodological situation and reminding of beside machines we have not to forget the men

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

    Science.gov (United States)

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

    2015-07-01

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

  15. A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine

    Directory of Open Access Journals (Sweden)

    Yuji Tada

    2013-01-01

    Full Text Available Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy.

  16. Focus on Therapeutic Strategies of Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Marilena Durazzo

    2012-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in the Western world (it affects 30% of the general adult population. The NAFLD encompasses a histological spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH, defined by steatosis, hepatocellular damage, and lobular inflammation in individuals without significant alcohol consumption and negative viral, congenital, and autoimmune liver disease markers. Currently, NAFLD is considered an emerging epidemic in light of the dramatic increase in obesity rates. With the progressive nature of NASH and its rising prevalence there is a significant need for a specific and targeted treatments since to date there has not been any validated therapies for NAFLD other than weight loss, which is well known to have a poor long-term success rate. In recent years, visceral adipose tissue has taken an important role in NAFLD pathogenesis, and current therapeutic approaches aim at reducing visceral obesity and free fatty acid overflow to the liver. This paper is focused on the treatments used for NAFLD and the potential new therapy.

  17. [Mantle cell lymphoma: Towards a personalized therapeutic strategy?].

    Science.gov (United States)

    Navarro Matilla, Belén; García-Marco, José A

    2015-06-22

    Mantle cell lymphoma (MCL) is a clinically heterogeneous non-Hodgkin lymphoma with an aggressive clinical behaviour and short survival in some cases and an indolent course in others. Advances in the biology and pathogenesis of MCL have unveiled several genes involved in deregulation of cell cycle checkpoints and the finding of subclonal populations with specific recurrent mutations (p53, ATM, NOTCH2) with an impact on disease progression and refractoriness to treatment. Prognostic stratification helps to distinguish between indolent and aggressive forms of MCL. Currently, younger fit patients benefit from more intensive front line chemotherapy regimens and consolidation with autologous transplantation, while older or frail patients are treated with less intensive regimens and rituximab maintenance. For relapsing disease, the introduction of bortezomib and lenalidomide containing regimens and B-cell receptor pathway inhibitors such as ibrutinib and idelalisib in combination with immunochemotherapy have emerged as therapeutic agents with promising clinical outcomes. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  18. Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Hiroshi Katoh

    2015-01-01

    Full Text Available Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs. Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

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

    Directory of Open Access Journals (Sweden)

    Jaume Folch

    2016-01-01

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

  20. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    Science.gov (United States)

    Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F.

    2011-01-01

    paraplegia, and multiple sclerosis, where mitochondrial dysfunction is also thought to be an important pathophysiological player. A number of vertebrate and invertebrate disease models has recently been established to circumvent the lack of human tissues, and these have already provided considerable insight by allowing direct RGC experimentation. The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies. PMID:21112411

  1. Optimal Therapeutic Strategy for Non-small Cell Lung Cancer with Mutated Epidermal Growth Factor Receptor

    Directory of Open Access Journals (Sweden)

    Zhong SHI

    2015-02-01

    Full Text Available Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs have been widely used in non-small cell lung cancer (NSCLC patients, it is still controversial about how to combine EGFR-TKI with chemotherapy and other targeted drugs. We have made a summary on the current therapeutic models of EGFR-TKI combined with chemotherapy/bevacizumab in this review and aimed to find the optimal therapeutic strategy for NSCLC patients with EGFR mutation.

  2. Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

    Science.gov (United States)

    Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

  3. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications

    Science.gov (United States)

    Kraehenmann, Rainer

    2017-01-01

    Background: A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or ‘classical’ psychedelics such as the prototypical psychedelic drug lysergic acid diethylamide (LSD) psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine) and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception mental imagery emotion activation fear memory extinction and sense of self and body. Differences between these two states are related to differential perceptual input from the environment clarity of consciousness and meta-cognitive abilities. Therefore psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. PMID:28625125

  4. Dreams and Psychedelics: Neurophenomenological Comparison and Therapeutic Implications.

    Science.gov (United States)

    Kraehenmann, Rainer

    2017-01-01

    A resurgence of neurobiological and clinical research is currently underway into the therapeutic potential of serotonergic or 'classical' psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,Ndimethyltryptamine), and ayahuasca - a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelicassisted therapy will be provided. Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine how therapeutic outcome is related to the acute dreamlike effects of psychedelics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Breast Cancer Stem Cell Therapeutics, Multiple Strategies Versus Using Engineered Mesenchymal Stem Cells With Notch Inhibitory Properties: Possibilities and Perspectives.

    Science.gov (United States)

    Bose, Bipasha; Sen, Utsav; Shenoy P, Sudheer

    2018-01-01

    Relapse cases of cancers are more vigorous and difficult to control due to the preponderance of cancer stem cells (CSCs). Such CSCs that had been otherwise dormant during the first incidence of cancer gradually appear as radiochemoresistant cancer cells. Hence, cancer therapeutics aimed at CSCs would be an effective strategy for mitigating the cancers during relapse. Alternatively, CSC therapy can also be proposed as an adjuvant therapy, along-with the conventional therapies. As regenerative stem cells (RSCs) are known for their trophic effects, anti-tumorogenicity, and better migration toward an injury site, this review aims to address the use of adult stem cells such as dental pulp derived; cord blood derived pure populations of regenerative stem cells for targeting CSCs. Indeed, pro-tumorogenicity of RSCs is of concern and hence has also been dealt with in relation to breast CSC therapeutics. Furthermore, as notch signaling pathways are upregulated in breast cancers, and anti-notch antibody based and sh-RNA based therapies are already in the market, this review focuses the possibilities of engineering RSCs to express notch inhibitory proteins for breast CSC therapeutics. Also, we have drawn a comparison among various possibilities of breast CSC therapeutics, about, notch1 inhibition. J. Cell. Biochem. 119: 141-149, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Undergraduate nursing students writing therapeutic letters to families: an educational strategy.

    Science.gov (United States)

    Erlingsson, Christen

    2009-02-01

    Writing therapeutic letters to families is discussed in this article as an educational strategy encouraging students to think reflectively about family nursing. At the University of Kalmar, Sweden, undergraduate nursing students in a primary care module interviewed families using the Calgary Family Assessment Model and wrote therapeutic letters to these families. This article describes (a) the examination process, which was the context for writing therapeutic letters, (b) results of analyses of the letters, and (c) student's post-examination evaluation comments. Results indicate that most students needed encouragement to focus on the family's strengths and resources instead of focusing on own feelings or problems they perceived the family as having. Students also needed support in relinquishing their hierarchical role of "expert nurse." Students' evaluation comments showed that writing therapeutic letters provided students with opportunities to reflect about the connections between family nursing theory and the family itself.

  7. Targeting Beta-Amyloid at the CSF: A New Therapeutic Strategy in Alzheimer's Disease.

    Science.gov (United States)

    Menendez-Gonzalez, Manuel; Padilla-Zambrano, Huber S; Alvarez, Gabriel; Capetillo-Zarate, Estibaliz; Tomas-Zapico, Cristina; Costa, Agustin

    2018-01-01

    Although immunotherapies against the amyloid-β (Aβ) peptide tried so date failed to prove sufficient clinical benefit, Aβ still remains the main target in Alzheimer's disease (AD). This article aims to show the rationale of a new therapeutic strategy: clearing Aβ from the CSF continuously (the "CSF-sink" therapeutic strategy). First, we describe the physiologic mechanisms of Aβ clearance and the resulting AD pathology when these mechanisms are altered. Then, we review the experiences with peripheral Aβ-immunotherapy and discuss the related hypothesis of the mechanism of action of "peripheral sink." We also present Aβ-immunotherapies acting on the CNS directly. Finally, we introduce alternative methods of removing Aβ including the "CSF-sink" therapeutic strategy. As soluble peptides are in constant equilibrium between the ISF and the CSF, altering the levels of Aβ oligomers in the CSF would also alter the levels of such proteins in the brain parenchyma. We conclude that interventions based in a "CSF-sink" of Aβ will probably produce a steady clearance of Aβ in the ISF and therefore it may represent a new therapeutic strategy in AD.

  8. Therapeutic immunization strategies against cervical cancer : induction of cell-mediated immunity in murine models

    NARCIS (Netherlands)

    Bungener, Laura Barbara

    2004-01-01

    The aim of the study described in this thesis is the development of a therapeutic immunization strategy against cervical cancer and pre-malignant precursor lesions of cervical cancer (CIN lesions). Cervical cancer is caused by high risk human papillomavirus (HPV). Two of the early proteins of high

  9. Targeting reactive nitrogen species: a promising therapeutic strategy for cerebral ischemia-reperfusion injury.

    Science.gov (United States)

    Chen, Xing-miao; Chen, Han-sen; Xu, Ming-jing; Shen, Jian-gang

    2013-01-01

    Ischemic stroke accounts for nearly 80% of stroke cases. Recanalization with thrombolysis is a currently crucial therapeutic strategy for re-building blood supply, but the thrombolytic therapy often companies with cerebral ischemia-reperfusion injury, which are mediated by free radicals. As an important component of free radicals, reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite (ONOO(-)), play important roles in the process of cerebral ischemia-reperfusion injury. Ischemia-reperfusion results in the production of nitric oxide (NO) and peroxynitrite (ONOO(-)) in ischemic brain, which trigger numerous molecular cascades and lead to disruption of the blood brain barrier and exacerbate brain damage. There are few therapeutic strategies available for saving ischemic brains and preventing the subsequent brain damage. Recent evidence suggests that RNS could be a therapeutic target for the treatment of cerebral ischemia-reperfusion injury. Herein, we reviewed the recent progress regarding the roles of RNS in the process of cerebral ischemic-reperfusion injury and discussed the potentials of drug development that target NO and ONOO(-) to treat ischemic stroke. We conclude that modulation for RNS level could be an important therapeutic strategy for preventing cerebral ischemia-reperfusion injury.

  10. Open data: An International comparison of strategies

    NARCIS (Netherlands)

    Huijboom, Noor; van den Broek, T.A.

    2011-01-01

    Ever more governments around the world are defining and implementing ``open data'' strategies in order to increase transparency, participation and/or government efficiency. The commonly accepted premise underlying these strategies is that the publishing of government data in a reusable format can

  11. [Psychic aspects of the premenstrual dysphoric disorders. New therapeutic strategies: our experience with Vitex agnus castus].

    Science.gov (United States)

    Ciotta, L; Pagano, I; Stracquadanio, M; Di Leo, S; Andò, A; Formuso, C

    2011-06-01

    The premenstrual dysphoric disorder (PMDD) is one of the main problems of the premenstrual phase. It consists of symptoms that sometimes invalidate the scope of employment, social and psycho-affective of patients, requiring thus a diagnostic and therapeutic approach as detailed and accurate as possible. The therapeutic strategies available for this disease are many, but recently the emphasis has been on Vitex agnus castus (VAC), considered by many as evidence drug of choice for both PMS and for the PMDD, being with satisfactory therapeutic properties and small side effects. Our study evaluated a group of patients suffering from PMDD and the clinical efficacy of treatment with VAC (and compared the effectiveness of the results of a more homogeneous group of patients treated with fluoxetine). This study confirms the data reported in the literature regarding the effectiveness of VAC therapy with no side effects.

  12. Therapeutic strategies with oral fluoropyrimidine anticancer agent, S-1 against oral cancer.

    Science.gov (United States)

    Harada, Koji; Ferdous, Tarannum; Ueyama, Yoshiya

    2017-08-01

    Oral cancer has been recognized as a tumor with low sensitivity to anticancer agents. However, introduction of S-1, an oral cancer agent is improving treatment outcome for patients with oral cancer. In addition, S-1, as a main drug for oral cancer treatment in Japan can be easily available for outpatients. In fact, S-1 exerts high therapeutic effects with acceptable side effects. Moreover, combined chemotherapy with S-1 shows higher efficacy than S-1 alone, and combined chemo-radiotherapy with S-1 exerts remarkable therapeutic effects. Furthermore, we should consider the combined therapy of S-1 and molecular targeting agents right now as these combinations were reportedly useful for oral cancer treatment. Here, we describe our findings related to S-1 that were obtained experimentally and clinically, and favorable therapeutic strategies with S-1 against oral cancer with bibliographic considerations.

  13. Cerebral collateral therapeutics in acute ischemic stroke: A randomized preclinical trial of four modulation strategies.

    Science.gov (United States)

    Beretta, Simone; Versace, Alessandro; Carone, Davide; Riva, Matteo; Dell'Era, Valentina; Cuccione, Elisa; Cai, Ruiyao; Monza, Laura; Pirovano, Silvia; Padovano, Giada; Stiro, Fabio; Presotto, Luca; Paternò, Giovanni; Rossi, Emanuela; Giussani, Carlo; Sganzerla, Erik P; Ferrarese, Carlo

    2017-10-01

    Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm 3 absolute mean difference; p Collateral therapeutics acutely increased cerebral perfusion in the medial (+40.8%; p collaterals is feasible and provides a tissue-saving effect in the hyperacute phase of ischemic stroke prior to recanalization therapy.

  14. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    Thomas L. Chenevert

    2002-10-01

    Full Text Available The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator of treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a non-volumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

  15. Crosstalk between Apoptosis and Autophagy: Molecular Mechanisms and Therapeutic Strategies in Cancer

    Directory of Open Access Journals (Sweden)

    Abdelouahid El-Khattouti

    2013-01-01

    Full Text Available Both apoptosis and autophagy are highly conserved processes that besides their role in the maintenance of the organismal and cellular homeostasis serve as a main target of tumor therapeutics. Although their important roles in the modulation of tumor therapeutic strategies have been widely reported, the molecular actions of both apoptosis and autophagy are counteracted by cancer protective mechanisms. While apoptosis is a tightly regulated process that is implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in lysosomal degradation and recycling of proteins and organelles, and thereby is considered an important survival/protective mechanism for cancer cells in response to metabolic stress or chemotherapy. Although the relationship between autophagy and cell death is very complicated and has not been characterized in detail, the molecular mechanisms that control this relationship are considered to be a relevant target for the development of a therapeutic strategy for tumor treatment. In this review, we focus on the molecular mechanisms of apoptosis, autophagy, and those of the crosstalk between apoptosis and autophagy in order to provide insight into the molecular mechanisms that may be essential for the balance between cell survival and death as well as their role as targets for the development of novel therapeutic approaches.

  16. Comparison of immunization strategies in geographical networks

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Aihara, Kazuyuki [Institute of Industrial Science, The University of Tokyo, Tokyo (Japan)] [ERATO Aihara Complexity Modelling Project, JST, Institute of Industrial Science, University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo, 153-8505 (Japan); Kim, Beom Jun, E-mail: beomjun@skku.ed [BK21 Physics Research Division and Department of Energy Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)] [Department of Computational Biology, School of Computer Science and Communication, Royal Institute of Technology, 100 44 Stockholm (Sweden)

    2009-10-12

    The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time, for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy, especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy, which may have potential applications for preventing the real epidemic spread.

  17. Comparison of immunization strategies in geographical networks

    International Nuclear Information System (INIS)

    Wang Bing; Aihara, Kazuyuki; Kim, Beom Jun

    2009-01-01

    The epidemic spread and immunizations in geographically embedded scale-free (SF) and Watts-Strogatz (WS) networks are numerically investigated. We make a realistic assumption that it takes time which we call the detection time, for a vertex to be identified as infected, and implement two different immunization strategies: one is based on connection neighbors (CN) of the infected vertex with the exact information of the network structure utilized and the other is based on spatial neighbors (SN) with only geographical distances taken into account. We find that the decrease of the detection time is crucial for a successful immunization in general. Simulation results show that for both SF networks and WS networks, the SN strategy always performs better than the CN strategy, especially for more heterogeneous SF networks at long detection time. The observation is verified by checking the number of the infected nodes being immunized. We found that in geographical space, the distance preferences in the network construction process and the geographically decaying infection rate are key factors that make the SN immunization strategy outperforms the CN strategy. It indicates that even in the absence of the full knowledge of network connectivity we can still stop the epidemic spread efficiently only by using geographical information as in the SN strategy, which may have potential applications for preventing the real epidemic spread.

  18. Ten national cyber security strategies: A comparison

    NARCIS (Netherlands)

    Luiijf, H.A.M.; Besseling, K. van; Spoelstra, M.; Graaf, P. de

    2013-01-01

    A number of nations developed and published a national cyber security strategy (NCSS). Most of them were published in the period 2009 - 2011. Despite the fact that each of these NCSS intends to address the cyber security threat, large differences exist between the NCSS approaches. This paper

  19. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury.

    Science.gov (United States)

    Pachori, Alok S; Melo, Luis G; Hart, Melanie L; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D; Stahl, Gregory L; Pratt, Richard E; Dzau, Victor J

    2004-08-17

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  20. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion tissue injury

    Science.gov (United States)

    Pachori, Alok S.; Melo, Luis G.; Hart, Melanie L.; Noiseux, Nicholas; Zhang, Lunan; Morello, Fulvio; Solomon, Scott D.; Stahl, Gregory L.; Pratt, Richard E.; Dzau, Victor J.

    2004-08-01

    Ischemia and reperfusion represent major mechanisms of tissue injury and organ failure. The timing of administration and the duration of action limit current treatment approaches using pharmacological agents. In this study, we have successfully developed a preemptive strategy for tissue protection using an adenoassociated vector system containing erythropoietin hypoxia response elements for ischemia-regulated expression of the therapeutic gene human heme-oxygenase-1 (hHO-1). We demonstrate that a single administration of this vector several weeks in advance of ischemia/reperfusion injury to multiple tissues such as heart, liver, and skeletal muscle yields rapid and timely induction of hHO-1 during ischemia that resulted in dramatic reduction in tissue damage. In addition, overexpression of therapeutic transgene prevented long-term pathological tissue remodeling and normalized tissue function. Application of this regulatable system using an endogenous physiological stimulus for expression of a therapeutic gene may be a feasible strategy for protecting tissues at risk of ischemia/reperfusion injury.

  1. Place of the brachytherapy in the therapeutic strategy of rhabdomyosarcomas of the nasogenian groove of children

    International Nuclear Information System (INIS)

    Breton-Callu, C.; Haie-Meder, C.; Oberlin, O.; Delapierre, M.; Gerbaulet, A.

    2000-01-01

    The brachytherapy in the treatment of rhabdomyosarcomas of the nasogenian groove has to be discussed when it exists a residual tumor after an initial chemotherapy and leads to good results, in term of local control. An advantage of the brachytherapy in comparison with external irradiation, in the treatment of children tumors, is the small size of the treated volume, that allows to decrease the aftereffects incidence. The brachytherapy comes in the frame of a therapeutic needing a multidisciplinary approach and a cooperation between surgeons, brachy-therapists and onco-pediatricians. (N.C.)

  2. A readily applicable strategy to convert peptides to peptoid-based therapeutics.

    Directory of Open Access Journals (Sweden)

    Minyoung Park

    Full Text Available Incorporation of unnatural amino acids and peptidomimetic residues into therapeutic peptides is highly efficacious and commonly employed, but generally requires laborious trial-and-error approaches. Previously, we demonstrated that C20 peptide has the potential to be a potential antiviral agent. Herein we report our attempt to improve the biological properties of this peptide by introducing peptidomimetics. Through combined alanine, proline, and sarcosine scans coupled with a competitive fluorescence polarization assay developed for identifying antiviral peptides, we enabled to pinpoint peptoid-tolerant peptide residues within C20 peptide. The synergistic benefits of combining these (and other commonly employed methods could lead to a easily applicable strategy for designing and refining therapeutically-attractive peptidomimetics.

  3. Promising Therapeutic Strategies for Mesenchymal Stem Cell-Based Cardiovascular Regeneration: From Cell Priming to Tissue Engineering

    Directory of Open Access Journals (Sweden)

    Seung Taek Ji

    2017-01-01

    Full Text Available The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

  4. Secular trends in mortality associated with new therapeutic strategies in surgical critical illness.

    Science.gov (United States)

    Hartl, Wolfgang H; Wolf, Hilde; Schneider, Christian P; Küchenhoff, Helmut; Jauch, Karl-Walter

    2007-10-01

    Since 1999 randomized controlled trials have shown that new therapeutic strategies, such as strict glycemic control, increased use of noninvasive ventilation and of lung-protective ventilation, and early goal-oriented shock therapy, may reduce mortality in selected groups of critically ill patients. Whether these benefits can be translated to a surgical clinical setting is unclear. We wanted to evaluate longitudinally the successive routine implementation of new therapeutic measures and its effect on postsurgical patients admitted to the intensive care unit. We performed a retrospective analysis on data collected prospectively from March 1, 1993 through February 28, 2005. A cohort of 1,802 consecutive cases requiring intensive care therapy for more than 4 days was analyzed. A significant decrease in mortality was observed in the last years of the study. With adjustment for relevant covariates, treatment after the implementation of new therapeutic strategies was identified as an independent factor linked with a reduced risk of death (odds ratio [OR] .518; 95% confidence interval [CI] .337-.796), whereas older age (OR 1.030; 95% CI 1.015-1.045), a high severity score on admission (OR 1.155; 95% CI 1.113-1.198) or during intensive care unit stay (OR 1.187; 95% CI 1.145-1.231), a high number of failing organs (OR 1.918; 95% CI 1.635-2.250), and peritonitis (OR 3.277; 95% CI 2.046-5.246) were independently associated with death. Implementing of a variety of new therapeutic measures into routine care of critically ill surgical patients was associated with improved survival after 2001.

  5. A comparison of WEC control strategies

    Energy Technology Data Exchange (ETDEWEB)

    Wilson, David G. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bacelli, Giorgio [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Coe, Ryan Geoffrey [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Bull, Diana L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Abdelkhalik, Ossama [Michigan Technological Univ., Houghton, MI (United States); Korde, Umesh A. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Robinett, Rush D. [Michigan Technological Univ., Houghton, MI (United States)

    2016-04-01

    The operation of Wave Energy Converter (WEC) devices can pose many challenging problems to the Water Power Community. A key research question is how to significantly improve the performance of these WEC devices through improving the control system design. This report summarizes an effort to analyze and improve the performance of WEC through the design and implementation of control systems. Controllers were selected to span the WEC control design space with the aim of building a more comprehensive understanding of different controller capabilities and requirements. To design and evaluate these control strategies, a model scale test-bed WEC was designed for both numerical and experimental testing (see Section 1.1). Seven control strategies have been developed and applied on a numerical model of the selected WEC. This model is capable of performing at a range of levels, spanning from a fully-linear realization to varying levels of nonlinearity. The details of this model and its ongoing development are described in Section 1.2.

  6. Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

    Science.gov (United States)

    de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

    2015-05-01

    HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

  7. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies.

    Science.gov (United States)

    Agnihotri, Sameer; Burrell, Kelly E; Wolf, Amparo; Jalali, Sharzhad; Hawkins, Cynthia; Rutka, James T; Zadeh, Gelareh

    2013-02-01

    Glioblastoma (GBM) is the most common and lethal primary brain tumor. Over the past few years tremendous genomic and proteomic characterization along with robust animal models of GBM have provided invaluable data that show that "GBM", although histologically indistinguishable from one another, are comprised of molecularly heterogenous diseases. In addition, robust pre-clinical models and a better understanding of the core pathways disrupted in GBM are providing a renewed optimism for novel strategies targeting these devastating tumors. Here, we summarize a brief history of the disease, our current molecular knowledge, lessons from animal models and emerging concepts of angiogenesis, invasion, and metabolism in GBM that may lend themselves to therapeutic targeting.

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

    Directory of Open Access Journals (Sweden)

    Christopher M. Mahoney

    2018-05-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  10. Therapeutic strategies in Sickle Cell Anemia: The past present and future.

    Science.gov (United States)

    Fernandes, Queenie

    2017-06-01

    Sickle Cell Anemia (SCA) was one of the first hemoglobinopathies to be discovered. It is distinguished by the mutation-induced expression of a sickle cell variant of hemoglobin (HbS) that triggers erythrocytes to take a characteristic sickled conformation. The complex physiopathology of the disease and its associated clinical complications has initiated multi-disciplinary research within its field. This review attempts to lay emphasis on the evolution, current standpoint and future scope of therapeutic strategies in SCA. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The Assessment of the Colo-rectal Polyps in Order to the New Diagnostic and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Raluca Diac Andreea

    2015-09-01

    Full Text Available Objective. Assessment of the histological and endoscopic features of the colo-rectal polyps is requered for the application of the new diagnostic and therapeutical strategies in the managment of the diminutive polyps.

  12. Encapsulation Strategies of Bacteriophage (Felix O1) for Oral Therapeutic Application.

    Science.gov (United States)

    Islam, Golam S; Wang, Qi; Sabour, Parviz M

    2018-01-01

    Due to emerging antibiotic-resistant strains among the pathogens, a variety of strategies, including therapeutic application of bacteriophages, have been suggested as a possible alternative to antibiotics in food animal production. As pathogen-specific biocontrol agents, bacteriophages are being studied intensively. Primarily their applications in the food industry and animal production have been recognized in the USA and Europe, for pathogens including Salmonella, Campylobacter, Escherichia coli, and Listeria. However, the viability of orally administered phage may rapidly reduce under the harsh acidic conditions of the stomach, presence of enzymes and bile. It is evident that bacteriophages, intended for phage therapy by oral administration, require efficient protection from the acidic environment of the stomach and should remain active in the animal's gastrointestinal tract where pathogen colonizes. Encapsulation of phages by spray drying or extrusion methods can protect phages from the simulated hostile gut conditions and help controlled release of phages to the digestive system when appropriate formulation strategy is implemented.

  13. Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

    Science.gov (United States)

    Simmons, Danielle A.

    2017-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

  14. The arsenal of pathogens and antivirulence therapeutic strategies for disarming them

    Directory of Open Access Journals (Sweden)

    Brannon JR

    2016-05-01

    Full Text Available John R Brannon,1 Maria Hadjifrangiskou1,21Division of Molecular Pathogenesis, Department of Pathology, Microbiology and Immunology, 2Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN, USAAbstract: Pathogens deploy an arsenal of virulence factors (VFs to establish themselves within their infectious niche. The discovery of antimicrobial compounds and their development into therapeutics has made a monumental impact on human and microbial populations. Although humans have used antimicrobials for medicinal and agricultural purposes, microorganism populations have developed and shared resistance mechanisms to persevere in the face of classical antimicrobials. However, a positive substitute is antivirulence therapy; antivirulence therapeutics prevent or interrupt an infection by counteracting a pathogen’s VFs. Their application can reduce the use of broad-spectrum antimicrobials and dampen the frequency with which resistant strains emerge. Here, we summarize the contribution of VFs to various acute and chronic infections. In correspondence with this, we provide an overview of the research and development of antivirulence strategies.Keywords: virulence factors, antivirulence therapeutics, biofilms, regulation, Escherichia coli, quorum sensing, persister cells

  15. Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

    Science.gov (United States)

    Gross, Christina; Berry-Kravis, Elizabeth M; Bassell, Gary J

    2012-01-01

    Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS. PMID:21796106

  16. Goethe's anxieties, depressive episodes and (self-)therapeutic strategies: a contribution to method integration in psychotherapy.

    Science.gov (United States)

    Holm-Hadulla, Rainer M

    2013-01-01

    In psychiatry and psychotherapy, abstract scientific principles need to be exemplified by narrative case reports to gain practical precision. Goethe was one of the most creative writers, productive scientists, and effective statesmen that ever lived. His descriptions of feelings, emotions, and mental states related to anxieties, depressive episodes, dysthymia, and creativity are unique in their phenomenological precision and richness. His life and work can thus serve as an excellent example enhancing our understanding of the relationship between anxiety, depression and creativity. Furthermore, he described (self-)therapeutic strategies that reinforce and refine modern views. Goethe's self-assessments in his works and letters, and the descriptions by others are analyzed under the perspective of current psychiatric classification. His therapeutic techniques and recommendations are compared with cognitive-behavioral, psychodynamic, and existential psychotherapy to amplify modern concepts of psychotherapy. From a scientific perspective, several distinctive depressive episodes can be diagnosed in Goethe's life. They were characterized by extended depressive moods, lack of drive, and loss of interest and self-esteem combined with social retreat. Goethe displayed diffuse and phobic anxieties as well as dysthymia. His (self-)therapeutic strategies were: (a) the systematic use of helping alliances, (b) behavioral techniques, (c) cognitive reflection on meanings and beliefs, (d) psychodynamic and psychoanalytic remembering, repeating, and working through, and (e) existential striving for self-actualization, social commitment, meaning, and creativity. In Goethe's life, creative incubation, illumination, and elaboration appear to have been associated with psychic instability and dysthymia, sometimes with depressive episodes in a clinical sense. On the one hand, his creative work was triggered by anxieties, dysthymia, and depressive moods. On the other hand, his creativity

  17. MSC transplantation: a promising therapeutic strategy to manage the onset and progression of diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Marcelo E Ezquer

    2012-01-01

    Full Text Available Currently, one of the main threats to public health is diabetes mellitus. Its most detrimental complication is diabetic nephropathy (DN, a clinical syndrome associated with kidney damage and an increased risk of cardiovascular disease. Irrespective of the type of diabetes, DN follows a well-known temporal course. The earliest detectable signs are microalbuminuria and histopathological changes including extracellular matrix deposition, glomerular basement membrane thickening, glomerular and mesangial expansion. Later on macroalbuminuria appears, followed by a progressive decline in glomerular filtration rate and the loss of glomerular podocytes, tubulointerstitial fibrosis, glomerulosclerosis and arteriolar hyalinosis. Tight glycemic and hypertension controls remain the key factors for preventing or arresting the progression of DN. Nevertheless, despite considerable educational effort to control the disease, a significant number of patients not only develop DN, but also progress to chronic kidney disease. Therefore, the availability of a strategy aimed to prevent, delay or revert DN would be highly desirable. In this article, we review the pathophysiological features of DN and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs. The perfect match between them, together with encouraging pre-clinical data available, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage DN onset and progression, not only because of the safety of this procedure, but mainly because of the renoprotective potential of MSCs.

  18. Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

    Science.gov (United States)

    Van Goethem, Alan; Yigit, Nurten; Moreno-Smith, Myrthala; Vasudevan, Sanjeev A; Barbieri, Eveline; Speleman, Frank; Shohet, Jason; Vandesompele, Jo; Van Maerken, Tom

    2017-08-22

    Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

  19. Neuroprotective and Therapeutic Strategies against Parkinson’s Disease: Recent Perspectives

    Directory of Open Access Journals (Sweden)

    Sumit Sarkar

    2016-06-01

    Full Text Available Parkinsonism is a progressive motor disease that affects 1.5 million Americans and is the second most common neurodegenerative disease after Alzheimer’s. Typical neuropathological features of Parkinson’s disease (PD include degeneration of dopaminergic neurons located in the pars compacta of the substantia nigra that project to the striatum (nigro-striatal pathway and depositions of cytoplasmic fibrillary inclusions (Lewy bodies which contain ubiquitin and α-synuclein. The cardinal motor signs of PD are tremors, rigidity, slow movement (bradykinesia, poor balance, and difficulty in walking (Parkinsonian gait. In addition to motor symptoms, non-motor symptoms that include autonomic and psychiatric as well as cognitive impairments are pressing issues that need to be addressed. Several different mechanisms play an important role in generation of Lewy bodies; endoplasmic reticulum (ER stress induced unfolded proteins, neuroinflammation and eventual loss of dopaminergic neurons in the substantia nigra of mid brain in PD. Moreover, these diverse processes that result in PD make modeling of the disease and evaluation of therapeutics against this devastating disease difficult. Here, we will discuss diverse mechanisms that are involved in PD, neuroprotective and therapeutic strategies currently in clinical trial or in preclinical stages, and impart views about strategies that are promising to mitigate PD pathology.

  20. Strategies for implementing and sustaining therapeutic lifestyle changes as part of hypertension management in African Americans.

    Science.gov (United States)

    Scisney-Matlock, Margaret; Bosworth, Hayden B; Giger, Joyce Newman; Strickland, Ora L; Harrison, R Van; Coverson, Dorothy; Shah, Nirav R; Dennison, Cheryl R; Dunbar-Jacob, Jacqueline M; Jones, Loretta; Ogedegbe, Gbenga; Batts-Turner, Marian L; Jamerson, Kenneth A

    2009-05-01

    African Americans with high blood pressure (BP) can benefit greatly from therapeutic lifestyle changes (TLC) such as diet modification, physical activity, and weight management. However, they and their health care providers face many barriers in modifying health behaviors. A multidisciplinary panel synthesized the scientific data on TLC in African Americans for efficacy in improving BP control, barriers to behavioral change, and strategies to overcome those barriers. Therapeutic lifestyle change interventions should emphasize patient self-management, supported by providers, family, and the community. Interventions should be tailored to an individual's cultural heritage, beliefs, and behavioral norms. Simultaneously targeting multiple factors that impede BP control will maximize the likelihood of success. The panel cited limited progress with integrating the Dietary Approaches to Stop Hypertension (DASH) eating plan into the African American diet as an example of the need for more strategically developed interventions. Culturally sensitive instruments to assess impact will help guide improved provision of TLC in special populations. The challenge of improving BP control in African Americans and delivery of hypertension care requires changes at the health system and public policy levels. At the patient level, culturally sensitive interventions that apply the strategies described and optimize community involvement will advance TLC in African Americans with high BP.

  1. Targeting lipid metabolism of cancer cells: A promising therapeutic strategy for cancer.

    Science.gov (United States)

    Liu, Qiuping; Luo, Qing; Halim, Alexander; Song, Guanbin

    2017-08-10

    One of the most important metabolic hallmarks of cancer cells is deregulation of lipid metabolism. In addition, enhancing de novo fatty acid (FA) synthesis, increasing lipid uptake and lipolysis have also been considered as means of FA acquisition in cancer cells. FAs are involved in various aspects of tumourigenesis and tumour progression. Therefore, targeting lipid metabolism is a promising therapeutic strategy for human cancer. Recent studies have shown that reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid signals during cancer progression. Moreover, accumulation of lipid droplets in cancer cells acts as a pivotal adaptive response to harmful conditions. Here, we provide a brief review of the crucial roles of FA metabolism in cancer development, and place emphasis on FA origin, utilization and storage in cancer cells. Understanding the regulation of lipid metabolism in cancer cells has important implications for exploring a new therapeutic strategy for management and treatment of cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Cell-based therapeutic strategies for replacement and preservation in retinal degenerative diseases

    Science.gov (United States)

    Jones, Melissa K.; Lu, Bin; Girman, Sergey; Wang, Shaomei

    2017-01-01

    Cell-based therapeutics offer diverse options for treating retinal degenerative diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). AMD is characterized by both genetic and environmental risks factors, whereas RP is mainly a monogenic disorder. Though treatments exist for some patients with neovascular AMD, a majority of retinal degenerative patients have no effective therapeutics, thus indicating a need for universal therapies to target diverse patient populations. Two main cell-based mechanistic approaches are being tested in clinical trials. Replacement therapies utilize cell-derived retinal pigment epithelial (RPE) cells to supplant lost or defective host RPE cells. These cells are similar in morphology and function to native RPE cells and can potentially supplant the responsibilities of RPE in vivo. Preservation therapies utilize supportive cells to aid in visual function and photoreceptor preservation partially by neurotrophic mechanisms. The goal of preservation strategies is to halt or slow the progression of disease and maintain remaining visual function. A number of clinical trials are testing the safety of replacement and preservation cell therapies in patients; however, measures of efficacy will need to be further evaluated. In addition, a number of prevailing concerns with regards to the immune-related response, longevity, and functionality of the grafted cells will need to be addressed in future trials. This review will summarize the current status of cell-based preclinical and clinical studies with a focus on replacement and preservation strategies and the obstacles that remain regarding these types of treatments. PMID:28111323

  3. Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Alana M. Horowitz

    2017-08-01

    Full Text Available Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

  4. Emerging Strategies for Developing Next-Generation Protein Therapeutics for Cancer Treatment.

    Science.gov (United States)

    Kintzing, James R; Filsinger Interrante, Maria V; Cochran, Jennifer R

    2016-12-01

    Protein-based therapeutics have been revolutionizing the oncology space since they first appeared in the clinic two decades ago. Unlike traditional small-molecule chemotherapeutics, protein biologics promote active targeting of cancer cells by binding to cell-surface receptors and other markers specifically associated with or overexpressed on tumors versus healthy tissue. While the first approved cancer biologics were monoclonal antibodies, the burgeoning field of protein engineering is spawning research on an expanded range of protein formats and modifications that allow tuning of properties such as target-binding affinity, serum half-life, stability, and immunogenicity. In this review we highlight some of these strategies and provide examples of modified and engineered proteins under development as preclinical and clinical-stage drug candidates for the treatment of cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

    Directory of Open Access Journals (Sweden)

    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  6. Interventional and surgical therapeutic strategies for pulmonary arterial hypertension: Beyond palliative treatments.

    Science.gov (United States)

    Sandoval, Julio; Gomez-Arroyo, Jose; Gaspar, Jorge; Pulido-Zamudio, Tomas

    2015-10-01

    Despite significant advances in pharmacological treatments, pulmonary arterial hypertension remains an incurable disease with an unreasonably high morbidity and mortality. Although specific pharmacotherapies have shifted the survival curves of patients and improved exercise endurance as well as quality of life, it is also true that these pharmacological interventions are not always accessible (particularly in developing countries) and, perhaps most importantly, not all patients respond similarly to these drugs. Furthermore, many patients will continue to deteriorate and will eventually require an additional, non-pharmacological, intervention. In this review we analyze the role of atrial septostomy and Potts anastomosis in the management of patients with pulmonary arterial hypertension, we summarize the current worldwide clinical experience (case reports and case series), and discuss why these interventional/surgical strategies might have a therapeutic role beyond that of a "bridge" to transplantation. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  7. Radical surgery after chemotherapy: a new therapeutic strategy to envision in grade II glioma.

    Science.gov (United States)

    Duffau, Hugues; Taillandier, Luc; Capelle, Laurent

    2006-11-01

    While surgery is proned in low-grade glioma (LGG), the invasion of functional areas frequently prevents a complete resection. We report the first case of a patient operated on for a left frontal LGG, diagnosed because of seizures, with partial resection due to an invasion of the controlateral hemisphere. Chemotherapy enabled a regression of this controlateral extension. Postchemotherapy surgery performed with intraoperative functional mapping then allowed a complete resection, without sequelae. The patient has a normal socio-professional life, with no seizure. No other treatment was given. There was no recurrence, with a follow-up of 2 years since the second surgery (3.5 years since the first symptom). We propose a new therapeutic strategy in unresectable LGG, with preoperative chemotherapy, to make a radical surgery possible in a second step, while preserving the quality of life.

  8. Altered cortical GABA neurotransmission in schizophrenia: insights into novel therapeutic strategies.

    Science.gov (United States)

    Stan, Ana D; Lewis, David A

    2012-06-01

    Altered markers of cortical GABA neurotransmission are among the most consistently observed abnormalities in postmortem studies of schizophrenia. The altered markers are particularly evident between the chandelier class of GABA neurons and their synaptic targets, the axon initial segment (AIS) of pyramidal neurons. For example, in the dorsolateral prefrontal cortex of subjects with schizophrenia immunoreactivity for the GABA membrane transporter is decreased in presynaptic chandelier neuron axon terminals, whereas immunoreactivity for the GABAA receptor α2 subunit is increased in postsynaptic AIS. Both of these molecular changes appear to be compensatory responses to a presynaptic deficit in GABA synthesis, and thus could represent targets for novel therapeutic strategies intended to augment the brain's own compensatory mechanisms. Recent findings that GABA inputs from neocortical chandelier neurons can be powerfully excitatory provide new ideas about the role of these neurons in the pathophysiology of cortical dysfunction in schizophrenia, and consequently in the design of pharmacological interventions.

  9. Advanced Therapeutic Strategies for Chronic Lung Disease Using Nanoparticle-Based Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ji Young Yhee

    2016-09-01

    Full Text Available Chronic lung diseases include a variety of obstinate and fatal diseases, including asthma, chronic obstructive pulmonary disease (COPD, cystic fibrosis (CF, idiopathic pulmonary fibrosis (IPF, and lung cancers. Pharmacotherapy is important for the treatment of chronic lung diseases, and current progress in nanoparticles offers great potential as an advanced strategy for drug delivery. Based on their biophysical properties, nanoparticles have shown improved pharmacokinetics of therapeutics and controlled drug delivery, gaining great attention. Herein, we will review the nanoparticle-based drug delivery system for the treatment of chronic lung diseases. Various types of nanoparticles will be introduced, and recent innovative efforts to utilize the nanoparticles as novel drug carriers for the effective treatment of chronic lung diseases will also be discussed.

  10. A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

    Directory of Open Access Journals (Sweden)

    Belayev Ludmila

    2016-01-01

    Full Text Available Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3 complexed to human albumin (DHA-Alb is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.

  11. Nanotechnological strategies for nerve growth factor delivery: Therapeutic implications in Alzheimer's disease.

    Science.gov (United States)

    Faustino, Célia; Rijo, Patrícia; Reis, Catarina Pinto

    2017-06-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-β peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications.

    Science.gov (United States)

    Liu, Chang; Zhang, Li; Liu, Hao; Cheng, Kun

    2017-11-28

    The CRISPR-Cas9 genome-editing system is a part of the adaptive immune system in archaea and bacteria to defend against invasive nucleic acids from phages and plasmids. The single guide RNA (sgRNA) of the system recognizes its target sequence in the genome, and the Cas9 nuclease of the system acts as a pair of scissors to cleave the double strands of DNA. Since its discovery, CRISPR-Cas9 has become the most robust platform for genome engineering in eukaryotic cells. Recently, the CRISPR-Cas9 system has triggered enormous interest in therapeutic applications. CRISPR-Cas9 can be applied to correct disease-causing gene mutations or engineer T cells for cancer immunotherapy. The first clinical trial using the CRISPR-Cas9 technology was conducted in 2016. Despite the great promise of the CRISPR-Cas9 technology, several challenges remain to be tackled before its successful applications for human patients. The greatest challenge is the safe and efficient delivery of the CRISPR-Cas9 genome-editing system to target cells in human body. In this review, we will introduce the molecular mechanism and different strategies to edit genes using the CRISPR-Cas9 system. We will then highlight the current systems that have been developed to deliver CRISPR-Cas9 in vitro and in vivo for various therapeutic purposes. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Neuropathic Pain and Lung Delivery of Nanoparticulate Drugs: An Emerging Novel Therapeutic Strategy.

    Science.gov (United States)

    Islam, Nazrul; Abbas, Muzaffar; Rahman, Shafiqur

    2017-01-01

    Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervous system in active form. These therapeutic agents also require daily treatment regimen that is inconvenient and potentially impact patient compliance. Application of nanoparticulate drugs for enhanced delivery system has been explored extensively in the last decades. Pulmonary delivery of nanomedicines for the management of various diseases has become an emerging treatment strategy that ensures the targeted delivery of drugs both for systemic and local effects with low dose and limited adverse effects. To the best of our knowledge, there are no inhaled drug products available on market for the treatment of neuropathic pain. The advantages of delivering therapeutics into deep lungs include non-invasive drug delivery, higher bioavailability with low dose, lower systemic toxicity, and potentially greater blood-brain barrier penetration. This review discusses and highlights the important issues on the application of emerging nanoparticulate lung delivery of drugs for the effective treatment of neuropathic pain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Oncogenic Human Papillomavirus: Application of CRISPR/Cas9 Therapeutic Strategies for Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Shuai Zhen

    2017-12-01

    Full Text Available Oncogenic human papillomaviruses (HPVs cause different types of cancer especially cervical cancer. HPV-associated carcinogenesis provides a classical model system for clustered regularly interspaced short palindromic repeats (CRISPR/Cas9 based cancer therapies since the viral oncogenes E6 and E7 are exclusively expressed in cancerous cells. Sequence-specific gene knockdown/knockout using CRISPR/Cas9 shows promise as a novel therapeutic approach for the treatment of a variety of diseases that currently lack effective treatments. However, CRISPR/Cas9-based targeting therapy requires further validation of its efficacy in vitro and in vivo to eliminate the potential off-target effects, necessitates verification of the delivery vehicles and the combinatory use of conventional therapies with CRISPR/Cas9 to ensure the feasibility and safety. In this review we discuss the potential of combining CRISPR/Cas9 with other treatment options as therapies for oncogenic HPVs-associated carcinogenesis. and present our assessment of the promising path to the development of CRISPR/Cas9 therapeutic strategies for clinical settings.

  15. TU-EF-210-00: Therapeutic Strategies and Image Guidance

    International Nuclear Information System (INIS)

    2015-01-01

    The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare

  16. TU-EF-210-00: Therapeutic Strategies and Image Guidance

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    The use of therapeutic ultrasound to provide targeted therapy is an active research area that has a broad application scope. The invited talks in this session will address currently implemented strategies and protocols for both hyperthermia and ablation applications using therapeutic ultrasound. The role of both ultrasound and MRI in the monitoring and assessment of these therapies will be explored in both pre-clinical and clinical applications. Katherine Ferrara: High Intensity Focused Ultrasound, Drug Delivery, and Immunotherapy Rajiv Chopra: Translating Localized Doxorubicin Delivery to Pediatric Oncology using MRI-guided HIFU Elisa Konofagou: Real-time Ablation Monitoring and Lesion Quantification using Harmonic Motion Imaging Keyvan Farahani: AAPM Task Groups in Interventional Ultrasound Imaging and Therapy Learning Objectives: Understand the role of ultrasound in localized drug delivery and the effects of immunotherapy when used in conjunction with ultrasound therapy. Understand potential targeted drug delivery clinical applications including pediatric oncology. Understand the technical requirements for performing targeted drug delivery. Understand how radiation-force approaches can be used to both monitor and assess high intensity focused ultrasound ablation therapy. Understand the role of AAPM task groups in ultrasound imaging and therapies. Chopra: Funding from Cancer Prevention and Research Initiative of Texas (CPRIT), Award R1308 Evelyn and M.R. Hudson Foundation; Research Support from Research Contract with Philips Healthcare; COI are Co-founder of FUS Instruments Inc Ferrara: Supported by NIH, UCDavis and California (CIRM and BHCE) Farahani: In-kind research support from Philips Healthcare.

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

    Science.gov (United States)

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

    2016-06-02

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

  18. IL8-CXCR2 pathway inhibition as a therapeutic strategy against MDS and AML stem cells.

    Science.gov (United States)

    Schinke, Carolina; Giricz, Orsolya; Li, Weijuan; Shastri, Aditi; Gordon, Shanisha; Barreyro, Laura; Barreryo, Laura; Bhagat, Tushar; Bhattacharyya, Sanchari; Ramachandra, Nandini; Bartenstein, Matthias; Pellagatti, Andrea; Boultwood, Jacqueline; Wickrema, Amittha; Yu, Yiting; Will, Britta; Wei, Sheng; Steidl, Ulrich; Verma, Amit

    2015-05-14

    Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Novel therapeutic targets against preleukemic stem cells need to be identified for potentially curative strategies. We conducted parallel transcriptional analysis of highly fractionated stem and progenitor populations in MDS, AML, and control samples and found interleukin 8 (IL8) to be consistently overexpressed in patient samples. The receptor for IL8, CXCR2, was also significantly increased in MDS CD34(+) cells from a large clinical cohort and was predictive of increased transfusion dependence. High CXCR2 expression was also an adverse prognostic factor in The Cancer Genome Atlas AML cohort, further pointing to the critical role of the IL8-CXCR2 axis in AML/MDS. Functionally, CXCR2 inhibition by knockdown and pharmacologic approaches led to a significant reduction in proliferation in several leukemic cell lines and primary MDS/AML samples via induction of G0/G1 cell cycle arrest. Importantly, inhibition of CXCR2 selectively inhibited immature hematopoietic stem cells from MDS/AML samples without an effect on healthy controls. CXCR2 knockdown also impaired leukemic growth in vivo. Together, these studies demonstrate that the IL8 receptor CXCR2 is an adverse prognostic factor in MDS/AML and is a potential therapeutic target against immature leukemic stem cell-enriched cell fractions in MDS and AML. © 2015 by The American Society of Hematology.

  19. An evaluation of oligonucleotide-based therapeutic strategies for polyQ diseases

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    Fiszer Agnieszka

    2012-03-01

    Full Text Available Abstract Background RNA interference (RNAi and antisense strategies provide experimental therapeutic agents for numerous diseases, including polyglutamine (polyQ disorders caused by CAG repeat expansion. We compared the potential of different oligonucleotide-based strategies for silencing the genes responsible for several polyQ diseases, including Huntington's disease and two spinocerebellar ataxias, type 1 and type 3. The strategies included nonallele-selective gene silencing, gene replacement, allele-selective SNP targeting and CAG repeat targeting. Results Using the patient-derived cell culture models of polyQ diseases, we tested various siRNAs, and antisense reagents and assessed their silencing efficiency and allele selectivity. We showed considerable allele discrimination by several SNP targeting siRNAs based on a weak G-G or G-U pairing with normal allele and strong G-C pairing with mutant allele at the site of RISC-induced cleavage. Among the CAG repeat targeting reagents the strongest allele discrimination is achieved by miRNA-like functioning reagents that bind to their targets and inhibit their translation without substantial target cleavage. Also, morpholino analog performs well in mutant and normal allele discrimination but its efficient delivery to cells at low effective concentration still remains a challenge. Conclusions Using three cellular models of polyQ diseases and the same experimental setup we directly compared the performance of different oligonucleotide-based treatment strategies that are currently under development. Based on the results obtained by us and others we discussed the advantages and drawbacks of these strategies considering them from several different perspectives. The strategy aimed at nonallele-selective inhibiting of causative gene expression by targeting specific sequence of the implicated gene is the easiest to implement but relevant benefits are still uncertain. The gene replacement strategy that

  20. A therapeutic HIV vaccine using coxsackie-HIV recombinants: a possible new strategy.

    Science.gov (United States)

    Halim, S S; Collins, D N; Ramsingh, A I

    2000-10-10

    The ultimate goal in the treatment of HIV-infected persons is to prevent disease progression. A strategy to accomplish this goal is to use chemotherapy to reduce viral load followed by immunotherapy to stimulate HIV-specific immune responses that are observed in long-term asymptomatic individuals. An effective, live, recombinant virus, expressing HIV sequences, would be capable of inducing both CTL and CD4(+) helper T cell responses. To accomplish these goals, the viral vector must be immunogenic yet retain its avirulent phenotype in a T cell-deficient host. We have identified a coxsackievirus variant, CB4-P, that can induce protective immunity against a virulent variant. In addition, the CB4-P variant remains avirulent in mice lacking CD4(+) helper T cells, suggesting that CB4-P may be uniquely suited as a viral vector for a therapeutic HIV vaccine. Two strategies designed to elicit CTL and CD4(+) helper T cell responses were used to construct CB4-P/HIV recombinants. Recombinant viruses were viable, genetically stable, and retained the avirulent phenotype of the parental virus. In designing a viral vector for vaccine development, an issue that must be addressed is whether preexisting immunity to the vector would affect subsequent administration of the recombinant virus. Using a test recombinant, we showed that prior exposure to the parental CB4-P virus did not affect the ability of the recombinant to induce a CD4(+) T cell response against the foreign sequence. The results suggest that a "cocktail" of coxsackie/HIV recombinants may be useful as a therapeutic HIV vaccine.

  1. Targeting the renin-angiotensin system as novel therapeutic strategy for pulmonary diseases.

    Science.gov (United States)

    Tan, Wan Shun Daniel; Liao, Wupeng; Zhou, Shuo; Mei, Dan; Wong, Wai-Shiu Fred

    2017-12-27

    The renin-angiotensin system (RAS) plays a major role in regulating electrolyte balance and blood pressure. RAS has also been implicated in the regulation of inflammation, proliferation and fibrosis in pulmonary diseases such as asthma, acute lung injury (ALI), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH). Current therapeutics suffer from some drawbacks like steroid resistance, limited efficacies and side effects. Novel intervention is definitely needed to offer optimal therapeutic strategy and clinical outcome. This review compiles and analyses recent investigations targeting RAS for the treatment of inflammatory lung diseases. Inhibition of the upstream angiotensin (Ang) I/Ang II/angiotensin receptor type 1 (AT 1 R) pathway and activation of the downstream angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor pathway are two feasible strategies demonstrating efficacies in various pulmonary disease models. More recent studies favor the development of targeting the downstream ACE2/Ang (1-7)/Mas receptor pathway, in which diminazene aceturate, an ACE2 activator, GSK2586881, a recombinant ACE2, and AV0991, a Mas receptor agonist, showed much potential for further development. As the pathogenesis of pulmonary diseases is so complex that RAS modulation may be used alone or in combination with existing drugs like corticosteroids, pirfenidone/nintedanib or endothelin receptor antagonists for different pulmonary diseases. Personalized medicine through genetic screening and phenotyping for angiotensinogen or ACE would aid treatment especially for non-responsive patients. This review serves to provide an update on the latest development in the field of RAS targeting for pulmonary diseases, and offer some insights into future direction. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

    Science.gov (United States)

    Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

    2017-08-01

    Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  3. Risk perception of diagnostic and therapeutic radiological applications. Comparison of experts and the public

    Energy Technology Data Exchange (ETDEWEB)

    Arranz, L. [Hospital Ramon y Cajal, Madrid (Spain); Macias, M.T. [CSIC, Madrid (Spain); Prades, A.; Sola, R. [Ciemat, Madrid (Spain); Martinez-Arias, R. [Universidad Complutense, Madrid (Spain)

    2000-05-01

    Recent research has found many differences between experts and lay people in judgements of radiological risks. However, most of these studies were carried out on experts from nuclear power plants, regulatory bodies etc. This paper analyses the differences among several groups of 'experts' coming from the Health area and the lay people. A survey was designed to assess the perceived seriousness of seven diagnostic and therapeutic applications: conventional diagnostic radiology, computed tomography, chemotherapy, ecography examinations, radiotherapy, and diagnostic and therapeutic nuclear medicine. The questionnaire was distributed to samples of experts (professionals exposed to ionizing radiations, and other health professionals), and outpatients. All samples were selected from ten countries: Argentine, Brazil, Colombia, Cuba, Ecuador, Mexico, Panama, Peru, Uruguay, and Spain, thanks to the collaboration of the different National Radioprotection Societies of the above mentioned countries, and of other concerned professionals (in case they didn't have any association at the time). The following comparisons will be presented: 1) Differences between experts' and the public; 2) differences among several groups of 'experts'; 3) within the 'expert' sample, differences between perceived seriousness as a patient and as a professional at risk; 4) within the public sample, individual differences related to some socio-demographic variables. A cross-cultural analysis of the above mentioned comparisons will also be carried out. (author)

  4. Risk perception of diagnostic and therapeutic radiological applications. Comparison of experts and the public

    International Nuclear Information System (INIS)

    Arranz, L.; Macias, M.T.; Prades, A.; Sola, R.; Martinez-Arias, R.

    2000-01-01

    Recent research has found many differences between experts and lay people in judgements of radiological risks. However, most of these studies were carried out on experts from nuclear power plants, regulatory bodies etc. This paper analyses the differences among several groups of 'experts' coming from the Health area and the lay people. A survey was designed to assess the perceived seriousness of seven diagnostic and therapeutic applications: conventional diagnostic radiology, computed tomography, chemotherapy, ecography examinations, radiotherapy, and diagnostic and therapeutic nuclear medicine. The questionnaire was distributed to samples of experts (professionals exposed to ionizing radiations, and other health professionals), and outpatients. All samples were selected from ten countries: Argentine, Brazil, Colombia, Cuba, Ecuador, Mexico, Panama, Peru, Uruguay, and Spain, thanks to the collaboration of the different National Radioprotection Societies of the above mentioned countries, and of other concerned professionals (in case they didn't have any association at the time). The following comparisons will be presented: 1) Differences between experts' and the public; 2) differences among several groups of 'experts'; 3) within the 'expert' sample, differences between perceived seriousness as a patient and as a professional at risk; 4) within the public sample, individual differences related to some socio-demographic variables. A cross-cultural analysis of the above mentioned comparisons will also be carried out. (author)

  5. Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

    International Nuclear Information System (INIS)

    Obermiller, Patrice S; Tait, David L; Holt, Jeffrey T

    2000-01-01

    Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

  6. Novel therapeutic strategies to target leukemic cells that hijack compartmentalized continuous hematopoietic stem cell niches.

    Science.gov (United States)

    Hira, Vashendriya V V; Van Noorden, Cornelis J F; Carraway, Hetty E; Maciejewski, Jaroslaw P; Molenaar, Remco J

    2017-08-01

    Acute myeloid leukemia and acute lymphoblastic leukemia cells hijack hematopoietic stem cell (HSC) niches in the bone marrow and become leukemic stem cells (LSCs) at the expense of normal HSCs. LSCs are quiescent and resistant to chemotherapy and can cause relapse of the disease. HSCs in niches are needed to generate blood cell precursors that are committed to unilineage differentiation and eventually production of mature blood cells, including red blood cells, megakaryocytes, myeloid cells and lymphocytes. Thus far, three types of HSC niches are recognized: endosteal, reticular and perivascular niches. However, we argue here that there is only one type of HSC niche, which consists of a periarteriolar compartment and a perisinusoidal compartment. In the periarteriolar compartment, hypoxia and low levels of reactive oxygen species preserve the HSC pool. In the perisinusoidal compartment, hypoxia in combination with higher levels of reactive oxygen species enables proliferation of progenitor cells and their mobilization into the circulation. Because HSC niches offer protection to LSCs against chemotherapy, we review novel therapeutic strategies to inhibit homing of LSCs in niches for the prevention of dedifferentiation of leukemic cells into LSCs and to stimulate migration of leukemic cells out of niches. These strategies enhance differentiation and proliferation and thus sensitize leukemic cells to chemotherapy. Finally, we list clinical trials of therapies that tackle LSCs in HSC niches to circumvent their protection against chemotherapy. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

    Directory of Open Access Journals (Sweden)

    Van Lint Carine

    2009-12-01

    Full Text Available Abstract The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway.

  8. RNA interference-based therapeutics: new strategies to fight infectious disease.

    Science.gov (United States)

    López-Fraga, M; Wright, N; Jiménez, A

    2008-12-01

    For many years, there has been an ongoing search for new compounds that can selectively alter gene expression as a new way to treat human disease by addressing targets that are otherwise "undruggable" with traditional pharmaceutical approaches involving small molecules or proteins. RNA interference (RNAi) strategies have raised a lot of attention and several compounds are currently being tested in clinical trials. Viruses are the obvious target for RNAi-therapy, as most are difficult to treat with conventional drugs, they become rapidly resistant to drug treatment and their genes differ substantially from human genes, minimizing side effects. Antisense strategy offers very high target specificity, i.e., any viral sequence could potentially be targeted using the complementary oligonucleotide sequence. Consequently, new antisense-based therapeutics have the potential to lead a revolution in the anti-infective drug development field. Additionally, the relatively short turnaround for efficacy testing of potential RNAi molecules and that any pathogen is theoretically amenable to rapid targeting, make them invaluable tools for treating a wide range of diseases. This review will focus on some of the current efforts to treat infectious disease with RNAi-based therapies and some of the obstacles that have appeared on the road to successful clinical intervention.

  9. Modulation of mitochondrial bioenergetics as a therapeutic strategy in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Isaac G Onyango

    2018-01-01

    Full Text Available Alzheimer's disease (AD is an increasingly pressing worldwide public-health, social, political and economic concern. Despite significant investment in multiple traditional therapeutic strategies that have achieved success in preclinical models addressing the pathological hallmarks of the disease, these efforts have not translated into any effective disease-modifying therapies. This could be because interventions are being tested too late in the disease process. While existing therapies provide symptomatic and clinical benefit, they do not fully address the molecular abnormalities that occur in AD neurons. The pathophysiology of AD is complex; mitochondrial bioenergetic deficits and brain hypometabolism coupled with increased mitochondrial oxidative stress are antecedent and potentially play a causal role in the disease pathogenesis. Dysfunctional mitochondria accumulate from the combination of impaired mitophagy, which can also induce injurious inflammatory responses, and inadequate neuronal mitochondrial biogenesis. Altering the metabolic capacity of the brain by modulating/potentiating its mitochondrial bioenergetics may be a strategy for disease prevention and treatment. We present insights into the mechanisms of mitochondrial dysfunction in AD brain as well as an overview of emerging treatments with the potential to prevent, delay or reverse the neurodegenerative process by targeting mitochondria.

  10. Therapeutic strategy for granulomatous lobular mastitis: a clinicopathological study of 12 patients.

    Science.gov (United States)

    Akahane, Kazuhisa; Tsunoda, Nobuyuki; Kato, Masamichi; Noda, Sumiyo; Shimoyama, Yoshie; Ishigakis, Satoko; Satake, Hiroko; Nakamura, Shigeo; Nagino, Masato

    2013-08-01

    Granulomatous lobular mastitis (GLM) is a rare inflammatory pseudotumor. No therapeutic modality for this disease has been established because of its rarity. The purpose of this study is to evaluate the treatment strategies of GLM. Twelve women who met the histological criteria for GLM were retrospectively studied. The clinical data and the presentation, histopathology, and management of the disease were analyzed by reviewing the patients' medical records. The diagnosis of GLM was confirmed histologically by core needle biopsy in 9 cases, by vacuum-assisted biopsy in 2 cases, and by excisional biopsy in 1 case. Ten patients received corticosteroid treatment and another two patients were treated with local excision or incision and drainage. The median initial dosage of corticosteroid (Prednisolone) was 30 mg/day (range: 15-60 mg/day), and the dosages were tapered according to improvement. The median duration of corticosteroid treatment was 5 months (range: 1-12 months). The median follow-up period was 22 months (range: 6-104 months), and no patient treated with corticosteroid demonstrated recurrence. However, patients treated with excision or incision and drainage had recurrences. These results suggest that steroid treatment may be the first choice in treatment strategies for GLM.

  11. Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

    Directory of Open Access Journals (Sweden)

    Zoey Harris

    2016-10-01

    Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

  12. Therapeutic Strategy for Targeting Aggressive Malignant Gliomas by Disrupting Their Energy Balance.

    Science.gov (United States)

    Hegazy, Ahmed M; Yamada, Daisuke; Kobayashi, Masahiko; Kohno, Susumu; Ueno, Masaya; Ali, Mohamed A E; Ohta, Kumiko; Tadokoro, Yuko; Ino, Yasushi; Todo, Tomoki; Soga, Tomoyoshi; Takahashi, Chiaki; Hirao, Atsushi

    2016-10-07

    Although abnormal metabolic regulation is a critical determinant of cancer cell behavior, it is still unclear how an altered balance between ATP production and consumption contributes to malignancy. Here we show that disruption of this energy balance efficiently suppresses aggressive malignant gliomas driven by mammalian target of rapamycin complex 1 (mTORC1) hyperactivation. In a mouse glioma model, mTORC1 hyperactivation induced by conditional Tsc1 deletion increased numbers of glioma-initiating cells (GICs) in vitro and in vivo Metabolic analysis revealed that mTORC1 hyperactivation enhanced mitochondrial biogenesis, as evidenced by elevations in oxygen consumption rate and ATP production. Inhibition of mitochondrial ATP synthetase was more effective in repressing sphere formation by Tsc1-deficient glioma cells than that by Tsc1-competent glioma cells, indicating a crucial function for mitochondrial bioenergetic capacity in GIC expansion. To translate this observation into the development of novel therapeutics targeting malignant gliomas, we screened drug libraries for small molecule compounds showing greater efficacy in inhibiting the proliferation/survival of Tsc1-deficient cells compared with controls. We identified several compounds able to preferentially inhibit mitochondrial activity, dramatically reducing ATP levels and blocking glioma sphere formation. In human patient-derived glioma cells, nigericin, which reportedly suppresses cancer stem cell properties, induced AMPK phosphorylation that was associated with mTORC1 inactivation and induction of autophagy and led to a marked decrease in sphere formation with loss of GIC marker expression. Furthermore, malignant characteristics of human glioma cells were markedly suppressed by nigericin treatment in vivo Thus, targeting mTORC1-driven processes, particularly those involved in maintaining a cancer cell's energy balance, may be an effective therapeutic strategy for glioma patients. © 2016 by The American

  13. MicroRNA modulation combined with sunitinib as a novel therapeutic strategy for pancreatic cancer

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    Passadouro M

    2014-07-01

    Full Text Available Marta Passadouro,1,2 Maria C Pedroso de Lima,1,2 Henrique Faneca11Center for Neuroscience and Cell Biology, 2Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, PortugalAbstract: Pancreatic ductal adenocarcinoma (PDAC is a highly aggressive and mortal cancer, characterized by a set of known mutations, invasive features, and aberrant microRNA expression that have been associated with hallmark malignant properties of PDAC. The lack of effective PDAC treatment options prompted us to investigate whether microRNAs would constitute promising therapeutic targets toward the generation of a gene therapy approach with clinical significance for this disease. In this work, we show that the developed human serum albumin–1-palmitoyl-2-oleoyl-sn-glycero-3-ethylphosphocholine:cholesterol/anti-microRNA oligonucleotides (+/– (4/1 nanosystem exhibits the ability to efficiently deliver anti-microRNA oligonucleotides targeting the overexpressed microRNAs miR-21, miR-221, miR-222, and miR-10 in PDCA cells, promoting an almost complete abolishment of microRNA expression. Silencing of these microRNAs resulted in a significant increase in the levels of their targets. Moreover, the combination of microRNA silencing, namely miR-21, with low amounts of the chemotherapeutic drug sunitinib resulted in a strong and synergistic antitumor effect, showing that this combined strategy could be of great importance for therapeutic application in PDAC. Keywords: pancreatic cancer gene therapy, anti-microRNAs oligonucleotides, delivery nanosystems, albumin-associated lipoplexes

  14. Potential antitumor therapeutic strategies of human amniotic membrane and amniotic fluid-derived stem cells.

    Science.gov (United States)

    Kang, N-H; Hwang, K-A; Kim, S U; Kim, Y-B; Hyun, S-H; Jeung, E-B; Choi, K-C

    2012-08-01

    As stem cells are capable of self-renewal and can generate differentiated progenies for organ development, they are considered as potential source for regenerative medicine and tissue replacement after injury or disease. Along with this capacity, stem cells have the therapeutic potential for treating human diseases including cancers. According to the origins, stem cells are broadly classified into two types: embryonic stem cells (ESCs) and adult stem cells. In terms of differentiation potential, ESCs are pluripotent and adult stem cells are multipotent. Amnion, which is a membranous sac that contains the fetus and amniotic fluid and functions in protecting the developing embryo during gestation, is another stem cell source. Amnion-derived stem cells are classified as human amniotic membrane-derived epithelial stem cells, human amniotic membrane-derived mesenchymal stem cells and human amniotic fluid-derived stem cells. They are in an intermediate stage between pluripotent ESCs and lineage-restricted adult stem cells, non-tumorigenic, and contribute to low immunogenicity and anti-inflammation. Furthermore, they are easily available and do not cause any controversial issues in their recovery and applications. Not only are amnion-derived stem cells applicable in regenerative medicine, they have anticancer capacity. In non-engineered stem cells transplantation strategies, amnion-derived stem cells effectively target the tumor and suppressed the tumor growth by expressing cytotoxic cytokines. Additionally, they also have a potential as novel delivery vehicles transferring therapeutic genes to the cancer formation sites in gene-directed enzyme/prodrug combination therapy. Owing to their own advantageous properties, amnion-derived stem cells are emerging as a new candidate in anticancer therapy.

  15. Pathophysiology and Therapeutic Strategies for Symptomatic Uncomplicated Diverticular Disease of the Colon.

    Science.gov (United States)

    Scaioli, Eleonora; Colecchia, Antonio; Marasco, Giovanni; Schiumerini, Ramona; Festi, Davide

    2016-03-01

    Colonic diverticulosis imposes a significant burden on industrialized societies. The current accepted causes of diverticula formation include low fiber content in the western diet with decreased intestinal content and size of the lumen, leading to the transmission of muscular contraction pressure to the wall of the colon, inducing the formation of diverticula usually at the weakest point of the wall where penetration of the blood vessels occurs. Approximately 20 % of the patients with colonic diverticulosis develop abdominal symptoms (i.e., abdominal pain and discomfort, bloating, constipation, and diarrhea), a condition which is defined as symptomatic uncomplicated diverticular disease (SUDD). The pathogenesis of SUDD symptoms remains uncertain and even less is known about how to adequately manage bowel symptoms. Recently, low-grade inflammation, altered intestinal microbiota, visceral hypersensitivity, and abnormal colonic motility have been identified as factors leading to symptom development, thus changing and improving the therapeutic approach. In this review, a comprehensive search of the literature regarding on SUDD pathogenetic hypotheses and pharmacological strategies was carried out. The pathogenesis of SUDD, although not completely clarified, seems to be related to an interaction between colonic microbiota alterations, and immune, enteric nerve, and muscular system dysfunction (Cuomo et al. in United Eur Gastroenterol J 2:413-442, 2014). Greater understanding of the inflammatory pathways and gut microbiota composition in subjects affected by SUDD has increased therapeutic options, including the use of gut-directed antibiotics, mesalazine, and probiotics (Bianchi et al. in Aliment Pharmacol Ther 33:902-910, 2011; Comparato et al. in Dig Dis Sci 52:2934-2941, 2007; Tursi et al. in Aliment Pharmacol Ther 38:741-751, 2013); however, more research is necessary to validate the safety, effectiveness, and cost-effectiveness of these interventions.

  16. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

    Science.gov (United States)

    Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

    2016-12-01

    Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  17. Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Anja Geiselhart

    2012-01-01

    Full Text Available Fanconi anemia (FA is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC. This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients.

  18. Targeting endoplasmic reticulum and/or mitochondrial Ca2+ fluxes as therapeutic strategy for HCV infection

    Science.gov (United States)

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-03-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  19. 3D bioprinting: A new insight into the therapeutic strategy of neural tissue regeneration.

    Science.gov (United States)

    Hsieh, Fu-Yu; Hsu, Shan-hui

    2015-01-01

    Acute traumatic injuries and chronic degenerative diseases represent the world's largest unmet medical need. There are over 50 million people worldwide suffering from neurodegenerative diseases. However, there are only a few treatment options available for acute traumatic injuries and neurodegenerative diseases. Recently, 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. In this commentary, the newly developed 3D bioprinting technique involving neural stem cells (NSCs) embedded in the thermoresponsive biodegradable polyurethane (PU) bioink is reviewed. The thermoresponsive and biodegradable PU dispersion can form gel near 37 °C without any crosslinker. NSCs embedded within the water-based PU hydrogel with appropriate stiffness showed comparable viability and differentiation after printing. Moreover, in the zebrafish embryo neural deficit model, injection of the NSC-laden PU hydrogels promoted the repair of damaged CNS. In addition, the function of adult zebrafish with traumatic brain injury was rescued after implantation of the 3D-printed NSC-laden constructs. Therefore, the newly developed 3D bioprinting technique may offer new possibilities for future therapeutic strategy of neural tissue regeneration.

  20. Targeting Endoplasmic Reticulum and/or Mitochondrial Ca2+ Fluxes as Therapeutic Strategy for HCV Infection.

    Science.gov (United States)

    Scrima, Rosella; Piccoli, Claudia; Moradpour, Darius; Capitanio, Nazzareno

    2018-01-01

    Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined. Most in vitro studies performed so far have shown that several of the hepatitis C virus (HCV) proteins also localize to mitochondria, but the consequences of these interactions on mitochondrial functions remain contradictory and need to be confirmed in the context of productively replicating virus and physiologically relevant in vitro and in vivo model systems. In the past decade we have been proposing a temporal sequence of events in the HCV-infected cell whereby the primary alteration is localized at the mitochondria-associated ER membranes and causes release of Ca 2+ from the ER, followed by uptake into mitochondria. This ensues successive mitochondrial dysfunction leading to the generation of reactive oxygen and nitrogen species and a progressive metabolic adaptive response consisting in decreased oxidative phosphorylation and enhanced aerobic glycolysis and lipogenesis. Here we resume the major results provided by our group in the context of HCV-mediated alterations of the cellular inter-compartmental calcium flux homeostasis and present new evidence suggesting targeting of ER and/or mitochondrial calcium transporters as a novel therapeutic strategy.

  1. New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Ebbe Toftgaard Poulsen

    2015-12-01

    Full Text Available The Amyloid Precursor Protein (APP has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ in Alzheimer’s disease (AD. However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y682 mutation in the 682YENPTY687 domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS on hippocampal tissue extracts of three month-old mice incubated with either the 682YENPTY687 peptide, its mutated form, 682GENPTY687 or its phosphorylated form, 682pYENPTY687. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc and its Adaptor Protein 2 (AP-2. Overall our results consolidate and refine the importance of Y682 in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.

  2. Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy.

    Science.gov (United States)

    Mohammadian, Mozhdeh; Abasi, Elham; Akbarzadeh, Abolfazl

    2016-08-01

    Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in bone marrow, fat, and so many other tissues, and can differentiate into a variety of cell types including osteoblasts, chondrocytes, and adipocytes, as well as myocytes and neurons. Moreover, they have great capacity for self-renewal while maintaining their multipotency. Their capacity for proliferation and differentiation, in addition to their immunomodulatory activity, makes them very promising candidates for cell-based regenerative medicine. Moreover, MSCs have the ability of mobilization to the site of damage; therefore, they can automatically migrate to the site of injury via their chemokine receptors following intravenous transplantation. In this respect, they can be applied for MSC-based gene therapy. In this new therapeutic method, genes of interest are introduced into MSCs via viral and non-viral-based methods that lead to transgene expression in them. Although stem cell-based gene therapy is a relatively new strategy, it lights a new hope for the treatment of a variety of genetic disorders. In the near future, MSCs can be of use in a vast number of clinical applications, because of their uncomplicated isolation, culture, and genetic manipulation. However, full consideration is still crucial before they are utilized for clinical trials, because the number of studies that signify the advantageous effects of MSC-based gene therapy are still limited.

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

    Directory of Open Access Journals (Sweden)

    Joanna Huszno

    2016-03-01

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

  4. Protein Homeostasis Defects of Alanine-Glyoxylate Aminotransferase: New Therapeutic Strategies in Primary Hyperoxaluria Type I

    Directory of Open Access Journals (Sweden)

    Angel L. Pey

    2013-01-01

    Full Text Available Alanine-glyoxylate aminotransferase catalyzes the transamination between L-alanine and glyoxylate to produce pyruvate and glycine using pyridoxal 5′-phosphate (PLP as cofactor. Human alanine-glyoxylate aminotransferase is a peroxisomal enzyme expressed in the hepatocytes, the main site of glyoxylate detoxification. Its deficit causes primary hyperoxaluria type I, a rare but severe inborn error of metabolism. Single amino acid changes are the main type of mutation causing this disease, and considerable effort has been dedicated to the understanding of the molecular consequences of such missense mutations. In this review, we summarize the role of protein homeostasis in the basic mechanisms of primary hyperoxaluria. Intrinsic physicochemical properties of polypeptide chains such as thermodynamic stability, folding, unfolding, and misfolding rates as well as the interaction of different folding states with protein homeostasis networks are essential to understand this disease. The view presented has important implications for the development of new therapeutic strategies based on targeting specific elements of alanine-glyoxylate aminotransferase homeostasis.

  5. Combined Gemcitabine and Metronidazole Is a Promising Therapeutic Strategy for Cancer Stem-like Cholangiocarcinoma.

    Science.gov (United States)

    Kawamoto, Makoto; Umebayashi, Masayo; Tanaka, Hiroto; Koya, Norihiro; Nakagawa, Sinichiro; Kawabe, Ken; Onishi, Hideya; Nakamura, Masafumi; Morisaki, Takashi

    2018-05-01

    Metronidazole (MNZ) is a common antibiotic that exerts disulfiram-like effects when taken together with alcohol. However, the relationship between MNZ and aldehyde dehydrogenase (ALDH) activity remains unclear. This study investigated whether MNZ reduces cancer stemness by suppressing ALDH activity and accordingly reducing the malignancy of cholangiocarcinoma (CCA). We developed gemcitabine (GEM)-resistant TFK-1 cells and originally established CCA cell line from a patient with GEM-resistant CCA. Using these cell lines, we analyzed the impacts of MNZ for cancer stem cell markers, invasiveness, and chemosensitivity. MNZ reduced ALDH activity in GEM-resistant CCA cells, leading to decreased invasiveness and enhanced chemosensitivity. MNZ diminished the invasiveness by inducing mesenchymal-epithelial transition and enhancing chemosensitivity by increasing ENT1 (equilibrative nucleoside transporter 1) and reducing RRM1 (ribonucleotide reductase M1). MNZ reduced cancer stemness in GEM-resistant CCA cells. Combined GEM and MNZ would be a promising therapeutic strategy for cancer stem-like CAA. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Targeting methionine cycle as a potential therapeutic strategy for immune disorders.

    Science.gov (United States)

    Li, Heng; Lu, Huimin; Tang, Wei; Zuo, Jianping

    2017-08-23

    Methionine cycle plays an essential role in regulating many cellular events, especially transmethylation reactions, incorporating the methyl donor S-adenosylmethionine (SAM). The transmethylations and substances involved in the cycle have shown complicated effects and mechanisms on immunocytes developments and activations, and exert crucial impacts on the pathological processes in immune disorders. Areas covered: Methionine cycle has been considered as an effective means of drug developments. This review discussed the role of methionine cycle in immune responses and summarized the potential therapeutic strategies based on the cycle, including SAM analogs, methyltransferase inhibitors, S-adenosylhomocysteine hydrolase (SAHH) inhibitors, adenosine receptors specific agonists or antagonists and homocysteine (Hcy)-lowering reagents, in treating human immunodeficiency virus (HIV) infections, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis (SSc) and other immune disorders. Expert opinion: New targets and biomarkers grown out of methionine cycle have developed rapidly in the past decades. However, impacts of epigenetic regulations on immune disorders are unclear and whether the substances in methionine cycle can be clarified as biomarkers remains controversial. Therefore, further elucidation on the role of epigenetic regulations and substances in methionine cycle may contribute to exploring the cycle-derived biomarkers and drugs in immune disorders.

  7. Degradation of misfolded proteins in neurodegenerative diseases: therapeutic targets and strategies.

    Science.gov (United States)

    Ciechanover, Aaron; Kwon, Yong Tae

    2015-03-13

    Mammalian cells remove misfolded proteins using various proteolytic systems, including the ubiquitin (Ub)-proteasome system (UPS), chaperone mediated autophagy (CMA) and macroautophagy. The majority of misfolded proteins are degraded by the UPS, in which Ub-conjugated substrates are deubiquitinated, unfolded and cleaved into small peptides when passing through the narrow chamber of the proteasome. The substrates that expose a specific degradation signal, the KFERQ sequence motif, can be delivered to and degraded in lysosomes via the CMA. Aggregation-prone substrates resistant to both the UPS and the CMA can be degraded by macroautophagy, in which cargoes are segregated into autophagosomes before degradation by lysosomal hydrolases. Although most misfolded and aggregated proteins in the human proteome can be degraded by cellular protein quality control, some native and mutant proteins prone to aggregation into β-sheet-enriched oligomers are resistant to all known proteolytic pathways and can thus grow into inclusion bodies or extracellular plaques. The accumulation of protease-resistant misfolded and aggregated proteins is a common mechanism underlying protein misfolding disorders, including neurodegenerative diseases such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), prion diseases and Amyotrophic Lateral Sclerosis (ALS). In this review, we provide an overview of the proteolytic pathways in neurons, with an emphasis on the UPS, CMA and macroautophagy, and discuss the role of protein quality control in the degradation of pathogenic proteins in neurodegenerative diseases. Additionally, we examine existing putative therapeutic strategies to efficiently remove cytotoxic proteins from degenerating neurons.

  8. Therapeutic strategy for the treatment of isolated spontaneous dissection of superior mesenteric arteries

    International Nuclear Information System (INIS)

    Xu Yongle; Xiong Jiang; Guo Wei; Liu Xiaoping; Liu Meng

    2010-01-01

    Objective: To summarize the treatment strategies of isolated superior mesenteric artery (SMA) dissection and to discuss the selection of therapeutic methods. Methods: The clinical data of ten patients, who were encountered during the period from Jan. 2007 to Feb. 2010 in General Hospital of Chinese PLA and diagnosed as isolated SMA dissection,were retrospectively analyzed. According to the presence or absence of intestinal ischemic necrosis and SMA rupture, the patients were divided into simple group (n = 9) and complicated group(n = 1). The treatments for different type of SMA dissection were discussed and the results and prognosis were analyzed. Results: Nine patients were divided into simple group and received conservative treatment, of which anticoagulation was not employed in 5. One patient was divided into complicated group and had to receive an iliomesenteric bypass surgery after the patient had failed to respond to conservative treatment. After the treatment the abdominal pain was relieved in all ten patients. Conclusion: With the wide use of computer tomography angiography and digital subtraction angiography, more and more isolated SMA dissections have been confirmed. For most patients with SMA dissection, especially for simple ones (i.e. without bowel ischemia or SMA rupture), excellent short-term results can be achieved by pure conservative treatment, even no anticoagulation needed. However, for the complicated isolated SMA dissections, vascular reconstruction procedure with various techniques, including open surgery, is necessary in order to obtain satisfactory short-term results. (authors)

  9. Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.

    Science.gov (United States)

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2015-01-14

    Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.

  10. Targeting Glutathione-S Transferase Enzymes in Musculoskeletal Sarcomas: A Promising Therapeutic Strategy

    Directory of Open Access Journals (Sweden)

    Michela Pasello

    2011-01-01

    Full Text Available Recent studies have indicated that targeting glutathione-S-transferase (GST isoenzymes may be a promising novel strategy to improve the efficacy of conventional chemotherapy in the three most common musculoskeletal tumours: osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma. By using a panel of 15 drug-sensitive and drug-resistant human osteosarcoma, Ewing's sarcoma, and rhabdomyosarcoma cell lines, the efficay of the GST-targeting agent 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthiohexanol (NBDHEX has been assessed and related to GST isoenzymes expression (namely GSTP1, GSTA1, GSTM1, and MGST. NBDHEX showed a relevant in vitro activity on all cell lines, including the drug-resistant ones and those with higher GSTs levels. The in vitro activity of NBDHEX was mostly related to cytostatic effects, with a less evident apoptotic induction. NBDHEX positively interacted with doxorubicin, vincristine, cisplatin but showed antagonistic effects with methotrexate. In vivo studies confirmed the cytostatic efficay of NBDHEX and its positive interaction with vincristine in Ewing's sarcoma cells, and also indicated a positive effect against the metastatisation of osteosarcoma cells. The whole body of evidence found in this study indicated that targeting GSTs in osteosarcoma, Ewing's sarcoma and rhabdomyosarcoma may be an interesting new therapeutic option, which can be considered for patients who are scarcely responsive to conventional regimens.

  11. EGFR conjunct FSCN1 as a Novel Therapeutic Strategy in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Wang, Chao-Qun; Li, Yang; Huang, Bi-Fei; Zhao, Yong-Ming; Yuan, Hui; Guo, Dongfang; Su, Chen-Ming; Hu, Gui-Nv; Wang, Qian; Long, Tengyun; Wang, Yan; Tang, Chih-Hsin; Li, Xiaoni

    2017-11-15

    Emerging evidence indicates that Fascin-1 (FSCN1) may possess a causal role in the development of several types of cancers and serves as a novel biomarker of aggressiveness in certain carcinomas. However, the regulatory mechanism of FSCN1 in triple-negative breast cancer (TNBC) cell invasion and migration is still largely unknown. In our study, we observed that the FSCN1 expression rates were significantly higher in invasive ductal carcinoma, compared with both usual ductal hyperplasia and ductal carcinoma in situ. FSCN1 expression was significantly higher in cases of TNBC compared with the non-TNBC subtype. Overexpression of FSCN1 promoted TNBC cell migration and invasion. Epidermal growth factor induced the expression of FSCN1 through activation of MAPK, which subsequently promoted cell migration and invasion. A significant decrease in FSCN1 expression following the co-treatment of FSCN1 siRNA and Gefitinib, compared with the separate treatment of FSCN1 siRNA or Gefitinib. Furthermore, we found that there was a significant association between FSCN1 expression and poor relapse-free survival and overall survival. Therefore, we suggest that co-targeting epidermal growth factor receptor and FSCN1 dual biomarker may be used as a novel therapeutic strategy for TNBC.

  12. Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis

    DEFF Research Database (Denmark)

    Köhler, Ralf; Wulff, Heike; Eichler, Ines

    2003-01-01

    hyperplasia was accompanied by decreased neointimal cell content, with no change in the rate of apoptosis or collagen content. CONCLUSIONS: The switch toward IKCa1 expression may promote excessive neointimal VSMC proliferation. Blockade of IKCa1 could therefore represent a new therapeutic strategy to prevent...

  13. Task demands determine comparison strategy in whole probe change detection.

    Science.gov (United States)

    Udale, Rob; Farrell, Simon; Kent, Chris

    2018-05-01

    Detecting a change in our visual world requires a process that compares the external environment (test display) with the contents of memory (study display). We addressed the question of whether people strategically adapt the comparison process in response to different decision loads. Study displays of 3 colored items were presented, followed by 'whole-display' probes containing 3 colored shapes. Participants were asked to decide whether any probed items contained a new feature. In Experiments 1-4, irrelevant changes to the probed item's locations or feature bindings influenced memory performance, suggesting that participants employed a comparison process that relied on spatial locations. This finding occurred irrespective of whether participants were asked to decide about the whole display, or only a single cued item within the display. In Experiment 5, when the base-rate of changes in the nonprobed items increased (increasing the incentive to use the cue effectively), participants were not influenced by irrelevant changes in location or feature bindings. In addition, we observed individual differences in the use of spatial cues. These results suggest that participants can flexibly switch between spatial and nonspatial comparison strategies, depending on interactions between individual differences and task demand factors. These findings have implications for models of visual working memory that assume that the comparison between study and test obligatorily relies on accessing visual features via their binding to location. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

    Science.gov (United States)

    Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

    2016-01-01

    The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

  15. [Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention].

    Science.gov (United States)

    Wallon, Martine; Kieffer, François; Binquet, Christine; Thulliez, Philippe; Garcia-Méric, Patricia; Dureau, Pascal; Franck, Jacqueline; Peyron, François; Bonnin, Alain; Villena, Isabelle; Bonithon-Kopp, Claire; Gouyon, Jean-Bernard; Masson, Sandrine; Félin, Alexandrin; Cornu, Catherine

    2011-01-01

    In France, children with confirmed congenital toxoplasmosis receive a treatment for a period of 12 to 24 months. Such prolonged treatment may generate potentially severe risks, in particular hematologic and cutaneous. Our objective is to compare the effectiveness of two therapeutic strategies on the prevention of retinochoroiditis by a randomized, non-inferiority, open-label, parallel study including 486 children, 3 to 6 months of age with a non-severe form of congenital toxoplasmosis. Following randomization, pyrimethamine-sulphonamide treatment is initiated for a period of three months, followed by a treatment with Fansidar(®) for 9 months, or therapeutic abstention. Follow-up visits during a two-year period will include an examination of the eye, a blood test, and questionnaires to evaluate the children's quality of life and their parents' anxiety. Confirming the non-inferiority of the effectiveness of a short-term treatment will improve the quality of life of parents and children. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  16. Targeting miRNAs by polyphenols: Novel therapeutic strategy for cancer.

    Science.gov (United States)

    Pandima Devi, Kasi; Rajavel, Tamilselvam; Daglia, Maria; Nabavi, Seyed Fazel; Bishayee, Anupam; Nabavi, Seyed Mohammad

    2017-10-01

    In the recent years, polyphenols have gained significant attention in scientific community owing to their potential anticancer effects against a wide range of human malignancies. Epidemiological, clinical and preclinical studies have supported that daily intake of polyphenol-rich dietary fruits have a strong co-relationship in the prevention of different types of cancer. In addition to direct antioxidant mechanisms, they also regulate several therapeutically important oncogenic signaling and transcription factors. However, after the discovery of microRNA (miRNA), numerous studies have identified that polyphenols, including epigallocatechin-3-gallate, genistein, resveratrol and curcumin exert their anticancer effects by regulating different miRNAs which are implicated in all the stages of cancer. MiRNAs are short, non-coding endogenous RNA, which silence the gene functions by targeting messenger RNA (mRNA) through degradation or translation repression. However, cancer associated miRNAs has emerged only in recent years to support its applications in cancer therapy. Preclinical experiments have suggested that deregulation of single miRNA is sufficient for neoplastic transformation of cells. Indeed, the widespread deregulation of several miRNA profiles of tumor and healthy tissue samples revealed the involvement of many types of miRNA in the development of numerous cancers. Hence, targeting the miRNAs using polyphenols will be a novel and promising strategy in anticancer chemotherapy. Herein, we have critically reviewed the potential applications of polyphenols on various human miRNAs, especially which are involved in oncogenic and tumor suppressor pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Photochemical Internalization of Peptide Antigens Provides a Novel Strategy to Realize Therapeutic Cancer Vaccination

    Directory of Open Access Journals (Sweden)

    Markus Haug

    2018-04-01

    Full Text Available Effective priming and activation of tumor-specific CD8+ cytotoxic T lymphocytes (CTLs is crucial for realizing the potential of therapeutic cancer vaccination. This requires cytosolic antigens that feed into the MHC class I presentation pathway, which is not efficiently achieved with most current vaccination technologies. Photochemical internalization (PCI provides an emerging technology to route endocytosed material to the cytosol of cells, based on light-induced disruption of endosomal membranes using a photosensitizing compound. Here, we investigated the potential of PCI as a novel, minimally invasive, and well-tolerated vaccination technology to induce priming of cancer-specific CTL responses to peptide antigens. We show that PCI effectively promotes delivery of peptide antigens to the cytosol of antigen-presenting cells (APCs in vitro. This resulted in a 30-fold increase in MHC class I/peptide complex formation and surface presentation, and a subsequent 30- to 100-fold more efficient activation of antigen-specific CTLs compared to using the peptide alone. The effect was found to be highly dependent on the dose of the PCI treatment, where optimal doses promoted maturation of immature dendritic cells, thus also providing an adjuvant effect. The effect of PCI was confirmed in vivo by the successful induction of antigen-specific CTL responses to cancer antigens in C57BL/6 mice following intradermal peptide vaccination using PCI technology. We thus show new and strong evidence that PCI technology holds great potential as a novel strategy for improving the outcome of peptide vaccines aimed at triggering cancer-specific CD8+ CTL responses.

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

    Directory of Open Access Journals (Sweden)

    Deyan Luan

    2007-07-01

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

  19. Limited-Sampling Strategies for Therapeutic Drug Monitoring of Moxifloxacin in Patients With Tuberculosis

    NARCIS (Netherlands)

    Pranger, Arianna D.; Kosterink, Jos G. W.; van Altena, Richard; Aarnoutse, Rob E.; van der Werf, Tjip S.; Uges, Donald R. A.; Alffenaar, Jan-Willem C.

    Background: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  20. Limited-sampling strategies for therapeutic drug monitoring of moxifloxacin in patients with tuberculosis

    NARCIS (Netherlands)

    Pranger, A.D.; Kosterink, J.G.W.; Altena, R. van; Aarnoutse, R.E.; Werf, T.S. van der; Uges, D.R.A.; Alffenaar, J.W.C.

    2011-01-01

    BACKGROUND: Moxifloxacin (MFX) is a potent drug for multidrug resistant tuberculosis(TB) treatment and is also useful if first-line agents are not tolerated. Therapeutic drug monitoring may help to prevent treatment failure. Obtaining a full concentration-time curve of MFX for therapeutic drug

  1. Comparisons of Particulate Size Distributions from Multiple Combustion Strategies

    Science.gov (United States)

    Zhang, Yizhou

    In this study, a comparison of particle size distribution (PSD) measurements from eight different combustion strategies was conducted at four different load-speed points. The PSDs were measured using a scanning mobility particle sizer (SMPS) together with a condensation particle counter (CPC). To study the influence of volatile particles, PSD measurements were performed with and without a volatile particle remover (thermodenuder, TD) at both low and high dilution ratios. The common engine platform utilized in the experiment helps to eliminate the influence of background particulate and ensures similarity in dilution conditions. The results show a large number of volatile particles were present under LDR sample conditions for most of the operating conditions. The use of a TD, especially when coupled with HDR, was demonstrated to be effective at removing volatile particles and provided consistent measurements across all combustion strategies. The PSD comparison showed that gasoline premixed combustion strategies such as HCCI and GCI generally have low PSD magnitudes for particle sizes greater than the Particle Measurement Programme (PMP) cutoff diameter (23 nm), and the PSDs were highly nuclei-mode particle dominated. The strategies using diesel as the only fuel (DLTC and CDC) generally showed the highest particle number emissions for particles larger than 23 nm and had accumulation-mode particle dominated PSDs. A consistent correlation between the increase of the direct-injection of diesel fuel and a higher fraction of accumulation-mode particles was observed over all combustion strategies. A DI fuel substitution study and injector nozzle geometry study were conducted to better understand the correlation between PSD shape and DI fueling. It was found that DI fuel properties has a clear impact on PSD behavior for CDC and NG DPI. Fuel with lower density and lower sooting tendency led to a nuclei-mode particle dominated PSD shape. For NG RCCI, accumulation

  2. Therapeutic Effects of Topical Tranexamic Acid in Comparison with Hydroquinone in Treatment of Women with Melasma.

    Science.gov (United States)

    Atefi, Najmolsadat; Dalvand, Behzad; Ghassemi, Mahammadreza; Mehran, Golnaz; Heydarian, Amir

    2017-09-01

    Few studies have focused on therapeutic as well as side effects of tranexamic acid (TXA) as a topical drug compared to other topical drugs in treating melasma. The present study aimed to assess and compare the beneficial therapeutic effects and also side effects of local TXA in comparison with hydroquinone in treating women with melasma. This randomized double-blinded clinical trial was performed on 60 women who suffered from melasma and were referred to the skin disorders clinic at the Rasoul-e-Akram hospital in Tehran in 2015. The patients were then randomly assigned via computerized randomization to two groups: group A received TXA%5 (topically twice a day for 12 weeks in the location of the melasma) and group B (received hydroquinone 2% with the same treatment order). Prior to intervention and at 12 weeks after intervention, the intensity and extension of melasma were assessed based on the Melasma Area and Severity Index (MASI) scoring method. The mean MASI score in both treatment groups decreased considerably after completion of treatment and was not significant between the two groups. No side effects were detected in group A, but 10% of those in group B complained of drug-related side effects including erythema and skin irritation (p = 0.131). Regarding the level of patient satisfaction, the patients in group A had a significantly higher level of satisfaction level of 33.3% compared with 6.7% in group B (p = 0.015) (Fig. 9). Multivariate linear regression modeling with the presence of age, history of systemic disorder, drug history, and family history of melasma demonstrated no difference in the mean MASI between the two groups. Topical use of TXA significantly reduced both melanin level and MASI score. Given its high efficiency and low drug side effects, this regimen results in high patient satisfaction compared with topical hydroquinone. IRCT code: IRCT2016040627220N2.

  3. STUDY OF THERAPEUTIC COMPARISON OF TACROLIMUS 0.1% AND MINOXIDIL 2% IN ALOPECIA AREATA

    Directory of Open Access Journals (Sweden)

    Kallappa C. Herkal

    2013-07-01

    Full Text Available Introduction: Alopecia areata is a unique, idiopathic disease in which there is patchy hair loss. The variable and uncertain natural history of alopecia areata is accounting for the multiplicity of uncritical claims for a large variety of therapeutic procedures. Aim: to find the therapeutic comparison between tacrolimus 0.1% ointment and minoxidil 2% solution. Material and Methods: Patients attending skin out patient department in Navodaya medical college hospital and research centre, Raichur were screened and the consenting consecutive cases of Aopecia Areata (AA from December 2010 to November 2011 were chosen for study. There were 75 patients in the study. It is a randomized, single blind, intension to treat study. The eligible patients for the study were randomly allocated into two groups-Group A and Group B (38 in Group A and 37 in Group B. Patients in Group A were treated with 2% Minoxidi solution to be applied twice daily over the alopecia patch, where as Patients in Group B were treated with Tacrolimus 0.1% ointment applied twice daily. Patients were followed up at 2, 4, 6, 8, 10 and 12 weeks. Alopecia Grading Score (AGS was calculated at baseline and 12 weeks. Regrowth Score (RGS was calculated at 12 weeks. Results: Total 69 patients completed the study (35 in Group A and 34 in Group B. In our study RGS ≥ 3 was observed in 65.71% of patients treated with Tinoxidil 2% solution and 44.12% of patients treated with Tacrolimus 0.1% ointment. Conclusion: In our study Minoxidil 2% solution had better stimulatory effect on hair growth compared to Tacrolimus 0.1% ointment in the treatment of mild to moderate patchy alopecia areata. The combination treatment may yield a better clinical response than either of the agents used singly.

  4. Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

    Science.gov (United States)

    Kumar, S; Peng, X; Daley, J; Yang, L; Shen, J; Nguyen, N; Bae, G; Niu, H; Peng, Y; Hsieh, H-J; Wang, L; Rao, C; Stephan, C C; Sung, P; Ira, G; Peng, G

    2017-04-17

    Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in replication and HR repair. Here we demonstrate that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA double strand break end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anticancer drugs by targeting druggable nuclease DNA2. We propose DNA2 inhibition as new strategy in cancer therapy by targeting

  5. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  6. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Science.gov (United States)

    Yadav, Saveg; Pandey, Shrish Kumar; Singh, Vinay Kumar; Goel, Yugal; Kumar, Ajay; Singh, Sukh Mahendra

    2017-01-01

    Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP), with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA) and propionic acid (PA), with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  7. Molecular docking studies of 3-bromopyruvate and its derivatives to metabolic regulatory enzymes: Implication in designing of novel anticancer therapeutic strategies.

    Directory of Open Access Journals (Sweden)

    Saveg Yadav

    Full Text Available Altered metabolism is an emerging hallmark of cancer, as malignant cells display a mammoth up-regulation of enzymes responsible for steering their bioenergetic and biosynthetic machinery. Thus, the recent anticancer therapeutic strategies focus on the targeting of metabolic enzymes, which has led to the identification of specific metabolic inhibitors. One of such inhibitors is 3-bromopyruvate (3-BP, with broad spectrum of anticancer activity due to its ability to inhibit multiple metabolic enzymes. However, the molecular characterization of its binding to the wide spectrum of target enzymes remains largely elusive. Therefore, in the present study we undertook in silico investigations to decipher the molecular nature of the docking of 3-BP with key target enzymes of glycolysis and TCA cycle by PatchDock and YASARA docking tools. Additionally, derivatives of 3-BP, dibromopyruvate (DBPA and propionic acid (PA, with reported biological activity, were also investigated for docking to important target metabolic enzymes of 3-BP, in order to predict their therapeutic efficacy versus that of 3-BP. A comparison of the docking scores with respect to 3-BP indicated that both of these derivatives display a better binding strength to metabolic enzymes. Further, analysis of the drug likeness of 3-BP, DBPA and PA by Lipinski filter, admetSAR and FAF Drug3 indicated that all of these agents showed desirable drug-like criteria. The outcome of this investigation sheds light on the molecular characteristics of the binding of 3-BP and its derivatives with metabolic enzymes and thus may significantly contribute in designing and optimizing therapeutic strategies against cancer by using these agents.

  8. Solid lipid nanoparticles as attractive drug vehicles: Composition, properties and therapeutic strategies.

    Science.gov (United States)

    Geszke-Moritz, Małgorzata; Moritz, Michał

    2016-11-01

    This work briefly reviews up-to-date developments in solid lipid nanoparticles (SLNs) as effective nanocolloidal system for drug delivery. It summarizes SLNs in terms of their preparation, surface modification and properties. The application of SLNs as a carrier system enables to improve the therapeutic efficacy of drugs from various therapeutic groups. Present uses of SLNs include cancer therapy, dermatology, bacterial infections, brain targeting and eye disorders among others. The usage of SLNs provides enhanced pharmacokinetic properties and modulated release of drugs. SLN ubiquitous application results from their specific features such as possibility of surface modification, increased permeation through biological barriers, resistance to chemical degradation, possibility of co-delivery of various therapeutic agents or stimuli-responsiveness. This paper will be useful to the scientists working in the domain of SLN-based drug delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Adenosine can thwart antitumor immune responses elicited by radiotherapy. Therapeutic strategies alleviating protumor ADO activities

    Energy Technology Data Exchange (ETDEWEB)

    Vaupel, Peter [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Multhoff, Gabriele [Klinikum rechts der Isar, Technische Universitaet Muenchen (TUM), Department of Radiation Oncology, Munich (Germany); Helmholtz Zentrum Muenchen, Institute for innovative Radiotherapy (iRT), Experimental Immune Biology, Neuherberg (Germany)

    2016-05-15

    By studying the bioenergetic status we could show that the development of tumor hypoxia is accompanied, apart from myriad other biologically relevant effects, by a substantial accumulation of adenosine (ADO). ADO has been shown to act as a strong immunosuppressive agent in tumors by modulating the innate and adaptive immune system. In contrast to ADO, standard radiotherapy (RT) can either stimulate or abrogate antitumor immune responses. Herein, we present ADO-mediated mechanisms that may thwart antitumor immune responses elicited by RT. An overview of the generation, accumulation, and ADO-related multifaceted inhibition of immune functions, contrasted with the antitumor immune effects of RT, is provided. Upon hypoxic stress, cancer cells release ATP into the extracellular space where nucleotides are converted into ADO by hypoxia-sensitive, membrane-bound ectoenzymes (CD39/CD73). ADO actions are mediated upon binding to surface receptors, mainly A2A receptors on tumor and immune cells. Receptor activation leads to a broad spectrum of strong immunosuppressive properties facilitating tumor escape from immune control. Mechanisms include (1) impaired activity of CD4 + T and CD8 + T, NK cells and dendritic cells (DC), decreased production of immuno-stimulatory lymphokines, and (2) activation of Treg cells, expansion of MDSCs, promotion of M2 macrophages, and increased activity of major immunosuppressive cytokines. In addition, ADO can directly stimulate tumor proliferation and angiogenesis. ADO mechanisms described can thwart antitumor immune responses elicited by RT. Therapeutic strategies alleviating tumor-promoting activities of ADO include respiratory hyperoxia or mild hyperthermia, inhibition of CD39/CD73 ectoenzymes or blockade of A2A receptors, and inhibition of ATP-release channels or ADO transporters. (orig.) [German] Untersuchungen des bioenergetischen Status ergaben, dass Tumorhypoxie neben vielen anderen bedeutsamen biologischen Effekten zu einem starken

  10. Emerging nanotechnology based strategies for diagnosis and therapeutics of urinary tract infections: A review.

    Science.gov (United States)

    Kumar, M S; Das, A P

    2017-11-01

    At present, various diagnostic and therapeutic approaches are available for urinary tract infections. But, still the quest for development of more rapid, accurate and reliable approach is an unending process. The pathogens, especially uropathogens are adapting to new environments and antibiotics day by day rapidly. Therefore, urinary tract infections are evolving as hectic and difficult to eradicate, increasing the economic burden to the society. The technological advances should be able to compete the adaptability characteristics of microorganisms to combat their growth in new environments and thereby preventing their infections. Nanotechnology is at present an extensively developing area of immense scientific interest since it has diverse potential applications in biomedical field. Nanotechnology may be combined with cellular therapy approaches to overcome the limitations caused by conventional therapeutics. Nanoantibiotics and drug delivery using nanotechnology are currently growing areas of research in biomedical field. Recently, various categories of antibacterial nanoparticles and nanocarriers for drug delivery have shown their potential in the treatment of infectious diseases. Nanoparticles, compared to conventional antibiotics, are more beneficial in terms of decreasing toxicity, prevailing over resistance and lessening costs. Nanoparticles present long term therapeutic effects since they are retained in body for relatively longer periods. This review focuses on recent advances in the field of nanotechnology, principally emphasizing diagnostics and therapeutics of urinary tract infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. RGD-based strategies for selective delivery of therapeutics and imaging agents to the tumour vasculature

    NARCIS (Netherlands)

    Temming, K; Molema, G; Kok, RJ

    2005-01-01

    During the past decade, RGD-peptides have become a popular tool for the targeting of drugs and imaging agents to a(v)beta(3)-integrin expressing tumour vasculature. RGD-peptides have been introduced by recombinant means into therapeutic proteins and viruses. Chemical means have been applied to

  12. Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies.

    Science.gov (United States)

    Yousefi, Bahman; Samadi, Nasser; Baradaran, Behzad; Shafiei-Irannejad, Vahid; Zarghami, Nosratollah

    2016-07-01

    Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. © 2016 John Wiley & Sons A/S.

  13. Therapeutic plasma exchange: a paired comparison of Fresenius AS104 vs. COBE Spectra.

    Science.gov (United States)

    Burgstaler, E A; Pineda, A A

    2001-01-01

    For therapeutic plasma exchange (TPE), continuous flow separators are known to be efficient as exemplified by Fresenius AS104 and COBE Spectra. The AS104 uses an interface monitoring system in the centrifuge during TPE, whereas Spectra uses computer algorithms to establish the plasma-cell interface. To determine the plasma collection efficiency (PLCE), anticoagulant (AC) volumes used, and platelets (PLT) lost of the AS104 and the Spectra, we performed a prospective paired comparison of 20 TPE (each machine). The study included 17 patients, 1.3 plasma volume exchanges (without AC), equal inlet rates, and AC ratio of 13:1. Processing times did not include reinfuse mode. Platelet loss was determined by sampling the collection bags. Inlet rates were between 60-110 ml/min. Diagnosis included peripheral neuropathies, TTP and cryoglobulinemia. The AS104 had significantly (P<0.0001) lower average whole blood processed (F:6,601 vs. S:8,584 ml), AC volume (F:532 vs. S:719 ml), and processing time (F:80 vs. S:102 minutes) than Spectra. The AS104 had significantly (P<0.0001) higher average plasma flow rates (F:53 vs. S:44 ml/minute), plasma collection efficiency (F:90 vs. S:69%), and platelet loss (F:2.0 vs. S:0.14 x 10(11) plt) than Spectra. Platelet loss correlated with inlet flow rate with the AS104 but not with the Spectra. The AS104 has a significantly higher collection efficiency than Spectra allowing it to remove the same amount of plasma in significantly less time, by processing significantly less blood, using significantly less AC, but removing significantly more platelets than Spectra. Copyright 2001 Wiley-Liss, Inc.

  14. Effectiveness of multiple therapeutic strategies in neovascular glaucoma patients: A PRISMA-compliant network meta-analysis.

    Science.gov (United States)

    Dong, Zixian; Gong, Jianyang; Liao, Rongfeng; Xu, Shaojun

    2018-04-01

    Neovascular glaucoma (NVG) is a severe secondary glaucoma with uncontrolled intraocular pressure that leads to serious eye pain and vision loss. Presently, the therapeutic strategies for NVG are diverse, but the therapeutic effects are still not ideal. We performed a network analysis to assess the effect of multiple therapeutic strategies on the treatment of NVG patients. We searched public electronic databases through April 2017 using the following keywords "neovascular glaucoma," "iris neovascularization," "hemorrhagic glaucoma," and "random" without language restrictions. The outcome considered in the present analysis was treatment success rate. A network meta-analysis and multilevel mixed-effects logistic regression were used to compare regimens. We included 27 articles assessing a total of 1884 NVG patients in our analysis. According to the network analysis, interferon and mitomycin plus trabeculectomy (94.9%), glaucoma valve implantation (86.9%), and iris photocoagulation plus trabeculectomy (81.9%) were the most likely to improve treatment success rate in NVG patients. The multilevel logistic regression analysis showed that glaucoma valve, bevacizumab, interferon, cyclophotocoagulation, trabeculectomy, iris photocoagulation, ranibizumab, and mitomycin had advantages in terms of improving treatment success rate in NVG patients. However, the application of retinal photocoagulation and vitrectomy reduced patient treatment success rate. The regimen including mitomycin, interferon, and trabeculectomy was the most likely to improve the treatment success rate in NVG patients. The application of glaucoma valve and bevacizumab were more beneficial for improving patient treatment success rate as a surgery and as an agent, respectively.

  15. Impact of the scintigraphy of somatostatin receptors upon the therapeutic strategy in patients bearing digestive endocrine tumors

    International Nuclear Information System (INIS)

    Lebtahi, R.; Cadiot, G.; Genin, R.; Delahaye, N.; Faraggi, M.; Daou, D.; Peker, C.; Migon, M.; Le Guludec, D.

    1997-01-01

    The scintigraphy of somatostatin receptors (SSR) is a sensible method for detecting the gastroenteric-pancreatic endocrine tumors and their metastases. The aim of this study is to evaluate the clinical impact of the results of SSR in taking patients in therapeutic charge. A hundred and sixty patients bearing biologically and/or histologically proved digestive endocrine tumors were prospectively studied. The patients were classified in 3 groups: group I - 90 patients with no known metastases; group II - 59 patients with liver metastases and group III - 11 patients with known extra-hepatic metastases. The results of the scintigraphy were compared with those of conventional imaging. The following results were obtained: in group 1 (90 patients) the conventional imaging has allowed detecting 53 primitive tumors in 44 patients. The SSR visualized 68% of these sites and has detected 26 supplementary primitive sites in 20 patients and 29 metastatic sites in 25 patients. In group II the scintigraphy has detected 95% of hepatic metastases and revealed 23 new metastasis sites and 18/59 patients. In group III the scintigraphy has detected 11 new sites in 7 patients. The results of scintigraphy modified the patient's classification in 38 cases (24%). The therapeutic strategy was modified for 40 patients (25%). In conclusion, the scintigraphy of somatostatin receptors is able to detect a significant number of digestive endocrine tumors what has important implications for therapeutical planning of the treatment of patients. It must be carried out during pre-therapeutic extension examination of these tumors

  16. Recent advances in therapeutic recruitment of mammalian RNAi and bacterial CRISPR-Cas DNA interference pathways as emerging antiviral strategies.

    Science.gov (United States)

    Chin, Wei-Xin; Ang, Swee Kim; Chu, Justin Jang Hann

    2017-01-01

    In invertebrate eukaryotes and prokaryotes, respectively, the RNAi and clustered regularly interspaced short palindromic repeats-CRISPR-associated (CRISPR-Cas) pathways are highly specific and efficient RNA and DNA interference systems, and are well characterised as potent antiviral systems. It has become possible to recruit or reconstitute these pathways in mammalian cells, where they can be directed against desired host or viral targets. The RNAi and CRISPR-Cas systems can therefore yield ideal antiviral therapeutics, capable of specific and efficient viral inhibition with minimal off-target effects, but development of such therapeutics can be slow. This review covers recent advances made towards developing RNAi or CRISPR-Cas strategies for clinical use. These studies address the delivery, toxicity or target design issues that typically plague the in vivo or clinical use of these technologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A Comparison of Therapeutic Modalities for Septated Tuberculous PleuraI Effusion on US

    Energy Technology Data Exchange (ETDEWEB)

    Cho, In Hwan; Kim, Kyeong Ah; Kim, Chul Joong; Kang, Eun Young; Cha, In Ho [Dae Rim St. Mary' s Hospital, Seoul (Korea, Republic of); Sim, Jae Jung [Korea University College of Medicine, Seoul (Korea, Republic of)

    1995-12-15

    To evaluate the utility of ultrasonography as a guide of determination of therapeutic modality an dto compare the therapeutic effects of modalities in patients with tuberculous pleural effusion. This study included 47 patients who had multiple septations on ultrasonography. We classified ultrasonographic pattern of pleural effusion into three groups according to pattern of septation : linear(n=6),moderate(n=19), honeycombing(n=22). We also classified therapeutic modalities into three groups : thoracentesis group(n=13), percutaneous catheter drainage group(n=11), intrapleural urokinase instillation group(n=23). We assessed the early and late therapeutic effects of these groups prospectively with follow-up chest radiographs. There was statistically no significant difference in therapeutic effect among the groups that had linear and moderate septa on ultrasonography(p<0.01). In patients with honeycombing septa, the therapeutic effects of catheter group and urokinase group were superior to conservative thoracentesis group(p<0.01). In urokinase group,mean duration of drainage(6.6 days) was significantly shorter than catheter group's(12.4 days) (p<0.01). Pattern of septation on ultrasonography could be an useful factor for determination of the therapeutic modality in patients with tuberculous pleural effusion. Percutaneous catheter drainage with urokinase instillation is a good therapeutic modality with shortened duration of drainage in treatment of pleural effusion with honeycombing septae

  18. A Comparison of Therapeutic Modalities for Septated Tuberculous PleuraI Effusion on US

    International Nuclear Information System (INIS)

    Cho, In Hwan; Kim, Kyeong Ah; Kim, Chul Joong; Kang, Eun Young; Cha, In Ho; Sim, Jae Jung

    1995-01-01

    To evaluate the utility of ultrasonography as a guide of determination of therapeutic modality an dto compare the therapeutic effects of modalities in patients with tuberculous pleural effusion. This study included 47 patients who had multiple septations on ultrasonography. We classified ultrasonographic pattern of pleural effusion into three groups according to pattern of septation : linear(n=6),moderate(n=19), honeycombing(n=22). We also classified therapeutic modalities into three groups : thoracentesis group(n=13), percutaneous catheter drainage group(n=11), intrapleural urokinase instillation group(n=23). We assessed the early and late therapeutic effects of these groups prospectively with follow-up chest radiographs. There was statistically no significant difference in therapeutic effect among the groups that had linear and moderate septa on ultrasonography(p<0.01). In patients with honeycombing septa, the therapeutic effects of catheter group and urokinase group were superior to conservative thoracentesis group(p<0.01). In urokinase group,mean duration of drainage(6.6 days) was significantly shorter than catheter group's(12.4 days) (p<0.01). Pattern of septation on ultrasonography could be an useful factor for determination of the therapeutic modality in patients with tuberculous pleural effusion. Percutaneous catheter drainage with urokinase instillation is a good therapeutic modality with shortened duration of drainage in treatment of pleural effusion with honeycombing septae

  19. A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes.

    Science.gov (United States)

    Xue, Shuai; Yin, Jianli; Shao, Jiawei; Yu, Yuanhuan; Yang, Linfeng; Wang, Yidan; Xie, Mingqi; Fussenegger, Martin; Ye, Haifeng

    2017-02-01

    Hepatogenous diabetes is a complex disease that is typified by the simultaneous presence of type 2 diabetes and many forms of liver disease. The chief pathogenic determinant in this pathophysiological network is insulin resistance (IR), an asymptomatic disease state in which impaired insulin signaling in target tissues initiates a variety of organ dysfunctions. However, pharmacotherapies targeting IR remain limited and are generally inapplicable for liver disease patients. Oleanolic acid (OA) is a plant-derived triterpenoid that is frequently used in Chinese medicine as a safe but slow-acting treatment in many liver disorders. Here, we utilized the congruent pharmacological activities of OA and glucagon-like-peptide 1 (GLP-1) in relieving IR and improving liver and pancreas functions and used a synthetic-biology-inspired design principle to engineer a therapeutic gene circuit that enables a concerted action of both drugs. In particular, OA-triggered short human GLP-1 (shGLP-1) expression in hepatogenous diabetic mice rapidly and simultaneously attenuated many disease-specific metabolic failures, whereas OA or shGLP-1 monotherapy failed to achieve corresponding therapeutic effects. Collectively, this work shows that rationally engineered synthetic gene circuits are capable of treating multifactorial diseases in a synergistic manner by multiplexing the targeting efficacies of single therapeutics. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Guijarro, Carlos; García-Díaz, Juan de Dios

    2013-01-01

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

  1. Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

    Directory of Open Access Journals (Sweden)

    Bernard Waeber

    2008-02-01

    Full Text Available Bernard Waeber1, Jean-Jacques Mourad21Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 2Hôpital Avicienne, Bobigny, FranceAbstract: A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118, a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108, or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103. The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 ± 70.5 (mean ± SD using the fixed-dose combination strategy, compared with –7.2 ± 81.0 using the sequential monotherapy approach and –17.5 ± 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril and a diuretic (indapamide.Keywords: antihypertensive therapy, tolerability, antihypertensive efficacy, fixed-dose combination, sequential monotherapy, stepped-care treatment

  2. Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.

    Science.gov (United States)

    Basson, Abigail R; Lam, Minh; Cominelli, Fabio

    2017-12-01

    The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

    Science.gov (United States)

    Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam

    2018-02-01

    Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Therapeutic strategies after coronary stenting in chronically anticoagulated patients: the MUSICA study.

    Science.gov (United States)

    Sambola, A; Ferreira-González, I; Angel, J; Alfonso, F; Maristany, J; Rodríguez, O; Bueno, H; López-Minguez, J R; Zueco, J; Fernández-Avilés, F; San Román, A; Prendergast, B; Mainar, V; García-Dorado, D; Tornos, P

    2009-09-01

    To identify the therapeutic regimens used at discharge in patients receiving oral anticoagulant therapy (OAT) who undergo stenting percutaneous coronary intervention and stent implantation (PCI-S), and to assess the safety and efficacy associated with different therapeutic regimens according to thromboembolic risk. A prospective multicentre registry. In hospital, after discharge and follow-up by telephone call. 405 patients (328 male/77 female; mean (SD) age 71 (9) years) receiving OAT who underwent PCI-S between November 2003 and June 2006 from nine catheterisation laboratories of tertiary care teaching hospitals in Spain and one in the United Kingdom were included. Three therapeutic regimens were identified at discharge: triple therapy (TT) -- that is, any anticoagulant (AC) plus double antiplatelet therapy (DAT; 278 patients (68.6%); AC and a single antiplatelet (AC+AT; 46 (11.4%)) and DAT only (81 (20%)). At 6 months, patients receiving TT showed the greatest rate of bleeding events. No patients receiving DAT at low thromboembolic risk presented a bleeding event (14.8% receiving TT, 11.8% receiving AC+AT and 0% receiving DAT, p = 0.033) or cardiovascular event (6.7% receiving TT, 0% receiving AC+AT and 0% receiving DAT, p = 0.126). The combination of AC+AT showed the worst rate of adverse events in the whole cohort, especially in patients at moderate-high thromboembolic risk. In patients receiving OAT, TT was the most commonly used regimen after PCI-S. DAT was associated with the lowest rate of bleeding events and a similar efficacy to TT in patients at low thromboembolic risk. TT should probably be restricted to patients at moderate-high thromboembolic risk.

  5. Comparison of phasing strategies for whole human genomes.

    Science.gov (United States)

    Choi, Yongwook; Chan, Agnes P; Kirkness, Ewen; Telenti, Amalio; Schork, Nicholas J

    2018-04-01

    Humans are a diploid species that inherit one set of chromosomes paternally and one homologous set of chromosomes maternally. Unfortunately, most human sequencing initiatives ignore this fact in that they do not directly delineate the nucleotide content of the maternal and paternal copies of the 23 chromosomes individuals possess (i.e., they do not 'phase' the genome) often because of the costs and complexities of doing so. We compared 11 different widely-used approaches to phasing human genomes using the publicly available 'Genome-In-A-Bottle' (GIAB) phased version of the NA12878 genome as a gold standard. The phasing strategies we compared included laboratory-based assays that prepare DNA in unique ways to facilitate phasing as well as purely computational approaches that seek to reconstruct phase information from general sequencing reads and constructs or population-level haplotype frequency information obtained through a reference panel of haplotypes. To assess the performance of the 11 approaches, we used metrics that included, among others, switch error rates, haplotype block lengths, the proportion of fully phase-resolved genes, phasing accuracy and yield between pairs of SNVs. Our comparisons suggest that a hybrid or combined approach that leverages: 1. population-based phasing using the SHAPEIT software suite, 2. either genome-wide sequencing read data or parental genotypes, and 3. a large reference panel of variant and haplotype frequencies, provides a fast and efficient way to produce highly accurate phase-resolved individual human genomes. We found that for population-based approaches, phasing performance is enhanced with the addition of genome-wide read data; e.g., whole genome shotgun and/or RNA sequencing reads. Further, we found that the inclusion of parental genotype data within a population-based phasing strategy can provide as much as a ten-fold reduction in phasing errors. We also considered a majority voting scheme for the construction of a

  6. Nanoparticles for the delivery of therapeutic antibodies: Dogma or promising strategy?

    Science.gov (United States)

    Sousa, Flávia; Castro, Pedro; Fonte, Pedro; Kennedy, Patrick J; Neves-Petersen, Maria Teresa; Sarmento, Bruno

    2017-10-01

    Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy. Another disadvantage inherent to antibody-based therapy is the limited stability of antibodies and the low level of tissue penetration. The use of nanoparticles as delivery systems for antibodies allows for a reduction in antibody dosing and may represent a suitable alternative to increase antibody stability Areas covered: We discuss different nanocarriers intended for the delivery of antibodies as well as the corresponding encapsulation methods. Recent developments in antibody nanoencapsulation, particularly the possible toxicity issues that may arise from entrapment of antibodies into nanocarriers, are also assessed. In addition, this review will discuss the alterations in antibody structure and bioactivity that occur with nanoencapsulation. Expert opinion: Nanocarriers can protect antibodies from degradation, ensuring superior bioavailability. Encapsulation of therapeutic antibodies may offer some advantages, including potential targeting, reduced immunogenicity and controlled release. Furthermore, antibody nanoencapsulation may aid in the incorporation of the antibodies into the cells, if intracellular components (e.g. intracellular enzymes, oncogenic proteins, transcription factors) are to be targeted.

  7. Novel therapeutic strategies in human malignancy: combining immunotherapy and oncolytic virotherapy

    Directory of Open Access Journals (Sweden)

    Sampath P

    2015-06-01

    Full Text Available Padma Sampath, Steve H Thorne Department of Surgery, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: Results from randomized clinical trials over the last several years have finally begun to demonstrate the potential of oncolytic viral therapies to treat a variety of cancers. One reason for these successes has been the realization that this platform is most effective when considered primarily as an immunotherapy. Cancer immunotherapy has also made dramatic strides recently with antibodies capable of blocking immune checkpoint inhibitors and adoptive T-cell therapies, notably CAR T-cells, leading a panel of novel and highly clinically effective therapies. It is clear therefore that an understanding of how and when these complementary approaches can most effectively be combined offers the real hope of moving beyond simply treating the disease and toward starting to talk about curative therapies. In this review we discuss approaches to combining these therapeutic platforms, both through engineering the viral vectors to more beneficially interact with the host immune response during therapy, as well as through the direct combinations of different therapeutics. This primarily, but not exclusively focuses on strains of oncolytic vaccinia virus. Some of the results reported to date, primarily in pre-clinical models but also in early clinical trials, are dramatic and hold great promise for the future development of similar therapies and their translation into cancer therapies. Keywords: oncolytic virus, CAR T-cell, adoptive cell therapy, immune checkpoint inhibitor 

  8. Specific transfection of inflamed brain by macrophages: a new therapeutic strategy for neurodegenerative diseases.

    Directory of Open Access Journals (Sweden)

    Matthew J Haney

    Full Text Available The ability to precisely upregulate genes in inflamed brain holds great therapeutic promise. Here we report a novel class of vectors, genetically modified macrophages that carry reporter and therapeutic genes to neural cells. Systemic administration of macrophages transfected ex vivo with a plasmid DNA (pDNA encoding a potent antioxidant enzyme, catalase, produced month-long expression levels of catalase in the brain resulting in three-fold reductions in inflammation and complete neuroprotection in mouse models of Parkinson's disease (PD. This resulted in significant improvements in motor functions in PD mice. Mechanistic studies revealed that transfected macrophages secreted extracellular vesicles, exosomes, packed with catalase genetic material, pDNA and mRNA, active catalase, and NF-κb, a transcription factor involved in the encoded gene expression. Exosomes efficiently transfer their contents to contiguous neurons resulting in de novo protein synthesis in target cells. Thus, genetically modified macrophages serve as a highly efficient system for reproduction, packaging, and targeted gene and drug delivery to treat inflammatory and neurodegenerative disorders.

  9. Photochemical internalisation, a minimally invasive strategy for light-controlled endosomal escape of cancer stem cell-targeting therapeutics.

    Science.gov (United States)

    Selbo, Pål Kristian; Bostad, Monica; Olsen, Cathrine Elisabeth; Edwards, Victoria Tudor; Høgset, Anders; Weyergang, Anette; Berg, Kristian

    2015-08-01

    Despite progress in radio-, chemo- and photodynamic-therapy (PDT) of cancer, treatment resistance still remains a major problem for patients with aggressive tumours. Cancer stem cells (CSCs) or tumour-initiating cells are intrinsically and notoriously resistant to conventional cancer therapies and are proposed to be responsible for the recurrence of tumours after therapy. According to the CSC hypothesis, it is imperative to develop novel anticancer agents or therapeutic strategies that take into account the biology and role of CSCs. The present review outlines our recent study on photochemical internalisation (PCI) using the clinically relevant photosensitiser TPCS2a/Amphinex® as a rational, non-invasive strategy for the light-controlled endosomal escape of CSC-targeting drugs. PCI is an intracellular drug delivery method based on light-induced ROS-generation and a subsequent membrane-disruption of endocytic vesicles, leading to cytosolic release of the entrapped drugs of interest. In different proof-of-concept studies we have demonstrated that PCI of CSC-directed immunotoxins targeting CD133, CD44, CSPG4 and EpCAM is a highly specific and effective strategy for killing cancer cells and CSCs. CSCs overexpressing CD133 are PDT-resistant; however, this is circumvented by PCI of CD133-targeting immunotoxins. In view of the fact that TPCS2a is not a substrate of the efflux pumps ABCG2 and P-glycoprotein (ABCB1), the PCI-method is a promising anti-CSC therapeutic strategy. Due to a laser-controlled exposure, PCI of CSC-targeting drugs will be confined exclusively to the tumour tissue, suggesting that this drug delivery method has the potential to spare distant normal stem cells.

  10. Induced-Decay of Glycine Decarboxylase Transcripts as an Anticancer Therapeutic Strategy for Non-Small-Cell Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Jing Lin

    2017-12-01

    Full Text Available Self-renewing tumor-initiating cells (TICs are thought to be responsible for tumor recurrence and chemo-resistance. Glycine decarboxylase, encoded by the GLDC gene, is reported to be overexpressed in TIC-enriched primary non-small-cell lung carcinoma (NSCLC. GLDC is a component of the mitochondrial glycine cleavage system, and its high expression is required for growth and tumorigenic capacity. Currently, there are no therapeutic agents against GLDC. As a therapeutic strategy, we have designed and tested splicing-modulating steric hindrance antisense oligonucleotides (shAONs that efficiently induce exon skipping (half maximal inhibitory concentration [IC50] at 3.5–7 nM, disrupt the open reading frame (ORF of GLDC transcript (predisposing it for nonsense-mediated decay, halt cell proliferation, and prevent colony formation in both A549 cells and TIC-enriched NSCLC tumor sphere cells (TS32. One candidate shAON causes 60% inhibition of tumor growth in mice transplanted with TS32. Thus, our shAONs candidates can effectively inhibit the expression of NSCLC-associated metabolic enzyme GLDC and may have promising therapeutic implications.

  11. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  12. Expression of PFKFB3 and Ki67 in lung adenocarcinomas and targeting PFKFB3 as a therapeutic strategy.

    Science.gov (United States)

    Li, Xiaoli; Liu, Jian; Qian, Li; Ke, Honggang; Yao, Chan; Tian, Wei; Liu, Yifei; Zhang, Jianguo

    2018-01-11

    Phosphofructokinase-2/fructose-2, 6-bisphosphatase 3 (PFKFB3) catalyzes the synthesis of F2,6BP, which is an allosteric activator of 6-phosphofructo-1-kinase (PFK-1): the rate-limiting enzyme of glycolysis. During tumorigenesis, PFKFB3 increases glycolysis, angiogenesis, and tumor progression. In this study, our aim was to investigate the significance of PFKFB3 and Ki67 in human lung adenocarcinomas and to target PFKFB3 as a therapeutic strategy. In this study, we determined the expression levels of PFKFB3 mRNA and proteins in cancerous and normal lung adenocarcinomas by quantitative reverse transcription PCR (qRT-PCR), Western blot analysis, and tissue microarray immunohistochemistry analysis, respectively. In human adenocarcinoma tissues, PFKFB3 and Ki67 protein levels were related to the clinical characteristics and overall survival. Both PFKFB3 mRNA and protein were significantly higher in lung adenocarcinoma cells (all P targeting PFKFB3, it inhibited cell viability and glycolytic activity. It also caused apoptosis and induced cell cycle arrest. Furthermore, the migration and invasion of A549 cells was inhibited. We conclude that PFKFB3 bears an oncogene-like regulatory element in lung adenocarcinoma progression. In the treatment of lung adenocarcinoma, targeting PFKFB3 would be a promising therapeutic strategy.

  13. Fight or buy? A comparison of internationalization strategies.

    OpenAIRE

    Roland Kirstein

    2013-01-01

    The paper evaluates three internationalization strategies of a company that considers invading a foreign market: • It can buy a firm that resides in the target market (acquisition strategy), • it can produce at home and export into the target market (export strategy), • or the two firms can agree upon produce in the invader's home country and sell the products in the target market (OEM strategy). For simplicity, we assume that the incumbent firm in the target country has a monopoly position. ...

  14. Comparison of mathematical problem solving strategies of primary school pupils

    OpenAIRE

    Wasilewská, Eliška

    2016-01-01

    The aim of this dissertation is to describe the role of educational strategy especially in field of the teaching of mathematics and to compare the mathematical problem solving strategies of primary school pupils which are taught by using different educational strategies. In the theoretical part, the main focus is on divergent educational strategies and their characteristics, next on factors affected teaching/learning process and finally on solving the problems. The empirical part of the disse...

  15. Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

    Science.gov (United States)

    Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

    2017-04-11

    CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

  16. MESENCHYMAL STEM CELLS AS A THERAPEUTIC STRATEGY FOR MULTIPLE SCLEROSIS: ISSUES AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    M. M. Zafranskaya

    2017-01-01

    Full Text Available The ability of mesenchymal stem cells (MSC to influence the regulatory/suppressive effect in the autoimmune process and promote remyelination allows to consider them a new method of multiple sclerosis (MS therapy, by means of modifying the disease activity. Genetic stability, proliferative potential, ability to migrate into the damaged tissue areas and agreed protocols for isolation and culture are the main advantages for successful autologous, as well as allogeneic MSC therapy. Preliminary results from clinical studies using MSC application in MS patients show efficiency and safety of this therapeutic approach. Nevertheless, successful demonstration of the cell therapy in MS is only possible after detailed analysis and understanding of MSC biology and mechanisms of appropriate intercellular interactions. The article reviews general experience in usage of immunomodulatory and neuroprotective properties of MSС in MS, and highlights the issues of validity in cell-based therapy taking into account both in vitro и in vivo studies.

  17. Novel strategies and therapeutic options for the management of primary biliary cholangitis.

    Science.gov (United States)

    Khanna, Amardeep; Jones, David E

    2017-10-01

    Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease. It has a varied course of progression ranging from being completely asymptomatic to aggressive disease leading to cirrhosis and resulting in liver transplantation. In addition, symptoms can be debilitating and can have a major impact on quality of life. For decades, there was only one anti-cholestatic agent available to target this disease and that was only effective in around half of patients, with little or no effect on symptoms. With increasing understanding of the pathogenic mechanisms of PBC and potential targets for drug treatment, pharmaceutical companies have shown a greater interest in this rare disease. A large number of novel therapeutic molecules have been developed and are currently being evaluated. In this review article all the novel molecules in use and in trials targeting cholestasis and symptoms in PBC are discussed.

  18. Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.

    LENUS (Irish Health Repository)

    Wander, Seth A

    2011-04-01

    Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

  19. Electrochemotherapy as a new therapeutic strategy in advanced Merkel cell carcinoma of head and neck region

    International Nuclear Information System (INIS)

    Scelsi, Daniele; Mevio, Niccolò; Bertino, Giulia; Occhini, Antonio; Brazzelli, Valeria; Morbini, Patrizia; Benazzo, Marco

    2013-01-01

    Merkel Cell Carcinoma (MCC) is a rare and aggressive tumour, arising from a cutaneous mechanoceptor cell located in the basal layer of epidermis, with poor prognosis. The treatment of choice for the initial stage of the disease is surgery and/or radiotherapy. The treatment of recurrent or advanced disease is still controversial. We report a case of 84 years old woman with a recurrent MCC of the chin treated with electrochemotherapy (ECT). During the period of 20 months, four sessions of ECT were employed, which resulted in an objective response of the tumour and good quality of residual life. Our case shows the effectiveness of ECT in the treatment of locally advanced MCC of the head and neck region in a patient not suitable for standard therapeutic options

  20. Shared epitope-antagonistic ligands: a new therapeutic strategy in mice with erosive arthritis.

    Science.gov (United States)

    Ling, Song; Liu, Ying; Fu, Jiaqi; Colletta, Alessandro; Gilon, Chaim; Holoshitz, Joseph

    2015-05-01

    The mechanisms underlying bone damage in rheumatoid arthritis (RA) are incompletely understood. We recently identified the shared epitope (SE), an HLA-DRB1-coded 5-amino acid sequence motif carried by the majority of RA patients as a signal transduction ligand that interacts with cell surface calreticulin and accelerates osteoclast (OC)-mediated bone damage in collagen-induced arthritis (CIA). Given the role of the SE/calreticulin pathway in arthritis-associated bone damage, we sought to determine the therapeutic targetability of calreticulin. A library of backbone-cyclized peptidomimetic compounds, all carrying an identical core DKCLA sequence, was synthesized. The ability of these compounds to inhibit SE-activated signaling and OC differentiation was tested in vitro. The effect on disease severity and OC-mediated bone damage was studied by weekly intraperitoneal administration of the compounds to DBA/1 mice with CIA. Two members of the peptidomimetics library were found to have SE-antagonistic effects and antiosteoclast differentiation effects at picomolar concentrations in vitro. The lead mimetic compound, designated HS(4-4)c Trp, potently ameliorated arthritis and bone damage in vivo when administered in picogram doses to mice with CIA. Another mimetic analog, designated HS(3-4)c Trp, was found to lack activity, both in vitro and in vivo. The differential activity of the 2 analogs depended on minor differences in their respective ring sizes and correlated with distinctive geometry when computationally docked to the SE binding site on calreticulin. These findings identify calreticulin as a novel therapeutic target in erosive arthritis and provide sound rationale and early structure/activity relationships for future drug design. © 2015, American College of Rheumatology.

  1. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

    Science.gov (United States)

    Shim, Hyunbo

    2011-10-31

    To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

  2. Comparison of Value Generation Strategies Between Planned and Emerging Strategies: A Study Based on Games of Companies

    Directory of Open Access Journals (Sweden)

    Marcos Paixão Garcez

    2012-06-01

    Full Text Available This study aims to analyze the economic results of the planned strategies compared to the emergent strategies in decision-making. The theoretical background emphasizes some aspects, like the strategy concept evolution throughout the time, the typology of strategies proposed by Mintzberg, the comparison between competition and cooperation, and the use of a business simulator as a tool for business research purposes. As a controlled experiment, the EGS simulator (Management Exercise Simulated allowed comparison of the economic results of the two decision-making situations. The findings show that when planned strategies were implemented without corrections, the value generated (expressed by the internal rate of return IRR = 1.51% was greater than in the case of adjusted emerging strategies in three periods (IRR= 1.40%. Comparing the two situations, it is possible to find a value added advantage of 7.86% in favor of the planned strategies, indicating the competition might be responsible for the value decreasing in real environment. Analyzing the performance degrees reached by the competitors, the ranking results show that there is no association between planned strategy and emerging strategies. Although the business simulators can be considered weak approximations for the business environment, the experiment contributed new evidence of the competition rise in oligopoly industries and a new methodological approach for studying this phenomenon.

  3. Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

    Energy Technology Data Exchange (ETDEWEB)

    Pauls, Sandra [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: sandra.pauls@uni-ulm.de; Kuerschner, Christian [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: chris.kuerschner@web.de; Dharaiya, Ekta [CT-Clinical Science, Philips Medical Systems, Highland Heights, OH 44143 (United States)], E-mail: ekta.shah@philips.com; Muche, Rainer [Institute of Biometrics, University of Ulm, Schwabstrasse 13, 89075 Ulm (Germany)], E-mail: rainer.muche@uni-ulm.de; Schmidt, Stefan A. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: stefan-a.schmidt@gmx.de; Krueger, Stefan [Department of Internal Medicine II, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: s.krueger@uniklinik-ulm.de; Brambs, Hans-Juergen [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: hans-juergen.brambs@uniklinik-ulm.de; Aschoff, Andrik J. [Department of Diagnostic and Interventional Radiology, University of Ulm, Robert-Koch-Strasse 8, 89081 Ulm (Germany)], E-mail: andrik.aschoff@uni-ulm.de

    2008-04-15

    Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant.

  4. Comparison of manual and automated size measurements of lung metastases on MDCT images: Potential influence on therapeutic decisions

    International Nuclear Information System (INIS)

    Pauls, Sandra; Kuerschner, Christian; Dharaiya, Ekta; Muche, Rainer; Schmidt, Stefan A.; Krueger, Stefan; Brambs, Hans-Juergen; Aschoff, Andrik J.

    2008-01-01

    Purpose: The goal of this study was to evaluate the influence of automated measurement of diameter, area, and volume from chest CT scans on therapeutic decisions of lung nodules as compared to manual 2-D measurements. Patients and method: The retrospective study involved 25 patients with 75 lung metastases. Contrast enhanced CT scans (16 row) of the lung were performed three times during chemotherapy with a mean time interval of 67.9 days between scans. In each patient, three metastases were evaluated (n = 225). Automatic measurements were compared to manual assessment for the following parameters: diameter, area, and density. The influence on the therapeutic decisions was evaluated using the RECIST criteria. Results: The maximum diameter measured by the automatic application was on an average 27% (S.D. 39; CI: 0.22-0.32; p < 0.0001) higher than the maximum diameter with manual assessment, and the differences depended on metastases size. Based on diameter calculation, manual and automated assessment disagreed in up to 32% of therapeutic decisions. Volumetric assessment tended towards more changes in therapy as compared to diameter calculation. The calculation of mean transversal area of metastases was 36% (S.D. 0.305; CI: -0.40 to -0.32; p < 0.0001) less with automated measurement. Therapeutic strategy would be changed in up to 25.7% of nodules using automated area calculation. Automated assessment of nodules' area and volume could influence the therapeutic decisions in up to 51.4% of all nodules. Density of the nodules was not validated to determine the influence on therapeutic decisions. Conclusion: There is a discrepancy between the manual and automated size measurement of lung metastases which could be significant

  5. Vatuximab(Trademark): Optimizing Therapeutic Strategies for Prostate Cancer Based on Dynamic MR Tumor Oximetry

    Science.gov (United States)

    2010-01-01

    159: 621-631, 2003. 37. Bourke , V. A., Zhao, D., Gilio, J., Chang, C.-H., Jiang, L., Hahn, E. W., and Mason, R. P. Correlation of Radiation...probe: comparison with a paired survival assay. Radiat Res, 158, 167-73 (2002) 27. Gu, Y. Q., V. A. Bourke , J. G. Kim, A. Constantinescu, R. P. Mason...Res. 1998; 150: 549–556. 10. Bourke VA, Zhao D, Gilio J, Chang C-H, Jiang L, Hahn EW, Mason RP. Correlation of radiation response with tumor oxygen

  6. A comparison of body image concern in candidates for rhinoplasty and therapeutic surgery.

    Science.gov (United States)

    Hashemi, Seyed Amirhosein Ghazizadeh; Edalatnoor, Behnoosh; Edalatnoor, Behnaz; Niksun, Omid

    2017-09-01

    Body dysmorphic disorder among patients referring for cosmetic surgeries is a disorder that if not diagnosed by a physician, can cause irreparable damage to the doctor and the patient. The aim of this study was to compare body image concern in candidates for rhinoplasty and therapeutic surgery. This was a cross-sectional study conducted on 212 patients referring to Loghman Hospital of Tehran for rhinoplasty and therapeutic surgery during the period from 2014 through 2016. For each person in a cosmetic surgery group, a person of the same sex and age in a therapeutic surgery group was matched, and the study was conducted on 60 subjects in the rhinoplasty group and 62 patients in the therapeutic surgery group. Then, the Body Image Concern Inventory and demographic data were filled by all patients and the level of body image concern in both groups was compared. Statistical analysis was conducted using SPSS 16, Chi-square test as well as paired-samples t-test. P-value of less than 0.05 was considered statistically significant. In this study, 122 patients (49 males and 73 females) with mean age of 27.1±7.3 between 18 and 55 years of age were investigated. Sixty subjects were candidates for rhinoplasty and 62 subjects for therapeutic surgery. Candidates for rhinoplasty were mostly male (60%) and single (63.3%). Results of the t-test demonstrated that body image concern and body dysmorphic disorder were higher in the rhinoplasty group compared to the therapeutic group (pconcern was higher in rhinoplasty candidates compared to candidates for other surgeries. Visiting and correct interviewing of people who referred for rhinoplasty is very important to measure their level of body image concern to diagnose any disorders available and to consider required treatments.

  7. Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Osamu Natsume

    2018-01-01

    Full Text Available Therapeutic strategy in late 20th century to prevent allergic diseases was derived from a conceptual framework of allergens elimination which was as same as that of coping with them after their onset. Manifold trials were implemented; however, most of them failed to verify the effectiveness of their preventive measures. Recent advancement of epidemiological studies and cutaneous biology revealed epidermal barrier dysfunction plays a major role of allergen sensitization and development of atopic dermatitis which ignites the inception of allergy march. For this decade, therapeutic strategy to prevent the development of food allergy has been confronted with a paradigm shift from avoidance and delayed introduction of allergenic foods based on the theoretical concept to early introduction of them based on the clinical and epidemiological evidences. Especially, prevention of peanut allergy and egg allergy has been established with the highest evidence verified by randomized controlled trials, although application in clinical practice should be done with attention. This paradigm shift concerning food allergy was also due to the discovery of cutaneous sensitization risk of food allergens for an infant with eczema revealed by prospective studies. Here we have recognized the increased importance of prevention of eczema/atopic dermatitis in infancy. Two randomized controlled trials using emollients showed successful results in prevention of atopic dermatitis in infancy; however, longer term safety and prognosis including allergy march should be pursued. To establish more fundamental strategy for prevention of the development of allergy, further studies clarifying the mechanisms of interaction between barrier dysfunction and microbial milieu are needed with macroscope to understand the relationship between allergic diseases and a diversity of environmental influences.

  8. Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: Case report

    Directory of Open Access Journals (Sweden)

    Altmeyer Peter

    2004-09-01

    Full Text Available Abstract Background Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. Case presentation We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1+ and anti-mastcell-tryptase+ cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. Conclusions Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition.

  9. Targeting protein neddylation: a novel therapeutic strategy for the treatment of cancer.

    Science.gov (United States)

    Wang, Meng; Medeiros, Bruno C; Erba, Harry P; DeAngelo, Daniel J; Giles, Francis J; Swords, Ronan T

    2011-03-01

    The NEDD8 (neural precursor cell-expressed developmentally downregulated 8) conjugation pathway regulates the post-translational modification of oncogenic proteins. This pathway has important potential for cancer therapeutics. Several proteins vital in cancer biology are regulated by protein neddylation. These observations led to the development of a small molecule inhibitor that disrupts protein neddylation and leads to cancer cell death and important activity in early phase clinical trials. This review provides an extensive coverage of cellular protein homeostasis with particular emphasis on the NEDD8 conjugation pathway. Insights into a new investigational drug that specifically disrupts the NEDD8 pathway are discussed. The clinical data for this agent are also updated. Neddylation controls key cellular pathways found to be dysregulated in many cancers. Protein neddylation is a relatively under-explored pathway for pharmacologic inhibition in cancer. Selective disruption of this pathway has demonstrated clinical activity in patients with myeloid neoplasms and is worth exploring further in combination with other anti-leukemia agents.

  10. The impact of cellular senescence in skin ageing: A notion of mosaic and therapeutic strategies.

    Science.gov (United States)

    Toutfaire, Marie; Bauwens, Emilie; Debacq-Chainiaux, Florence

    2017-10-15

    Cellular senescence is now recognized as one of the nine hallmarks of ageing. Recent data show the involvement of senescent cells in tissue ageing and some age-related diseases. Skin represents an ideal model for the study of ageing. Indeed, skin ageing varies between individuals depending on their chronological age but also on their exposure to various exogenous factors (mainly ultraviolet rays). If senescence traits can be detected with ageing in the skin, the senescent phenotype varies among the various skin cell types. Moreover, the origin of cellular senescence in the skin is still unknown, and multiple origins are possible. This reflects the mosaic of skin ageing. Senescent cells can interfere with their microenvironment, either via the direct secretion of factors (the senescence-associated secretory phenotype) or via other methods of communication, such as extracellular vesicles. Knowledge regarding the impact of cellular senescence on skin ageing could be integrated into dermatology research, especially to limit the appearance of senescent cells after photo(chemo)therapy or in age-related skin diseases. Therapeutic approaches include the clearance of senescent cells via the use of senolytics or via the cooperation with the immune system. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Multiple sclerosis in children: an update on clinical diagnosis, therapeutic strategies, and research

    Science.gov (United States)

    Waldman, Amy; Ghezzi, Angelo; Bar-Or, Amit; Mikaeloff, Yann; Tardieu, Marc; Banwell, Brenda

    2015-01-01

    The clinical features, diagnostic challenges, neuroimaging appearance, therapeutic options, and pathobiological research progress in childhood—and adolescent—onset multiple sclerosis have been informed by many new insights in the past 7 years. National programmes in several countries, collaborative research efforts, and an established international paediatric multiple sclerosis study group have contributed to revised clinical diagnostic definitions, identified clinical features of multiple sclerosis that differ by age of onset, and made recommendations regarding the treatment of paediatric multiple sclerosis. The relative risks conveyed by genetic and environmental factors to paediatric multiple sclerosis have been the subject of several large cohort studies. MRI features have been characterised in terms of qualitative descriptions of lesion distribution and applicability of MRI aspects to multiple sclerosis diagnostic criteria, and quantitative studies have assessed total lesion burden and the effect of the disease on global and regional brain volume. Humoral-based and cell-based assays have identified antibodies against myelin, potassium-channel proteins, and T-cell profiles that support an adult-like T-cell repertoire and cellular reactivity against myelin in paediatric patients with multiple sclerosis. Finally, the safety and efficacy of standard first-line therapies in paediatric multiple sclerosis populations are now appreciated in more detail, and consensus views on the future conduct and feasibility of phase 3 trials for new drugs have been proposed. PMID:25142460

  12. Gene Editing and CRISPR Therapeutics: Strategies Taught by Cell and Gene Therapy.

    Science.gov (United States)

    Ramirez, Juan C

    2017-01-01

    A few years ago, we assisted in the demonstration for the first time of the revolutionary idea of a type of adaptive-immune system in the bacteria kingdom. This system, named CRISPR, and variants engineered in the lab, have been demonstrated as functional with extremely high frequency and fidelity in almost all eukaryotic cells studied to date. The capabilities of this RNA-guided nuclease have added to the interest that was announced with the advent of previous technologies for genome editing tools, such as ZFN and TALEN. The capabilities exhibited by these gene editors, opens up a novel scenario that indicates the promise of a next-generation medicine based on precision and personalized objectives, mostly due to the change in the paradigm regarding gene-surgery. This has certainly attracted, like never before, the attention of the biotech business and investor community. This chapter offers a brief overview of some of the factors that have contributed to a rapid entry into the biotech and pharmaceutical company's pipeline, focusing on how cell and gene therapies (CGT), collectively known as advanced therapies, have become the driving forces toward the therapeutic uses of gene editing technology. The sum of all those efforts for more than 30years has contributed to the new paradigm of considering genes as medicines. Copyright © 2017. Published by Elsevier Inc.

  13. [Therapeutics strategies for the management of urinary tract infection in children].

    Science.gov (United States)

    Launay, E; Bingen, E; Cohen, R

    2012-11-01

    Urinary tract infections is one of the most common bacterial infections in pediatrics The increasing involvement of multiresistant bacteria including E. coli producing extended spectrum ß-lactamase (ESBL) makes its management difficult. The purpose of this article is to evaluate the state of the art and to propose ways of thinking about the management of E. coli urinary tract infection in children. The current percentage (less than 10%) of E. coli strains resistant to third generation cephalosporins and the relative efficiency of the latter, should not led to an immediate change of our protocols. Nevertheless, we should verify as soon as possible susceptibility of E. coli responsible for urinary tract infections and consider other therapeutic options for initial therapy and adaptation after obtaining antibiogram. The use of an aminoglycosid as initial treatment seems very interesting. Aminoglycosides have a very good distribution in the renal parenchyma and are still working on the majority of ESBL-producing bacteria. A rapid oral relay after 48 to 72 hours may be proposed according to the results of the susceptibility with either cotrimoxazole, cefixime, ciprofloxacin or an association cefixime-amoxicilline/clavulanate. The treatment of cystitis due to ESBL E. coli is much less problematic given the good urinary beta-lactam antibiotics diffusion. If clinical improvement occurs, even if antibiogram shows that the strain is resistant to the antibiotic prescribed, it is usually unnecessary to change treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  14. The third therapeutic system: faith healing strategies in the context of a generalized AIDS epidemic.

    Science.gov (United States)

    Manglos, Nicolette D; Trinitapoli, Jenny

    2011-03-01

    Faith healing in sub-Saharan Africa has primarily been studied qualitatively among Pentecostal-Charismatic groups, and considered as its own phenomenon with little attention to its relationship to other modes of healing. Using data from Malawi, a religiously diverse African country with high HIV prevalence, we find that faith healing is pervasive across multiple religious traditions. For individuals, attending a faith healing congregation is associated with lower levels of generalized worry about AIDS, and this association is driven by those who switched churches before AIDS became widespread in rural areas. Use of condoms and traditional medicine are, on the other hand, positively associated with worry about AIDS. We argue that faith healing can be understood as a third therapeutic system that coexists with the well-documented biomedical and traditional systems. The success of faith healing approaches lies in their unique ability to combine individual-pragmatic and communal-ritualized aspects of healing to inform interpretations of the AIDS epidemic and its consequences.

  15. Bariatric Surgery for Adolescents with Type 2 Diabetes: an Emerging Therapeutic Strategy.

    Science.gov (United States)

    Stefater, M A; Inge, T H

    2017-08-01

    Type 2 diabetes (T2D) is a growing public health problem in youth, but conventional treatments are often insufficient to treat this disease and its comorbidities. We review evidence supporting an emerging role for bariatric surgery as a treatment for adolescent T2D. Paralleling what has been seen in adult patients, bariatric surgery dramatically improves glycemic control in patients with T2D. In fact, remission of T2D has been observed in as many as 95-100% of adolescents with diabetes after bariatric surgery, particularly vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) surgery. This striking outcome may be due to both weight-dependent- and weight-independent factors, and recent studies suggest that T2D-related comorbidities may also improve after surgery. Bariatric surgery including RYGB and VSG is a powerful therapeutic option for obese adolescents with T2D. Benefits must be weighed against risk for postoperative complications such as nutritional deficiencies, but earlier surgical intervention might lead to more complete metabolic remission in obese patients with T2D.

  16. Mini-Review: Novel Therapeutic Strategies to Blunt Actions of Pneumolysin in the Lungs

    Directory of Open Access Journals (Sweden)

    Martin Leustik

    2013-07-01

    Full Text Available Severe pneumonia is the main single cause of death worldwide in children under five years of age. The main etiological agent of pneumonia is the G+ bacterium Streptococcus pneumoniae, which accounts for up to 45% of all cases. Intriguingly, patients can still die days after commencing antibiotic treatment due to the development of permeability edema, although the pathogen was successfully cleared from their lungs. This condition is characterized by a dramatically impaired alveolar epithelial-capillary barrier function and a dysfunction of the sodium transporters required for edema reabsorption, including the apically expressed epithelial sodium channel (ENaC and the basolaterally expressed sodium potassium pump (Na+-K+-ATPase. The main agent inducing this edema formation is the virulence factor pneumolysin, a cholesterol-binding pore-forming toxin, released in the alveolar compartment of the lungs when pneumococci are being lysed by antibiotic treatment or upon autolysis. Sub-lytic concentrations of pneumolysin can cause endothelial barrier dysfunction and can impair ENaC-mediated sodium uptake in type II alveolar epithelial cells. These events significantly contribute to the formation of permeability edema, for which currently no standard therapy is available. This review focuses on discussing some recent developments in the search for the novel therapeutic agents able to improve lung function despite the presence of pore-forming toxins. Such treatments could reduce the potentially lethal complications occurring after antibiotic treatment of patients with severe pneumonia.

  17. The Third Therapeutic System: Faith Healing Strategies in the Context of a Generalized AIDS Epidemic

    Science.gov (United States)

    Manglos, Nicolette D.; Trinitapoli, Jenny

    2014-01-01

    Faith healing in sub-Saharan Africa has primarily been studied qualitatively among Pentecostal-Charismatic groups, and considered as its own phenomenon with little attention to its relationship to other modes of healing. Using data from Malawi, a religiously diverse African country with high HIV prevalence, we find that faith healing is pervasive across multiple religious traditions. For individuals, attending a faith healing congregation is associated with lower levels of generalized worry about AIDS, and this association is driven by those who switched churches before AIDS became widespread in rural areas. Use of condoms and traditional medicine are, on the other hand, positively associated with worry about AIDS. We argue that faith healing can be understood as a third therapeutic system that coexists with the well-documented biomedical and traditional systems. The success of faith healing approaches lies in their unique ability to combine individual-pragmatic and communal-ritualized aspects of healing to inform interpretations of the AIDS epidemic and its consequences. PMID:21362615

  18. Comparison of loads for wind turbine down-regulation strategies

    DEFF Research Database (Denmark)

    Zhu, Jiangsheng; Ma, Kuichao; N. Soltani, Mohsen

    2017-01-01

    For wind farm active power setpoint tracking, both farm level and turbine level down regulation strategies should to be optimized. Several down regulation strategies are chosen to analyse the wind turbine load performance according to different wind speed and power reference. In this paper we...... suggest appropriate down regulation strategy to control wind turbine for active power reference tracking. we compare four different control strategies, namely Const-Ω, Const-λ, Max-Ω and Min-Ct and discuss the loads on main components and downwind speed by presenting analysis of several wind scenarios...

  19. Multidisciplinary perspectives for Alzheimer's and Parkinson's diseases: hydrogels for protein delivery and cell-based drug delivery as therapeutic strategies.

    Science.gov (United States)

    Giordano, Carmen; Albani, Diego; Gloria, Antonio; Tunesi, Marta; Batelli, Sara; Russo, Teresa; Forloni, Gianluigi; Ambrosio, Luigi; Cigada, Alberto

    2009-12-01

    This review presents two intriguing multidisciplinary strategies that might make the difference in the treatment of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The first proposed strategy is based on the controlled delivery of recombinant proteins known to play a key role in these neurodegenerative disorders that are released in situ by optimized polymer-based systems. The second strategy is the use of engineered cells, encapsulated and delivered in situ by suitable polymer-based systems, that act as drug reservoirs and allow the delivery of selected molecules to be used in the treatment of Alzheimer's and Parkinson's diseases. In both these scenarios, the design and development of optimized polymer-based drug delivery and cell housing systems for central nervous system applications represent a key requirement. Materials science provides suitable hydrogel-based tools to be optimized together with suitably designed recombinant proteins or drug delivering-cells that, once in situ, can provide an effective treatment for these neurodegenerative disorders. In this scenario, only interdisciplinary research that fully integrates biology, biochemistry, medicine and materials science can provide a springboard for the development of suitable therapeutic tools, not only for the treatment of Alzheimer's and Parkinson's diseases but also, prospectively, for a wide range of severe neurodegenerative disorders.

  20. Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases

    Directory of Open Access Journals (Sweden)

    Singh R

    2018-03-01

    Full Text Available Rajan Singh,1,2 Shehla Pervin,1,2 Se-Jin Lee,3,4 Alan Kuo,5 Victor Grijalva,6 John David,7 Laurent Vergnes,8 Srinivasa T Reddy1,6 1Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA, USA; 2Division of Endocrinology and Metabolism, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; 3The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA; 4Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, CT, USA; 5Department of Biology, California State University Dominguez Hills, CA, USA; 6Department of Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA, USA; 7Department of Comparative Medicine, Pfizer Inc, San Diego, CA, USA; 8Department of Human Genetics, UCLA School of Medicine, Los Angeles, CA, USA Background: Follistatin (Fst promotes brown adipocyte characteristics in adipose tissues.Methods: Abdominal fat volume (CT scan, glucose clearance (GTT test, and metabolomics analysis (mass spectrometry of adipose tissues from Fst transgenic (Fst-Tg and wild type (WT control mice were analyzed. Oxygen consumption (Seahorse Analyzer and lipidomics (gas chromatography was analyzed in 3T3-L1 cells.Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice. Furthermore, overexpression of Fst in 3T3-L1 cells resulted in up regulation of key brown/beige markers and changes in lipidomics profiles. Conclusion: Fst modulates key factors involved in promoting metabolic syndrome and could be used for therapeutic intervention. Keywords: follistatin, transgenic, adipocyte, fibroblast growth factor 21, AdipoQ

  1. Cost-effectiveness of diagnostic-therapeutic strategies for paediatric visceral leishmaniasis in Morocco.

    Science.gov (United States)

    Alonso, Sergi; Tachfouti, Nabil; Najdi, Adil; Sicuri, Elisa; Picado, Albert

    2017-01-01

    Visceral leishmaniasis (VL) is a neglected parasitic disease with a high fatality rate if left untreated. Endemic in Morocco, as well as in other countries in the Mediterranean basin, VL mainly affects children living in rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow (BM) aspirates is used to diagnose VL and meglumine antimoniate (SB) is the first line of treatment. Less invasive, more efficacious and safer alternatives exist. In this study we estimate the cost-effectiveness of alternative diagnostic-therapeutic algorithms for paediatric VL in Morocco. A decision tree was used to estimate the cost-effectiveness of using BM or rapid diagnostic tests (RDTs) as diagnostic tools and/or SB or two liposomal amphotericin B (L-AmB) regimens: 6-day and 2-day courses to treat VL. Incremental cost-effectiveness ratios, expressed as cost per death averted, were estimated by comparing costs and effectiveness of the alternative algorithms. A threshold analysis evaluated at which price L-AmB became cost-effective compared with current practices. Implementing RDT and/or L-AmB treatments would be cost-effective in Morocco according to the WHO thresholds. Introducing the 6-day course L-AmB, current second-line treatment, would be highly cost-effective if L-AmB price was below US$100/phial. The 2-day L-AmB treatment, current standard treatment of paediatric VL in France, is highly cost-effective, with L-AmB at its market price (US$165/phial). The results of this study should encourage the implementation of RDT and/or short-course L-AmB treatments for paediatric VL management in Morocco and other North African countries.

  2. Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

    Science.gov (United States)

    Malik, Shabana T; Birch, Brian R; Voegeli, David; Fader, Mandy; Foria, Vipul; Cooper, Alan J; Walls, Andrew F; Lwaleed, Bashir A

    2018-05-15

    To identify the presence and geographical distribution of mast cell (MC) subtypes: MC T (tryptase positive-chymase negative) and MC TC (tryptase positive-chymase positive) in bladder tissue. Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MC T and MC TC ) and anti-MC chymase (for MC TC ). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MC TC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MC TC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Therapeutic Strategies against Epstein-Barr Virus-Associated Cancers Using Proteasome Inhibitors.

    Science.gov (United States)

    Hui, Kwai Fung; Tam, Kam Pui; Chiang, Alan Kwok Shing

    2017-11-21

    Epstein-Barr virus (EBV) is closely associated with several lymphomas (endemic Burkitt lymphoma, Hodgkin lymphoma and nasal NK/T-cell lymphoma) and epithelial cancers (nasopharyngeal carcinoma and gastric carcinoma). To maintain its persistence in the host cells, the virus manipulates the ubiquitin-proteasome system to regulate viral lytic reactivation, modify cell cycle checkpoints, prevent apoptosis and evade immune surveillance. In this review, we aim to provide an overview of the mechanisms by which the virus manipulates the ubiquitin-proteasome system in EBV-associated lymphoid and epithelial malignancies, to evaluate the efficacy of proteasome inhibitors on the treatment of these cancers and discuss potential novel viral-targeted treatment strategies against the EBV-associated cancers.

  4. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

    Science.gov (United States)

    Manna, Prasenjit

    2015-01-01

    Abstract Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue

  5. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

    Science.gov (United States)

    Manna, Prasenjit; Jain, Sushil K

    2015-12-01

    Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in

  6. Imbalanced pattern completion vs. separation in cognitive disease: network simulations of synaptic pathologies predict a personalized therapeutics strategy

    Directory of Open Access Journals (Sweden)

    Hanson Jesse E

    2010-08-01

    Full Text Available Abstract Background Diverse Mouse genetic models of neurodevelopmental, neuropsychiatric, and neurodegenerative causes of impaired cognition exhibit at least four convergent points of synaptic malfunction: 1 Strength of long-term potentiation (LTP, 2 Strength of long-term depression (LTD, 3 Relative inhibition levels (Inhibition, and 4 Excitatory connectivity levels (Connectivity. Results To test the hypothesis that pathological increases or decreases in these synaptic properties could underlie imbalances at the level of basic neural network function, we explored each type of malfunction in a simulation of autoassociative memory. These network simulations revealed that one impact of impairments or excesses in each of these synaptic properties is to shift the trade-off between pattern separation and pattern completion performance during memory storage and recall. Each type of synaptic pathology either pushed the network balance towards intolerable error in pattern separation or intolerable error in pattern completion. Imbalances caused by pathological impairments or excesses in LTP, LTD, inhibition, or connectivity, could all be exacerbated, or rescued, by the simultaneous modulation of any of the other three synaptic properties. Conclusions Because appropriate modulation of any of the synaptic properties could help re-balance network function, regardless of the origins of the imbalance, we propose a new strategy of personalized cognitive therapeutics guided by assay of pattern completion vs. pattern separation function. Simulated examples and testable predictions of this theorized approach to cognitive therapeutics are presented.

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

    Science.gov (United States)

    Dobrovolskaia, Marina A; McNeil, Scott E

    2015-07-01

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

  8. A comparison of the radiochemical stability of different iodine-131 labelled metaiodobenzylguanidine formulations for therapeutic use

    International Nuclear Information System (INIS)

    Wafelman, A.R.; Beijnen, J.H.; Hoefnagel, C.A.; Maes, R.A.A.

    1994-01-01

    The results of a stability study of three commercially available formulations of [ 131 I]MIBG for therapeutic use and an unstabilized formulation, stored under various conditions, are presented. The stability was followed for 20 days. In all formulations tested, free [ 131 I]iodide, formed by radiolysis, was the most important radiochemical impurity. The pharmaceutical formulation with the largest amount of stabilizer was radiochemically - but not chemically -most stable. (author)

  9. Novel Therapeutic Strategies in the Management of Non-Variceal Upper Gastrointestinal Bleeding

    Directory of Open Access Journals (Sweden)

    Ari Garber

    2016-09-01

    Full Text Available Non-variceal upper gastrointestinal bleeding, the most common etiology of which is peptic ulcer disease, remains a persistent challenge despite a reduction in both its incidence and mortality. Both pharmacologic and endoscopic techniques have been developed to achieve hemostasis, with varying degrees of success. Among the pharmacologic therapies, proton pump inhibitors remain the mainstay of treatment, as they reduce the risk of rebleeding and requirement for recurrent endoscopic evaluation. Tranexamic acid, a derivative of the amino acid lysine, is an antifibrinolytic agent whose role requires further investigation before application. Endoscopically delivered pharmacotherapy, including Hemospray (Cook Medical, EndoClot (EndoClot Plus Inc., and Ankaferd Blood Stopper (Ankaferd Health Products, in addition to standard epinephrine, show promise in this regard, although their mechanisms of action require further investigation. Non-pharmacologic endoscopic techniques use one of the following two methods to achieve hemostasis: ablation or mechanical tamponade, which may involve using endoscopic clips, cautery, argon plasma coagulation, over-the-scope clipping devices, radiofrequency ablation, and cryotherapy. This review aimed to highlight these novel and fundamental hemostatic strategies and the research supporting their efficacy.

  10. Interplay Between Peripheral and Central Inflammation in Autism Spectrum Disorders: Possible Nutritional and Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Claudia Cristiano

    2018-03-01

    Full Text Available Pre- and post-natal factors can affect brain development and function, impacting health outcomes with particular relevance to neurodevelopmental diseases, such as autism spectrum disorders (ASDs. Maternal obesity and its associated complications have been related to the increased risk of ASDs in offspring. Indeed, animals exposed to maternal obesity or high fat diets are prone to social communication impairment and repetitive behavior, the hallmarks of autism. During development, fatty acids and sugars, as well as satiety hormones, like insulin and leptin, and inflammatory factors related to obesity-induced low grade inflammation, could play a role in the impairment of neuroendocrine system and brain neuronal circuits regulating behavior in offspring. On the other side, post-natal factors, such as mode of delivery, stress, diet, or antibiotic treatment are associated to a modification of gut microbiota composition, perturbing microbiota-gut-brain axis. Indeed, the interplay between the gastrointestinal tract and the central nervous system not only occurs through neural, hormonal, and immune pathways, but also through microbe-derived metabolic products. The modification of unhealthy perinatal and postnatal environment, manipulation of gut microbiota, nutritional, and dietary interventions could represent possible strategies in preventing or limiting ASDs, through targeting inflammatory process and gut microbiota.

  11. Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells.

    Science.gov (United States)

    Silva, Luisa H A; Cruz, Fernanda F; Morales, Marcelo M; Weiss, Daniel J; Rocco, Patricia R M

    2017-03-09

    Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

  12. Targeting Hsp90-Cdc37: A Promising Therapeutic Strategy by Inhibiting Hsp90 Chaperone Function.

    Science.gov (United States)

    Wang, Lei; Li, Li; Gu, Kai; Xu, Xiao-Li; Sun, Yuan; You, Qi-Dong

    2017-01-01

    The Hsp90 chaperone protein regulates the folding, maturation and stability of a wide variety of oncoproteins. In recent years, many Hsp90 inhibitors have entered into the clinical trials while all of them target ATPase showing similar binding capacity and kinds of side-effects so that none have reached to the market. During the regulation progress, numerous protein- protein interactions (PPI) such as Hsp90 and client proteins or cochaperones are involved. With the Hsp90-cochaperones PPI networks being more and more clear, many cancerous proteins have been reported to be tightly correlated to Hsp90-cochaperones PPI. Among them, Hsp90-Cdc37 PPI has been widely reported to associate with numerous protein kinases, making it a novel target for the treatment of cancers. In this paper, we briefly review the strategies and modulators targeting Hsp90-Cdc37 complex including direct and indirect regulation mechanism. Through these discussions we expect to present inspirations for new insights into an alternative way to inhibit Hsp90 chaperone function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Review: Pichia pastoris represents an alternative for human glycoprotein production for therapeutic use. Fermentation strategies

    Directory of Open Access Journals (Sweden)

    Henry Córdoba Ruiz

    2003-07-01

    Full Text Available Producing human proteins in lower organisms' cells using recombinant technology represents a very promising approach for treating many diseases produced by a particular protein deficiency, including close to 40 lysosomal storage diseases. Although E. coli has been the first host successfully employed in expressing human recombinant proteins, it has some limitations owing to its inability to perform some post-traductional steps such as glycosylation. The yeast Saccharomyces cerevisiae (S. cerevisiae has thusbeen initially considered and used. However, S. cerevisiae glycosylates proteins in a very different way to human cells producing highly antigenic proteins and thus some other non-conventional yeasts such as Pichia pastoris have been used recently. Human protein expression is not assodated with growth in this system; growth may occur at high cell concentrations, increasing heterologous protein productivity and yield. The system employs a very efficient, methanol-induced promoter which may be used as sole carbon and energy source. Post-traductional modifications seem more similar to human cells than those produced by other non-mammalian systems used in producing human glycoproteins; they do not secrete large amounts of endogenous proteins, simplifying expressed protein purification. This review presents some strategies for producing heterologous proteins in high density cultures using P. pastoris as an expression system.

  14. Nanomedicine targeting the tumor microenvironment: Therapeutic strategies to inhibit angiogenesis, remodel matrix, and modulate immune responses

    Directory of Open Access Journals (Sweden)

    Elizabeth L. Siegler

    2016-11-01

    Full Text Available Increasing attention has been given to the tumor microenvironment (TME, which includes cellular and structural components such as fibroblasts, immune cells, vasculature, and extracellular matrix (ECM that surround tumor sites. These components contribute to tumor growth and metastasis and are one reason why traditional chemotherapy often is insufficient to eradicate the tumor completely. Newer treatments that target aspects of the TME, such as antiangiogenic and immunostimulatory therapies, have seen limited clinical success despite promising preclinical results. This can be attributed to a number of reasons, including a lack of drug penetration deeper into the necrotic tumor core, nonspecific delivery, rapid clearance from serum, or toxic side effects at high doses. Nanoparticles offer a potential solution to all of these obstacles, and many recent studies have shown encouraging results using nanomedicine to target TME vasculature, ECM, and immune response. While few of these platforms have made it to clinical trials to date, these strategies are relatively new and may offer a way to improve the effects of anticancer therapies.

  15. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    Science.gov (United States)

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  16. Disrupting established tumor blood vessels: an emerging therapeutic strategy for cancer.

    Science.gov (United States)

    McKeage, Mark J; Baguley, Bruce C

    2010-04-15

    The unique characteristics of tumor vasculature represent an attractive target that may be exploited by vascular-targeting anticancer agents. A promising strategy involves the selective disruption of established tumor blood vessels by tumor-vascular disrupting agents (tumor-VDAs), which exhibit antivascular activity, resulting in inhibition of tumor blood flow and extensive necrosis within the tumor core. The tumor-VDA class can be subdivided into flavonoid compounds, which are related to flavone acetic acid, and tubulin-binding compounds. ASA404, of the flavonoid class, is the most advanced tumor-VDA in clinical development and has been evaluated preclinically and in several phase 1 and phase 2 studies. Preclinical studies have demonstrated the selective apoptosis of tumor endothelial cells and the inhibition of tumor blood flow. Synergistic activity was observed with ASA404 and with several chemotherapeutic agents, particularly taxanes. In clinical trials, compared with chemotherapy alone, ASA404 was tolerated well and produced improved activity in patients with nonsmall cell lung cancer when combined with paclitaxel and carboplatin. Phase 3 clinical trials are ongoing. Selectively targeting established tumor vasculature with tumor-VDAs represents a promising and innovative approach to improving the efficacy of standard anticancer therapies. (c) 2010 American Cancer Society.

  17. Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

    Science.gov (United States)

    Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

    2017-08-22

    Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

  18. Transcutaneous spinal stimulation as a therapeutic strategy for spinal cord injury: state of the art

    Directory of Open Access Journals (Sweden)

    Grecco LH

    2015-03-01

    Full Text Available Leandro H Grecco,1,3,4,* Shasha Li,1,5,* Sarah Michel,1,6,* Laura Castillo-Saavedra,1 Andoni Mourdoukoutas,7 Marom Bikson,7 Felipe Fregni1,21Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, 2Spaulding-Harvard Spinal Cord Injury Model System, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA, USA; 3Special Laboratory of Pain and Signaling, Butantan Institute, 4Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil; 5Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China; 6Department of Pharmacy and Biomedical Sciences, University of Namur, Belgium; 7Department of Biomedical Engineering, The City College of New York, New York, NY, USA*These authors contributed equally to this workAbstract: Treatments for spinal cord injury (SCI still have limited effects. Electrical stimulation might facilitate plastic changes in affected spinal circuitries that may be beneficial in improving motor function and spasticity or SCI-related neuropathic pain. Based on available animal and clinical evidence, we critically reviewed the physiological basis and therapeutic action of transcutaneous spinal cord stimulation in SCI. We analyzed the literature published on PubMed to date, looking for the role of three main noninvasive stimulation techniques in the recovery process of SCI and focusing mainly on transcutaneous spinal stimulation. This review discusses the main clinical applications, latest advances, and limitations of noninvasive electrical stimulation of the spinal cord. Although most recent research in this topic has focused on transcutaneous spinal direct current stimulation (tsDCS, we also reviewed the technique of transcutaneous electric nerve stimulation (TENS and neuromuscular electrical stimulation (NMES as potential methods to modulate spinal cord

  19. Comparison of Mathematics and Humanitarian Sciences Students’ Metacognitive Strategies

    Directory of Open Access Journals (Sweden)

    Gholam Hossein Javanmard

    2014-09-01

    Full Text Available Abstract The purpose of this study was to compare the differences of using meta-cognitive strategies in high school students who study in the fields of mathematics and humanities. For do this, 140 high school students were selected randomly. The Swanson’s Meta-cognition Strategies Test was administrated for sample groups. The acquired means for two regroups were compared with t-test for two independent groups’ method. Results indicated that two groups were meaningfully differed from each other (sig=0.01 in using meta-cognitive strategies, and mean of students in mathematics field were high. Also there was a meaningful difference in task component between two groups (sig=0.002, and the mean of students in mathematics field was higher than from students in humanities field in this component. The high school students in mathematics field use more metacognitive strategies, especially task component, than the students in humanities field.

  20. A clinical feature and therapeutic strategy in pituitary adenomas associated with intracranial aneurysms

    International Nuclear Information System (INIS)

    Sasagawa, Yasuo; Tachibana, Osamu; Shiraga, Shunsuke; Takata, Hisasi; Akai, Takuya; Iizuka, Hideaki

    2012-01-01

    We studied the clinical feature and treatment strategy of pituitary adenomas associated with intracranial aneurysms. Among 102 pituitary adenoma patients (mean age: 54.8 years old) who received MR angiography and/or 3D-CT angiography,seven patients (6.9%) had intracranial aneurysms. The association of an aneurysm was more common in large size adenomas (p<0.05). According to the location of the aneurysms,five patients had these in the paraclinoid portion or cavernous portion of the internal carotid artery. Using MR images,we classified the aneurysms associated with pituitary adenomas as non-adjacent,adjacent,and intra-adenoma types. In non-adjacent types,an aneurysm is located apart from the adenoma,and has less chance of exposure during transsphenoidal surgery. In adjacent types,an aneurysm is located adjacent to the adenoma,and could be exposed during transsphenoidal surgery. In intra-adenoma types,an aneurysm is encased in the adenoma. In non-adjacent type aneurysms,a resection of the pituitary adenoma can be carried out before aneurysm treatment due to the low risk of rupture during surgery. In adjacent types,a tumor resection can precede aneurysm treatment in cases of low rupture risk aneurysms and untreatable aneurysms. In intra-adenoma types,adenoma resection should come after treatment of the aneurysms. Neurosurgeons should be careful about not only the presence of aneurysms in preoperative images during transsphenoidal surgery planning,but also their locations and proximity to adenomas. Such information may be crucial in deciding the order of treatment. (author)

  1. Deciphering the therapeutic stem cell strategies of large and midsize pharmaceutical firms.

    Science.gov (United States)

    Vertès, Alain A

    2014-01-01

    The slow adoption of cytotherapeutics remains a vexing hurdle given clinical progress achieved to date with a variety of stem cell lineages. Big and midsize pharmaceutical companies as an asset class still delay large-scale investments in this arena until technological and market risks will have been further reduced. Nonetheless, a handful of stem cell strategic alliance and licensing transactions have already been implemented, indicating that progress is actively monitored, although most of these involve midsize firms. The greatest difficulty is, perhaps, that the regenerative medicine industry is currently only approaching the point of inflexion of the technology development S-curve, as many more clinical trials read out. A path to accelerating technology adoption is to focus on innovation outliers among healthcare actors. These can be identified by analyzing systemic factors (e.g., national science policies and industry fragmentation) and intrinsic factors (corporate culture, e.g., nimble decision-making structures; corporate finance, e.g., opportunity costs and ownership structure; and operations, e.g., portfolio management strategies, threats on existing businesses and patent expirations). Another path is to accelerate the full clinical translation and commercialization of an allogeneic cytotherapeutic product in any indication to demonstrate the disease-modifying potential of the new products for treatment and prophylaxis, ideally for a large unmet medical need such as dry age-related macular degeneration, or for an orphan disease such as biologics-refractory acute graft-versus-host disease. In times of decreased industry average research productivities, regenerative medicine products provide important prospects for creating new franchises with a market potential that could very well mirror that achieved with the technology of monoclonal antibodies.

  2. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

    Directory of Open Access Journals (Sweden)

    Kenneth Maiese

    2016-01-01

    Full Text Available Throughout the globe, diabetes mellitus (DM is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1 and mTOR Complex 2 (mTORC2 and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K, protein kinase B (Akt, AMP activated protein kinase (AMPK, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae (SIRT1, Wnt1 inducible signaling pathway protein 1 (WISP1, and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

  3. Strategies for targeting tetraspanin proteins: potential therapeutic applications in microbial infections.

    Science.gov (United States)

    Hassuna, Noha; Monk, Peter N; Moseley, Gregory W; Partridge, Lynda J

    2009-01-01

    The identification of novel targets and strategies for therapy of microbial infections is an area of intensive research due to the failure of conventional vaccines or antibiotics to combat both newly emerging diseases (e.g. viruses such as severe acute respiratory syndrome (SARS) and new influenza strains, and antibiotic-resistant bacteria) and entrenched, pandemic diseases exemplified by HIV. One clear approach to this problem is to target processes of the host organism rather than the microbe. Recent data have indicated that members of the tetraspanin superfamily, proteins with a widespread distribution in eukaryotic organisms and 33 members in humans, may provide such an approach. Tetraspanins traverse the membrane four times, but are distinguished from other four-pass membrane proteins by the presence of conserved charged residues in the transmembrane domains and a defining 'signature' motif in the larger of the two extracellular domains (the EC2). They characteristically form promiscuous associations with one another and with other membrane proteins and lipids to generate a specialized type of microdomain: the tetraspanin-enriched microdomain (TEM). TEMs are integral to the main role of tetraspanins as 'molecular organizers' involved in functions such as membrane trafficking, cell-cell fusion, motility, and signaling. Increasing evidence demonstrates that tetraspanins are used by intracellular pathogens as a means of entering and replicating within human cells. Although previous investigations focused mainly on viruses such as hepatitis C and HIV, it is now becoming clear that other microbes associate with tetraspanins, using TEMs as a 'gateway' to infection. In this article we review the properties and functions of tetraspanins/TEMs that are relevant to infective processes and discuss the accumulating evidence that shows how different pathogens exploit these properties in infection and in the pathogenesis of disease. We then investigate the novel and exciting

  4. A comparison of non-fi nancial strategy disclosure in the annual ...

    African Journals Online (AJOL)

    A comparison of non-fi nancial strategy disclosure in the annual reports of South African ... Southern African Business Review ... Overall, however, there are vast differences in the levels of non-fi nancial strategy disclosure in both countries, ...

  5. Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

    Science.gov (United States)

    Del Río-Sancho, S; Serna-Jiménez, C E; Sebastián-Morelló, M; Calatayud-Pascual, M A; Balaguer-Fernández, C; Femenía-Font, A; Kalia, Y N; Merino, V; López-Castellano, A

    2017-01-30

    Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81μgcm -2 h -1 whereas the highest iontophoretic transport was 46.4±3.6μgcm -2 h -1 . These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Comparison of Power Control Strategies for DFIG Wind Turbines

    DEFF Research Database (Denmark)

    Teodorescu, Remus; Luna, A.; Rodríguez, P.

    2008-01-01

    The classical control techniques for regulating the active and reactive power delivery in doubly fed induction generators (DFIG), for wind power applications, are normally based on voltage oriented control (VOC) strategies. Among these algorithms, those that work in a synchronous reference frame...... VOC strategy able to control the operation of a DFIG in the αβ reference frame, with no need of flux position estimation, something that conducts to a more simple and robust algorithm. In order to evaluate the advantages of this new control proposal, namely VOC-RRF, their performance will be compared...

  7. Shifting social identities as a strategy for deflecting threatening social comparisons.

    Science.gov (United States)

    Mussweiler, T; Gabriel, S; Bodenhausen, G V

    2000-09-01

    Results of three studies suggest that the multifaceted nature of identity provides a strategic basis for reducing the threat involved in upward social comparisons. After performing worse than a comparison standard, people may strategically emphasize aspects of their identity that differentiate them from the standard, thereby making the standard less relevant for self-evaluation. On the basis of previous research showing that persons low in self-esteem are less likely to make effective use of self-protection strategies, we hypothesized that this strategy of deflecting the threat involved in upward comparison (i.e., decreasing perceived comparability by emphasizing an unshared social identity) would be used primarily by persons who are characteristically high in self-esteem. This pattern was confirmed in three studies. Moreover, use of the strategy was associated with relatively more positive affect following threatening upward comparisons.

  8. Rework and postponement: a comparison of bottling strategies

    NARCIS (Netherlands)

    R.H. Teunter (Ruud); S.D.P. Flapper

    2003-01-01

    textabstractThis paper presents the results of a case study in a batch production facility for biological vaccines. The problem considered is that of finding the best bottling strategy for produced batches. A batch can be bottled directly after production, after positive intermediate test results,

  9. Comparison of Two Educational Strategies in Teaching Preventive Cardiology.

    Science.gov (United States)

    Stroup-Benham, Christine A.; And Others

    This study assessed the impact of two educational strategies: text only versus text plus small group discussion, among two groups of third-year internal medicine clerkship students in a preventive cardiology course. The course was a required, 12-week Internal Medical clerkship at the University of Texas Medical Branch. The first group reviewed…

  10. Comparison of different strategies for decommissioning a tritium laboratory

    International Nuclear Information System (INIS)

    Kris Dylst

    2009-01-01

    Full text: Between 2003 and 2009 two rooms that served as tritium laboratory at SCK-CEN and its ventilation system were decommissioned. Initially, the decommissioning strategy was to free release as much materials as possible. The low free release limit imposed by the Belgian authorities made decommissioning of the first laboratory room very labor intensive. Timing restrictions forced us to use a different strategy for the ventilation system. Steel that could not be easily decontaminated was disposed to a nuclear melting facility. Compared to similar work done on steel in the lab, the new strategy took less than 80% of the man hours in only 40% of the calendar days. For the second laboratory a similar strategy was used: contaminated steel was disposed to a nuclear melting facility, other materials that could not be easily decontaminated were disposed as nuclear waste. Compared to the first laboratory the decommissioning was done in less than 40% of the time using merely one third of the man hours, although at the expense of extra waste generation. Economically, as far as not easily decontaminated materials are concerned, steel is best disposed to a nuclear melting and it is worth to invest in the decontamination of other materials. (author)

  11. Comparison of empirical strategies to maximize GENEHUNTER lod scores.

    Science.gov (United States)

    Chen, C H; Finch, S J; Mendell, N R; Gordon, D

    1999-01-01

    We compare four strategies for finding the settings of genetic parameters that maximize the lod scores reported in GENEHUNTER 1.2. The four strategies are iterated complete factorial designs, iterated orthogonal Latin hypercubes, evolutionary operation, and numerical optimization. The genetic parameters that are set are the phenocopy rate, penetrance, and disease allele frequency; both recessive and dominant models are considered. We selected the optimization of a recessive model on the Collaborative Study on the Genetics of Alcoholism (COGA) data of chromosome 1 for complete analysis. Convergence to a setting producing a local maximum required the evaluation of over 100 settings (for a time budget of 800 minutes on a Pentium II 300 MHz PC). Two notable local maxima were detected, suggesting the need for a more extensive search before claiming that a global maximum had been found. The orthogonal Latin hypercube design was the best strategy for finding areas that produced high lod scores with small numbers of evaluations. Numerical optimization starting from a region producing high lod scores was the strategy that found the highest maximum observed.

  12. Multiple function benefit - cost comparison of conservation buffer placement strategies

    Science.gov (United States)

    Z. Qiu; M.G. Dosskey

    2012-01-01

    Conservation buffers are considered to be effective practices for repairing impaired streams and restoring multiple ecosystem functions in degraded agricultural watersheds. Six different planning strategies for targeting their placement within watersheds were compared in terms of cost-effectiveness for environmental improvement in the 144 km² Neshanic River...

  13. A Novel Therapeutic Strategy for the Treatment of Glioma, Combining Chemical and Molecular Targeting of Hsp90α

    International Nuclear Information System (INIS)

    Mehta, Adi; Shervington, Leroy; Munje, Chinmay; Shervington, Amal

    2011-01-01

    Hsp90α's vital role in tumour survival and progression, together with its highly inducible expression profile in gliomas and its absence in normal tissue and cell lines validates it as a therapeutic target for glioma. Hsp90α was downregulated using the post-transcriptional RNAi strategy (sihsp90α) and a post-translational inhibitor, the benzoquinone antibiotic 17-AAG. Glioblastoma U87-MG and normal human astrocyte SVGp12 were treated with sihsp90α, 17-AAG and concurrent sihsp90α/17-AAG (combined treatment). Both Hsp90α gene silencing and the protein inhibitor approaches resulted in a dramatic reduction in cell viability. Results showed that sihsp90α, 17-AAG and a combination of sihsp90α/17-AAG, reduced cell viability by 27%, 75% and 88% (p < 0.001), respectively, after 72 h. hsp90α mRNA copy numbers were downregulated by 65%, 90% and 99% after 72 h treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG, respectively. The relationship between Hsp90α protein expression and its client Akt kinase activity levels were monitored following treatment with sihsp90α, 17-AAG and sihsp90α/17-AAG. Akt kinase activity was downregulated as a direct consequence of Hsp90α inhibition. Both Hsp90α and Akt kinase levels were significantly downregulated after 72 h. Although, 17-AAG when used as a single agent reduces the Hsp90α protein and the Akt kinase levels, the efficacy demonstrated by combinatorial treatment was found to be far more effective. Combination treatment reduced the Hsp90α protein and Akt kinase levels to 4.3% and 43%, respectively, after 72 h. hsp90α mRNA expression detected in SVGp12 was negligible compared to U87-MG, also, the combination treatment did not compromise the normal cell viability. Taking into account the role of Hsp90α in tumour progression and the involvement of Akt kinase in cell signalling and the anti-apoptotic pathways in tumours, this double targets treatment infers a novel therapeutic strategy

  14. A Comparison of Three Online Recruitment Strategies for Engaging Parents.

    Science.gov (United States)

    Dworkin, Jodi; Hessel, Heather; Gliske, Kate; Rudi, Jessie H

    2016-10-01

    Family scientists can face the challenge of effectively and efficiently recruiting normative samples of parents and families. Utilizing the Internet to recruit parents is a strategic way to find participants where they already are, enabling researchers to overcome many of the barriers to in-person recruitment. The present study was designed to compare three online recruitment strategies for recruiting parents: e-mail Listservs, Facebook, and Amazon Mechanical Turk (MTurk). Analyses revealed differences in the effectiveness and efficiency of data collection. In particular, MTurk resulted in the most demographically diverse sample, in a short period of time, with little cost. Listservs reached a large number of participants and resulted in a comparatively homogeneous sample. Facebook was not successful in recruiting a general sample of parents. Findings provide information that can help family researchers and practitioners be intentional about recruitment strategies and study design.

  15. Comparison of different control strategies on FMD in Denmark

    DEFF Research Database (Denmark)

    Boklund, Anette; Hisham Beshara Halasa, Tariq; Christiansen, Lasse Engbo

    2012-01-01

    The purpose of this study was to compare different control strategies that could be used in Denmark during an outbreak of FMD, based on epidemiological, ethical and economic parameters. Nearly a hundred different control strategies and more than 30 sensitivity analyses were run, changing between...... to extract the essence of the results. All results will be presented in the final project report, which will be available on request to the authors. Comparing epidemiological outputs showed that extra control measures will always reduce the average duration and size of an epidemic. However, the variations...... in duration and size of epidemics are large, and if epidemics are small, extra control measures may not always be necessary. Comparing depopulation to suppressive and protective vaccination shows that from an epidemiologic point of view, vaccination will be beneficial. However, comparing the economy...

  16. Comparison of equalisation strategies for multi-carrier CDMA

    OpenAIRE

    Cooper, MA; Armour, SMD; Bian, YQ; McGeehan, JP

    2003-01-01

    This paper focuses on the bit error rate (BER) performance of equalisation strategies for a downlink MC-CDMA based system. Simulation results utilising maximal ratio combining (MRC), orthogonal restoring combining (ORC), equal gain combining (EGC) and minimum mean square error combining (MMSEC) for a multiuser scenario are presented. In addition, we analyse the relative complexities of each scheme and discuss their suitability for implementation in future consumer products

  17. Therapeutic drug monitoring of digoxin in cardiac heart failure outpatients: comparisons of two analytical methods

    Directory of Open Access Journals (Sweden)

    Isabel Cristina Medeiros Barros

    2014-01-01

    Full Text Available Objective: To compare two analytical techniques used in the determination of plasma digoxin (LC-MS/MS and immunoassay and to verify which one better answer the need of the clinical monitoring routine of patients with cardiac heart failure. Method: The clinical findings in 15 cardiac heart failure (CHF outpatients of the Cardiac Heart Service of the Goias Federal University Clinical Hospital were investigated. Blood samples of the patients were collected and analysed by Immunoassay and by Liquid Chromatography coupled to Mass Spectrometry (LC-MS/MS. Results: The results of the statistic test (Student p = 0,05 showed a significant difference between the analytical methods: immunoassay concentrations were higher than the concentrations determined by LCMS/ MS. The explanation may be because immunoassay method measures digoxin plus other metabolites and endogenous substances, while the LC-MS/MS method measures only the digoxin molecule. None of the patients, showed relevant clinical data suggestive of digitalis intoxication, even several drugs with potential interaction were associated with treatment. Conclusion: It was concluded, therefore, that LC-MS/MS me thod is safer, more selective and specific than immunoassay, being an option for therapeutic drug monitoring of digoxin, since the reference values would be obtain for digoxinemia by LC-MS/MS.

  18. Comparison of therapeutic lipid target achievements among high-risk patients in Oman.

    Science.gov (United States)

    Al-Waili, Khalid; Al-Zakwani, Ibrahim; Al-Dughaishi, Tamima; Baneerje, Yajnavalka; Al-Sabti, Hilal; Al-Hashmi, Khamis; Farhan, Hatem; Habsi, Khadija Al; Al-Hinai, Ali T; Al-Rasadi, Khalid

    2014-05-01

    We compared therapeutic lipid target achievements among patients with diabetes or coronary heart disease (CHD) in Oman. A retrospective chart review of 94 patients was conducted at an outpatient clinic in Sultan Qaboos University Hospital, Muscat, Oman. The variables included low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apo B). The overall mean age of the cohort was 59 ± 12 years, 54% were male, 66% were diabetic, 48% hypertensive, 45% had CHD, 94% were on simvastatin, 4% were on fenofibrate, and 2% were on both simvastatin and fenofibrate. Lipid goal attainments of calculated LDL-C (<2.6 mmol/L), apo B (<0.9 g/L), and non-HDL-C (<3.36 mmol/L) were reached in 52%, 39%, and 53% of the patients, respectively. A significant proportion of high-risk patients treated with lipid-lowering agents reach LDL-C but not the apo B treatment targets, suggesting that the use of apo B target values should also be considered.

  19. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    International Nuclear Information System (INIS)

    Motoo, Yoshiharu; Shimasaki, Takeo; Ishigaki, Yasuhito; Nakajima, Hideo; Kawakami, Kazuyuki; Minamoto, Toshinari

    2011-01-01

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation

  20. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Energy Technology Data Exchange (ETDEWEB)

    Motoo, Yoshiharu, E-mail: motoo@kanazawa-med.ac.jp [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Shimasaki, Takeo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan); Ishigaki, Yasuhito [Medical Research Institute, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Nakajima, Hideo [Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293 (Japan); Kawakami, Kazuyuki; Minamoto, Toshinari [Division of Translational & Clinical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa (Japan)

    2011-01-24

    Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  1. Disrupted Signaling through the Fanconi Anemia Pathway Leads to Dysfunctional Hematopoietic Stem Cell Biology: Underlying Mechanisms and Potential Therapeutic Strategies

    Science.gov (United States)

    Geiselhart, Anja; Lier, Amelie; Walter, Dagmar; Milsom, Michael D.

    2012-01-01

    Fanconi anemia (FA) is the most common inherited bone marrow failure syndrome. FA patients suffer to varying degrees from a heterogeneous range of developmental defects and, in addition, have an increased likelihood of developing cancer. Almost all FA patients develop a severe, progressive bone marrow failure syndrome, which impacts upon the production of all hematopoietic lineages and, hence, is thought to be driven by a defect at the level of the hematopoietic stem cell (HSC). This hypothesis would also correlate with the very high incidence of MDS and AML that is observed in FA patients. In this paper, we discuss the evidence that supports the role of dysfunctional HSC biology in driving the etiology of the disease. Furthermore, we consider the different model systems currently available to study the biology of cells defective in the FA signaling pathway and how they are informative in terms of identifying the physiologic mediators of HSC depletion and dissecting their putative mechanism of action. Finally, we ask whether the insights gained using such disease models can be translated into potential novel therapeutic strategies for the treatment of the hematologic disorders in FA patients. PMID:22675615

  2. Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies

    Directory of Open Access Journals (Sweden)

    Toshinari Minamoto

    2011-01-01

    Full Text Available Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer. We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.

  3. Survey and comparison of nuclear power strategy and concepts worldwide

    International Nuclear Information System (INIS)

    Kupitz, J.; Breidenbach, L.

    1995-01-01

    The steady growth of the world's population and the enhancement of the standard of living will make the demand for energy grow correspondingly. Not only for economic reasons, but also in the interest of the environment and the global climate will strategies for meeting the global energy demand have recourse to nuclear energy. One can even expect a renaissance of nuclear technology based on evolutionary and innovative developments, as nuclear energy is the sole energy source offering the potentials of power generation at justifiable technological risk and economic investment, while contributing to curbing CO 2 emissions. Nuclear technology transfer to the developing countries however is an important task in this strategy for the future. Transfer of know-how and simpler technical standards are required (common problems, common rules, common products). Also, the development of breeder reactors and high-temperature reactors should be a major objective, in order to fully exploit the nuclear option, i.e. conserve energy resources, and meet the demand for process heat. The wide range of tasks ahead in the development of advanced nuclear reactors requires enhanced cooperation and exchange of information at international level. Experience and capacities of the IAEA make this organisation the proper and sole available global forum for performing the tasks to be fulfilled, and Member Countries of the IAEA should support the organisation also in their own interest. (orig.) [de

  4. Comparison of different strategies for soybean antioxidant extraction.

    Science.gov (United States)

    Chung, Hyun; Ji, Xiangming; Canning, Corene; Sun, Shi; Zhou, Kequan

    2010-04-14

    Three extraction strategies including Soxhlet extraction, conventional solid-liquid extraction, and ultrasonic-assisted extraction (UAE) were compared for their efficiency to extract phenolic antioxidants from Virginia-grown soybean seeds. Five extraction solvents were evaluated in UAE and the conventional extraction. The soybean extracts were compared for their total phenolic contents (TPC), oxygen radical absorbance capacity (ORAC), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)) scavenging activities. The results showed that UAE improved the extraction of soybean phenolic compounds by >54% compared to the conventional and Soxhlet extractions. Among the tested solvents, 50% acetone was the most efficient for extracting soybean phenolic compounds. There was no significant correlation between the TPC and antioxidant activities of the soybean extracts. The extracts prepared by 70% ethanol had the highest ORAC values. Overall, UAE with 50% acetone or 70% ethanol is recommended for extracting soybean antioxidants on the basis of the TPC and ORAC results.

  5. Comparison of sedation strategies for critically ill patients

    DEFF Research Database (Denmark)

    Hutton, Brian; Burry, Lisa D.; Kanji, Salmaan

    2016-01-01

    Background: Sedatives and analgesics are administered to provide sedation and manage agitation and pain in most critically ill mechanically ventilated patients. Various sedation administration strategies including protocolized sedation and daily sedation interruption are used to mitigate drug...... their efficacy and safety for mechanically ventilated patients. Methods: We will search the following from 1980 to March 2016: Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science. We will also search the Cochrane Library, gray literature, and the International Clinical Trials Registry Platform. We...... of interest include duration of mechanical ventilation, time to first extubation, ICU and hospital length of stay, re-intubation, tracheostomy, mortality, total sedative and opioid exposure, health-related quality of life, and adverse events. To inform our NMA, we will first conduct conventional pair...

  6. Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs in comparison with terbinafine.

    Science.gov (United States)

    Ohsumi, Keisuke; Murai, Hidetsugu; Nakamura, Ikko; Watanabe, Masato; Fujie, Akihiko

    2014-10-01

    AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has potent inhibitory activity against Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III) and potent fungicidal activity against T. mentagrophytes, as measured in vitro. Here, we compared the effects of AS2077715 and terbinafine in a guinea pig model of tinea pedis. In a treatment regimen started from the day 7 after infection, 10 daily oral doses of 10 and 20 mg kg(-1) AS2077715 and 20 mg kg(-1) of terbinafine significantly decreased fungal colony-forming units (CFUs) in foot pad skin. In a treatment regimen started from the day 11 after infection, 20 mg kg(-1) AS2077715 significantly reduced fungal CFUs in foot pad skin after 7 daily doses in comparison with 20 mg kg(-1) terbinafine-treated guinea pigs. Our findings suggest that in vivo potency and efficacy of AS2077715 are equal to or greater than that of terbinafine, positioning AS2077715 as a good candidate for use in treating trichophytosis.

  7. Comparison among nonlinear excitation control strategies used for damping power system oscillations

    International Nuclear Information System (INIS)

    Leon, A.E.; Solsona, J.A.; Valla, M.I.

    2012-01-01

    Highlights: ► A description and comparison of nonlinear control strategies for synchronous generators are presented. ► Advantages of using nonlinear controllers are emphasized against the use of classical PSSs. ► We find that a particular selection of IDA gains achieve the same performance that FL controllers. - Abstract: This work is focused on the problem of power system stability. A thorough description of nonlinear control strategies for synchronous generator excitation, which are designed for damping oscillations and improving transient stability on power systems, is presented along with a detailed comparison among these modern strategies and current solutions based on power system stabilizers. The performance related to damping injection in each controller, critical time enhancement, robustness against parametric uncertainties, and control signal energy consumption is analyzed. Several tests are presented to validate discussions on various advantages and disadvantages of each control strategy.

  8. Model-based comparison of strategies for reduction of stormwater micropollutant emissions

    DEFF Research Database (Denmark)

    Vezzaro, Luca; Sharma, Anitha Kumari; Mikkelsen, Peter Steen

    to improve the recipient quality by reducing the fluxes of heavy metals (copper, zinc) and organic compounds (fluoranthene) to natural waters. MP sources were identified by using GIS land usage data. When comparing the different control strategies, the integrated model showed the greater benefits......Strategies for reduction of micropollutant (MP) emissions from stormwater systems require the comparison of different scenarios including source control, end-of-pipe treatment, or their combination. Dynamic integrated models can be important tools for this comparison, as they can integrate...... the limited data provided by monitoring campaigns and evaluate the performance of different strategies based on model simulation results. This study presents an example where an integrated dynamic model, in combination with stormwater quality measurements, was used to evaluate 6 different strategies...

  9. Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

    Science.gov (United States)

    Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

    2013-01-01

    [Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

  10. Comparison of Teaching Strategies for Cultural Humility in Physical Therapy.

    Science.gov (United States)

    Paparella-Pitzel, Susan; Eubanks, Robin; Kaplan, Sandra L

    2016-01-01

    Cultural competence and cultural humility are ongoing processes that healthcare professionals should continually strive for in order to provide effective and comprehensive plans of care for patients. This 2-year, longitudinal, educational pilot study describes the levels of competency in second-year entry-level physical therapy students and compares the outcomes of three teaching strategies for cultural competence and cultural humility. All students received a standard 2-hour lecture; study volunteers were randomly assigned to one of two enriched educational groups, involving a standardized patient or a paper case enrichment. Students shifted from initial levels of "culturally incompetent" and/or "culturally aware" to "culturally competent" as measured by the Inventory for Assessing the Process of Cultural Competence Among Healthcare Professionals-Revised. This shift was maintained after 1.5 yrs following the exposure. Because the enriched educational groups were underpowered, preliminary quantitative data are inconclusive, but qualitative feedback from students is strongly positive. A minimal dose of a structured 2-hr lecture with a skilled instructor, who creates a safe environment for cultural learning, produced positive shifts toward greater cultural competence. Five processes emerged for teaching cultural humility that may assist in designing comprehensive educational experiences on this topic. A framework for organizing course content is presented.

  11. Performance Comparison of Geobroadcast Strategies for Winding Roads

    Directory of Open Access Journals (Sweden)

    Edgar Talavera

    2018-03-01

    Full Text Available Vehicle-to-X (V2X communications allow real-time information sharing between vehicles and Roadside Units (RSUs. These kinds of technologies allow for the improvement of road safety and can be used in combination with other systems. Advanced Driver Assistance Systems (ADAS are an example and can be used along with V2X communications to improve performance and enable Cooperative Systems. A key element of vehicular communications is that the information transmitted through the network is always linked to a GPS position related to origin and destination (GeoNetworking protocol in order to adjust the data broadcast to the dynamic road environment needs. In this paper, we present the implementation and development of Institute for Automobile Research (INSIA V2X communication modules that follow the European vehicular networking standards in a close curve in a winding road where poor visibility causes a risk to the safety of road users. The technology chosen to support these communications is ETSI ITS-G5, which has the capability to enable specific services that support GeoNetworking protocols, specifically the Geobroadcast (GBC algorithm. These functionalities have been implemented and validated in a real environment in order to demonstrate the performance of the communication devices in real V2V (Vehicle-to-Vehicle and V2I (Vehicle-to-Infrastructure situations. GBC messages are also compared with two different configurations of emission area. A comparison with/without RSU modules in critical areas of the road with previous knowledge of the road cartography has also been made.

  12. Comparison of the therapeutic effect between sodium bicarbonate and insulin on acute propafenone toxicity.

    Science.gov (United States)

    Yi, Hwa Yeon; Lee, Jang Young; Lee, Won Suk; Sung, Won Young; Seo, Sang Won

    2014-10-01

    Unlike other sodium-channel-blocking antiarrhythmic agents, propafenone has β-blocking effects and calcium-channel-blocking effects. Yi et al recently studied insulin's treatment effect on acute propafenone toxicity in rats. However, because the degree of effectiveness of insulin compared to the previously known antidote sodium bicarbonate (NaHCO3) was not studied, the 2 treatment methods were compared for propafenone intoxication in rats. Rats received intravenous propafenone (36 mg/[kg h]) for 12 minutes. After the induction of toxicity, rats (n = 10 per group) received normal saline solution (NSS), NaHCO3, or insulin with glucose as treatment. Animals in the NSS, NaHCO3, and Insulin groups received an intravenous infusion of 36 mg/(kg h) propafenone until death occurred. For each animal, the mean arterial pressure (MAP, heart rate, PR interval, QRS duration, total hemoglobin, sodium, potassium, potential of hydrogen, bicarbonate, glucose, lactate, and central venous oxygen saturation (Scvo2) were measured and compared among the groups. Survival of the Insulin group was greater than that of the NSS group by log-rank test (P = .021). Sodium bicarbonate prevented the decline of MAP for 55 minutes. In comparison, insulin prevented the decline of MAP and heart rate, and the elongation of the PR interval and QRS duration for 55 minutes (P < .05). Propafenone toxicity led to decreased Ca(2+), potential of hydrogen, and Scvo2 and increased lactate levels. Insulin prevented the decrease of Ca(2+) and Scvo2, whereas NaHCO3 prevented the increase in lactate. Insulin treatment was more effective than NaHCO3 on acute propafenone toxicity in rat. Therefore, when propafenone-induced cardiotoxicity occurs, which is unresponsive to current treatment methods, glucose-insulin infusion may be considered. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. A comparison of mental strategies during athletic skills performance.

    Science.gov (United States)

    Peluso, Eugenio A; Ross, Michael J; Gfeller, Jeffrey D; Lavoie, Donna J

    2005-12-01

    The current study examined the effects of performance enhancement techniques (PET's) on motor skill performance. Specifically, one hundred fifty college student volunteers (Men = 41; 27.3% and Women = 109; 72.6%) were randomly assigned to one of the nine conditions (Cond): Cond 1 and 2, simultaneous, externally verbalized self-talk or imagery (e.g., participants were instructed to say "aim, back, birdie "or engaged in imagery out loud while putting); Cond 3 and 4, delayed externally verbalized self-talk or imagery (e.g., participants were instructed to say "aim, back, birdie "or engaged in imagery out loud before putting); Cond 5 and 6, simultaneous, internally verbalized self-talk or imagery (e.g., participants were instructed to say "aim, back, birdie "or engaged in imagery silently to oneself while putting); Cond 7 and 8, delayed internally verbalized (e.g., participant were instructed to say "aim, back, birdie "or engaged in imagery silently to oneself before putting); and Cond 9, no instruction control group. All participants were asked to perform a golf-putting task. Results indicated that participants who implemented several (PET's) increased their putting accuracy across overall difference score evaluations F (8, 141) = 4.01, p focus.Results of the current study suggest that participants who engaged in several performance enhancement techniques exhibited enhanced performance on a golf putting task when compared to participants in a control condition.Participants who endorsed limited athletic familiarity and activity (e.g., ten hours or less) preferred self-talk practice whereas participants who endorsed higher ratings scores of athletic familiarity and activity (e.g., ten hours or more) preferred imagery strategies.The results of this study demonstrate the flexibility of Performance Enhancement Techniques (e.g., imagery v. self-talk, internal v. external, simultaneous v. delayed) and how they can be implemented to help an athlete reach his or her full

  14. Comparison of treatment strategies for Space Motion Sickness

    Science.gov (United States)

    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. Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

    Science.gov (United States)

    Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

    2018-04-07

    Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Mitochondrial protection impairs BET bromodomain inhibitor-mediated cell death and provides rationale for combination therapeutic strategies.

    Science.gov (United States)

    Lasorsa, E; Smonksey, M; Kirk, J S; Rosario, S; Hernandez-Ilizaliturri, F J; Ellis, L

    2015-12-10

    Inhibitors of the bromodomain and extraterminal domain family (BETI) have recently entered phase I clinical trials. In patients with advanced leukemia's, potent antileukemia activity was displayed with minimum dose-limiting toxicity. In preclinical models of hematological malignancies, including aggressive B-cell lymphomas, BETI induced cell-cycle arrest and apoptosis. However, the underlying cell death mechanisms are still not well understood. Dissecting the mechanisms required by BETI to mediate cell death would provide strong direction on how to best utilize BETI to treat patients with aggressive hematological malignancies. Herein, we provide understanding of the molecular mechanisms underlying BETI-mediated cell death using I-BET762. Induction of cell death occurred in primary murine and human B-cell lymphomas through apoptosis. Genetic dissection using Eμ-myc B-cell lymphoma compound mutants demonstrated that I-BET762-induced apoptosis does not require the p53 pathway. Furthermore, deletion of Apaf1, and thus the absence of a functional apoptosome, is associated with a delayed drug response but do not provide long-term resistance. Prolonged treatment of this model in fact fails to suppress the therapeutic efficacy of the drug and is associated with biochemical features of autophagy. However, lack of mitochondrial permeability completely inhibited I-BET762-mediated tumor cell death, indicating mitochondrial damage as key events for its activity. Combination of I-BET762 with BH3-only mimetics ABT-263 or obatoclax, restored sensitivity to I-BET762 lymphoma killing; however, success was determined by expression of Bcl-2 family antiapoptotic proteins. Our study provides critical insight for clinical decisions regarding the appropriate strategy for using BETI as a single agent or in combination to treat patients with aggressive B-cell lymphomas.

  17. Anti-S1P Antibody as a Novel Therapeutic Strategy for VEGFR TKI-Resistant Renal Cancer.

    Science.gov (United States)

    Zhang, Liang; Wang, Xiaoen; Bullock, Andrea J; Callea, Marcella; Shah, Harleen; Song, Jiaxi; Moreno, Kelli; Visentin, Barbara; Deutschman, Douglas; Alsop, David C; Atkins, Michael B; Mier, James W; Signoretti, Sabina; Bhasin, Manoj; Sabbadini, Roger A; Bhatt, Rupal S

    2015-04-15

    VEGFR2 tyrosine kinase inhibition (TKI) is a valuable treatment approach for patients with metastatic renal cell carcinoma (RCC). However, resistance to treatment is inevitable. Identification of novel targets could lead to better treatment for patients with TKI-naïve or -resistant RCC. In this study, we performed transcriptome analysis of VEGFR TKI-resistant tumors in a murine model and discovered that the SPHK-S1P pathway is upregulated at the time of resistance. We tested sphingosine-1-phosphate (S1P) pathway inhibition using an anti-S1P mAb (sphingomab), in two mouse xenograft models of RCC, and assessed tumor SPHK expression and S1P plasma levels in patients with metastatic RCC. Resistant tumors expressed several hypoxia-regulated genes. The SPHK1 pathway was among the most highly upregulated pathways that accompanied resistance to VEGFR TKI therapy. SPHK1 was expressed in human RCC, and the product of SPHK1 activity, S1P, was elevated in patients with metastatic RCC, suggesting that human RCC behavior could, in part, be due to overproduction of S1P. Sphingomab neutralization of extracellular S1P slowed tumor growth in both mouse models. Mice bearing tumors that had developed resistance to sunitinib treatment also exhibited tumor growth suppression with sphingomab. Sphingomab treatment led to a reduction in tumor blood flow as measured by MRI. Our findings suggest that S1P inhibition may be a novel therapeutic strategy in patients with treatment-naïve RCC and also in the setting of resistance to VEGFR TKI therapy. ©2015 American Association for Cancer Research.

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

    Directory of Open Access Journals (Sweden)

    Hanumantha Rao Madala

    2018-02-01

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

  19. Comparison of therapeutic dosimetric data from passively scattered proton and photon craniospinal irradiations for medulloblastoma

    Directory of Open Access Journals (Sweden)

    Howell Rebecca M

    2012-07-01

    Full Text Available Abstract Background For many decades, the standard of care radiotherapy regimen for medulloblastoma has been photon (megavoltage x-rays craniospinal irradiation (CSI. The late effects associated with CSI are well-documented in the literature and are in-part attributed to unwanted dose to healthy tissue. Recently, there is growing interest in using proton therapy for CSI in pediatric and adolescent patients to reduce this undesirable dose. Previous comparisons of dose to target and non-target organs from conventional photon CSI and passively scattered proton CSI have been limited to small populations (n ≤ 3 and have not considered the use of age-dependent target volumes in proton CSI. Methods Standard of care treatment plans were developed for both photon and proton CSI for 18 patients. This cohort included both male and female medulloblastoma patients whose ages, heights, and weights spanned a clinically relevant and representative spectrum (age 2–16, BMI 16.4–37.9 kg/m2. Differences in plans were evaluated using Wilcoxon signed rank tests for various dosimetric parameters for the target volumes and normal tissue. Results Proton CSI improved normal tissue sparing while also providing more homogeneous target coverage than photon CSI for patients across a wide age and BMI spectrum. Of the 24 parameters (V5, V10, V15, and V20 in the esophagus, heart, liver, thyroid, kidneys, and lungs Wilcoxon signed rank test results indicated 20 were significantly higher for photon CSI compared to proton CSI (p ≤ 0.05 . Specifically, V15 and V20 in all six organs and V5, V10 in the esophagus, heart, liver, and thyroid were significantly higher with photon CSI. Conclusions Our patient cohort is the largest, to date, in which CSI with proton and photon therapies have been compared. This work adds to the body of literature that proton CSI reduces dose to normal tissue compared to photon CSI for pediatric patients who are at substantial risk for

  20. Comparison of therapeutic dosimetric data from passively scattered proton and photon craniospinal irradiations for medulloblastoma

    International Nuclear Information System (INIS)

    Howell, Rebecca M; Giebeler, Annelise; Koontz-Raisig, Wendi; Mahajan, Anita; Etzel, Carol J; D’Amelio, Anthony M Jr; Homann, Kenneth L

    2012-01-01

    For many decades, the standard of care radiotherapy regimen for medulloblastoma has been photon (megavoltage x-rays) craniospinal irradiation (CSI). The late effects associated with CSI are well-documented in the literature and are in-part attributed to unwanted dose to healthy tissue. Recently, there is growing interest in using proton therapy for CSI in pediatric and adolescent patients to reduce this undesirable dose. Previous comparisons of dose to target and non-target organs from conventional photon CSI and passively scattered proton CSI have been limited to small populations (n ≤ 3) and have not considered the use of age-dependent target volumes in proton CSI. Standard of care treatment plans were developed for both photon and proton CSI for 18 patients. This cohort included both male and female medulloblastoma patients whose ages, heights, and weights spanned a clinically relevant and representative spectrum (age 2–16, BMI 16.4–37.9 kg/m2). Differences in plans were evaluated using Wilcoxon signed rank tests for various dosimetric parameters for the target volumes and normal tissue. Proton CSI improved normal tissue sparing while also providing more homogeneous target coverage than photon CSI for patients across a wide age and BMI spectrum. Of the 24 parameters (V 5 , V 10 , V 15 , and V 20 in the esophagus, heart, liver, thyroid, kidneys, and lungs) Wilcoxon signed rank test results indicated 20 were significantly higher for photon CSI compared to proton CSI (p ≤ 0.05) . Specifically, V 15 and V 20 in all six organs and V 5 , V 10 in the esophagus, heart, liver, and thyroid were significantly higher with photon CSI. Our patient cohort is the largest, to date, in which CSI with proton and photon therapies have been compared. This work adds to the body of literature that proton CSI reduces dose to normal tissue compared to photon CSI for pediatric patients who are at substantial risk for developing radiogenic late effects. Although the present study

  1. The therapeutic and prophylactic role of oral zinc sulfate in management of recurrent aphthous stomatitis ras in comparison with dapsone

    International Nuclear Information System (INIS)

    Sharique, Khalifa E.; Najim, Rafid A.; Al-Nuaimy, Adil A.; Al-Hayani, Raafa K.; Maroof, Darseem M.

    2008-01-01

    Objective was to evaluate the therapeutic and prophylactic effectiveness of oral zinc sulfate in recurrent aphthous stomatitis RAS in comparison with dapsone. A double-blind placebo controlled study, conducted in the Department of Dermatology, Baghdad Teaching Hospitals, Baghdad, Iraq between May 2005 and October 2006, in which 45 patents with RAS were recruited and divided into 3 equal groups: group A on zinc sulfate 150 mg twice daily, group B on dapsone 50 mg twice daily and group C on glucose 250 mg as placebo. The drugs were prepared in identical capsules and patents were instructed to take the capsules twice daily after meals in a double blind manner. Assessment of each patient was carried out by the Oral Clinical Manifestation Index OCMI and the diameter of the ulcers at day 0, day 4 and the second, fourth, sixth, eighth, tenth and twelfth weeks of the therapy. Forty-five patients were included in the study 25 males and 20 females and their ages ranged between 16-45 years mean +/-SD 31.24+/-8.14. In group A, the mean of OCMI and diameters of the ulcers improved, with a p=0.0001 for OCMI, and 0.0001 for the diameter for ulcers at the end of the twelfth week of therapy, which was statistically significant. Group B also showed significant improvement, however, the action was lower and slower p=0.0001 for OCMI and 0.001 for the diameter for ulcers. Group C revealed slight non-significant improvement p=0.028 for OCMI and 0.034 for the diameter of ulcers. In the sixth week of therapy, zinc sulfate was more effective than dapsone in reducing in reducing the reducing the OCMI of the ulcers p=0.007. The present study showed that both zinc sulfate and dapsone had significant therapeutic and prophylactic affects in controlling RAS, however, zinc sulfate had much more rapid and sustained action. (author)

  2. Overview: clinical and physiological comparison of meditation with other self-control strategies.

    Science.gov (United States)

    Shapiro, D H

    1982-03-01

    In 1977 the American Psychiatric Association called for a critical examination of the clinical effectiveness of meditation. The author provides a review of the literature bearing on clinical and physiological comparisons of meditation with other self-control strategies. He begins by providing a definition of mediation and then cites the literature comparing mediation with such self-regulation strategies as biofeedback, hypnosis, and progressive relaxation. He pays particular attention to the "uniqueness" of mediation as a clinical intervention strategy a well as the adverse effects of meditation. Finally, he offers suggestions and guidelines for future research.

  3. Rational behavior in decision making. A comparison between humans, computers and fast and frugal strategies

    NARCIS (Netherlands)

    Snijders, C.C.P.

    2007-01-01

    Rational behavior in decision making. A comparison between humans, computers, and fast and frugal strategies Chris Snijders and Frits Tazelaar (Eindhoven University of Technology, The Netherlands) Real life decisions often have to be made in "noisy" circumstances: not all crucial information is

  4. Effects Comparison of Different Resilience Enhancing Strategies for Municipal Water Distribution Network: A Multidimensional Approach

    Directory of Open Access Journals (Sweden)

    Xudong Zhao

    2015-01-01

    Full Text Available Water distribution network (WDN is critical to the city service, economic rehabilitation, public health, and safety. Reconstructing the WDN to improve its resilience in seismic disaster is an important and ongoing issue. Although a considerable body of research has examined the effects of different reconstruction strategies on seismic resistance, it is still hard for decision-makers to choose optimal resilience enhancing strategy. Taking the pipeline ductile retrofitting and network meshed expansion as demonstration, we proposed a feasible framework to contrast the resilience enhancing effects of two reconstruction strategies—units retrofitting strategy and network optimization strategy—in technical and organizational dimension. We also developed a new performance response function (PRF which is based on network equilibrium theory to conduct the effects comparison in integrated technical and organizational dimension. Through the case study of municipal WDN in Lianyungang, China, the comparison results were thoroughly shown and the holistic decision-making support was provided.

  5. [Are therapeutics decisions homogeneous in multidisciplinary onco-urology staff meeting? Comparison of therapeutic options taken in four departments from Paris].

    Science.gov (United States)

    Audenet, F; Lejay, V; Mejean, A; De La Taille, A; Abbou, C-C; Lebret, T; Botto, H; Bitker, M-O; Roupret, M

    2012-06-01

    One of the priorities of the "Plan against the Cancer" in France is to ensure the discussion of all cancer cases in a multidisciplinary meeting staff (RCP). The multidisciplinary collaboration is proposed to guarantee a discussion between specialists in every cases, particularly in complex cases. The aim of this study was to compare the therapeutic decision taken in four RCP in Paris Île-de-France academic centres for three identical cases. Three cases of urological oncology (prostate cancer [PCa], renal cell carcinoma [RCC] and bladder tumour) were selected by a single urologist, not involved in further discussion. These cases were blindly presented in four academic urology department from Paris: Pitié-Salpêtrière Hospital, Mondor Hospital, the Georges-Pompidou European Hospital and Foch Hospital. The four centres met the criteria of quality of RCP in terms of multidisciplinarity, frequency and standardization. The therapeutic suggestions were similar in the RCC cases, there were differences in the surgical approaches and preoperative work-up in the PCa case and, lastly, the proposals were different for the bladder cancer case. The decisions relies on clinical data and preoperative work-up but also on the experience and habits of the centre of excellence. For complex cases that does not fit with current guidelines, the panel discussion can lead to different therapeutic options from a centre to another and is largely influenced by the local organisation of the RCP. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  6. Plasma extraction rate and collection efficiency during therapeutic plasma exchange with Spectra Optia in comparison with Haemonetics MCS+.

    Science.gov (United States)

    Lambert, Catherine; Gericke, Marion; Smith, Richard; Hermans, Cedric

    2011-01-01

    For therapeutic plasma exchange (TPE), continuous and intermittent flow separators are known to be efficient. This study was undertaken to compare the performances of the Spectra Optia, a continuous flow centrifugal apheresis system recently developed by CaridianBCT, with the Haemonetics Multicomponents System (MCS)+ apheresis system based on intermittent flow centrifugation. The primary objective of the study was to compare the time required to exchange one total plasma volume with both separators. The secondary objectives were to determine the plasma exchange efficiency, the plasma extraction rate, the percentage of target exchange volume achieved, and the loss of cellular components. The study involved prospectively paired comparison of 16 TPE on each device performed in patients with chronic diseases treated with TPE. The time required to exchange 1 total plasma volume was 182 ± 36 minutes for MCS+ procedures and 100 ± 20 minutes for the Spectra Optia procedures (P higher plasma extraction rate was achieved (30.2 ± 4.3 vs 16.8 ± 3.4 mL/min, respectively, P exchange efficiency was slightly better with the Spectra Optia compared with the MCS+ procedures (83.4 ± 7.0 vs 80.0 ± 8.5%, P higher extraction rate and exchange efficiency than the MCS+ allowing to remove the same amount of plasma in less time, by processing less blood. It also removes significantly less platelets than the MCS+ separator. Copyright © 2010 Wiley-Liss, Inc.

  7. Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies Against Prostate Cancer

    National Research Council Canada - National Science Library

    O'Keefe, Denise

    2002-01-01

    Prostate-Specific Membrane Antigen (PSMA) appears to be an ideal prostate cancer marker and potential therapeutic target, however there have been reports of PSMA expression in non-prostatic tissues, including brain, kidney and liver...

  8. Preclinical models for an innovative glioblastoma therapeutical strategy by 188Re-SSS encapsulated in nano-tools: translational view

    International Nuclear Information System (INIS)

    Cikankowitz, A.; Belloche, C.; Verger, E.; Garcion, E.; Hindre, F.; Chassain, G.; Fellah, B.; Abadie, J.; Chouin, N.; Ibisch, C.; Davodeau, F.; Couez, D.; Lepareur, N.; Lacoeuille, F.; Menei, P.

    2015-01-01

    Full text of publication follows. Aim: Glioblastoma (GBM) is the most frequent cancer of the nervous system and therapies currently used cannot treat definitively this disease. By the way of NucSan (Nuclear for health) program which supports research development about the use of radio pharmaceutics in oncology, the aim of the proposed work is to provide evidences that internal radiotherapy through lipid nanocapsules loaded with Rhenium-188 (LNC 188 Re-SSS) is an alternative therapeutic strategy for GBM that can be translated to human medicine. Previous works have shown a remarkable efficiency of this tool among syngeneic rats linked with local and peripheral recruitments of the immune system's effectors. In this context, two animal models have been chosen to validate the feasibility of this new innovative therapy design (LNC 188 Re-SSS stereotactic injection). Materials and methods: the syngeneic six weeks old C57BL/6J female mice were treated 6 or 12 days after stereotactic GL261 cells implantation, by a single injection of increasing activities of LNC 188 Re-SSS (0,925; 1,85 and 2,7 MBq/5μl). MRI was used to follow tumor progression to determine the mass volume through the selection of regions of interest. The increased median survival time (IMST) was also assessed for treated mice versus control mice (stereotactic injection of saline solution). For long time survival animals (3 times the median survival time), they were rechallenged through the same procedure in the other hemisphere. The brachy-cephalic dog bearing spontaneous tumor will lead to additional evidences to specifically highlight the potential of this innovative technology for GBM treatment. In order to validate procedures of intracerebral injections, a stereotactic head frame specially designed for dog has been conceived which allow both images acquisition (MRI-SPECT and PET) and the achievement of biopsies. Results/Perspectives: as previously observed on rat models, the preliminary data show

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

    Directory of Open Access Journals (Sweden)

    Myung-Hoon Han

    2016-12-01

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

  10. The Comparison Among Antibacterial Activity of Mespilus germanica Extracts and Number of Common Therapeutic Antibiotics “In Vitro”

    Directory of Open Access Journals (Sweden)

    Farideh Tabatabaei-Yazdi

    2015-12-01

    Full Text Available Background: Antibiotic resistance is a serious and growing phenomenon in contemporary medicine and has emerged as one of the pre-eminent public health concerns of the 21st century. Objectives: In this study, antibacterial activity of Mespilus germanica extract against some pathogenic bacterial strains (Streptococcus pyogene, Listeria innocua, Enterobacter aerogenes and Klebsiella pneumoniae was evaluated. Materials and Methods: In this experimental study, maceration extraction method was used for M. germanica extract. Disk diffusion method was used to evaluate the antimicrobial effect and broth microdilution method was used to determine the minimum inhibitory concentration and minimum bactericidal concentration. Then, the data were entered into the SPSS-18 statistical software and analyzed using one-way ANOVA and Tukey test. Results: Antimicrobial activity was assessed by inhibition diameters which were found to range from 8 to 21.5 mm for the two extracts against all the bacterial strains tested. The minimum inhibitory concentrations (MIC for the extracts were later determined by three fold serial dilutions method and they ranged 2 - 64 mg/mL against all the strains and minimum bactericidal concentrations (MBC for the extracts were later determined by three fold serial dilutions method and they ranged 4 - 128 mg/mL against all the strains. Conclusions: The M. germanica extract showed the more effective impact on the growth S. pyogene and L. innocua than E. aerogenes and K. pneumoniae (P < 0.05. M. germanica in comparison with common therapeutic antibiotics had more inhibitory effect on some of the studied strains in vitro.

  11. Comparison of Conflict Management Strategies of Physical Education Office Managers Based on some Demographic Characteristics

    OpenAIRE

    Fatemeh Ghorbanalizadeh Ghaziani; Mohsen Moadi; Siavash Khodaparast Sareshkeh

    2013-01-01

    The purpose of study was comparison of conflict management strategies of physical education office managers based on their some demographic characteristics. All of managers of physical education office of Mazandaran (n = 15) and Guilan (n = 16) province and their assistant [(n = 15) and (n =16) respectively] response to Putnam and Wilson’s “organizational communication conflict instrument (OCCI)”.Analysis showed that Mazandaran’s and Guilan’s managers and their assistant hadn’t differences to...

  12. COMPARISON OF DIFFERENT STRATEGIES OF ANTIHYPERTENSIVE THERAPY IN OUT-PATIENT CLINIC

    Directory of Open Access Journals (Sweden)

    O. A. Plejko

    2008-01-01

    Full Text Available Aim. To compare different strategies of start antihypertensive therapy in out-patients.Material and methods. 120 out-patients with arterial hypertension (HT 1-2 stages were included in the study and randomized in 3 groups. Patients of group «A» received start treatment in compliance with age, clinical features and mechanisms of hypertension. Patients of group «B» received step-by-step start antihypertensive therapy based on doses titration and addition of the second (third drug if necessary. Patients of group «C» received fixed drug combination with addition of other antihypertensive medicines if necessary. Decrease of BP level and number of visits were used as criteria of therapy efficacy. Pharmacoeconomic analysis of antihypertensive therapy was done in all groups.Results. Strategy of HT start therapy in group «C» had advantages in speed of blood pressure normalization, number of necessary visits and in pharmacoeconomic efficacy in comparison with the strategies in group «A» and «B».Conclusion. HT start therapy with implementation of fixed low dose combination leads to the best result in comparison with other strategy based on step-by-step drug replacement (as well as their combining or monotherapy dose titration.

  13. Cross-gender Comparison of Metacognitive Strategies Utilized by Omani Students in Reading Comprehension Classes

    Directory of Open Access Journals (Sweden)

    Manizheh Alami

    2016-07-01

    Full Text Available Given the fact that English is the language of the latest technological and scientific developments, comprehending English texts has priority for students to gain the knowledge and skills they will need in the future. However, most Omani students are not efficient L2 readers and do not have sufficient competence in reading authentic English texts. There is a variety of factors that might affect Omani students’ ability to read and comprehend English texts effectively. To find out what factors are involved in Omani students’ reading comprehension, in the first place, it is necessary to know what strategies they employ in reading. To this end, the current study attempts  to explore Omani students reported use of reading strategies using ‘Metacognitive Awareness of Reading Strategies Inventory’ (MARSI developed by Mokhtari and Reichard (2002. The self-reported survey completed by 200 students (90 female and110 male who enrolled for Advanced Foundation program (level 4 at Salalah College of Technology (SCT. The results show that SCT students’ awareness of metacognitive strategies is at medium level (3.46. Furthermore, the comparison between two gender groups (Males Vs. Females shows that male students use metacognitive reading strategies moderately (3.28 while female students use them more frequently (3.64. The outcomes of the study contribute to the improvement of SCT students reading ability and can be used by teachers to teach students different strategies to build meaning of the reading material which is among the goals of any educational system.

  14. Analysis and Comparison of Shading Strategies to Increase Human Thermal Comfort in Urban Areas

    Directory of Open Access Journals (Sweden)

    Ivan Lee

    2018-03-01

    Full Text Available With the expected increase in warmer conditions caused by climate change, heat-related illnesses are becoming a more pressing issue. One way that humans can protect themselves from this is to seek shade. The design of urban spaces can provide individuals with a variety of ways to obtain this shade. The objective of this study was to perform a detailed evaluation and comparison of three shading strategies that could be used in an urban environment: shade from a building, from a tree, and from an umbrella. This was done through using field measurements to calculate the impact of each strategy on a thermal comfort index (Comfort Formula (COMFA in two urban settings during sunny days of the summer of 2013 and 2014 in London, Canada. Building shade was found to be the most effective cooling strategy, followed by the tree strategy and the umbrella strategy. As expected, the main determinant of this ranking was a strategy’s ability to block incoming shortwave radiation. Further analysis indicated that changes in the convective loss of energy and in longwave radiation absorption had a smaller impact that caused variations in the strategy effectiveness between settings. This suggests that under non-sunny days, these rankings could change.

  15. Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

    Science.gov (United States)

    Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

    2017-09-01

    Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

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

    Directory of Open Access Journals (Sweden)

    Apoorva Shankar

    2017-09-01

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

  17. Comparison of the Effects of Seated, Supine, and Walking Interset Rest Strategies on Work Rate.

    Science.gov (United States)

    Ouellette, Kristen A; Brusseau, Timothy A; Davidson, Lance E; Ford, Candus N; Hatfield, Disa L; Shaw, Janet M; Eisenman, Patricia A

    2016-12-01

    Ouellette, KA, Brusseau, TA, Davidson, LE, Ford, CN, Hatfield, DL, Shaw, JM, and Eisenman, PA. Comparison of the effects of seated, supine, and walking interset rest strategies on work rate. J Strength Cond Res 30(12): 3396-3404, 2016-The idea that an upright posture should be maintained during the interset rest periods of training sessions is pervasive. The primary aim of this study was to determine differences in work rate associated with 3 interset rest strategies. Male and female members of the CrossFit community (male n = 5, female n = 10) were recruited to perform a strenuous training session designed to enhance work capacity that involved both cardiovascular and muscular endurance exercises. The training session was repeated on 3 separate occasions to evaluate 3 interset rest strategies, which included lying supine on the floor, sitting on a flat bench, and walking on a treadmill (0.67 m·s). Work rate was calculated for each training session by summing session joules of work and dividing by the time to complete the training session (joules of work per second). Data were also collected during the interset rest periods (heart rate [HR], respiratory rate [RR], and volume of oxygen consumed) and were used to explain why one rest strategy may positively impact work rate compared with another. Statistical analyses revealed significant differences (p ≤ 0.05) between the passive and active rest strategies, with the passive strategies allowing for improved work rate (supine = 62.77 ± 7.32, seated = 63.66 ± 8.37, and walking = 60.61 ± 6.42 average joules of work per second). Results also suggest that the passive strategies resulted in superior HR, RR, and oxygen consumption recovery. In conclusion, work rate and physiological recovery were enhanced when supine and seated interset rest strategies were used compared with walking interset rest.

  18. LC-MS/MS strategies for therapeutic antibodies and investigation into the quantitative impact of antidrug-antibodies.

    Science.gov (United States)

    Ewles, Matthew; Mannu, Ranbir; Fox, Chris; Stanta, Johannes; Evans, Graeme; Goodwin, Lee; Duffy, James; Bell, Len; Estdale, Sian; Firth, David

    2016-12-01

    We aimed to establish novel, high-throughput LC-MS/MS strategies for quantification of monoclonal antibodies in human serum and examine the potential impact of antidrug antibodies. We present two strategies using a thermally stable immobilized trypsin. The first strategy uses whole serum digestion and the second introduces Protein G enrichment to improve the selectivity. The impact of anti-trastuzumab antibodies on the methods was tested. Whole serum digestion has been validated for trastuzumab (LLOQ 0.25 µg/ml). Protein G enrichment has been validated for trastuzumab (LLOQ 0.1 µg/ml), bevacizumab (LLOQ 0.1 µg/ml) and adalimumab (LLOQ 0.25 µg/ml). We have shown the potential for anti-drug antibodies to impact on the quantification and we have subsequently established a strategy to overcome this impact where total quantification is desired.

  19. Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

    Science.gov (United States)

    Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

    2015-07-01

    Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

  20. Comparison of various decentralised structural and cavity feedback control strategies for transmitted noise reduction through a double panel structure

    NARCIS (Netherlands)

    Ho, J.; Berkhoff, Arthur P.

    This paper compares various decentralised control strategies, including structural and acoustic actuator–sensor configuration designs, to reduce noise transmission through a double panel structure. The comparison is based on identical control stability indexes. The double panel structure consists of

  1. Comparison of various decentralised structural and cavity feedback control strategies for transmitted noise reduction through a double panel structure

    NARCIS (Netherlands)

    Ho, J.H.; Berkhoff, A.P.

    2014-01-01

    This paper compares various decentralised control strategies, including structural and acoustic actuator-sensor configuration designs, to reduce noise transmission through a double panel structure. The comparison is based on identical control stability indexes. The double panel structure consists of

  2. Managing radioactive waste issues and misunderstandings (radiation realities, energy comparison, waste strategies)

    International Nuclear Information System (INIS)

    Rosen, M.

    2001-01-01

    The technical specialist is confident that radioactive waste can be safely managed, but many in the public remain totally unconvinced. There are issues and deep-seated misunderstandings that drive public doubts. Currently, a growing concern with pollution from other industrial waste is enabling radioactive waste issues to be debated in a wider context that allows comparisons with other potentially hazardous waste, particularly from energy generation sources. Health effects and time period issues are not unique to radioactive waste. This paper concentrates on 3 topics. The first concerns radiation health effects where the real realities of radiation are covered. The large misunderstandings that exist about radiation and its health effects have led to an almost zero health impact regulatory policy. A policy which must be more fully understood and dealt with. The second topic deals with a few revealing comparisons about the various energy generation systems. Nuclear power's 10 thousand fold lower fuel requirements, compared with a comparable fossil fuelled plant, is a dominating factor decisively minimising environmental impacts. The third topic examines waste disposal strategies. Extraordinarily small radioactive waste quantities permit a confinement strategy for disposal as opposed to the more common dispersion strategy for most toxic waste. The small quantities coupled with radioactive decay, contrary to the public perception, make any potential hazard from both low and high level radioactive waste exceedingly small. (author)

  3. Research strategy of the therapeutic quality of mud and salty water from Ursu(Bear Lake, Sovata, 

    Directory of Open Access Journals (Sweden)

    Munteanu Constantin

    2012-05-01

    Full Text Available Infertility (sterility is a health problem affecting 15% of couples of reproductive age. Today only a few are known about causes and treatment options involved in the pathology of infertility, while a number of issues remain unknown. Currently natural therapeutic factors from Sovata are used, based on experience over the years, for the following causes of infertility: tubal obstruction, laparoscopic postneosalpingostomiei recovery treatment (prevention of restenozations, sequelae after pelvic inflammatory disease, peritonitis, post-inflammatory adhesions; secretory ovarian dysfunction (estrogen, progesterone, polycystic ovarian syndrome, endometriosis, infertility induced by stress.

  4. The Use of Humor and Storytelling with African American Men: Innovative Therapeutic Strategies for Success in Counseling

    Science.gov (United States)

    Vereen, Linwood G.; Hill, Nicole R.; Butler, S. Kent

    2013-01-01

    In recent years, the use of culturally appropriate humor as a tool for change within the parameters of counseling has grown within the literature. In comparison, the art of storytelling has had little attention within the literature as a tool for strategic change. This article outlines a framework for the use of humor and storytelling as…

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

    Science.gov (United States)

    D’Ostilio, Kevin; Garraux, Gaëtan

    2016-01-01

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

  6. Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs.

    Science.gov (United States)

    Lin, Chun-Yuan; Wang, Chung-Hung; Hung, Che-Lun; Lin, Yu-Shiang

    2015-01-01

    Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n (2)), where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC). The intrinsic time complexity of MCC problem is O(k (2) n (2)) with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results.

  7. Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs

    Directory of Open Access Journals (Sweden)

    Chun-Yuan Lin

    2015-01-01

    Full Text Available Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n2, where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore, it still will be time-consuming when comparing with a large amount of compounds (seen as a multiple compound comparison problem, abbreviated to MCC. The intrinsic time complexity of MCC problem is O(k2n2 with k compounds of maximal length n. In this paper, we propose a GPU-based algorithm for MCC problem, called CUDA-MCC, on single- and multi-GPUs. Four LINGO-based load-balancing strategies are considered in CUDA-MCC in order to accelerate the computation speed among thread blocks on GPUs. CUDA-MCC was implemented by C+OpenMP+CUDA. CUDA-MCC achieved 45 times and 391 times faster than its CPU version on a single NVIDIA Tesla K20m GPU card and a dual-NVIDIA Tesla K20m GPU card, respectively, under the experimental results.

  8. Assessment of refractive astigmatism and simulated therapeutic refractive surgery strategies in coma-like-aberrations-dominant corneal optics.

    Science.gov (United States)

    Zhou, Wen; Stojanovic, Aleksandar; Utheim, Tor Paaske

    2016-01-01

    The aim of the study is to raise the awareness of the influence of coma-like higher-order aberrations (HOAs) on power and orientation of refractive astigmatism (RA) and to explore how to account for that influence in the planning of topography-guided refractive surgery in eyes with coma-like-aberrations-dominant corneal optics. Eleven eyes with coma-like-aberrations-dominant corneal optics and with low lenticular astigmatism (LA) were selected for astigmatism analysis and for treatment simulations with topography-guided custom ablation. Vector analysis was used to evaluate the contribution of coma-like corneal HOAs to RA. Two different strategies were used for simulated treatments aiming to regularize irregular corneal optics: With both strategies correction of anterior corneal surface irregularities (corneal HOAs) were intended. Correction of total corneal astigmatism (TCA) and RA was intended as well with strategies 1 and 2, respectively. Axis of discrepant astigmatism (RA minus TCA minus LA) correlated strongly with axis of coma. Vertical coma influenced RA by canceling the effect of the with-the-rule astigmatism and increasing the effect of the against-the-rule astigmatism. After simulated correction of anterior corneal HOAs along with TCA and RA (strategies 1 and 2), only a small amount of anterior corneal astigmatism (ACA) and no TCA remained after strategy 1, while considerable amount of ACA and TCA remained after strategy 2. Coma-like corneal aberrations seem to contribute a considerable astigmatic component to RA in eyes with coma-like-aberrations dominant corneal optics. If topography-guided ablation is programmed to correct the corneal HOAs and RA, the astigmatic component caused by the coma-like corneal HOAs will be treated twice and will result in induced astigmatism. Disregarding RA and treating TCA along with the corneal HOAs is recommended instead.

  9. Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases?

    Science.gov (United States)

    Jansen, Manon A A; Spiering, Rachel; Broere, Femke; van Laar, Jacob M; Isaacs, John D; van Eden, Willem; Hilkens, Catharien M U

    2018-01-01

    Tolerogenic dendritic cells (tolDCs) are a promising therapeutic tool to restore immune tolerance in autoimmune diseases. The rationale of using tolDCs is that they can specifically target the pathogenic T-cell response while leaving other, protective, T-cell responses intact. Several ways of generating therapeutic tolDCs have been described, but whether these tolDCs should be loaded with autoantigen(s), and if so, with which autoantigen(s), remains unclear. Autoimmune diseases, such as rheumatoid arthritis, are not commonly defined by a single, universal, autoantigen. A possible solution is to use surrogate autoantigens for loading of tolDCs. We propose that heat-shock proteins may be a relevant surrogate antigen, as they are evolutionarily conserved between species, ubiquitously expressed in inflamed tissues and have been shown to induce regulatory T cells, ameliorating disease in various arthritis mouse models. In this review, we provide an overview on how immune tolerance may be restored by tolDCs, the problem of selecting relevant autoantigens for loading of tolDCs, and why heat-shock proteins could be used as surrogate autoantigens. © 2017 John Wiley & Sons Ltd.

  10. Antisense targeting of 3' end elements involved in DUX4 mRNA processing is an efficient therapeutic strategy for facioscapulohumeral dystrophy: a new gene-silencing approach.

    Science.gov (United States)

    Marsollier, Anne-Charlotte; Ciszewski, Lukasz; Mariot, Virginie; Popplewell, Linda; Voit, Thomas; Dickson, George; Dumonceaux, Julie

    2016-04-15

    Defects in mRNA 3'end formation have been described to alter transcription termination, transport of the mRNA from the nucleus to the cytoplasm, stability of the mRNA and translation efficiency. Therefore, inhibition of polyadenylation may lead to gene silencing. Here, we choose facioscapulohumeral dystrophy (FSHD) as a model to determine whether or not targeting key 3' end elements involved in mRNA processing using antisense oligonucleotide drugs can be used as a strategy for gene silencing within a potentially therapeutic context. FSHD is a gain-of-function disease characterized by the aberrant expression of the Double homeobox 4 (DUX4) transcription factor leading to altered pathogenic deregulation of multiple genes in muscles. Here, we demonstrate that targeting either the mRNA polyadenylation signal and/or cleavage site is an efficient strategy to down-regulate DUX4 expression and to decrease the abnormally high-pathological expression of genes downstream of DUX4. We conclude that targeting key functional 3' end elements involved in pre-mRNA to mRNA maturation with antisense drugs can lead to efficient gene silencing and is thus a potentially effective therapeutic strategy for at least FSHD. Moreover, polyadenylation is a crucial step in the maturation of almost all eukaryotic mRNAs, and thus all mRNAs are virtually eligible for this antisense-mediated knockdown strategy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. The Impact of Price Comparison Service on Pricing Strategy in a Dual-Channel Supply Chain

    Directory of Open Access Journals (Sweden)

    Qi Xu

    2013-01-01

    Full Text Available Recently, price comparison service (PCS websites are more and more popular due to its features in facilitating transparent price and promoting rational purchase decision. Motivated by the industrial practices, in this study, we examine the pricing strategies of retailers and supplier in a dual-channel supply chain influenced by the signals of PCS. We categorize and discuss three situations according to the signal availability of PCS, under which the optimal pricing strategies are derived. Finally, we conduct a numerical study and find that in fact the retailers and supplier are all more willing to avoid the existence of PCS with the objective of profit maximization. When both of retailers are affected by the PCS, the supplier is more willing to reduce the availability of price information. Important managerial insights are discussed.

  12. The National Strategy of Ecological Transition towards Sustainable Development - International comparisons

    International Nuclear Information System (INIS)

    Kleiber, Florence; Vey, Frederic; Moreau, Sylvain; Bottin, Anne; Baudu-Baret, Claude

    2017-05-01

    The National Strategy of Ecological Transition towards Sustainable Development (SNTEDD) 2015-2020 follows on from the 2010-2013 National Strategy for Sustainable Development. Adopted at the Council of Ministers meeting of 4 February 2015, the SNTEDD identifies four major ecological challenges and nine strategic areas of action. The SNTEDD is monitored by 72 indicators developed via a collaborative process of selection implemented by a special commission of the National Council for Ecological Transition (CNTE) responsible for the indicators. This 'indicators' commission has sought to obtain a perspective on outcomes by means of international comparisons. This study presents initial elements of an analysis of France's situation compared with that of other countries (mostly EU or OECD members) with regard to each of the challenges and areas of action identified in the SNTEDD

  13. Comparison of therapeutic response of keloids and hypertrophic scars to cryotherapy plus intralesional steroid and bleomycin tattoo

    Directory of Open Access Journals (Sweden)

    Farahnaz Fatemi

    2005-01-01

    Full Text Available Keloids and hypertrophic scars are abnormal responses of body to skin injuries. Overproduction of compacted fibrous tissue is the basic cause of these lesions. In this study the result of treatment of these skin conditions with bleomycin tattoo are compared with cryotherapy and triamcinolone injection. This study involved 45 patients with hypertrophic scar or keloid. Patients were divided into two groups consecutively. Group A (23 patients was treated with bleomycin tattoo and the group B with cryotherapy and triamcinolone injection. There were four therapeutic sessions one month apart. All patients were followedup for three month after the end of treatment .The therapeutic response was determined as reduction of lesion size or flattening relative to initial size. Therapeutic response was 88.3±14% in group A and 67.4 ±22.5% in group B (p<0.001. In group A 69%, but in group B only 49% of patients were asymptomatic after the end of treatment. In group A there was no relation between therapeutic response and lesion size (p=0.58 but in group B lesions those were smaller (<100mm2 had better therapeutic response than larger ones (p=0.007. It was concluded that bleomycin tattoo is more effective in treatment of hypertrophic scar and keloid than traditional treatment, cryotherapy plus triamcinolone injection especially in larger ones.

  14. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

    Science.gov (United States)

    GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

    2016-01-01

    MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

  15. Comparison of Strategies for Climate Change Adaptation of Water Supply and Flood Control Reservoirs

    Science.gov (United States)

    Ng, T. L.; Yang, P.; Bhushan, R.

    2016-12-01

    With climate change, streamflows are expected to become more fluctuating, with more frequent and intense floods and droughts. This complicates reservoir operation, which is highly sensitive to inflow variability. We make a comparative evaluation of three strategies for adapting reservoirs to climate-induced shifts in streamflow patterns. Specifically, we examine the effectiveness of (i) expanding the capacities of reservoirs by way of new off-stream reservoirs, (ii) introducing wastewater reclamation to augment supplies, and (iii) improving real-time streamflow forecasts for more optimal decision-making. The first two are hard strategies involving major infrastructure modifications, while the third a soft strategy entailing adjusting the system operation. A comprehensive side-by-side comparison of the three strategies is as yet lacking in the literature despite the many past studies investigating the strategies individually. To this end, we developed an adaptive forward-looking linear program that solves to yield the optimal decisions for the current time as a function of an ensemble forecast of future streamflows. Solving the model repeatedly on a rolling basis with regular updating of the streamflow forecast simulates the system behavior over the entire operating horizon. Results are generated for two hypothetical water supply and flood control reservoirs of differing inflows and demands. Preliminary findings suggest that of the three strategies, improving streamflow forecasts to be most effective in mitigating the effects of climate change. We also found that, in average terms, both additional reservoir capacity and wastewater reclamation have potential to reduce water shortage and downstream flooding. However, in the worst case, the potential of the former to reduce water shortage is limited, and similarly so the potential of the latter to reduce downstream flooding.

  16. Therapeutic strategies to address neuronal nitric oxide synthase deficiency and the loss of nitric oxide bioavailability in Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Timpani, Cara A; Hayes, Alan; Rybalka, Emma

    2017-05-25

    Duchenne Muscular Dystrophy is a rare and fatal neuromuscular disease in which the absence of dystrophin from the muscle membrane induces a secondary loss of neuronal nitric oxide synthase and the muscles capacity for endogenous nitric oxide synthesis. Since nitric oxide is a potent regulator of skeletal muscle metabolism, mass, function and regeneration, the loss of nitric oxide bioavailability is likely a key contributor to the chronic pathological wasting evident in Duchenne Muscular Dystrophy. As such, various therapeutic interventions to re-establish either the neuronal nitric oxide synthase protein deficit or the consequential loss of nitric oxide synthesis and bioavailability have been investigated in both animal models of Duchenne Muscular Dystrophy and in human clinical trials. Notably, the efficacy of these interventions are varied and not always translatable from animal model to human patients, highlighting a complex interplay of factors which determine the downstream modulatory effects of nitric oxide. We review these studies herein.

  17. Comparison of various online IGRT strategies: The benefits of online treatment plan re-optimization

    International Nuclear Information System (INIS)

    Schulze, Derek; Liang, Jian; Yan, Di; Zhang Tiezhi

    2009-01-01

    Purpose: To compare the dosimetric differences of various online IGRT strategies and to predict potential benefits of online re-optimization techniques in prostate cancer radiation treatments. Materials and methods: Nine prostate patients were recruited in this study. Each patient has one treatment planning CT images and 10-treatment day CT images. Five different online IGRT strategies were evaluated which include 3D conformal with bone alignment, 3D conformal re-planning via aperture changes, intensity modulated radiation treatment (IMRT) with bone alignment, IMRT with target alignment and IMRT daily re-optimization. Treatment planning and virtual treatment delivery were performed. The delivered doses were obtained using in-house deformable dose mapping software. The results were analyzed using equivalent uniform dose (EUD). Results: With the same margin, rectum and bladder doses in IMRT plans were about 10% and 5% less than those in CRT plans, respectively. Rectum and bladder doses were reduced as much as 20% if motion margin is reduced by 1 cm. IMRT is more sensitive to organ motion. Large discrepancies of bladder and rectum doses were observed compared to the actual delivered dose with treatment plan predication. The therapeutic ratio can be improved by 14% and 25% for rectum and bladder, respectively, if IMRT online re-planning is employed compared to the IMRT bone alignment approach. The improvement of target alignment approach is similar with 11% and 21% dose reduction to rectum and bladder, respectively. However, underdosing in seminal vesicles was observed on certain patients. Conclusions: Online treatment plan re-optimization may significantly improve therapeutic ratio in prostate cancer treatments mostly due to the reduction of PTV margin. However, for low risk patient with only prostate involved, online target alignment IMRT treatment would achieve similar results as online re-planning. For all IGRT approaches, the delivered organ-at-risk doses may be

  18. A therapeutic-only versus prophylactic platelet transfusion strategy for preventing bleeding in patients with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

    Science.gov (United States)

    Crighton, Gemma L; Estcourt, Lise J; Wood, Erica M; Trivella, Marialena; Doree, Carolyn; Stanworth, Simon

    2015-01-01

    expected by The Cochrane Collaboration. Main results We identified seven RCTs that compared therapeutic platelet transfusions to prophylactic platelet transfusions in haematology patients undergoing myelosuppressive chemotherapy or HSCT. One trial is still ongoing, leaving six trials eligible with a total of 1195 participants. These trials were conducted between 1978 and 2013 and enrolled participants from fairly comparable patient populations. We were able to critically appraise five of these studies, which contained separate data for each arm, and were unable to perform quantitative analysis on one study that did not report the numbers of participants in each treatment arm. Overall the quality of evidence per outcome was low to moderate according to the GRADE approach. None of the included studies were at low risk of bias in every domain, and all the studies identified had some threats to validity. We deemed only one study to be at low risk of bias in all domains other than blinding. Two RCTs (801 participants) reported at least one bleeding episode within 30 days of the start of the study. We were unable to perform a meta-analysis due to considerable statistical heterogeneity between studies. The statistical heterogeneity seen may relate to the different methods used in studies for the assessment and grading of bleeding. The underlying patient diagnostic and treatment categories also appeared to have some effect on bleeding risk. Individually these studies showed a similar effect, that a therapeutic-only platelet transfusion strategy was associated with an increased risk of clinically significant bleeding compared with a prophylactic platelet transfusion policy. Number of days with a clinically significant bleeding event per participant was higher in the therapeutic-only group than in the prophylactic group (one RCT; 600 participants; mean difference 0.50, 95% confidence interval (CI) 0.10 to 0.90; moderate-quality evidence). There was insufficient evidence to determine

  19. Recombinant Endolysins as Potential Therapeutics against Antibiotic-Resistant Staphylococcus aureus: Current Status of Research and Novel Delivery Strategies.

    Science.gov (United States)

    Haddad Kashani, Hamed; Schmelcher, Mathias; Sabzalipoor, Hamed; Seyed Hosseini, Elahe; Moniri, Rezvan

    2018-01-01

    Staphylococcus aureus is one of the most common pathogens of humans and animals, where it frequently colonizes skin and mucosal membranes. It is of major clinical importance as a nosocomial pathogen and causative agent of a wide array of diseases. Multidrug-resistant strains have become increasingly prevalent and represent a leading cause of morbidity and mortality. For this reason, novel strategies to combat multidrug-resistant pathogens are urgently needed. Bacteriophage-derived enzymes, so-called endolysins, and other peptidoglycan hydrolases with the ability to disrupt cell walls represent possible alternatives to conventional antibiotics. These lytic enzymes confer a high degree of host specificity and could potentially replace or be utilized in combination with antibiotics, with the aim to specifically treat infections caused by Gram-positive drug-resistant bacterial pathogens such as methicillin-resistant S. aureus . LysK is one of the best-characterized endolysins with activity against multiple staphylococcal species. Various approaches to further enhance the antibacterial efficacy and applicability of endolysins have been demonstrated. These approaches include the construction of recombinant endolysin derivatives and the development of novel delivery strategies for various applications, such as the production of endolysins in lactic acid bacteria and their conjugation to nanoparticles. These novel strategies are a major focus of this review. Copyright © 2017 American Society for Microbiology.

  20. Structural and functional outcomes of a therapeutic strategy targeting low disease activity in patients with elderly-onset rheumatoid arthritis: a prospective cohort study (CRANE).

    Science.gov (United States)

    Sugihara, Takahiko; Ishizaki, Tatsuro; Hosoya, Tadashi; Iga, Shoko; Yokoyama, Waka; Hirano, Fumio; Miyasaka, Nobuyuki; Harigai, Masayoshi

    2015-05-01

    The aim of this study was to evaluate structural damage and physical disability in patients with elderly-onset RA (EORA) who were treated in clinical practice with a therapeutic strategy targeting low disease activity (LDA). Data from 151 MTX-naive patients (mean age 74.9 years) with EORA from a prospective, monocentric registry were analysed. Treatment was adjusted every 3 months targeting LDA [28-joint DAS using ESR (DAS28-ESR) target strategy was observed in 83.4% of the 151 patients at week 24 and in 75.5% at week 52. At week 52, 67.6% of the patients were receiving a nbDMARD alone, 31.0% a TNFi with or without MTX and 1.4% tocilizumab. At week 52, structural remission (ΔmTSS/yr ≤0.5) was achieved in 49.7% of the patients, functional remission (HAQ-DI ≤0.5) in 63.4% and LDA in 51.0%. Clinical responses at weeks 12 and 24 were significant independent predictors of CRRP. Cumulative disease activity during the first 12 weeks predicted CRRP with a C-statistic of 0.888. Achieving structural remission, functional remission and LDA in clinical practice in EORA patients are realistic goals. Our results indicate significant benefits for a therapeutic strategy targeting LDA for EORA patients in clinical practice. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Haemophilia at various stages of life: design of new therapeutic strategies through an interactive course--the Kogeniale project.

    Science.gov (United States)

    Santagostino, Elena; Messina, Maria; Tagliaferri, Annarita; Iorio, Alfonso; Morfini, Massimo

    2013-04-01

    High-quality evidence is lacking in several areas of haemophilia treatment, in part because little time is allocated to the treatment and care of haemophilia in university education in Italy. Physicians caring for patients with haemophilia must, therefore, rely on their information on background pathophysiology and more experienced colleagues. This makes diagnostic and therapeutic choices difficult, especially when the patient has concomitant disorders or psychological issues. This article describes a course to educate young physicians who were already engaged in the management of haemophilia on the emerging and unmet issues of haemophilia care and to implement existing guidelines. Physicians (n=53) already caring for patients with haemophilia in their haematology, internal medicine, or paediatric practices in Italy attended the course. Problem-solving group activity and open discussion were the methods chosen to formulate consensus statements. During the specifically designed interactive course, three clinical cases were simulated: a young child with congenital dislocation of the hip, an adolescent refusing prophylactic treatment, and an elderly man with cardiovascular disorders. The physicians were asked questions during the course and, through a Wi-Fi console, were able to answer and discuss each case interactively. Following discussion of each case, agreement was reached regarding general statements on the management of patients with severe haemophilia A in the three different age ranges considered. This project helped to outline useful decision-making tools for handling diagnostic and treatment issues in the field of haemophilia.

  2. Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy

    DEFF Research Database (Denmark)

    Balvers, K.; van Dieren, S.; Baksaas-Aasen, K.

    2017-01-01

    Background: The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing......) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes ‘alive and free from massive...... number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies...

  3. Effectiveness comparison of partially executed t-way test suite based generated by existing strategies

    Science.gov (United States)

    Othman, Rozmie R.; Ahmad, Mohd Zamri Zahir; Ali, Mohd Shaiful Aziz Rashid; Zakaria, Hasneeza Liza; Rahman, Md. Mostafijur

    2015-05-01

    Consuming 40 to 50 percent of software development cost, software testing is one of the most resource consuming activities in software development lifecycle. To ensure an acceptable level of quality and reliability of a typical software product, it is desirable to test every possible combination of input data under various configurations. Due to combinatorial explosion problem, considering all exhaustive testing is practically impossible. Resource constraints, costing factors as well as strict time-to-market deadlines are amongst the main factors that inhibit such consideration. Earlier work suggests that sampling strategy (i.e. based on t-way parameter interaction or called as t-way testing) can be effective to reduce number of test cases without effecting the fault detection capability. However, for a very large system, even t-way strategy will produce a large test suite that need to be executed. In the end, only part of the planned test suite can be executed in order to meet the aforementioned constraints. Here, there is a need for test engineers to measure the effectiveness of partially executed test suite in order for them to assess the risk they have to take. Motivated by the abovementioned problem, this paper presents the effectiveness comparison of partially executed t-way test suite generated by existing strategies using tuples coverage method. Here, test engineers can predict the effectiveness of the testing process if only part of the original test cases is executed.

  4. The Wound Healing and Antibacterial Activity of Five Ethnomedical Calophyllum inophyllum Oils: An Alternative Therapeutic Strategy to Treat Infected Wounds.

    Directory of Open Access Journals (Sweden)

    Teddy Léguillier

    Full Text Available Calophyllum inophyllum L. (Calophyllaceae is an evergreen tree ethno-medically used along the seashores and islands of the Indian and Pacific Oceans, especially in Polynesia. Oil extracted from the seeds is traditionally used topically to treat a wide range of skin injuries from burn, scar and infected wounds to skin diseases such as dermatosis, urticaria and eczema. However, very few scientific studies reported and quantified the therapeutic properties of Calophyllum inophyllum oil (CIO. In this work, five CIO from Indonesia (CIO1, Tahiti (CIO2, 3, Fiji islands (CIO4 and New Caledonia (CIO5 were studied and their cytotoxic, wound healing, and antibacterial properties were presented in order to provide a scientific support to their traditional use and verify their safety.The safety of the five CIO was ascertained using the Alamar blue assay on human keratinocyte cells. CIO wound healing properties were determined using the scratch test assay on human keratinocyte cells. CIO-stimulated antibacterial innate immune response was evaluated using ELISA by measuring β defensin-2 release in human derivative macrophage cells. CIO antibacterial activity was tested using oilogramme against twenty aerobic Gram- bacteria species, twenty aerobic Gram+ bacteria species, including a multi-drug resistant Staphylococcus aureus strain and two anaerobic Gram+ bacteria species e.g. Propionibacterium acnes and Propionibacterium granulosum. To detect polarity profile of the components responsible of the antibacterial activity, we performed bioautography against a Staphylococcus aureus strain.Based on Alamar Blue assay, we showed that CIO can be safely used on keratinocyte cells between 2.7% and 11.2% depending on CIO origin. Concerning the healing activity, all the CIO tested accelerated in vitro wound closure, the healing factor being 1.3 to 2.1 higher compared to control when keratinocytes were incubated after scratch with CIO at 0.1%. Furthermore, our results

  5. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Directory of Open Access Journals (Sweden)

    Protim Sarker

    Full Text Available BACKGROUND: Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18 in the large intestinal epithelia. AIMS: To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB, a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. METHODS: The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR and release of the CAP-18 peptide/protein in stool (Western blot. PRINCIPAL FINDINGS: Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. CONCLUSION: Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from

  6. Phenylbutyrate counteracts Shigella mediated downregulation of cathelicidin in rabbit lung and intestinal epithelia: a potential therapeutic strategy.

    Science.gov (United States)

    Sarker, Protim; Ahmed, Sultan; Tiash, Snigdha; Rekha, Rokeya Sultana; Stromberg, Roger; Andersson, Jan; Bergman, Peter; Gudmundsson, Gudmundur H; Agerberth, Birgitta; Raqib, Rubhana

    2011-01-01

    Cathelicidins and defensins are endogenous antimicrobial peptides (AMPs) that are downregulated in the mucosal epithelia of the large intestine in shigellosis. Oral treatment of Shigella infected rabbits with sodium butyrate (NaB) reduces clinical severity and counteracts the downregulation of cathelicidin (CAP-18) in the large intestinal epithelia. To develop novel regimen for treating infectious diseases by inducing innate immunity, we selected sodium 4-phenylbutyrate (PB), a registered drug for a metabolic disorder as a potential therapeutic candidate in a rabbit model of shigellosis. Since acute respiratory infections often cause secondary complications during shigellosis, the systemic effect of PB and NaB on CAP-18 expression in respiratory epithelia was also evaluated. The readouts were clinical outcomes, CAP-18 expression in mucosa of colon, rectum, lung and trachea (immunohistochemistry and real-time PCR) and release of the CAP-18 peptide/protein in stool (Western blot). Significant downregulation of CAP-18 expression in the epithelia of rectum and colon, the site of Shigella infection was confirmed. Interestingly, reduced expression of CAP-18 was also noticed in the epithelia of lung and trachea, indicating a systemic effect of the infection. This suggests a causative link to acute respiratory infections during shigellosis. Oral treatment with PB resulted in reduced clinical illness and upregulation of CAP-18 in the epithelium of rectum. Both PB and NaB counteracted the downregulation of CAP-18 in lung epithelium. The drug effect is suggested to be systemic as intravenous administration of NaB could also upregulate CAP-18 in the epithelia of lung, rectum and colon. Our results suggest that PB has treatment potential in human shigellosis. Enhancement of CAP-18 in the mucosal epithelia of the respiratory tract by PB or NaB is a novel discovery. This could mediate protection from secondary respiratory infections that frequently are the lethal causes in

  7. A low-molecular-weight compound K7174 represses hepcidin: possible therapeutic strategy against anemia of chronic disease.

    Directory of Open Access Journals (Sweden)

    Tohru Fujiwara

    Full Text Available Hepcidin is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of the hepcidin gene, HAMP, is increased in patients with anemia of chronic disease. Previously, the synthetic compound K7174 was identified through chemical screening as a novel inhibitor of the adhesion of monocytes to cytokine-stimulated endothelial cells. K7174 also ameliorated anemia induced by inflammatory cytokines in mice, which suggests a possible involvement of hepcidin regulation. The present study was performed to assess the impact of K7174 on hepcidin expression in a human hematoma cell line and in mice in vivo. We first demonstrated that K7174 treatment in HepG2 cells significantly decreased HAMP expression. Then, we conducted microarray analysis to determine the molecular mechanism by which K7174 inhibits HAMP expression. Transcriptional profiling confirmed the downregulation of HAMP. Surprisingly, we found that K7174 strongly induced GDF15, known as a negative regulator of HAMP expression. Western blotting analysis as well as ELISA confirmed the induction of GDF15 by K7174 treatment. Furthermore, K7174-mediated HAMP suppression was rescued by the silencing of GDF15 expression. Interestingly, we found that K7174 also upregulates CEBPB. Promoter analysis and chromatin immunoprecipitation analysis revealed that CEBPB could contribute to K7174-mediated transcriptional activation of GDF15. Subsequently, we also examined whether K7174 inhibits hepcidin expression in mice. Quantitative RT-PCR analysis with liver samples from K7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp expression, as compared to control mice. Furthermore, serum hepcidin concentration was also significantly decreased in K7174-treated mice. In conclusion, K7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 may be a potential therapeutic option to treat

  8. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

    Science.gov (United States)

    Anusuya, Shanmugam; Natarajan, Jeyakumar

    2012-12-01

    Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Combined effect of therapeutic strategies for bleeding injury on early survival, transfusion needs and correction of coagulopathy.

    Science.gov (United States)

    Balvers, K; van Dieren, S; Baksaas-Aasen, K; Gaarder, C; Brohi, K; Eaglestone, S; Stanworth, S; Johansson, P I; Ostrowski, S R; Stensballe, J; Maegele, M; Goslings, J C; Juffermans, N P

    2017-02-01

    The combined effects of balanced transfusion ratios and use of procoagulant and antifibrinolytic therapies on trauma-induced exsanguination are not known. The aim of this study was to investigate the combined effect of transfusion ratios, tranexamic acid and products containing fibrinogen on the outcome of injured patients with bleeding. A prospective multicentre observational study was performed in six level 1 trauma centres. Injured patients who received at least 4 units of red blood cells (RBCs) were analysed and divided into groups receiving a low (less than 1 : 1) or high (1 or more : 1) ratio of plasma or platelets to RBCs, and in receipt or not of tranexamic acid or fibrinogen products (fibrinogen concentrates or cryoprecipitate). Logistic regression models were used to assess the effect of transfusion strategies on the outcomes 'alive and free from massive transfusion' (at least 10 units of RBCs in 24 h) and early 'normalization of coagulopathy' (defined as an international normalized ratio of 1·2 or less). A total of 385 injured patients with ongoing bleeding were included in the study. Strategies that were independently associated with an increased number of patients alive and without massive transfusion were a high platelet to RBC ratio (odds ratio (OR) 2·67, 95 per cent c.i. 1·24 to 5·77; P = 0·012), a high plasma to RBC ratio (OR 2·07, 1·03 to 4·13; P = 0·040) and treatment with tranexamic acid (OR 2·71, 1·29 to 5·71; P = 0·009). No strategies were associated with correction of coagulopathy. A high platelet or plasma to RBC ratio, and use of tranexamic acid were associated with a decreased need for massive transfusion and increased survival in injured patients with bleeding. Early normalization of coagulopathy was not seen for any transfusion ratio, or for use of tranexamic acid or fibrinogen products. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  10. Comparison of different options for harvest of a therapeutic protein product from high cell density yeast fermentation broth.

    Science.gov (United States)

    Wang, Alice; Lewus, Rachael; Rathore, Anurag S

    2006-05-05

    Recovery of therapeutic protein from high cell density yeast fermentations at commercial scale is a challenging task. In this study, we investigate and compare three different harvest approaches, namely centrifugation followed by depth filtration, centrifugation followed by filter-aid enhanced depth filtration, and microfiltration. This is achieved by presenting a case study involving recovery of a therapeutic protein from Pichia pastoris fermentation broth. The focus of this study is on performance of the depth filtration and the microfiltration steps. The experimental data has been fitted to the conventional models for cake filtration to evaluate specific cake resistance and cake compressibility. In the case of microfiltration, the experimental data agrees well with flux predicted by shear induced diffusion model. It is shown that, under optimal conditions, all three options can deliver the desired product recovery ( >80%), harvest time ( making a final decision on a harvesting approach.

  11. Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

    Science.gov (United States)

    Padilla-Zambrano, Huber S.; Tomás-Zapico, Cristina; García, Benjamin Fernández

    2018-01-01

    This concept article aims to show the rationale of targeting extracellular α-Synuclein (α-Syn) from cerebrospinal fluid (CSF) as a new strategy to remove this protein from the brain in Parkinson’s disease (PD). Misfolding and intracellular aggregation of α-synuclein into Lewy bodies are thought to be crucial in the pathogenesis of PD. Recent research has shown that small amounts of monomeric and oligomeric α-synuclein are released from neuronal cells by exocytosis and that this extracellular alpha-synuclein contributes to neurodegeneration, progressive spreading of alpha-synuclein pathology, and neuroinflammation. In PD, extracellular oligomeric-α-synuclein moves in constant equilibrium between the interstitial fluid (ISF) and the CSF. Thus, we expect that continuous depletion of oligomeric-α-synuclein in the CSF will produce a steady clearance of the protein in the ISF, preventing transmission and deposition in the brain. PMID:29570693

  12. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  13. Comparison between double-balloon and single-balloon enteroscopy in therapeutic ERC after Roux-en-Y entero-enteric anastomosis.

    Science.gov (United States)

    Moreels, Tom G; Pelckmans, Paul A

    2010-09-16

    To compare the efficacy of double-balloon enteroscopy (DBE) and single-balloon enteroscopy (SBE) in therapeutic endoscopic retrograde cholangiography (ERC) in patients with Roux-en-Y entero-enteric anastomosis. Retrospective analysis of our patient cohort revealed 4 patients with enterobiliary anastomosis and Roux-en-Y entero-enteric anastomosis who underwent repeated ERC with DBE and SBE because of recurrent cholangitis. A total of 38 endoscopic retrograde cholangiopancreatography procedures were performed in 25 patients with Roux-en-Y entero-enteric anastomosis. DBE was used in 29 procedures and SBE in 9. The 4 patients who underwent repeated ERC with DBE and SBE suffered from recurrent cholangitis due to stenosis of the enterobiliary anastomosis. ERC was performed repeatedly to achieve balloon dilation with/without biliary stone extraction and multiple stent placement at the level of the enterobiliary anastomosis. In all 4 patients DBE and SBE were equally successful. Compared to DBE, SBE was equally effective in passing the Roux-en-Y entero-enteric anastomosis, reaching the enterobiliary anastomosis and performing therapeutic ERC. This retrospective comparison shows that DBE and SBE are equally successful in the performance of therapeutic ERC at the level of the enterobiliary anastomosis after Roux-en-Y entero-enteric anastomosis.

  14. Identification of new tumor associated antigens and their usage for new therapeutic strategies based on the combination of chemotherapy and immunotherapy for colorectal cancer patients

    International Nuclear Information System (INIS)

    Proietti, E.; Maccalli, C.; Rosenberg, S.A.; Robbins, P.F.

    2009-01-01

    The main general objective of this project was to characterize a new colorectal carcinoma (CRC) tumor-associated antigen (TAA) and validate a new therapeutic strategy combining chemotherapy and tumor vaccination for the treatment of cancer patients. To this purpose a strategic interaction between Drs. Proietti/Maccali at the ISS and the group of Drs. Rosenberg/Robbins at the NIH was established. A stage of Dr. Maccalli at the NIH allowed to carry out the first steps for the identification and the initial characterization of the CRC TAA named COA-1. A laboratory meeting with Dr. Robbins has been planned on May 24-25 2006 at the ISS, during the International Meeting on Immunotherapy of Cancer: Challenges and Needs, for discussing results and perspectives of this research project

  15. Rescue therapeutic strategy combining ultra-protective mechanical ventilation with extracorporeal CO2 removal membrane in near-fatal asthma with severe pulmonary barotraumas: A case report.

    Science.gov (United States)

    Pavot, Arthur; Mallat, Jihad; Vangrunderbeeck, Nicolas; Thevenin, Didier; Lemyze, Malcolm

    2017-10-01

    Mechanical ventilation of severe acute asthma is still considered a challenging issue, mainly because of the gas trapping phenomenon with the potential for life-threatening barotraumatic pulmonary complications. Herein, we describe 2 consecutive cases of near-fatal asthma for whom the recommended protective mechanical ventilation approach using low tidal volume of 6 mL/kg and small levels of PEEP was rapidly compromised by giant pneumomediastinum with extensive subcutaneousemphysema. Near fatal asthma. A rescue therapeutic strategy combining extracorporeal CO2 removal membrane with ultra-protective extremely low tidal volume (3 mL/kg) ventilation was applied. Both patients survived hospital discharge. These 2 cases indicate that ECCO2R associated with ultra-protective ventilation could be an alternative to surgery in case of life-threatening barotrauma occurring under mechanical ventilation.

  16. Therapeutic strategies evaluated by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) Core Set Questionnaire in more than 1000 patients with cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Sigges, Johanna; Biazar, Cyrus; Landmann, Aysche

    2013-01-01

    The aim of this prospective, cross-sectional, multicentre study performed by the European Society of Cutaneous Lupus Erythematosus (EUSCLE) was to investigate different therapeutic strategies and their efficacies in cutaneous lupus erythematosus (CLE) throughout Europe. Using the EUSCLE Core Set...... Questionnaire, topical and systemic treatment options were analysed in a total of 1002 patients (768 females and 234 males) with different CLE subtypes. The data were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the criteria of the American College...... of Rheumatology (ACR) for the classification of systemic lupus erythematosus. Sunscreens were applied by 84.0% of the study cohort and showed a high efficacy in preventing skin lesions in all disease subtypes, correlating with a lower CLASI activity score. Topical steroids were used in 81.5% of the patients...

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

    Science.gov (United States)

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

    2017-12-01

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

  18. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection.

    Science.gov (United States)

    French, Martyn A; Abudulai, Laila N; Fernandez, Sonia

    2013-08-09

    The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of "protective" immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8⁺ T-cell responses restricted by "protective" HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  19. Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection

    Directory of Open Access Journals (Sweden)

    Sonia Fernandez

    2013-08-01

    Full Text Available The development of vaccines to treat and prevent human immunodeficiency virus (HIV infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK cell responses and plasmacytoid dendritic cell (pDC responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection.

  20. A comparison of fuzzy logic-PID control strategies for PWR pressurizer control

    International Nuclear Information System (INIS)

    Kavaklioglu, K.; Ikonomopoulos, A.

    1993-01-01

    This paper describes the results obtained from a comparison performed between classical proportional-integral-derivative (PID) and fuzzy logic (FL) controlling the pressure in a pressurized water reactor (PWR). The two methodologies have been tested under various transient scenarios, and their performances are evaluated with respect to robustness and on-time response to external stimuli. One of the main concerns in the safe operation of PWR is the pressure control in the primary side of the system. In order to maintain the pressure in a PWR at the desired level, the pressurizer component equipped with sprayers, heaters, and safety relief valves is used. The control strategy in a Westinghouse PWR is implemented with a PID controller that initiates either the electric heaters or the sprayers, depending on the direction of the coolant pressure deviation from the setpoint

  1. Targeting Sentinel Proteins and Extrasynaptic Glutamate Receptors: a Therapeutic Strategy for Preventing the Effects Elicited by Perinatal Asphyxia?

    Science.gov (United States)

    Herrera-Marschitz, Mario; Perez-Lobos, Ronald; Lespay-Rebolledo, Carolyne; Tapia-Bustos, Andrea; Casanova-Ortiz, Emmanuel; Morales, Paola; Valdes, Jose-Luis; Bustamante, Diego; Cassels, Bruce K

    2018-02-01

    Perinatal asphyxia (PA) is a relevant cause of death at the time of labour, and when survival is stabilised, associated with short- and long-term developmental disabilities, requiring inordinate care by health systems and families. Its prevalence is high (1 to 10/1000 live births) worldwide. At present, there are few therapeutic options, apart from hypothermia, that regrettably provides only limited protection if applied shortly after the insult.PA implies a primary and a secondary insult. The primary insult relates to the lack of oxygen, and the secondary one to the oxidative stress triggered by re-oxygenation, formation of reactive oxygen (ROS) and reactive nitrogen (RNS) species, and overactivation of glutamate receptors and mitochondrial deficiencies. PA induces overactivation of a number of sentinel proteins, including hypoxia-induced factor-1α (HIF-1α) and the genome-protecting poly(ADP-ribose) polymerase-1 (PARP-1). Upon activation, PARP-1 consumes high amounts of ATP at a time when this metabolite is scarce, worsening in turn the energy crisis elicited by asphyxia. The energy crisis also impairs ATP-dependent transport, including glutamate re-uptake by astroglia. Nicotinamide, a PARP-1 inhibitor, protects against the metabolic cascade elicited by the primary stage, avoiding NAD + exhaustion and the energetic crisis. Upon re-oxygenation, however, oxidative stress leads to nuclear translocation of the NF-κB subunit p65, overexpression of the pro-inflammatory cytokines IL-1β and TNF-α, and glutamate-excitotoxicity, due to impairment of glial-glutamate transport, extracellular glutamate overflow, and overactivation of NMDA receptors, mainly of the extrasynaptic type. This leads to calcium influx, mitochondrial impairment, and inactivation of antioxidant enzymes, increasing further the activity of pro-oxidant enzymes, thereby making the surviving neonate vulnerable to recurrent metabolic insults whenever oxidative stress is involved. Here, we discuss

  2. Expression and prognostic value of hemopoietic cytokine receptors in acute myeloid leukemia (AML): implications for future therapeutical strategies.

    Science.gov (United States)

    Graf, Michaela; Hecht, Karin; Reif, Susanne; Pelka-Fleischer, Renate; Pfister, Karin; Schmetzer, Helga

    2004-02-01

    Hemopoietic cytokines regulate hemopoietic cell functions via specific cell surface receptors. There is evidence to suggest, that those receptors (R) could play a role in leukemia with respect to cell differentiations and its regulation, prognosis, and pathobiology. Knowledge of individual cytokine receptor (CKR) profiles could provide new discoveries about CKR-supported therapeutic considerations. We have studied the expression of CKR on mononuclear bone marrow (BM) cells of 89 patients with acute myeloid leukemia (AML) at first diagnosis, three patients at relapse or with persisting AML and eight healthy probands by fluorescence-activated cell sorting (FACS) analysis using directly fluorescein-conjugated antibodies: CD114 (hG-CSF-R), CD116 (hGM-CSF-R), CD117 (hSCF-R), CD123 (hIL-3-R), CD130 (gp130subunit), CD135 (hFL-R). A case was defined as positive, if more than 20% of the cells expressed the regarding CKR. All investigated CKR were more frequently expressed in AML-samples than in healthy BM-samples, except CD130, which was only expressed on 5-6% of AML-blasts in all and with only one healthy BM-sample being CD130(+). Within the French-American-British (FAB) types we observed a maturation- and lineage (granulocytic/monocytic)-committed expression profile. Monocytic subtypes (FAB-type M4/M5) showed significantly more GM-CSF-R(+) (P = 0.001) and FL-R(+) (P = 0.001) and significantly less stem cell factor-R (SCF-R(+)) (P = 0.02) cases. Highest proportions of G-CSF-R(+) blasts were observed in FAB-type M3. In undifferentiated leukemias (FAB-type M1, M2) high amounts of SCF-R(+), IL-3-R(+), and FL-R(+) blasts could be detected. FL-R was the only CKR, which was positive in FAB-type M0 (n = 2). No differences in CKR-expression were detected between primary (p) and secondary (s). Separating our patient cohorts in cytogenetic risk groups we could detect a significant higher proportion of G-CSF-R(+) blasts in the cytogenetic good risk group than in the bad risk group (P

  3. Adverse events and therapeutic efficacy associated with TACE for hepatocellular carcinoma with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension

    International Nuclear Information System (INIS)

    Araki, Takuji; Okada, Taiki; Kimura, Kazufumi; Sawada, Eiichi; Sano, Katushiro; Araki, Tsutomu

    2012-01-01

    The aim of this study was to evaluate the short-term adverse events and therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension. Of patients who underwent TACE for unresectable HCCs in 2009 and 2010, twenty-nine and twenty-seven patients underwent TACE using cisplatin-lipiodol suspension (C-LS) and miriplatin-lipiodol suspension (M-LS), respectively. Adverse events of fever, pain, nausea, anorexia, elevation of aspartate aminotransferase (AST), total bilirubin, creatinine and a decrease in platelet count were evaluated by the National Cancer Institute Common Toxicity Criteria Ver.4. to compare the C-LS and M-LS groups. The short-term therapeutic efficacy of both groups was evaluated by the treatment effect (TE) on the CT images three months after TACE according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer (the 5th edition, Revised Version). With regard to the adverse events, the M-LS group had significantly less fever and anorexia than the C-LS group. No critical adverse events were observed in either group. The therapeutic efficacy was not significantly different between the groups. TACE with M-LS had fewer adverse events than TACE with C-LS, but neither TACE led to any critical adverse events. The short-term therapeutic efficacy of TACE with M-LS was equivalent to that of TACE with C-LS. (author)

  4. EBNA1: Oncogenic Activity, Immune Evasion and Biochemical Functions Provide Targets for Novel Therapeutic Strategies against Epstein-Barr Virus- Associated Cancers

    Directory of Open Access Journals (Sweden)

    Joanna B. Wilson

    2018-04-01

    Full Text Available The presence of the Epstein-Barr virus (EBV-encoded nuclear antigen-1 (EBNA1 protein in all EBV-carrying tumours constitutes a marker that distinguishes the virus-associated cancer cells from normal cells and thereby offers opportunities for targeted therapeutic intervention. EBNA1 is essential for viral genome maintenance and also for controlling viral gene expression and without EBNA1, the virus cannot persist. EBNA1 itself has been linked to cell transformation but the underlying mechanism of its oncogenic activity has been unclear. However, recent data are starting to shed light on its growth-promoting pathways, suggesting that targeting EBNA1 can have a direct growth suppressing effect. In order to carry out its tasks, EBNA1 interacts with cellular factors and these interactions are potential therapeutic targets, where the aim would be to cripple the virus and thereby rid the tumour cells of any oncogenic activity related to the virus. Another strategy to target EBNA1 is to interfere with its expression. Controlling the rate of EBNA1 synthesis is critical for the virus to maintain a sufficient level to support viral functions, while at the same time, restricting expression is equally important to prevent the immune system from detecting and destroying EBNA1-positive cells. To achieve this balance EBNA1 has evolved a unique repeat sequence of glycines and alanines that controls its own rate of mRNA translation. As the underlying molecular mechanisms for how this repeat suppresses its own rate of synthesis in cis are starting to be better understood, new therapeutic strategies are emerging that aim to modulate the translation of the EBNA1 mRNA. If translation is induced, it could increase the amount of EBNA1-derived antigenic peptides that are presented to the major histocompatibility (MHC class I pathway and thus, make EBV-carrying cancers better targets for the immune system. If translation is further suppressed, this would provide another

  5. [Results of therapeutics strategy of protein-energy wasting in chronic hemodialysis: a prospective study during 12 months].

    Science.gov (United States)

    Mpio, Ignace; Cleaud, Christine; Arkouche, Walid; Laville, Maurice

    2015-04-01

    Undernutrition (UN) in chronic hemodialysis (CHD) is a recurrent complication and constitutes a major public health problem. This work aims to evaluate the effects of our nutritional strategy (NS) developed among malnourished patients (pts) in CHD. This is a prospective observational study conducted for 12 months (M) in a cohort of 132 pts in CHD including 49 women, mean age 66 ± 16 years and the dialysis vintage 72 ± 74 months. This NS is based on the action of a multidisciplinary team; it provides for moderate UN pts one first phase of an optimization of protein and energy intake in the daily meals; then depending on the clinical course a second phase of oral supplementation at home. For severe UN pts, the optimization of daily meals and the oral supplements at home are reinforced with perdialytic oral supplementation. This modality was also prescribed for moderate UN pts with poor compliance at home. In case of loss of appetite, anorexia, gastrointestinal intolerance or inadequate oral intakes the relay is made by the intradialytic parenteral nutrition (IPN). Methods consist in the evaluation of the serum albumin (ALB), CRP, normalized PCR (nPCR), and Kt/V ratio of urea at baseline (day (D) 0) and at endpoint (M12). The ALB was measured by immunoturbidimetry. Three nutritional profiles were defined, severe UN if ALB ≤ 35 g/L, moderate UN if 35 treatment. The control of inflammation and optimizing dialysis are decisive factors of success. Copyright © 2014 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  6. Pregnancy in epileptic patients: comparison between well-established therapeutic strategies and opportunities coming from new drugs

    Directory of Open Access Journals (Sweden)

    Francesca Pizzo

    2013-12-01

    Full Text Available Treating women affected by epilepsy during pregnancy is challenging.  Clinicians have to consider both the teratogenic effects of Antiepileptic Drugs (AEDs and the risk of seizure recurrence. Pharmacokinetic changes during pregnancy are rapid and conspicuous so that the serum concentration of drugs can be modified and the effectiveness of AEDs cannot be guaranteed. The aim of this study is to evaluate the risk of Major Congenital Malformation (MCM associated with AEDs treatment during the first trimester of pregnancy. We collected data from 338 patients who contacted the Teratology Information Services of XXX University Hospital and we found that only the variable monotherapy vs politherapy had statistical significance for MCM. More studies are needed to assess the efficacy and safety of newer AEDs.

  7. [Identification, during development, of a methodology targeted at determining the positioning of new drugs for therapeutic strategies: examples of rheumatoid arthritis and cardiac insufficiency].

    Science.gov (United States)

    Le Jeunne, C; Plétan, Y; Boissel, J P

    2002-01-01

    The Marketing Authorization (MA) granted to a new molecular entity does not allow for proper anticipation of its future positioning within the therapeutic strategy. A specific methodology should be devised as early as during the pre-MA development phase that could result in an initial positioning that should be subjected to further reappraisal with regard to scientific advances, the arrival of new treatments and further developments with this molecule. A methodology is thus proposed, based on early optimisation of the development plan, the granting of subsequent MAs, and reappraisal of the positioning within the strategy, based on analysis of all available data. It should be possible to take into account the economic context, within an agreed system with pre-defined medico-economic criteria. This may in turn raise the issue of the role of the various parties involved in this assessment, as well as how to understand the respective opinions of stakeholders: authorities, sponsors, prescribers and patients, each of whom has a specific view of the definition of the strategic objective that should apply to the disease concerned.

  8. Oxidative Stress: A Unifying Mechanism for Cell Damage Induced by Noise, (Water-Pipe) Smoking, and Emotional Stress-Therapeutic Strategies Targeting Redox Imbalance.

    Science.gov (United States)

    Golbidi, Saeid; Li, Huige; Laher, Ismail

    2018-03-20

    Modern technologies have eased our lives but these conveniences can impact our lifestyles in destructive ways. Noise pollution, mental stresses, and smoking (as a stress-relieving solution) are some environmental hazards that affect our well-being and healthcare budgets. Scrutinizing their pathophysiology could lead to solutions to reduce their harmful effects. Recent Advances: Oxidative stress plays an important role in initiating local and systemic inflammation after noise pollution, mental stress, and smoking. Lipid peroxidation and release of lysolipid by-products, disturbance in activation and function of nuclear factor erythroid 2-related factor 2 (Nrf2), induction of stress hormones and their secondary effects on intracellular kinases, and dysregulation of intracellular Ca 2+ can all potentially trigger other vicious cycles. Recent clinical data suggest that boosting the antioxidant system through nonpharmacological measures, for example, lifestyle changes that include exercise have benefits that cannot easily be achieved with pharmacological interventions alone. Indiscriminate manipulation of the cellular redox network could lead to a new series of ailments. An ideal approach requires meticulous scrutiny of redox balance mechanisms for individual pathologies so as to create new treatment strategies that target key pathways while minimizing side effects. Extrapolating our understanding of redox balance to other debilitating conditions such as diabetes and the metabolic syndrome could potentially lead to devising a unifying therapeutic strategy. Antioxid. Redox Signal. 28, 741-759.

  9. Comparison of Depletion Strategies for the Enrichment of Low-Abundance Proteins in Urine.

    Science.gov (United States)

    Filip, Szymon; Vougas, Konstantinos; Zoidakis, Jerome; Latosinska, Agnieszka; Mullen, William; Spasovski, Goce; Mischak, Harald; Vlahou, Antonia; Jankowski, Joachim

    2015-01-01

    Proteome analysis of complex biological samples for biomarker identification remains challenging, among others due to the extended range of protein concentrations. High-abundance proteins like albumin or IgG of plasma and urine, may interfere with the detection of potential disease biomarkers. Currently, several options are available for the depletion of abundant proteins in plasma. However, the applicability of these methods in urine has not been thoroughly investigated. In this study, we compared different, commercially available immunodepletion and ion-exchange based approaches on urine samples from both healthy subjects and CKD patients, for their reproducibility and efficiency in protein depletion. A starting urine volume of 500 μL was used to simulate conditions of a multi-institutional biomarker discovery study. All depletion approaches showed satisfactory reproducibility (n=5) in protein identification as well as protein abundance. Comparison of the depletion efficiency between the unfractionated and fractionated samples and the different depletion strategies, showed efficient depletion in all cases, with the exception of the ion-exchange kit. The depletion efficiency was found slightly higher in normal than in CKD samples and normal samples yielded more protein identifications than CKD samples when using both initial as well as corresponding depleted fractions. Along these lines, decrease in the amount of albumin and other targets as applicable, following depletion, was observed. Nevertheless, these depletion strategies did not yield a higher number of identifications in neither the urine from normal nor CKD patients. Collectively, when analyzing urine in the context of CKD biomarker identification, no added value of depletion strategies can be observed and analysis of unfractionated starting urine appears to be preferable.

  10. Comparison of Quality of Life and Coping Strategies in Diabetic and Non Diabetic People

    Directory of Open Access Journals (Sweden)

    J Babapour Kheirodin

    2013-01-01

    Full Text Available Introduction: Diabetic patients face with different physical and psychological challenging factors which impress their quality of life. The major problem of these patients, which has made their life circumstances more complicated, is coping and adapting styles with the illness. So, this study aimed to determine quality of life and also different kinds of coping strategies in patients with type 2 diabetes and also to compare it with those of healthy people. Methods: In this study, sixty diabetic patients (30 male, 30 female, were chosen by available sampling method from the people who referred to Sina Diabetes center in Tabriz and were compared with sixty non diabetic people (30 male, 30 female. Data were collected by two questionnaires including the short form health survey (SF-36 and coping style Inventories. MANOVA method was used to analyze the research data. Results: The study results showed that non diabetics were significantly higher than diabetic patients in regard to quality of life and its dimensions (p<0.001. Also results revealed that non diabetic people used the problem–oriented styles (p<0.001, however diabetic patients used emotional-oriented coping and avoidance strategies more (p<0.05. In this study (in both groups, females in comparison with males had lower score in quality of life and used more emotion-oriented coping styles and less problem-oriented styles. Conclusion: The results indicated that individuals’ quality of life was affected by their coping style with different affairs. Emotional-oriented coping and avoidance strategies were related with decrease of quality of life in diabetic patients whereas problem-oriented styles enhanced it. Therefore, it is necessary to perform interventions for teaching problem solving coping in order to improve these patients' quality of life.

  11. PSA-selective activation of cytotoxic human serine proteases within the tumor microenvironment as a therapeutic strategy to target prostate cancer.

    Science.gov (United States)

    Rogers, Oliver C; Anthony, Lizamma; Rosen, D Marc; Brennen, W Nathaniel; Denmeade, Samuel R

    2018-04-27

    Prostate cancer is the most diagnosed malignancy and the second leading cause of cancer-related death in American men. While localized therapy is highly curative, treatments for metastatic prostate cancer are largely palliative. Thus, new innovative therapies are needed to target metastatic tumors. Prostate-Specific Antigen (PSA) is a chymotrypsin-like protease with a unique substrate specificity that is secreted by both normal and malignant prostate epithelial cells. Previous studies demonstrated the presence of high levels (μM-mM) of enzymatically active PSA is present in the extracellular fluid of the prostate cancer microenvironment. Because of this, PSA is an attractive target for a protease activated pro-toxin therapeutic strategy. Because prostate cancers typically grow very slowly, a strategy employing a proliferation-independent cytotoxic payload is preferred. Recently, it was shown that the human protease Granzyme B (GZMB), at low micromolar concentrations in the extracellular space, can cleave an array of extracellular matrix (ECM) proteins thus perturbing cell growth, signaling, motility, and integrity. It is also well established that other human proteases such as trypsin can induce similar effects. Because both enzymes require N-terminal proteolytic activation, we propose to convert these proteins into PSA-activated cytotoxins. In this study, we examine the enzymatic and cell targeting parameters of these PSA-activated cytotoxic serine proteases. These pro-enzymes were activated robustly by PSA and induced ECM damage that led to the death of prostate cancer cells in vitro thus supporting the potential use of this strategy as means to target metastatic prostate cancers.

  12. The accuracy of PiCCO® in measuring cardiac output in patients under therapeutic hypothermia: Comparison with transthoracic echocardiography.

    Science.gov (United States)

    Souto Moura, T; Aguiar Rosa, S; Germano, N; Cavaco, R; Sequeira, T; Alves, M; Papoila, A L; Bento, L

    2018-03-01

    Invasive cardiac monitoring using thermodilution methods such as PiCCO® is widely used in critically ill patients and provides a wide range of hemodynamic variables, including cardiac output (CO). However, in post-cardiac arrest patients subjected to therapeutic hypothermia, the low body temperature possibly could interfere with the technique. Transthoracic Doppler echocardiography (ECHO) has long proved its accuracy in estimating CO, and is not influenced by temperature changes. To assess the accuracy of PiCCO® in measuring CO in patients under therapeutic hypothermia, compared with ECHO. Thirty paired COECHO/COPiCCO measurements were analyzed in 15 patients subjected to hypothermia after cardiac arrest. Eighteen paired measurements were obtained at under 36°C and 12 at ≥36°C. A value of 0.5l/min was considered the maximum accepted difference between the COECHO and COPiCCO values. Under conditions of normothermia (≥36°C), the mean difference between COECHO and COPiCCO was 0.030 l/min, with limits of agreement (-0.22, 0.28) - all of the measurements differing by less than 0.5 l/min. In situations of hypothermia (<36°C), the mean difference in CO measurements was -0.426 l/min, with limits of agreement (-1.60, 0.75), and only 44% (8/18) of the paired measurements fell within the interval (-0.5, 0.5). The calculated temperature cut-off point maximizing specificity was 35.95°C: above this temperature, specificity was 100%, with a false-positive rate of 0%. The results clearly show clinically relevant discordance between COECHO and COPiCCO at temperatures of <36°C, demonstrating the inaccuracy of PiCCO® for cardiac output measurements in hypothermic patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  13. Randomized Comparison of the Therapeutic Effect of Acupuncture, Massage, and Tachibana-Style-Method on Stiff Shoulders by Measuring Muscle Firmness, VAS, Pulse, and Blood Pressure

    Directory of Open Access Journals (Sweden)

    Kazuhiro Tachibana

    2012-01-01

    Full Text Available To compare the therapeutic efficacy of acupuncture, massage, and Tachibana-Ryojutsu (one of Japanese traditional body balance therapy techniques (SEITAI, on stiff shoulders, the subjects’ muscle firmness, blood pressure, pulse, VAS, and body temperature were measured before and after the treatment. Forty-seven volunteer subjects gave written informed consent to participate in this study. The subjects were randomly divided into three groups to receive acupuncture, massage, or Tachibana-Ryojutsu. Each therapy lasted for 90 seconds. The acupuncture treatment was applied by a retaining-needle at GB-21, massage was conducted softly on the shoulders, and Tachibana-Ryojutsu treated only the muscles and joints from the legs to buttocks without touching the shoulders or backs. The study indicated that the muscle firmness and VAS of the Tachibana-Ryojutsu group decreased significantly in comparison with the acupuncture and massage groups after treatment.

  14. Operation and maintenance of waste incinerators - A comparison of two techniques and strategies; Drift och underhaall av avfallsfoerbraenningsanlaeggningar - En jaemfoerelse av tvaa tekniker och strategier

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Andreas [SP Technical Research Inst. of Sweden, Boraas (Sweden); Hoegskolan i Boraas, Boraas (Sweden); Niklasson, Fredrik [SP Technical Research Inst. of Sweden, Boraas (Sweden); Johnsson, Anders [Boraas Energi och Miljoe, Boraas (Sweden); Fredaeng, Julia [Dalkia, Stockholm (Sweden); Wettergren, Hans [Renova AB, Goeteborg (Sweden)

    2009-06-15

    This work has developed and demonstrated a simple method for comparison of operation and maintenance cost for various waste combustion techniques and plants. The principal of the method is to coarsely and initially divide cost into comparable posts. Post of specific interest is thereafter compared on a more detailed level. This procedure allows comparison with a modest consumption of time and effort. There is a lack of such comparison because of the effort needed to in detail compare the, often for each plant unique, selection of techniques and strategies. A consequence of the lack of comparisons is that success stories become invisible. The same can be said about common research needs. The demonstrated method visualizes the effects of various selections of techniques and strategies. It also points out bottlenecks for further improvement of the investigated units. The method has been simple to use and it is therefore considered as suitable to use in a larger investigation covering several waste combustion units. Thus, the project has accomplished its aims.

  15. Comparison of therapeutic effects between pulsed and continuous wave 810-nm wavelength laser irradiation for traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Takahiro Ando

    Full Text Available Transcranial low-level laser therapy (LLLT using near-infrared light can efficiently penetrate through the scalp and skull and could allow non-invasive treatment for traumatic brain injury (TBI. In the present study, we compared the therapeutic effect using 810-nm wavelength laser light in continuous and pulsed wave modes in a mouse model of TBI.TBI was induced by a controlled cortical-impact device and 4-hours post-TBI 1-group received a sham treatment and 3-groups received a single exposure to transcranial LLLT, either continuous wave or pulsed at 10-Hz or 100-Hz with a 50% duty cycle. An 810-nm Ga-Al-As diode laser delivered a spot with diameter of 1-cm onto the injured head with a power density of 50-mW/cm(2 for 12-minutes giving a fluence of 36-J/cm(2. Neurological severity score (NSS and body weight were measured up to 4 weeks. Mice were sacrificed at 2, 15 and 28 days post-TBI and the lesion size was histologically analyzed. The quantity of ATP production in the brain tissue was determined immediately after laser irradiation. We examined the role of LLLT on the psychological state of the mice at 1 day and 4 weeks after TBI using tail suspension test and forced swim test.The 810-nm laser pulsed at 10-Hz was the most effective judged by improvement in NSS and body weight although the other laser regimens were also effective. The brain lesion volume of mice treated with 10-Hz pulsed-laser irradiation was significantly lower than control group at 15-days and 4-weeks post-TBI. Moreover, we found an antidepressant effect of LLLT at 4-weeks as shown by forced swim and tail suspension tests.The therapeutic effect of LLLT for TBI with an 810-nm laser was more effective at 10-Hz pulse frequency than at CW and 100-Hz. This finding may provide a new insight into biological mechanisms of LLLT.

  16. Evaluation of the effect of transcytolemmal water exchange analysis for therapeutic response assessment using DCE-MRI: a comparison study.

    Science.gov (United States)

    Wang, Chunhao; Subashi, Ergys; Liang, Xiao; Yin, Fang-Fang; Chang, Zheng

    2016-07-07

    This study compares the shutter-speed (SS) and the Tofts models as used in assessing therapeutic response in a longitudinal DCE-MRI experiment. Sixteen nu/nu mice with implanted colorectal adenocarcinoma cell line (LS-174T) were randomly assigned into treatment/control groups (n  =  8/group) and received bevacizumab/saline twice weekly (Day1/Day4/Day8). All mice were scanned at one pre- (Day0) and two post-treatment (Day2/Day9) time points using a high spatiotemporal resolution DCE-MRI pulse sequence. The CA extravasation rate constant [Formula: see text] from the Tofts/SS model and the mean intracellular water residence time [Formula: see text] from the SS model were analyzed. A biological subvolume (BV) within the tumor was identified based on the [Formula: see text] intensity distribution, and the SS model parameters within the BV ([Formula: see text] and [Formula: see text]) were analyzed. It is found that [Formula: see text] and [Formula: see text] have a similar spatial distribution in the tumor volume. The Bayesian information criterion results show that the SS model was a better fit for all scans. At Day9, the treatment group had significantly higher tumor mean [Formula: see text] (p  =  0.021), [Formula: see text] (p  =  0.021) and [Formula: see text] (p  = 0.045). When BV from transcytolemmal water exchange analysis was adopted, the treatment group had higher mean [Formula: see text] at both Day2 (p  =  0.038) and Day9 (p  =  0.007). Additionally, at Day9, the treatment group had higher mean [Formula: see text] (p  =  0.045) and higher [Formula: see text] spatial heterogeneity indices (Rényi dimensions) d 1 (p  = 0.010) and d 2 (p  = 0.021). When mean [Formula: see text] and its coefficient of variation (CV) were used to separate treatment/control group samples using supporting vector machine, the accuracy of treatment/control classification was 68.8% at Day2 and 87.5% at Day9; in contrast, the

  17. The Comparison of Attention Biases to Opiates in Substance Dependent and Treated Clients of Therapeutic Clinics and Narcotics Anonymous Memberships

    Directory of Open Access Journals (Sweden)

    Javad Enayat

    2012-11-01

    Full Text Available Aim: The purpose of this study was to compare the attention bias about tempting incentives related to opium materials in treated, addicted and normal people. Duration of consumption and treating were also considered. Method: In this causal-comparative study population was all addicted people who were referred to the rehabilitation offices, addiction treatment clinic, rebirthing centers and Narcotics Anonymous of East Azerbaijan. This study consisted of five groups of men, including addicted to opium materials which are divided into two groups namely: long consumption period and people with short consumption period, also, treated people including long term treated and short term treated, and a normal control group. Altogether, 103 selected people were studied. Sample groups were similar in terms of age, education, and sex. For measuring attention bias towards tempting stimuli related opiates, a words recognition test was used. This test included three subtests and one recognition test. The recognition scores for the three categories of words were measured. Results: The findings indicated that there was a difference in attention against opium material incentives between control group and the mild and severe consumers groups. Also there were significant differences between treated people with the short time distance and control group, and control group had less temptation and biases in comparison to the other groups. Finally, those who have mild consumption are threatened more in comparison with the control group. Conclusion: The findings have applied implications.

  18. Role of Pre-therapeutic 18F-FDG PET/CT in Guiding the Treatment Strategy and Predicting Prognosis in Patients with Esophageal Carcinoma

    Directory of Open Access Journals (Sweden)

    Teik Hin Tan

    2016-07-01

    Full Text Available Objective(s: The present study aimed to evaluate the role of pretherapeutic 18fluorine-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PET-CT and maximum standardized uptake value (SUVmax in guiding the treatment strategy and predicting the prognosis of esophageal carcinoma, using the survival data of thepatients.Methods: The present retrospective, cohort study was performed on 40 consecutive patients with esophageal carcinoma (confirmed by endoscopic biopsy, who underwent pre-operative 18F-FDG PET-CTstaging between January 2009 and June 2014. All the patients underwent contrast-enhanced CT and non-contrasted 18F-FDG PET-CT evaluations.The patients were followed-up over 12 months to assess the changes in therapeutic strategies. Survival analysis was done considering the primary tumor SUVmax, using the Kaplan–Meier product-limit method.Results: In a total of 40 patients, 18F-FDG PET-CT scan led to changes in disease stage in 26n (65.0% cases, with upstaging and downstaging reported in 10n (25.0% and 16n (40.0% patients, respectively. The management strategy changed from palliative to curative in 10 out of 24 patients and from curative to palliative in 7 out of 16 cases. Based on the18F-FDG PET-CT scan alone, the median survival of patients in the palliative group was 4.0n (95 % CI 3.0-5.0 months, whereas the median survival in the curative group has not been reached, based on the 12-month followup.Selection of treatment strategy on the basis of 18F-FDG PET/CT alone was significantly associated with the survival outcomes at nine months (P=0.03 and marginally significant at 12 months (P=0.05. On the basisof SUVmax, the relation between survival and SUVmax was not statistically significant.Conclusion: 18F-FDG PET/CT scan had a significant impact on stage stratification and subsequently, selection of a stage-specific treatment approach and the overall survival outcome in patients with esophageal carcinoma. However, pre

  19. Comparison of Ready-to-Use Therapeutic Food with cereal legume-based khichri among malnourished children.

    Science.gov (United States)

    Dube, Brinda; Rongsen, Temsunaro; Mazumder, Sarmila; Taneja, Sunita; Rafiqui, Farhana; Bhandari, Nita; Bhan, M K

    2009-05-01

    To compare the acceptability and energy intake of Ready-to-Use Therapeutic Food (RUTF) with cereal legume based khichri among malnourished children. An acceptability trial with cross-over design. Urban low to middle socioeconomic neighbor-hoods in Delhi. 31 children aged > or =6 to or = -3 SD, with no clinical signs of infection or edema. Children were offered weighed amounts of RUTF and khichri in unlimited amounts for 2 days, one meal of each on both days. Water was fed on demand. Caregivers interviews and observations were conducted on the second day. Acceptability of RUTF compared to khichri based on direct observation and energy intake for test and control meals. The proportion of children who accepted RUTF eagerly was 58% as against 77% for khichri. 42% children on RUTF and 23% on khichri accepted the meal but not eagerly. The median (IQR) energy intake over the two day period in children aged 6 to 36 months from RUTF was 305 (153, 534) kcal, and from khichri was 242 (150, 320) kcal (P=0.02). RUTF and khichri were both well accepted by study children. The energy intake from RUTF was higher due to its extra energy density.

  20. Comparison of the therapeutic effects of prednisolone and nonsteroidal anti-inflammatory drugs in patients with subacute thyroiditis.

    Science.gov (United States)

    Sato, Junko; Uchida, Toyoyoshi; Komiya, Koji; Goto, Hiromasa; Takeno, Kageumi; Suzuki, Ruriko; Honda, Akira; Himuro, Miwa; Watada, Hirotaka

    2017-01-01

    Subacute thyroiditis is a transient inflammatory thyroid disease of unknown etiology. The primary goal for treatment is to mitigate inflammation. The aim of this retrospective study was to compare the therapeutic effects of prednisolone and nonsteroidal anti-inflammation drugs in patients with subacute thyroiditis. In this study, 53 consecutive Japanese patients who had been diagnosed with were referred to our hospital for further management. After excluding 11 patients (9 did not need treatment, 2 did not meet the criteria for diagnosis of subacute thyroiditis), the remaining 42 patients were treated either with prednisolone (n = 25) or loxoprofen (n = 17). We compared the time periods required for resolution of clinical symptoms and signs and normalization of thyroid function between the two groups. The mean dose of prednisolone was 15.0 (range, 14-16) mg/day and that of loxoprofen was 180 mg/day. The time period to normalization of thyroid function was comparable between the prednisolone and loxoprofen groups (25, 18-36, vs 32, 21-39 days, p = 0.388). However, the time period for resolution of symptoms was shorter under prednisolone than loxoprofen (7, 7-12 days, vs 21, 14-32 days, p thyroiditis was superior to nonsteroidal anti-inflammation drugs with regard to resolution of symptoms.

  1. The comparison of the effectiveness of conventional therapeutic exercises and Pilates on pain and function in patients with knee osteoarthritis.

    Science.gov (United States)

    Mazloum, Vahid; Rabiei, Pouya; Rahnama, Nader; Sabzehparvar, Elnaz

    2017-10-22

    The aim of this study was to investigate the effectiveness of two different interventions on pain and disability in patients with knee osteoarthritis (KOA). Forty-one individuals (Mean ± SD: Age 52.1 ± 8.9 years, Height 172.8 ± 6.6 cm, Weight 80.2 ± 6.9 kg) with KOA were randomly allocated into Pilates (N = 14), conventional therapeutic exercise (CTE) (N = 14), and control (N = 13) groups. Joint position sense (JPS), functional performance, pain, and disability were examined using Biodex system, aggregate time of four daily activities, and Lequesne Index. One-Way ANOVA, and Post Hoc Scheffe test were administrated to analyze the data (P Pilates training compared to CTE. It seemed that Pilates training was more effective than the CTE to improve pain and disability in individuals with KOA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Comparison of minimalist footwear strategies for simulating barefoot running: a randomized crossover study.

    Directory of Open Access Journals (Sweden)

    Karsten Hollander

    Full Text Available Possible benefits of barefoot running have been widely discussed in recent years. Uncertainty exists about which footwear strategy adequately simulates barefoot running kinematics. The objective of this study was to investigate the effects of athletic footwear with different minimalist strategies on running kinematics. Thirty-five distance runners (22 males, 13 females, 27.9 ± 6.2 years, 179.2 ± 8.4 cm, 73.4 ± 12.1 kg, 24.9 ± 10.9 km x week(-1 performed a treadmill protocol at three running velocities (2.22, 2.78 and 3.33 m x s(-1 using four footwear conditions: barefoot, uncushioned minimalist shoes, cushioned minimalist shoes, and standard running shoes. 3D kinematic analysis was performed to determine ankle and knee angles at initial foot-ground contact, rate of rear-foot strikes, stride frequency and step length. Ankle angle at foot strike, step length and stride frequency were significantly influenced by footwear conditions (p<0.001 at all running velocities. Posthoc pairwise comparisons showed significant differences (p<0.001 between running barefoot and all shod situations as well as between the uncushioned minimalistic shoe and both cushioned shoe conditions. The rate of rear-foot strikes was lowest during barefoot running (58.6% at 3.33 m x s(-1, followed by running with uncushioned minimalist shoes (62.9%, cushioned minimalist (88.6% and standard shoes (94.3%. Aside from showing the influence of shod conditions on running kinematics, this study helps to elucidate differences between footwear marked as minimalist shoes and their ability to mimic barefoot running adequately. These findings have implications on the use of footwear applied in future research debating the topic of barefoot or minimalist shoe running.

  3. Comparison of minimalist footwear strategies for simulating barefoot running: a randomized crossover study.

    Science.gov (United States)

    Hollander, Karsten; Argubi-Wollesen, Andreas; Reer, Rüdiger; Zech, Astrid

    2015-01-01

    Possible benefits of barefoot running have been widely discussed in recent years. Uncertainty exists about which footwear strategy adequately simulates barefoot running kinematics. The objective of this study was to investigate the effects of athletic footwear with different minimalist strategies on running kinematics. Thirty-five distance runners (22 males, 13 females, 27.9 ± 6.2 years, 179.2 ± 8.4 cm, 73.4 ± 12.1 kg, 24.9 ± 10.9 km x week(-1)) performed a treadmill protocol at three running velocities (2.22, 2.78 and 3.33 m x s(-1)) using four footwear conditions: barefoot, uncushioned minimalist shoes, cushioned minimalist shoes, and standard running shoes. 3D kinematic analysis was performed to determine ankle and knee angles at initial foot-ground contact, rate of rear-foot strikes, stride frequency and step length. Ankle angle at foot strike, step length and stride frequency were significantly influenced by footwear conditions (prunning velocities. Posthoc pairwise comparisons showed significant differences (prunning barefoot and all shod situations as well as between the uncushioned minimalistic shoe and both cushioned shoe conditions. The rate of rear-foot strikes was lowest during barefoot running (58.6% at 3.33 m x s(-1)), followed by running with uncushioned minimalist shoes (62.9%), cushioned minimalist (88.6%) and standard shoes (94.3%). Aside from showing the influence of shod conditions on running kinematics, this study helps to elucidate differences between footwear marked as minimalist shoes and their ability to mimic barefoot running adequately. These findings have implications on the use of footwear applied in future research debating the topic of barefoot or minimalist shoe running.

  4. Comparison of E-Book Acquisitions Strategies Across Disciplines Finds Differences in Cost and Usage

    Directory of Open Access Journals (Sweden)

    Laura Costello

    2017-03-01

    other studies of this kind so the conclusions made are appropriate for local application, even if they are not broadly generalizable. The authors also relied on combined subject designations and use for each of their package collections. Because the authors used three broad disciplinary categories and did not consider large interdisciplinary packages, this likely did not significantly influence the results. Future studies approaching this question might use a common subject classification for all acquisitions strategies, especially when considering databases with general content. Future studies could also move beyond descriptive statistics for ranking and examine the statistical significance of differences in cost and cost per use. This study represents an important contribution to the landscape of findings on this topic, particularly for collections and acquisitions librarians. The results of this article persuaded the authors to change acquisitions processes to favor more cost-effective methods. Further research, including more meta-analysis of acquisitions strategies, is needed before these results can be generalized to all libraries, but librarians assessing their own collections will find this a good template for comparison.

  5. REFLECTIONS ON BLUE OCEAN STRATEGY: A COMPARISON WITH ANSOFF’S, PORTER’S, AND HAX AND WILDE’S STRATEGIES

    Directory of Open Access Journals (Sweden)

    Ailton Conde Jussani

    2010-11-01

    Full Text Available Within the context of the globalized environment, competitiveness has become a critical issue for business. The use of research to inform strategic decisions is thus important for firms on the path to competitiveness, regardless of their market of operation. This paper provides an overview of four strategies—Kim and Mauborgne’s Blue Ocean Strategy, Ansoff’s Matrix, Porter’s Generic Strategies, and Hax and Wilde’s Delta model—in order to find the similarities and approximations among them. Applying the scientific reading method, we conducted a comprehensive review of the literature on strategy to draw up a comparative matrix among the four strategies analyzed so as to discuss the typologies for strategy formation modes. This matrix is intended to be used in future field studies. The comparison led to the observation that several possible approaches exist, each suited for distinctive businesses and business environments. This article aims to contribute to a better knowledge of administrative techniques that can help firms - and their executives - improve strategic decision making by choosing the strategy that best fits the competitive environment in which their business operates. Key-words: Strategic decisions. Strategic approaches. Comparative matrix. 

  6. [Alzheimer's disease: New therapeutic strategies].

    Science.gov (United States)

    Villegas, Sandra

    2015-07-20

    The rapid increase in prevalence rates of Alzheimer's disease means that treatments to prevent, stop or reverse this devastating disease are urgently needed. Despite advances in understanding its molecular pathology, there are no drugs that can halt its progression. This review takes a tour through phase 2, or higher studies, probing receptor agonist agents interfering with aggregation, inhibitors/modulators of secretases, lipid-lowering agents, and, finally and most extensively, immunotherapy. The fact that phase 3 studies with bapineuzumab and solaneuzumab have recently failed does not invalidate the potential of immunotherapy, as more information is available and new clinical trials are being initiated. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  7. Therapeutic strategy with artificially-designed i-lncRNA targeting multiple oncogenic microRNAs exhibits effective antitumor activity in diffuse large B-cell lymphoma.

    Science.gov (United States)

    Su, Yinghan; Sun, Bin; Lin, Xuejing; Zhao, Xinying; Ji, Weidan; He, Miaoxia; Qian, Haihua; Song, Xianmin; Yang, Jianmin; Wang, Jianmin; Chen, Jie

    2016-08-02

    In diffuse large B-cell lymphoma (DLBCL), many oncogenic microRNAs (OncomiRs) are highly expressed to promote disease development and progression by inhibiting the expression and function of certain tumor suppressor genes, and these OncomiRs comprise a promising new class of molecular targets for the treatment of DLBCL. However, most current therapeutic studies have focused on a single miRNA, with limited treatment outcomes. In this study, we generated tandem sequences of 10 copies of the complementary binding sequences to 13 OncomiRs and synthesized an interfering long non-coding RNA (i-lncRNA). The highly-expressed i-lncRNA in DLBCL cells would compete with the corresponding mRNAs of OncomiR target genes for binding OncomiRs, thereby effectively consuming a large amount of OncomiRs and protecting many tumor suppressor genes. The in vitro experiments confirmed that the i-lncRNA expression significantly inhibited cell proliferation, induced cell cycle arrest and apoptosis in DLBCL cell lines, mainly through upregulating the expression of PTEN, p27kip1, TIMP3, RECK and downregulating the expression of p38/MAPK, survivin, CDK4, c-myc. In the established SUDHL-4 xenografts in nude mice, the treatment strategy involving adenovirus-mediated i-lncRNA expression significantly inhibited the growth of DLBCL xenografts. Therefore, this treatment would specifically target the carcinogenic effects of many OncomiRs that are usually expressed in DLBCL and not in normal cells, such a strategy could improve anti-tumor efficacy and safety and may be a good prospect for clinical applications.

  8. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

    Science.gov (United States)

    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

  9. Comparison of INSURE method with conventional mechanical ventilation after surfactant administration in preterm infants with respiratory distress syndrome: therapeutic challenge.

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadat Nayeri

    2014-08-01

    Full Text Available Administration of endotracheal surfactant is potentially the main treatment for neonates suffering from RDS (Respiratory Distress Syndrome, which is followed by mechanical ventilation. Late and severe complications may develop as a consequence of using mechanical ventilation. In this study, conventional methods for treatment of RDS are compared with surfactant administration, use of mechanical ventilation for a brief period and NCPAP (Nasal Continuous Positive Airway Pressure, (INSURE method ((Intubation, Surfactant administration and extubation. A randomized clinical trial study was performed, including all newborn infants with diagnosed RDS and a gestational age of 35 weeks or less, who were admitted in NICU of Valiasr hospital. The patients were then divided randomly into two CMV (Conventional Mechanical Ventilation and INSURE groups. Surfactant administration and consequent long-term mechanical ventilation were done in the first group (CMV group. In the second group (INSURE group, surfactant was administered followed by a short-term period of mechanical ventilation. The infants were then extubated, and NCPAP was embedded. The comparison included crucial duration of mechanical ventilation and oxygen therapy, IVH (Intraventricular Hemorrhage, PDA (Patent Ductus Arteriosus, air-leak syndromes, BPD (Broncho-Pulmonary Dysplasia and mortality rate. The need for mechanical ventilation in 5th day of admission was 43% decreased (P=0.005 in INSURE group in comparison to CMV group. A decline (P=0.01 in the incidence of IVH and PDA was also achieved. Pneumothorax, chronic pulmonary disease and mortality rates, were not significantly different among two groups. (P=0.25, P=0.14, P=0.25, respectively. This study indicated that INSURE method in the treatment of RDS decreases the need for mechanical ventilation and oxygen-therapy in preterm neonates. Moreover, relevant complications as IVH and PDA were observed to be reduced. Thus, it seems rationale to

  10. A Comparison of Therapeutic and Anti-inflammatory Properties of Triamcinolone and Placebo (Vitamin A in Treatment of Paederus Dermatitis

    Directory of Open Access Journals (Sweden)

    Seyed Hasan Nikookar

    2014-09-01

    Full Text Available Abstract Background and purpose: Paederus associated dermatitis has always been considered as a health problem in the northern of Iran. Since until now, the traditional method and some corticosteroids have been used in the treatment of Paederus dermatitis (PD and no comprehensive studies have been carried out on the new method of treatment. Therefore, this study was aimed to compare the anti-inflammatory effects of triamcinolone with placebo in treatment of PD. Materials and Methods: This randomized double-blind clinical trial was performed during 6 months period in the clinics of Sari and Neka, Iran. Experimental group received triamcinolone and control group received placebo. The therapeutic effects of topically applied triamcinolone in 15 dermatitis patients and 15 control subjects were compared. The study subjects were visited in three separate times in the 1st, 7th and 14th day of the treatment. The data were collected in the questionnaire and compared in both groups by introducing the data into SPSS 11 software and analyzed by means of χ 2 test. Results: A total of 15 patients, 10 and 5 cases were undertaken for treatment in the Sari and Neka Townships, respectively. 40% and 50% of the patients from Sari and Neka Townships had lesion size 6-10 cm2, respectively. In this study, 90% and 100% of the patients from Sari and Neka had complete recovery 7 days after treatment, respectively. Statistical analysis indicated a significant difference between the case and control groups (P < 0.05. Conclusion: Insignificant difference was observed for treatment between the patients from the two Townships under study.

  11. A comparison of Reactivity Controlled Compression Ignition (RCCI) and Gasoline Compression Ignition (GCI) strategies at high load, low speed conditions

    International Nuclear Information System (INIS)

    Kavuri, Chaitanya; Paz, Jordan; Kokjohn, Sage L.

    2016-01-01

    Highlights: • Targeting high load-low speed, optimizations of RCCI and GCI strategies were performed. • The two strategies were compared in terms of performance, controllability and stability. • The optimum cases had high gross indicated efficiency (∼47%) and low NOx emissions. • RCCI strategy showed better combustion control but had higher soot emissions. • GCI strategy was relatively more sensitive to fluctuations in charge conditions. - Abstract: Past research has shown that Reactivity Controlled Compression Ignition (RCCI) and Gasoline Compression Ignition (GCI) combustion are promising approaches to improve efficiency and reduce pollutant emissions. However, the benefits have generally been confined to mid-load operating conditions. To enable practical application, these approaches must be able to operate over the entire engine map. A particularly challenging area is high load, low speed operation. Accordingly, the present work uses detailed CFD modeling and engine experiments to compare RCCI and GCI combustion strategies at a high load, low speed condition. Computational optimizations of RCCI and GCI combustion were performed at 20 bar gross indicated mean effective pressure (IMEP) and 1300 rev/min. The optimum points from the two combustion strategies were verified using engine experiments and were used to make the comparisons between RCCI and GCI combustion. The comparison showed that both the strategies had very similar combustion characteristics with a near top dead center injection initiating combustion. A parametric study was performed to identify the key input parameters that control combustion for the RCCI and GCI strategies. For both strategies, the combustion phasing could be controlled by the start of injection (SOI) timing of the near TDC injection. The short ignition delay of diesel fuel gave the RCCI strategy better control over combustion than the GCI strategy, but also had a simultaneous tradeoff with soot emissions. With the GCI

  12. A Comparison of Single-Cycle Versus Multiple-Cycle Proof Testing Strategies

    Science.gov (United States)

    McClung, R. C.; Chell, G. G.; Millwater, H. R.; Russell, D. A.; Millwater, H. R.

    1999-01-01

    Single-cycle and multiple-cycle proof testing (SCPT and MCPT) strategies for reusable aerospace propulsion system components are critically evaluated and compared from a rigorous elastic-plastic fracture mechanics perspective. Earlier MCPT studies are briefly reviewed. New J-integral estimation methods for semielliptical surface cracks and cracks at notches are derived and validated. Engineering methods are developed to characterize crack growth rates during elastic-plastic fatigue crack growth (FCG) and the tear-fatigue interaction near instability. Surface crack growth experiments are conducted with Inconel 718 to characterize tearing resistance, FCG under small-scale yielding and elastic-plastic conditions, and crack growth during simulated MCPT. Fractography and acoustic emission studies provide additional insight. The relative merits of SCPT and MCPT are directly compared using a probabilistic analysis linked with an elastic-plastic crack growth computer code. The conditional probability of failure in service is computed for a population of components that have survived a previous proof test, based on an assumed distribution of initial crack depths. Parameter studies investigate the influence of proof factor, tearing resistance, crack shape, initial crack depth distribution, and notches on the MCPT versus SCPT comparison. The parameter studies provide a rational basis to formulate conclusions about the relative advantages and disadvantages of SCPT and MCPT. Practical engineering guidelines are proposed to help select the optimum proof test protocol in a given application.

  13. SU-F-T-212: A Comparison of Treatment Strategies for Intracranial Stereotactic Radiosurgery

    International Nuclear Information System (INIS)

    Lamberton, T; Slater, J; Wroe, A

    2016-01-01

    Purpose: Stereotactic radiosurgery is an effective and noninvasive treatment for intracranial lesions that uses highly focused radiation beams in a single treatment fraction. The purpose of this study is to investigate the dosimetric differences between the treatment brain metastasis with a proton beam vs. intensity modulated radiation therapy (IMRT). Methods: Ten separate brain metastasis targets where chosen and treatment plans were created for each, using three different strategies: custom proton beam shaping devices, standardized proton beam shaping devices, and IMRT. Each plan was required to satisfy set parameters for providing adequate coverage and minimizing risk to adjacent tissues. The effectiveness of each plan was calculated by comparing the homogeneity index, conformity index, and V12 for each target using a paired one tailed T-test (α=0.05). Specific comparison of the conformity indices was also made using a subcategory containing targets with volume>1cc. Results: There was no significant difference between the homogeneity indices of the three plans (p>0.05), showing that each plan has the capability of adequately covering the targets. There was a statistically significant difference (p 1cc) there was no statistical difference between the proton plans and the IMRT treatment for the conformity index. Conclusion: A custom proton plan is the recommended treatment explored in this study as it is the most reliable way of effectively treating the target while sparing the maximum amount of normal tissue.

  14. Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

    Science.gov (United States)

    Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

    2009-11-01

    We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

  15. Diagnostic and therapeutic strategy in Menière's disease. Guidelines of the French Otorhinolaryngology-Head and Neck Surgery Society (SFORL).

    Science.gov (United States)

    Nevoux, J; Franco-Vidal, V; Bouccara, D; Parietti-Winkler, C; Uziel, A; Chays, A; Dubernard, X; Couloigner, V; Darrouzet, V; Mom, T

    2017-12-01

    The authors present the guidelines of the French Otorhinolaryngology-Head and Neck Surgery Society (Société française d'oto-rhino-laryngologie et de chirurgie de la face et du cou: SFORL) for diagnostic and therapeutic strategy in Menière's disease. A work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, then read over by an editorial group independent of the work group. The guidelines were graded according to the literature analysis and recommendations grading guide published by the French National Agency for Accreditation and Evaluation in Health (January 2000). Menière's disease is diagnosed in the presence of the association of four classical clinical items and after eliminating differential diagnoses on MRI. In case of partial presentation, objective audiovestibular tests are recommended. Therapy comprises medical treatment and surgery, either conservative or sacrificing vestibular function. Medical treatment is based on lifestyle improvement, betahistine, diuretics or transtympanic injection of corticosteroids or gentamicin. The main surgical treatments, in order of increasing aggressiveness, are endolymphatic sac surgery, vestibular neurotomy and labyrinthectomy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  16. Comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial.

    Science.gov (United States)

    Doğan, Nurettin Özgür; Avcu, Nazire; Yaka, Elif; Yılmaz, Serkan; Pekdemir, Murat

    2015-07-01

    The present study aimed to compare the therapeutic efficacy of dimenhydrinate and piracetam in patients with vertigo. A blinded, parallel group, superiority, randomised clinical trial was carried out on patients who presented to the emergency department (ED) with vertigo. Healthy adult patients presenting to the ED with undifferentiated vertigo were included in the study. The efficacy of intravenous dimenhydrinate (100 mg) and intravenous piracetam (2000 mg) for reducing the intensity of vertigo was compared in two randomised treatment groups using a 10-point numeric rating scale (NRS). The determination of NRS scores was performed at presentation and at the 30th minute of presentation, after the study drug was implemented, both in immobile and ambulatory positions. The primary outcome variable was reduction in vertigo intensity documented on the NRS at the 30th minute after medication administration, analysed by intention to treat. A total of 94 patients were included in the randomisation (n=47 in both groups). The baseline NRS scores were 7.55±2.00 in the dimenhydrinate group and 8.19±1.79 in the piracetam group. The changes from baseline for dimenhydrinate and piracetam were 2.92±3.11 and 3.75±3.40 (difference -0.83 (95% CI -2.23 to 0.57)) in the immobile position and were 2.04±3.07 and 2.72±2.91 (difference -0.68 (95% CI -2.03 to 0.67)) in the ambulatory position. Rescue medication need was similar in both treatment groups (p=0.330), and only one adverse reaction was reported. We found no evidence of a difference between dimenhydrinate and piracetam in relieving the symptoms of vertigo. Clinical Trials Registration ID: NCT01890538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. A comparison of HK-CONWIP and BK-CONWIP control strategies in a multi-product manufacturing system

    Directory of Open Access Journals (Sweden)

    Chukwunonyelum Emmanuel Onyeocha

    2015-12-01

    Full Text Available This paper evaluates the performance of the Hybrid Kanban Constant Work-In-Process control strategy and Basestock Kanban Constant Work-In-Process control strategy operating Shared Kanban Allocation Policy (S-KAP and Dedicated Kanban Allocation Policy (D-KAP in a multi-product serial flow line. We explored the effect of an increase of product types on the WIP inventory in the system. A simulation-based optimisation technique was used in determining the optimal settings for the strategies. The strategies were compared via pairwise comparison technique and Nelson’s ranking and selection procedure. S-KAP responds quicker to demand than D-KAP. BK-CONWIP outperforms HK-CONWIP in a serial manufacturing system. It was shown that an increase in the number of product-type increases the number of PAC and WIP inventory.

  18. Preliminary comparison of the therapeutic efficacy of accelerated relative to conventional fractionation radiotherapy by treatment of spontaneous canine malignancies

    International Nuclear Information System (INIS)

    Denman, David L.; Levin, Rebecca; Buncher, C. Ralph; Aron, Bernard S.

    1996-01-01

    Purpose/Objective: This study's ultimate goals involve development of an accelerated fractionation (AF) regimen with an integrated final concomitant boost (CB) and examination of factors prognostic of the CB's therapeutic efficacy which could be measured during the initial AF portion to determine for which patients CB should be used. These endpoints can be accurately determined quickly by evaluating the treatment (tx) of spontaneous canine veterinary patient tumors. Because surviving tumor clonogen growth rate increases after radiotherapy (RT) begins, this accelerated repopulation (AR) should be reduced by AF. Furthermore, CB using a small field encompassing only the tumor bed, given as a second daily tx during the last week of RT, should further reduce AR. The initial portion of this project which is nearing completion was designed to determine if incidentally treated normal tissues could tolerate the AF regimen and project whether addition of the tumor bed CB would also be tolerated. Materials and Methods: Currently 20 canine patients with biopsy proven localized tumors have received canine AF radiotherapy given as 3.2Gy/fraction(fx) administered 5 days a week (Mon-Fri) to a total of 15 fxs (48Gy) within 18 elapsed days. RT is given with a 60 Co teletherapy unit. Their tumor response, control, survival, and acute normal tissue responses are being directly compared to results we previously obtained from canines receiving a nearly equivalent dose/fx and total dose conventional fractionation (CF) regimen which was given alone or with adjuvant hyperthermia (HT). In that study the canines were stratified by tumor histology and anatomic site and randomly assigned to receive canine CF (3.5Gy/fx, 3 fxs/week [Mon-Wed-Fri] to 14 fxs (49Gy) in an elapsed time of approx. 30 days) either alone or followed weekly by local HT (44 deg. +/- 2 deg. C) for 30 minutes (5 HT fxs). As is currently done, these CF+/-HT patients were followed up to 3 years to quantitate the magnitudes

  19. Therapeutic potential of inhibiting ABCE1 and eRF3 genes via siRNA strategy using chitosan nanoparticles in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Cengiz, Bagdat Burcu; Asik, Mehmet Dogan [Hacettepe University, Nanotechnology and Nanomedicine Division (Turkey); Kara, Goknur [Hacettepe University, Biochemistry Division, Chemistry Department (Turkey); Turk, Mustafa [Kirikkale University, Bioengineering Department (Turkey); Denkbas, Emir Baki, E-mail: denkbas@hacettepe.edu.tr [Hacettepe University, Biochemistry Division, Chemistry Department (Turkey)

    2015-04-15

    In recent years, targeted cancer therapy strategies have begun to take the place of the conventional treatments. Inhibition of the specific genes, involved in cancer progress, via small interfering RNA (siRNA) has become one of the promising therapeutic approaches for cancer therapy. However, due to rapid nuclease degradation and poor cellular uptake of siRNA, a suitable carrier for siRNA penetration inside the cells is required. We used chitosan nanoparticles (CS-NPs) to efficiently deliver ATP-binding casette E1 (ABCE1) and eukaryotic release factor 3 (eRF3)-targeting siRNAs, individually and together, to reduce the proliferation and induce the apoptosis of breast cancer cells. The CS-NPs were generated by ionic gelation method using tripolyphosphate (TPP) as a crosslinker. Nanoparticles (NPs) were obtained with diameters ranging between 110 and 230 nm and the zeta potential of approximately 27 mV optimizing the solution pH to 4.5 and CS/TPP mass ratio to 3:1. Loading efficiencies of 98.69 % ± 0.051 and 98.83 % ± 0.047 were achieved when ABCE1 siRNA and eRF3 siRNA were entrapped into the NPs, respectively. Cell proliferation assay demonstrated that siRNA-loaded CS-NPs were more effective on cancer cells when compared to siRNAs without CS-NPs. Parallel results were also obtained by apoptosis/necrosis, double-staining analysis. Within our study, the potency of ABCE1 and eRF3 siRNAs were shown for the first time with this kind of polymeric delivery system. The results also indicated that ABCE1 and eRF3, important molecules in protein synthesis, could serve as effective targets to inhibit the cancer cells.

  20. Involvement of pro-inflammatory cytokines and growth factors in the pathogenesis of Dupuytren's contracture: a novel target for a possible future therapeutic strategy?

    Science.gov (United States)

    Bianchi, Enrica; Taurone, Samanta; Bardella, Lia; Signore, Alberto; Pompili, Elena; Sessa, Vincenzo; Chiappetta, Caterina; Fumagalli, Lorenzo; Di Gioia, Cira; Pastore, Francesco S; Scarpa, Susanna; Artico, Marco

    2015-10-01

    Dupuytren's contracture (DC) is a benign fibro-proliferative disease of the hand causing fibrotic nodules and fascial cords which determine debilitating contracture and deformities of fingers and hands. The present study was designed to characterize pro-inflammatory cytokines and growth factors involved in the pathogenesis, progression and recurrence of this disease, in order to find novel targets for alternative therapies and strategies in controlling DC. The expression of pro-inflammatory cytokines and of growth factors was detected by immunohistochemistry in fibrotic nodules and normal palmar fascia resected respectively from patients affected by DC and carpal tunnel syndrome (CTS; as negative controls). Reverse transcription (RT)-PCR analysis and immunofluorescence were performed to quantify the expression of transforming growth factor (TGF)-β1, interleukin (IL)-1β and vascular endothelial growth factor (VEGF) by primary cultures of myofibroblasts and fibroblasts isolated from Dupuytren's nodules. Histological analysis showed high cellularity and high proliferation rate in Dupuytren's tissue, together with the presence of myofibroblastic isotypes; immunohistochemical staining for macrophages was completely negative. In addition, a strong expression of TGF-β1, IL-1β and VEGF was evident in the extracellular matrix and in the cytoplasm of fibroblasts and myofibroblasts in Dupuytren's nodular tissues, as compared with control tissues. These results were confirmed by RT-PCR and by immunofluorescence in pathological and normal primary cell cultures. These preliminary observations suggest that TGF-β1, IL-1β and VEGF may be considered potential therapeutic targets in the treatment of Dupuytren's disease (DD). © 2015 Authors; published by Portland Press Limited.

  1. Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies.

    Science.gov (United States)

    Deng, Changchun; Lipstein, Mark R; Scotto, Luigi; Jirau Serrano, Xavier O; Mangone, Michael A; Li, Shirong; Vendome, Jeremie; Hao, Yun; Xu, Xiaoming; Deng, Shi-Xian; Realubit, Ronald B; Tatonetti, Nicholas P; Karan, Charles; Lentzsch, Suzanne; Fruman, David A; Honig, Barry; Landry, Donald W; O'Connor, Owen A

    2017-01-05

    Phosphoinositide 3-kinase (PI3K) and the proteasome pathway are both involved in activating the mechanistic target of rapamycin (mTOR). Because mTOR signaling is required for initiation of messenger RNA translation, we hypothesized that cotargeting the PI3K and proteasome pathways might synergistically inhibit translation of c-Myc. We found that a novel PI3K δ isoform inhibitor TGR-1202, but not the approved PI3Kδ inhibitor idelalisib, was highly synergistic with the proteasome inhibitor carfilzomib in lymphoma, leukemia, and myeloma cell lines and primary lymphoma and leukemia cells. TGR-1202 and carfilzomib (TC) synergistically inhibited phosphorylation of the eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), leading to suppression of c-Myc translation and silencing of c-Myc-dependent transcription. The synergistic cytotoxicity of TC was rescued by overexpression of eIF4E or c-Myc. TGR-1202, but not other PI3Kδ inhibitors, inhibited casein kinase-1 ε (CK1ε). Targeting CK1ε using a selective chemical inhibitor or short hairpin RNA complements the effects of idelalisib, as a single agent or in combination with carfilzomib, in repressing phosphorylation of 4E-BP1 and the protein level of c-Myc. These results suggest that TGR-1202 is a dual PI3Kδ/CK1ε inhibitor, which may in part explain the clinical activity of TGR-1202 in aggressive lymphoma not found with idelalisib. Targeting CK1ε should become an integral part of therapeutic strategies targeting translation of oncogenes such as c-Myc. © 2017 by The American Society of Hematology.

  2. Vitamin A-coupled liposome system targeting free cholesterol accumulation in hepatic stellate cells offers a beneficial therapeutic strategy for liver fibrosis.

    Science.gov (United States)

    Furuhashi, Hirotaka; Tomita, Kengo; Teratani, Toshiaki; Shimizu, Motonori; Nishikawa, Makoto; Higashiyama, Masaaki; Takajo, Takeshi; Shirakabe, Kazuhiko; Maruta, Koji; Okada, Yoshikiyo; Kurihara, Chie; Watanabe, Chikako; Komoto, Shunsuke; Aosasa, Suefumi; Nagao, Shigeaki; Yamamoto, Junji; Miura, Soichiro; Hokari, Ryota

    2018-04-01

    Liver fibrosis is a life-threatening disorder for which no approved therapy is available. Recently, we reported that mouse hepatic stellate cell (HSC) activation increased free cholesterol (FC) accumulation, partly by enhancing signaling through sterol regulatory element-binding protein 2 (SREBP2) and microRNA-33a (miR-33a), which resulted in HSC sensitization to transforming growth factor-β (TGFβ)-induced activation in a "vicious cycle" of liver fibrosis. Human HSCs were isolated from surgical liver specimens from control patients and patients with liver fibrosis. C57BL/6 mice were treated with carbon tetrachloride for 4 weeks and concurrently given SREBP2-siRNA- or anti-miR-33a-bearing vitamin A-coupled liposomes. In human activated HSCs obtained from patients with liver fibrosis, FC accumulation was enhanced independently of serum cholesterol levels through increased signaling by both SREBP2 and miR-33a. This increased FC accumulation enhanced Toll-like receptor 4 (TLR4) protein levels and lowered the TGFβ-pseudoreceptor Bambi (bone morphogenetic protein and activin membrane-bound inhibitor) mRNA levels in HSCs. Notably, in a mouse liver fibrosis model, reduction of FC accumulation, specifically in activated HSCs by suppression of SREBP2 or miR-33a expression using SREBP2-siRNA- or anti-miR-33a-bearing vitamin A-coupled liposomes, downregulated TLR4 signaling, increased Bambi expression, and consequently ameliorated liver fibrosis. Our results suggest that FC accumulation in HSCs, as an intracellular mediator promoting HSC activation, contributes to a vicious cycle of HSC activation in human and mouse liver fibrosis independent of serum cholesterol levels. Targeting FC accumulation-related molecules in HSCs through a vitamin A-coupled liposomal system represents a favorable therapeutic strategy for liver fibrosis. © 2017 The Japan Society of Hepatology.

  3. Wharton’s Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Joseph P. McGuirk

    2015-04-01

    Full Text Available Allogeneic hematopoietic cell transplantation (allo-HCT, a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD. The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton’s jelly (WJ-derived mesenchymal stromal cells (MSCs as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.

  4. Two replenishment strategies for the lost sales inventory model: a comparison

    NARCIS (Netherlands)

    Donselaar, van K.H.; Kok, de A.G.; Rutten, W.G.M.M.

    1996-01-01

    For the lost sales inventory system we distinguish two different replenishment strategies. The simplest strategy is the classical ‘fixed reorder level’ replenishment rule: every period the inventory position in the system is raised up to a fixed quantity S. For this simple strategy we derive and

  5. Accelerating Multiple Compound Comparison Using LINGO-Based Load-Balancing Strategies on Multi-GPUs

    OpenAIRE

    Lin, Chun-Yuan; Wang, Chung-Hung; Hung, Che-Lun; Lin, Yu-Shiang

    2015-01-01

    Compound comparison is an important task for the computational chemistry. By the comparison results, potential inhibitors can be found and then used for the pharmacy experiments. The time complexity of a pairwise compound comparison is O(n 2), where n is the maximal length of compounds. In general, the length of compounds is tens to hundreds, and the computation time is small. However, more and more compounds have been synthesized and extracted now, even more than tens of millions. Therefore,...

  6. A Comparison of the Habitual Landing Strategies from Differing Drop Heights of Parkour Practitioners (Traceurs) and Recreationally Trained Individuals.

    Science.gov (United States)

    Standing, Regan J; Maulder, Peter S

    2015-12-01

    Parkour is an activity that encompasses methods of jumping, climbing and vaulting. With landing being a pertinent part of this practise, Parkour participants (traceurs) have devised their own habitual landing strategies, which are suggested to be a safer and more effective style of landing. The purpose of this study was to compare the habitual landing strategies of traceurs and recreationally trained individuals from differing drop heights. Comparisons between landing sound and mechanical parameters were also assessed to gauge the level of landing safety. Ten recreationally trained participants and ten traceurs performed three landings from 25% and 50% body height using their own habitual landing strategies. Results at 25% showed significantly lower maximal vertical force (39.9%, p strike analysis revealed traceurs landed using forefoot or forefoot-midfoot strategies in 93.2% of trials; whereas recreationally trained participants used these styles in only 8.3% of these landings. To conclude, the habitual landings of traceurs are more effective at lowering the kinetic landing variables associated with a higher injury risk in comparison to recreationally trained individuals. Sound as a measure of landing effectiveness and safety holds potential significance; however requires further research to confirm. Key pointsHabitual traceur landings were observed to be safer landing techniques in comparison to those utilised by recreationally trained individuals, due to the lower maximal vertical forces, slower times to maximal vertical force, lesser loading rates and lower maximal sound.Traceurs predominantly landed with the forefoot only, whereas recreationally trained individuals habitually utilised a forefoot to heel landing strategy.The habitual landing techniques performed by traceurs may be beneficial for other landing sports to incorporate into training to reduce injury.

  7. Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes.

    Science.gov (United States)

    Salvador-Rosés, H; López-Ben, S; Casellas-Robert, M; Planellas, P; Gómez-Romeu, N; Farrés, R; Ramos, E; Codina-Cazador, A; Figueras, J

    2017-12-22

    The goal of treatment for patients with synchronous liver metastases (SLM) from rectal cancer is to achieve a complete resection of both tumor locations. For patients with symptomatic locally advanced rectal cancer with resectable SLM at diagnosis, our usual strategy has been the rectum first approach (RF). However, since 2014, we advocate for the interval approach (IS) that involves the administration of chemo-radiotherapy followed by the resection of the SLM in the interval of time between rectal cancer radiation and rectal surgery. From 2010 to 2016, 16 patients were treated according to this new strategy and 19 were treated according RF strategy. Data were collected prospectively and analyzed with an intention-to-treat perspective. Complete resection rate, duration of the treatment and morbi-mortality were the main outcomes. The complete resection rate in the IS was higher (100%, n = 16) compared to the RF (74%, n = 14, p = 0.049) and the duration of the strategy was shorter (6 vs. 9 months, respectively, p = 0.006). The incidence of severe complications after liver surgery was 14% (n = 2) in the RF and 0% in the IS (p = 1.000), and after rectal surgery was 24% (n = 4) and 12% (n = 2), respectively (p = 1.000). The IS is a feasible and safe strategy that procures higher level of complete resection rate in a shorter period of time compared to RF strategy.

  8. Experimental study and nuclear model calculations on the $^{192}Os (p, n)^{192}$Ir reaction Comparison of reactor and cyclotron production of the therapeutic radionuclide $^{192}$Ir

    CERN Document Server

    Hilgers, K; Sudar, S; 10.1016/j.apradiso.2004.12.010

    2005-01-01

    In a search for an alternative route of production of the important therapeutic radionuclide /sup 192/Ir (T/sub 1/2/=78.83 d), the excitation function of the reaction /sup 192/Os(p, n)/sup 192/Ir was investigated from its threshold up to 20MeV. Thin samples of enriched /sup 192/Os were obtained by electrodeposition on Ni, and the conventional stacked-foil technique was used for cross section measurements. The experimental data were compared with the results of theoretical calculations using the codes EMPIRE-II and ALICE-IPPE. Good agreement was found with EMPIRE-II, but slightly less with the ALICE-IPPE calculations. The theoretical thick target yield of /sup 192/Ir over the energy range E/sub p/=16 to 8MeV amounts to only 0.16MBq/ mu A.h. A comparison of the reactor and cyclotron production methods is given. In terms of yield and radionuclidic purity of /sup 192/Ir the reactor method appears to be superior; the only advantage of the cyclotron method could be the higher specific activity of the product.

  9. Enhanced neuro-therapeutic potential of Wharton's Jelly-derived mesenchymal stem cells in comparison with bone marrow mesenchymal stem cells culture.

    Science.gov (United States)

    Drela, Katarzyna; Lech, Wioletta; Figiel-Dabrowska, Anna; Zychowicz, Marzena; Mikula, Michał; Sarnowska, Anna; Domanska-Janik, Krystyna

    2016-04-01

    Substantial inconsistencies in mesenchymal stem (stromal) cell (MSC) therapy reported in early translational and clinical studies may indicate need for selection of the proper cell population for any particular therapeutic purpose. In the present study we have examined stromal stem cells derived either from umbilical cord Wharton's Jelly (WJ-MSC) or bone marrow (BM-MSC) of adult, healthy donors. The cells characterized in accordance with the International Society for Cellular Therapy (ISCT) indications as well as other phenotypic and functional parameters have been compared under strictly controlled culture conditions. WJ-MSC, in comparison with BM-MSC, exhibited a higher proliferation rate, a greater expansion capability being additionally stimulated under low-oxygen atmosphere, enhanced neurotrophic factors gene expression and spontaneous tendency toward a neural lineage differentiation commitment confirmed by protein and gene marker induction. Our data suggest that WJ-MSC may represent an example of immature-type "pre-MSC," where a substantial cellular component is embryonic-like, pluripotent derivatives with the default neural-like differentiation. These cells may contribute in different extents to nearly all classical MSC populations adversely correlated with the age of cell donors. Our data suggest that neuro-epithelial markers, like nestin, stage specific embryonic antigens-4 or α-smooth muscle actin expressions, may serve as useful indicators of MSC culture neuro-regeneration-associated potency. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  10. Comparison of strategies for model predictive control for home heating in future energy systems

    DEFF Research Database (Denmark)

    Vogler-Finck, Pierre Jacques Camille; Popovski, Petar; Wisniewski, Rafal

    2017-01-01

    Model predictive control is seen as one of the key future enabler in increasing energy efficiency in buildings. This paper presents a comparison of the performance of the control for different formulations of the objective function. This comparison is made in a simulation study on a single buildi...

  11. COMPARISON OF FAST PERIMETRIC STRATEGIES USING G2 PROGRAM ON OCTOPUS 101 PERIMETER

    Directory of Open Access Journals (Sweden)

    Jernej Pajek

    2002-12-01

    Full Text Available Background. The duration of the perimetric examination was significantly shortened by development of fast perimetric strategies. By analyzing the results of normal, dynamic and TOP strategy we studied the differences in determination of MD, LV, in determination of number of all points with a deficit and number of points with a significant deficit of p < 0.5%.Methods. 22 normal visual fields of 17 subjects (mean age 33 ± 15 years and 22 visual fields with defects of 17 patients (47 ± 16 years having different types and degrees of visual lesions were examined. All visual fields were examined once with each strategy in alternating order using Octopus 101 perimeter with the G2 program.Results. No statistically significant differences were measured in MD values. In abnormal visual fields group, TOP strategy showed 11 ± 14 dB2 lower LV values compared to dynamic strategy (p < 0.01 and 9.8 ± 16 dB2 lower LV values compared to normal strategy (p = 0.02. In the abnormal visual fields group the dynamic strategy measured in average 3 points with the deficit less compared to the other two strategies (p < 0.05. There were no significant differences between strategies in the number of points with a deficit of p < 0.5%.Conclusions. With the exception of lower LV values measured with TOP strategy, the differences between TOP, dynamic strategy results are small and the time sparing benefits are substantial. Therefore the usage of fast perimetric strategies is clinically justified.

  12. Reproducibility of R-fMRI metrics on the impact of different strategies for multiple comparison correction and sample sizes.

    Science.gov (United States)

    Chen, Xiao; Lu, Bin; Yan, Chao-Gan

    2018-01-01

    Concerns regarding reproducibility of resting-state functional magnetic resonance imaging (R-fMRI) findings have been raised. Little is known about how to operationally define R-fMRI reproducibility and to what extent it is affected by multiple comparison correction strategies and sample size. We comprehensively assessed two aspects of reproducibility, test-retest reliability and replicability, on widely used R-fMRI metrics in both between-subject contrasts of sex differences and within-subject comparisons of eyes-open and eyes-closed (EOEC) conditions. We noted permutation test with Threshold-Free Cluster Enhancement (TFCE), a strict multiple comparison correction strategy, reached the best balance between family-wise error rate (under 5%) and test-retest reliability/replicability (e.g., 0.68 for test-retest reliability and 0.25 for replicability of amplitude of low-frequency fluctuations (ALFF) for between-subject sex differences, 0.49 for replicability of ALFF for within-subject EOEC differences). Although R-fMRI indices attained moderate reliabilities, they replicated poorly in distinct datasets (replicability < 0.3 for between-subject sex differences, < 0.5 for within-subject EOEC differences). By randomly drawing different sample sizes from a single site, we found reliability, sensitivity and positive predictive value (PPV) rose as sample size increased. Small sample sizes (e.g., < 80 [40 per group]) not only minimized power (sensitivity < 2%), but also decreased the likelihood that significant results reflect "true" effects (PPV < 0.26) in sex differences. Our findings have implications for how to select multiple comparison correction strategies and highlight the importance of sufficiently large sample sizes in R-fMRI studies to enhance reproducibility. Hum Brain Mapp 39:300-318, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Structure, coercive control, and autonomy promotion: A comparison of fathers' and mothers' food parenting strategies.

    Science.gov (United States)

    Pratt, Mercedes; Hoffmann, Debra; Taylor, Maija; Musher-Eizenman, Dara

    2017-05-01

    This study explored differences in mothers' and fathers' food parenting strategies, specifically coercive control, structure, and autonomy promotion, and whether parenting style and parental responsibility for food parenting related to the use of these strategies. Parents of children aged 2.5-7.5 years ( N = 497) reported about their parenting practices and food parenting strategies. Parenting style accounted for the majority of the variance in food parenting. Fathers were more authoritarian than mothers. Authoritarian and permissive parenting practices were related to more coercive strategies. Mothers reported more food parenting responsibility. Responsibility was related to less coercive practices and more autonomy promotion and structure.

  14. Treatment with Rutin - A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases - Anti-inflammatory Effects of Rutin on Neutrophils -

    Directory of Open Access Journals (Sweden)

    Bahareh Abd Nikfarjam

    2017-03-01

    due to its inhibiting NO and TNF-α productions, as well as MPO activity, in activated human neutrophils. Treatment with rutin may be considered as a therapeutic strategy for neutrophil-mediated inflammatory/ autoimmune diseases.

  15. Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyung Su [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jeon, Seong-Uk; Lee, Chan-Ju; Kim, Young-Eun; Bok, Seoyeon; Hong, Beom-Ju; Park, Dong-Young [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Ahn, G-One, E-mail: goneahn@postech.ac.kr [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-07-01

    in the irradiated esophagus suggests that EGF may be a potential therapeutic intervention strategy to treat RIE.

  16. Targeting immune co-stimulatory effects of PD-L1 and PD-L2 might represent an effective therapeutic strategy in stroke

    Directory of Open Access Journals (Sweden)

    Sheetal eBodhankar

    2014-08-01

    Full Text Available Stroke outcome is worsened by the infiltration of inflammatory immune cells into ischemic brains. Our recent study demonstrated that PD-L1- and to a lesser extent PD-L2-deficient mice had smaller brain infarcts and fewer brain-infiltrating cells vs. WT mice, suggesting a pathogenic role for PD-Ligands in experimental stroke. We sought to ascertain PD-L1 and PD-L2-expressing cell types that affect T-cell activation, post-stroke in the context of other known co-stimulatory molecules. Thus, cells from male WT and PD-L-deficient mice undergoing 60 min of middle cerebral artery occlusion (MCAO followed by 96h of reperfusion were treated with neutralizing antibodies to study co-stimulatory and co-inhibitory interactions between CD80, CTLA-4, PD-1 and PD-Ls that regulate CD8+ and CD4+ T-cell activation. We found that antibody neutralization of PD-1 and CTLA-4 signaling post-MCAO resulted in higher proliferation in WT CD8+ and CD4+ T-cells, confirming an inhibitory role of PD-1 and CTLA-4 on T-cell activation. Also, CD80/CD28 interactions played a prominent regulatory role for the CD8+ T-cells and the PD-1/PD-L2 interactions were dominant in controlling the CD4+ T-cell responses in WT mice after stroke. A suppressive phenotype in PD-L1-deficient mice was attributed to CD80/CTLA-4 and PD-1/PD-L2 interactions. PD-L2 was crucial in modulating CD4+ T-cell responses, whereas PD-L1 regulated both CD8+ and CD4+ T-cells. To establish the contribution of PD-L1 and PD-L2 on regulatory B-cells (Bregs, infarct volumes were evaluated in male PD-L1- and PD-L2-deficient mice receiving IL-10+ B-cells 4h post-MCAO. PD-L2- but not PD-L1-deficient recipients of IL-10+ B-cells had markedly reduced infarct volumes, indicating a regulatory role of PD-L2 on Bregs. These results imply that PD-L1 and PD-L2 differentially control induction of T- and Breg-cell responses after MCAO, thus suggesting that selective targeting of PD-L1 and PD-L2 might represent a valuable therapeutic

  17. Marketing therapeutic recreation services.

    Science.gov (United States)

    Thorn, B E

    1984-01-01

    The use of marketing strategies can enhance the delivery of therapeutic recreation services. This article discusses how agencies can adapt marketing techniques and use them to identify potential markets, improve image, evaluate external pressures, and maximize internal strengths. Four variables that can be controlled and manipulated in a proposed marketing plan are product, price, place and promotion.

  18. Comparison of Coping Strategies of Student Teachers Based on Their Subject of Specialisation

    Science.gov (United States)

    P. M., Majitha; Sajan, K. S.

    2015-01-01

    The purpose of the study was to find out the difference in the mean scores of coping strategies of student teachers based on their subject of specialisation. A total of 558 student teachers were selected for the study. Results indicate that there exists a significant difference in the mean scores of Coping Strategies of student teachers of Arts…

  19. The Effects of Computer-Assisted Feedback Strategies in Technology Education: A Comparison of Learning Outcomes

    Science.gov (United States)

    Adams, Ruifang Hope; Strickland, Jane

    2012-01-01

    This study investigated the effects of computer-assisted feedback strategies that have been utilized by university students in a technology education curriculum. Specifically, the study examined the effectiveness of the computer-assisted feedback strategy "Knowledge of Response feedback" (KOR), and the "Knowledge of Correct Responses feedback"…

  20. Diverging business strategies towards climate change : a USA-Europe comparison for four sectors of industry

    NARCIS (Netherlands)

    Woerd, van der K.F.; Wit, de C.M.; Kolk, A.; Levy, D.L.; Vellinga, P.; Behlyarova, E.

    2004-01-01

    The research project has investigated what strategies specific sectors of industry develop to limit greenhouse gas emissions. In an USA-Europe co-operation, researchers have analysed emerging climate strategies in the oil industry, the automobile industry, the chemical industry and the bank and

  1. Magnetic resonance colonography with limited bowel preparation: a comparison of three strategies

    NARCIS (Netherlands)

    Florie, Jasper; van Gelder, Rogier E.; Haberkorn, Brigitte; Birnie, Erwin; Lavini, Cristina; Reitsma, Johannes B.; Stoker, Jaap

    2007-01-01

    PURPOSE: To prospectively compare three strategies of magnetic resonance colonography (MRC) with fecal tagging. MATERIALS AND METHODS: Three strategies were compared: (S1) gadolinium as oral tagging agent and a gadolinium-water mixture for rectal filling (bright lumen), (S2) oral barium and water

  2. A Comparison of Two Strategies for Teaching Third Graders to Summarize Information Text

    Science.gov (United States)

    Dromsky, Ann Marie

    2011-01-01

    Summarizing text is one of the most effective comprehension strategies (National Institute of Child Health and Human Development, 2000) and an effective way to learn from information text (Dole, Duffy, Roehler, & Pearson, 1991; Pressley & Woloshyn, 1995). In addition, much research supports the explicit instruction of such strategies as…

  3. The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy

    NARCIS (Netherlands)

    Boer, K.; Smit, C.; Flier, M. van der; Wolf, F. de; Koopmans †, P.P.; Crevel, R. van; Eggink, A.J.; Groot, R. de; Keuter, M.; Post, F.; Ven, A.J.A.M. van der; Warris, A.; et al.,

    2011-01-01

    BACKGROUND: In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in

  4. The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy

    NARCIS (Netherlands)

    Boer, Kees; Smit, Colette; van der Flier, Michiel; de Wolf, Frank; Bezemer, D. O.; Gras, L. A. J.; Kesselring, A. M.; van Sighem, A. I.; Smit, C.; Zhang, S.; Zaheri, S.; Bronsveld, W.; Hillebrand-Haverkort, M. E.; Prins, J. M.; Branger, J.; Eeftinck Schattenkerk, J. K. M.; Gisolf, J.; Godfried, M. H.; Lange, J. M. A.; Lettinga, K. D.; van der Meer, J. T. M.; Nellen, F. J. B.; van der Poll, T.; Reiss, P.; Ruys, Th A.; Steingrover, R.; van Twillert, G.; Vermeulen, J. N.; Vrouenraets, S. M. E.; van Vugt, M.; Wit, F. W. M. N.; Kuijpers, T. W.; Pajkrt, D.; Scherpbier, H. J.; van Eeden, A.; Brinkman, K.; van den Berk, G. E. L.; Blok, W. L.; Frissen, P. H. J.; Roos, J. C.; Schouten, W. E. M.; Bekendam, D. J.; Weigel, H. M.; Mulder, J. W.; van Gorp, E. C. M.; Wagenaar, J.; Veenstra, J.; Danner, S. A.; van Agtmael, M. A.; Claessen, F. A. P.

    2011-01-01

    In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of

  5. Cross-national comparisons of complex problem-solving strategies in two microworlds.

    Science.gov (United States)

    Güss, C Dominik; Tuason, Ma Teresa; Gerhard, Christiane

    2010-04-01

    Research in the fields of complex problem solving (CPS) and dynamic decision making using microworlds has been mainly conducted in Western industrialized countries. This study analyzes the CPS process by investigating thinking-aloud protocols in five countries. Participants were 511 students from Brazil, Germany, India, the Philippines, and the United States who worked on two microworlds. On the basis of cultural-psychological theories, specific cross-national differences in CPS strategies were hypothesized. Following theories of situatedness of cognition, hypotheses about the specific frequency of problem-solving strategies in the two microworlds were developed. Results of the verbal protocols showed (a) modification of the theoretical CPS model, (b) task dependence of CPS strategies, and (c) cross-national differences in CPS strategies. Participants' CPS processes were particularly influenced by country-specific problem-solving strategies. Copyright © 2009 Cognitive Science Society, Inc.

  6. Study and Comparison Between Personality Traits and Coping Strategies Among Opium Addicts (within the age of 30-36

    Directory of Open Access Journals (Sweden)

    Alireza Jazayeri

    2003-05-01

    Full Text Available The research is looking into the study and comparison between personality traits and coping strategies and their relationship with one another among opium addicts within the age of 30-36. For this purpose, a research group comprising 50 opium addicts was selected with respect to control variables. In order to compare the results, 50 other individuals were selected as a observation group and with regard to control variables both groups were matched together. The five-factor personality trait inventory (NEO-FFI and the coping strategy inventory of Carver and Shearer were used. Moreover, in order to control the effects of depression and anxiety on personality traits, Beck’s test for anxiety and depression was used. The results indicated that without taking the effects of depression and anxiety into account, the addicts showed higher neuroticism trait but lower extraversion, agreeableness and conscientious traits. But when the effects of depression and anxiety were taken into account, the two groups showed a meaningful difference in the conscientious trait. Furthermore, addicts rarely use concentrated coping strategies and usually use non-effective strategies. Non-effective strategies had direct relationship with neuroticism and opposite relationship with conscientiousness.

  7. Lurking: a challenge or a fruitful strategy? A comparison between lurkers and active participants in an online corporate community of practice

    NARCIS (Netherlands)

    Mirjam, Neelen; Sibren, Fetter

    2011-01-01

    Neelen, M., & Fetter, S. (2010). Lurking: a challenge or a fruitful strategy? A comparison between lurkers and active participants in an online corporate community of practice. International Journal of Knowledge and Learning, 6(4), 269-284.

  8. Recurrent unexplained palpitations (RUP) study comparison of implantable loop recorder versus conventional diagnostic strategy.

    Science.gov (United States)

    Giada, Franco; Gulizia, Michele; Francese, Maura; Croci, Francesco; Santangelo, Lucio; Santomauro, Maurizio; Occhetta, Eraldo; Menozzi, Carlo; Raviele, Antonio

    2007-05-15

    The aim of the study was to compare the diagnostic yield and the costs of implantable loop recorder (ILR) with those of the conventional strategy in patients with unexplained palpitations. In patients with unexplained palpitations, especially in those with infrequent symptoms, the conventional strategy, including short-term ambulatory electrocardiogram (ECG) monitoring and electrophysiological study, sometimes fails to establish a diagnosis. We studied 50 patients with infrequent (1 min) palpitations. Before enrollment, patients had a negative initial evaluation, including history, physical examination, and ECG. Patients were randomized either to conventional strategy (24-h Holter recording, a 4-week period of ambulatory ECG monitoring with an external recorder, and electrophysiological study) (n = 24) or to ILR implantation with 1-year monitoring (n = 26). Hospital costs of the 2 strategies were calculated. A diagnosis was obtained in 5 patients in the conventional strategy group, and in 19 subjects in the ILR group (21% vs. 73%, p < 0.001). Despite the higher initial cost, the cost per diagnosis in the ILR group was lower than in the conventional strategy group (euro 3,056 +/- euro 363 vs. euro 6,768 +/- euro 6,672, p = 0.012). In subjects without severe heart disease and with infrequent palpitations, ILR is a safe and more cost-effective diagnostic approach than conventional strategy.

  9. A Comparison of Two Strategies for Building an Exposure Prediction Model.

    Science.gov (United States)

    Heiden, Marina; Mathiassen, Svend Erik; Garza, Jennifer; Liv, Per; Wahlström, Jens

    2016-01-01

    Cost-efficient assessments of job exposures in large populations may be obtained from models in which 'true' exposures assessed by expensive measurement methods are estimated from easily accessible and cheap predictors. Typically, the models are built on the basis of a validation study comprising 'true' exposure data as well as an extensive collection of candidate predictors from questionnaires or company data, which cannot all be included in the models due to restrictions in the degrees of freedom available for modeling. In these situations, predictors need to be selected using procedures that can identify the best possible subset of predictors among the candidates. The present study compares two strategies for selecting a set of predictor variables. One strategy relies on stepwise hypothesis testing of associations between predictors and exposure, while the other uses cluster analysis to reduce the number of predictors without relying on empirical information about the measured exposure. Both strategies were applied to the same dataset on biomechanical exposure and candidate predictors among computer users, and they were compared in terms of identified predictors of exposure as well as the resulting model fit using bootstrapped resamples of the original data. The identified predictors were, to a large part, different between the two strategies, and the initial model fit was better for the stepwise testing strategy than for the clustering approach. Internal validation of the models using bootstrap resampling with fixed predictors revealed an equally reduced model fit in resampled datasets for both strategies. However, when predictor selection was incorporated in the validation procedure for the stepwise testing strategy, the model fit was reduced to the extent that both strategies showed similar model fit. Thus, the two strategies would both be expected to perform poorly with respect to predicting biomechanical exposure in other samples of computer users. © The

  10. Risk comparison of different treatment and disposal strategies of high level liquid radioactive waste

    International Nuclear Information System (INIS)

    Fang Dong

    1997-01-01

    The risk of different treatment and disposal strategies of high level liquid radioactive waste from spent fuel reprocessing is estimated and compared. The conclusions obtained are that risk difference from these strategies is very small and high level liquid waste can be reduced to middle and low level waste, if the decontamination factor for 99 Tc is large enough, which is the largest risk contributor in the high level radioactive waste from spent fuel reprocessing. It is also shown that the risk of high level radioactive waste could be reduced by the technical strategy of combining partitioning and transmutation

  11. Comparison of control strategies for Doubly fed induction generator under recurring grid faults

    DEFF Research Database (Denmark)

    Chen, Wenjie; Blaabjerg, Frede; Zhu, Nan

    2014-01-01

    The new grid codes demand the wind turbine systems to ride through recurring grid faults. Many control strategies have been proposed for the Doubly Fed Induction Generator under single grid fault, but their performance under recurring grid faults have not been studied yet. In this paper, five...... different control strategies for DFIG to ride through single grid faults are presented, and their performance under recurring grid faults are analyzed. The controllable range, stator time constant and torque fluctuations of the DFIG with different control strategies are compared. The results are verified...

  12. Locating the difference: A comparison of pedagogic strategies in high and low performing schools

    Directory of Open Access Journals (Sweden)

    Kaylianne Rialda Aploon-Zokufa

    2013-12-01

    Full Text Available A number of research studies have suggested that specific pedagogic strategies can have a positive impact on learning, and in turn, have a positive impact on school performance, in particular for children being schooled in disadvantaged contexts. This analysis describes and measures how four of these pedagogic strategies identified in research – the pacing of a lesson, the sequence and coherence of a lesson, cognitive demand and the nature of feedback within a lesson – are displayed in higher and lower performing schools located in lower-income communities in the Western Cape. The analysis forms part of a broader research project, SPADE (Schools Performing Above Demographic Expectation, and is based on fifteen video-recorded Grade 3 numeracy lessons. The analysis suggests a relationship between specific pedagogic strategies and higher performance for individual learners and for schools. The analysis also identifies further effective pedagogic strategies in higher performing schools in lower-income communities.

  13. A Comparison of Alternative Strategies for Cost-Effective Water Quality Management in Lakes

    Science.gov (United States)

    Kramer, Daniel Boyd; Polasky, Stephen; Starfield, Anthony; Palik, Brian; Westphal, Lynne; Snyder, Stephanie; Jakes, Pamela; Hudson, Rachel; Gustafson, Eric

    2006-09-01

    Roughly 45% of the assessed lakes in the United States are impaired for one or more reasons. Eutrophication due to excess phosphorus loading is common in many impaired lakes. Various strategies are available to lake residents for addressing declining lake water quality, including septic system upgrades and establishing riparian buffers. This study examines 25 lakes to determine whether septic upgrades or riparian buffers are a more cost-effective strategy to meet a phosphorus reduction target. We find that riparian buffers are the more cost-effective strategy in every case but one. Large transaction costs associated with the negotiation and monitoring of riparian buffers, however, may be prohibiting lake residents from implementing the most cost-effective strategy.

  14. A Comparison of Emotion Regulation Strategies of Blind Students With Sighted Students

    Directory of Open Access Journals (Sweden)

    Samaneh Salimi

    2016-06-01

    Discussion: Emotion regulation is a possible influential factor in many problems that blind people suffer from, more than sighted ones, and using interventions that target emotion regulation strategies would be useful.

  15. A comparison of information functions and search strategies for sensor planning in target classification.

    Science.gov (United States)

    Zhang, Guoxian; Ferrari, Silvia; Cai, Chenghui

    2012-02-01

    This paper investigates the comparative performance of several information-driven search strategies and decision rules using a canonical target classification problem. Five sensor models are considered: one obtained from classical estimation theory and four obtained from Bernoulli, Poisson, binomial, and mixture-of-binomial distributions. A systematic approach is presented for deriving information functions that represent the expected utility of future sensor measurements from mutual information, Rènyi divergence, Kullback-Leibler divergence, information potential, quadratic entropy, and the Cauchy-Schwarz distance. The resulting information-driven strategies are compared to direct-search, alert-confirm, task-driven (TS), and log-likelihood-ratio (LLR) search strategies. Extensive numerical simulations show that quadratic entropy typically leads to the most effective search strategy with respect to correct-classification rates. In the presence of prior information, the quadratic-entropy-driven strategy also displays the lowest rate of false alarms. However, when prior information is absent or very noisy, TS and LLR strategies achieve the lowest false-alarm rates for the Bernoulli, mixture-of-binomial, and classical sensor models.

  16. Economic Evaluation of a Multifaceted Implementation Strategy for the Prevention of Hand Eczema Among Healthcare Workers in Comparison with a Control Group: The Hands4U Study.

    NARCIS (Netherlands)

    Van Der Meer, Esther W C; van Dongen, J.M.; Boot, C.R.; van der Gulden, J.W.; Bosmans, J.E.; Anema, J.R.

    2016-01-01

    The aim of this study was to evaluate the cost-effectiveness of a multifaceted implementation strategy for the prevention of hand eczema in comparison with a control group among healthcare workers. A total of 48 departments (n=1,649) were randomly allocated to the implementation strategy or the

  17. Economic Evaluation of a Multifaceted Implementation Strategy for the Prevention of Hand Eczema Among Healthcare Workers in Comparison with a Control Group: The Hands4U Study

    NARCIS (Netherlands)

    Meer, E.W. van der; Dongen, J.M. van; Boot, C.R.; Gulden, J.W.J. van der; Bosmans, J.E.; Anema, J.R.

    2016-01-01

    The aim of this study was to evaluate the cost-effectiveness of a multifaceted implementation strategy for the prevention of hand eczema in comparison with a control group among healthcare workers. A total of 48 departments (n=1,649) were randomly allocated to the implementation strategy or the

  18. The Comparison of Politeness Strategies in Chinese Culture and in Eng-lish Speaking Context

    Institute of Scientific and Technical Information of China (English)

    李庆龄

    2015-01-01

    In contemporary society, as the development of globalization a growing tendency of how to communication effective⁃ly between different culture and languages has becoming a matter of fact. Even though a great number of communication strate⁃gies used to reduce the culture shock, obstacles in cultural exchanges still remains due to the culture differences. Politeness theory, as an important communication strategy, is still the most important and influential theory for cross-cultural communication. While there still has a few controversial arguments being conducted. It results in the issue of this article:Is there different compar⁃ing Chinese culture with English Speaking Culture in Terms of Politeness Strategies? In this paper, I will present a general review of classic politeness theories including Brown&Levinson, Leech’s research in English speaking culture and Gu and Xu’s findings in Chinese culture. Among their theories some specific politeness strategies such as face-saving strategy, politeness principle and its maxims will be used to give an image of the difference between Chinese culture and English speaking culture in terms of po⁃liteness strategies. In the definition of‘politeness’, two characteristics are worth mentioning:universality as well as culture-specif⁃ic. Therefore the article concludes by the arguing that, in spite of a few similarities, there are differences between in Chinese cul⁃ture and in English speaking context in politeness.

  19. Comparison of advertising strategies between the indoor tanning and tobacco industries.

    Science.gov (United States)

    Greenman, Jennifer; Jones, David A

    2010-04-01

    The indoor tanning industry is large and continues to grow, with 2007 domestic sales in excess of $5 billion. Advertising is central to shaping the consumer's perception of indoor tanning as well as driving industry demand. This article aims to identify key drivers of consumer appeal by comparing tanning advertising strategies to those used by tobacco marketers. Tobacco advertising was selected as a reference framework because it is both well documented and designed to promote a product with known health hazards. Two thousand advertisements from 4 large tobacco advertisement databases were analyzed for type of advertisement strategy used, and 4 advertising method categories were devised to incorporate the maximum number of advertisements reviewed. Subsequently, contemporary tanning advertisements were collected from industry magazines and salon websites and evaluated relative to the identified strategy profiles. Both industries have relied on similar advertising strategies, including mitigating health concerns, appealing to a sense of social acceptance, emphasizing psychotropic effects, and targeting specific population segments. This examination is a small observational study, which was conducted without rigorous statistical analysis, and which is limited both by the number of advertisements and by advertising strategies examined. Given the strong parallels between tobacco and tanning advertising methodologies, further consumer education and investigation into the public health risks of indoor tanning is needed. Copyright 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  20. Comparison of Personality Characteristics and Coping Strategies in Patients With Multiple Sclerosis and Control Group

    Directory of Open Access Journals (Sweden)

    Mohammadi

    2015-09-01

    Full Text Available Background The present study aimed to investigate personality traits and coping strategies in patients with multiple sclerosis (MS who were admitted to Sina hospital compared with healthy individuals. Objectives The aim of the present study was to compare personality characteristics and coping strategies between patients with MS and healthy controls. Materials and Methods The study sample included 55 patients with MS and 57 matched healthy control individuals. The data were gathered via a demographic form, the ways of coping questionnaire, and the NEO five-factor inventory. The data were analyzed by multivariate analysis of variance (MANOVA, Pearson’s correlation coefficient, and logistic regression. Results No significant differences in personality characteristics were observed between patients and healthy controls (all P > 0.05. Only the coping strategy subscale of Distancing was significant between patients and healthy controls (P 0.05. Only the Neuroticism personality trait and the Distancing coping strategy were predictive of group membership (i.e., healthy or patient. Conclusions Our study suggests that the personality traits of patients with MS and healthy individuals are not significantly different. Patients with MS are likely to use the same coping strategies as healthy individuals, except in the subscale of Distancing.

  1. Macromolecular therapeutics.

    Science.gov (United States)

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

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

  2. Comparison among different retrofitting strategies for the vulnerability reduction of masonry bell towers

    Science.gov (United States)

    Milani, Gabriele; Shehu, Rafael; Valente, Marco

    2017-11-01

    This paper investigates the effectiveness of reducing the seismic vulnerability of masonry towers by means of innovative and traditional strengthening techniques. The followed strategy for providing the optimal retrofitting for masonry towers subjected to seismic risk relies on preventing active failure mechanisms. These vulnerable mechanisms are pre-assigned failure patterns based on the crack patterns experienced during the past seismic events. An upper bound limit analysis strategy is found suitable to be applied for simplified tower models in their present state and the proposed retrofitted ones. Taking into consideration the variability of geometrical features and the uncertainty of the strengthening techniques, Monte Carlo simulations are implemented into the limit analysis. In this framework a wide range of idealized cases are covered by the conducted analyses. The retrofitting strategies aim to increase the shear strength and the overturning load carrying capacity in order to reduce vulnerability. This methodology gives the possibility to use different materials which can fulfill the structural implementability requirements.

  3. SMEs Going Global: A Comparison of the Internationalization Strategies of Publishers and Online Social Networks

    Directory of Open Access Journals (Sweden)

    Bettina Lis

    2012-01-01

    Full Text Available Up to now, most research has been conducted on the internationalization strategies of large media companies and groups. But tapping new foreign markets is also relevant to small- and medium-sized enterprises (SMEs of all media sectors. This paper therefore focuses on the internationalization strategies of different types of media SMEs. It aims at describing and comparing the motives for becoming an international player as well as the specific market selection, market entry, and market development strategies. Furthermore, it focuses on the main organizational implications. On the basis of a multiple-case design we compare two German regional newspaper publishers with two German special interest publishers and two online social business networks. Results show similarities and differences between these media sectors according to the nature of the media businesses. The cases also highlight the importance of international management skills also in the context of SMEs.

  4. Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

    Science.gov (United States)

    Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

    2001-11-01

    To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and

  5. Comparison of Various Online Strategies to Account for Interfractional Variations for Pancreatic Cancer

    International Nuclear Information System (INIS)

    Ahunbay, Ergun E.; Kimura, Brad; Liu, Feng; Erickson, Beth A.; Li, X. Allen

    2013-01-01

    Purpose: To identify practical techniques to address the large interfractional variations for pancreas irradiation by comparing various used/proposed online strategies. Methods and Materials: The daily computed tomography (CT) images acquired using a respiration-gated in-room CT (CTVision; Siemens) for 10 pancreatic cancer patients treated with image guided radiation therapy (IGRT) were analyzed. The contours of the pancreas and organs at risk on each daily CT set were generated by populating from the planning CT using a deformable registration tool (ABAS; Elekta) with manual editing. Nine online strategies were considered: (1) standard IGRT (ie, IGRT with 0-mm additional margin [AM]); (2) IGRT with 2-mm AM; (3) IGRT with 5-mm AM; (4) IGRT with plan renormalized to maintain 95% planning target volume (PTV) coverage; (5) full-scale reoptimization; (6) reoptimization starting from the original plan; (7) segment aperture morphing (SAM) from the original plan, based on PTV shape change; (8) SAM plus segment weight optimization; and (9) reoptimization starting from the SAM plan. One-way analysis of variance was applied to plan qualities for the 9 strategies to assess statistical significance in difference. Results: The 3 IGRT strategies (1-3) lead to either inadequate PTV coverage or higher doses to critical structures, indicating that the additional margins alone are not adequate to account for the changes. The full-scale reoptimization results in the best plan but requires the delineation of several structures, which is time consuming. The SAM strategy (7) was the fastest one, because it requires delineating only 1 structure (target), and its plan quality was comparable to that for the full-scale reoptimization. Conclusion: Online replanning strategies can lead to either reduced organs-at-risk dose and/or improved target coverage as compared with the current practice of IGRT. The SAM-based online replanning is comparable to full-scale reoptimization and is efficient

  6. [Curriculum analysis and comparison between strategies or programs for early child development in Mexico].

    Science.gov (United States)

    Vargas-López, Guillermo; Guadarrama-Orozco, Jessica Haydee; Rizzoli-Córdoba, Antonio; Narcizo-Cenobio, Francisco Javier; Medrano-Loera, Gerónimo; Villagrán, Daniel Aceves; O'Shea Cuevas, Gabriel; Muñoz Hernández, Onofre

    Most of the strategies or programs that support early child development in Mexico are independent efforts that vary in scale, services offered and means of providing them. For the evaluation of the quality of these programs, an important aspect is the curriculum content. The aim of this study was to analyze and compare the curriculum content of the different strategies or programs focused on the promotion and intervention of early child development, which are offered by the Federal Government in Health and Education sectors in Mexico. We conducted a review of the curriculum content of the strategies and programs. The qualitative phase consisted of a comparative analysis where 75 indicators proposed by the Inter-American Development Bank were identified. The quantitative phase consisted of a descriptive analysis of the indicators. Finally, the analyses were compared to establish the performance of each one. Six strategies or programs were identified. In the analysis of the presence of indicators, the Oportunidades de Aprendizaje (Learning Opportunities, LO) strategy showed a larger number of indicators. In the amplitude analysis, both PEI-CONAFE and LO were the best balanced. Finally, in-depth analysis of the indicators LO and Skills for life were the best balanced while PEI-CONAFE was the best balanced in the social-emotional area, CeNSIA program for language and LO for cognitive development area. LO strategy showed the closest level of contents established by the Inter-American Development Bank. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

  7. Comparison of Various Online Strategies to Account for Interfractional Variations for Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ahunbay, Ergun E., E-mail: eahunbay@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Kimura, Brad; Liu, Feng; Erickson, Beth A.; Li, X. Allen [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

    2013-08-01

    Purpose: To identify practical techniques to address the large interfractional variations for pancreas irradiation by comparing various used/proposed online strategies. Methods and Materials: The daily computed tomography (CT) images acquired using a respiration-gated in-room CT (CTVision; Siemens) for 10 pancreatic cancer patients treated with image guided radiation therapy (IGRT) were analyzed. The contours of the pancreas and organs at risk on each daily CT set were generated by populating from the planning CT using a deformable registration tool (ABAS; Elekta) with manual editing. Nine online strategies were considered: (1) standard IGRT (ie, IGRT with 0-mm additional margin [AM]); (2) IGRT with 2-mm AM; (3) IGRT with 5-mm AM; (4) IGRT with plan renormalized to maintain 95% planning target volume (PTV) coverage; (5) full-scale reoptimization; (6) reoptimization starting from the original plan; (7) segment aperture morphing (SAM) from the original plan, based on PTV shape change; (8) SAM plus segment weight optimization; and (9) reoptimization starting from the SAM plan. One-way analysis of variance was applied to plan qualities for the 9 strategies to assess statistical significance in difference. Results: The 3 IGRT strategies (1-3) lead to either inadequate PTV coverage or higher doses to critical structures, indicating that the additional margins alone are not adequate to account for the changes. The full-scale reoptimization results in the best plan but requires the delineation of several structures, which is time consuming. The SAM strategy (7) was the fastest one, because it requires delineating only 1 structure (target), and its plan quality was comparable to that for the full-scale reoptimization. Conclusion: Online replanning strategies can lead to either reduced organs-at-risk dose and/or improved target coverage as compared with the current practice of IGRT. The SAM-based online replanning is comparable to full-scale reoptimization and is efficient

  8. Comparison of strategies for substantiating freedom from scrapie in a sheep flock.

    Science.gov (United States)

    Durand, Benoit; Martinez, Marie-José; Calavas, Didier; Ducrot, Christian

    2009-04-30

    The public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led European animal health authorities to launch large screening and genetic selection programmes. If demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. In this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapie. Classical approaches, based on surveys designed to detect disease presence, do not account for scrapie specificities: the genetic variations of susceptibility and the absence of live diagnostic test routinely available. Adapting these approaches leads to a paradoxical situation in which a greater amount of testing is needed to substantiate disease freedom in genetically resistant flocks than in susceptible flocks, whereas probability of disease freedom is a priori higher in the former than in the latter. The goal of this study was to propose, evaluate and compare several qualification strategies for demonstrating a flock is free from scrapie. A probabilistic framework was defined that accounts for scrapie specificities and allows solving the preceding paradox. Six qualification strategies were defined that combine genotyping data, diagnostic tests results and flock pedigree. These were compared in two types of simulated flocks: resistant and susceptible flocks. Two strategies allowed demonstrating disease freedom in several years, for the majority of simulated flocks: a strategy in which all the flock animals are genotyped, and a strategy in which only founders animals are genotyped, the flock pedigree being known. In both cases, diagnostic tests are performed on culled animals. The less costly strategy varied according to the genetic context (resistant or susceptible) and to the relative costs of a genotyping exam and of a diagnostic test. This work demonstrates that

  9. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  10. Mechanical exposure implications of rationalization: A comparison of two flow strategies in a Swedish manufacturing plant

    DEFF Research Database (Denmark)

    Palmerud, Gunnar; Forsman, Mikael; Neumann, W. Patrick

    2012-01-01

    The aim of this case study was to (1) investigate differences in mechanical exposure (i.e. mechanical forces arising in the body of the operator) between two production strategies: long-cycle parallelised flow assembly (OLD) and conventional serial flow assembly (NEW), and (2) estimate potential ...

  11. Comparison of Learning Strategies for Mathematics Achievement in Turkey with Eight Countries

    Science.gov (United States)

    Kilic, Serpil; Cene, Erhan; Demir, Ibrahim

    2012-01-01

    The purpose of this study was to examine learning strategies accounted for mathematics achievement across Turkey and neighboring countries. Turkey, Bulgaria, Greece, Azerbaijan, Russian Federation, Israel, Serbia, Romania and Jordan were involved in Programme for International Student Assessment (PISA 2009) study. Since other neighbors of Turkey…

  12. Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

    Science.gov (United States)

    Yang, Lixue; Chen, Kean

    2015-11-01

    To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy.

  13. An experimental comparison of coded modulation strategies for 100 Gb/s transceivers

    NARCIS (Netherlands)

    Sillekens, E.; Alvarado, A.; Okonkwo, C.; Thomsen, B.C.

    2016-01-01

    Coded modulation is a key technique to increase the spectral efficiency of coherent optical communication systems. Two popular strategies for coded modulation are turbo trellis-coded modulation (TTCM) and bit-interleaved coded modulation (BICM) based on low-density parity-check (LDPC) codes.

  14. A Comparison of Alternative Strategies for Cost-Effective Water Quality Management in Lakes

    Science.gov (United States)

    Daniel Boyd Kramer; Stephen Polasky; Anthony Starfield; Brian Palik; Lynn Westphal; Stephanie Snyder; Pamela Jakes; Rachel Hudson; Eric Gustafson

    2006-01-01

    Roughly 45% of the assessed lakes in the United States are impaired for one or more reasons. Eutrophication due to excess phosphorus loading is common in many impaired lakes. Various strategies are available to lake residents for addressing declining lake water quality, including septic system upgrades and establishing riparian buffers. This study examines 25 lakes to...

  15. Comparison of Meaning and Graphophonemic Feedback Strategies for Guided Reading Instruction of Children with Language Delays

    Science.gov (United States)

    Kouri, Theresa A.; Selle, Carrie A.; Riley, Sarah A.

    2006-01-01

    Purpose: Guided reading is a common practice recommended for children in the early stages of literacy development. While experts agree that oral reading facilitates literacy skills, controversy exists concerning which corrective feedback strategies are most effective. The purpose of this study was to compare feedback procedures stemming from 2…

  16. Comparison of between-training-sessions recovery strategies for world-class BMX pilots.

    Science.gov (United States)

    Marquet, Laurie-Anne; Hausswirth, Christophe; Hays, Arnaud; Vettoretti, Fabrice; Brisswalter, Jeanick

    2015-03-01

    To assess the impact of between-training-sessions recovery strategies (passive [PAS], active [ACT], cold-water immersion [CWI], and ingestion of a recovery drink [NUTR]) on maximal cycling performance, perceptions of delayed-onset muscle soreness (DOMS), and fatigue in world-class BMX riders. Eleven elite BMX athletes, members of the French national team (top country in the 2011 international ranking, 4 medals at the 2012 World Championships, top European country), participated in the study, which involved standardized training periods. Athletes performed 3 maximal-sprint power tests: the first day of the week before the training session and before and after training on the third day of the week (D3). The recovery strategy was randomly assigned to each participant on day 2 immediately after the last training period of the day. Perceptions of DOMS and general fatigue were recorded on D3. After training on D3, the decrease in maximal-sprint power (Pmax) was significantly greater for PAS than with CWI (P=.02) and NUTR (P=.018). Similar results were found with ACT (vs CWI P=.044, and vs NUTR P=.042). Self-reported DOMS and fatigue were significantly greater after PAS than after other strategies. For elite BMX riders, between training days, nutritional and/or CWI recovery strategies appear to be best for reducing muscle fatigue and increasing the capacity to withstand the training schedule.

  17. Economic Analysis of HPAI Control in the Netherlands II: Comparison of Control Strategies

    NARCIS (Netherlands)

    Longworth, N.J.; Mourits, Monique C.M.; Saatkamp, H.W.

    2014-01-01

    A combined epidemiological-economic modelling approach was used to analyse strategies for highly pathogenic avian influenza (HPAI) control for the Netherlands. The modelling framework used was InterSpread Plus (ISP), a spatially based, stochastic and dynamic simulation model. A total of eight

  18. A Comparison of Low Performing Students' Achievements in Factoring Cubic Polynomials Using Three Different Strategies

    Science.gov (United States)

    Ogbonnaya, Ugorji I.; Mogari, David L.; Machisi, Eric

    2013-01-01

    In this study, repeated measures design was employed to compare low performing students' achievements in factoring cubic polynomials using three strategies. Twenty-five low-performing Grade 12 students from a secondary school in Limpopo province took part in the study. Data was collected using achievement test and was analysed using repeated…

  19. A New Comparison of Active Learning Strategies to Traditional Lectures for Teaching College Astronomy

    Science.gov (United States)

    LoPresto, Michael C.; Slater, Timothy F.

    2016-01-01

    Although traditional lectures are still the dominant form of undergraduate instruction, there have been relatively few studies comparing various learner-centered and active learning teaching strategies to one another in order to guide professors in making informed instructional decisions. To study the impact of different active learning…

  20. Economical and ecological comparison of granular activated carbon (GAC) adsorber refill strategies.

    Science.gov (United States)

    Bayer, Peter; Heuer, Edda; Karl, Ute; Finkel, Michael

    2005-05-01

    Technical constraints can leave a considerable freedom in the design of a technology, production or service strategy. Choosing between economical or ecological decision criteria then characteristically leads to controversial solutions of ideal systems. For the adaptation of granular-activated carbon (GAC) fixed beds, various technical factors determine the adsorber volume required to achieve a desired service life. In considering carbon replacement and recycling, a variety of refill strategies are available that differ in terms of refill interval, respective adsorber volume, and time-dependent use of virgin, as well as recycled GAC. Focusing on the treatment of contaminant groundwater, we compare cost-optimal reactor configurations and refill strategies to the ecologically best alternatives. Costs and consumption of GAC are quantified within a technical-economical framework. The emissions from GAC production out of hard coal, transport and recycling are equally derived through a life cycle impact assessment. It is shown how high discount rates lead to a preference of small fixed-bed volumes, and accordingly, a high number of refills. For fixed discount rates, the investigation reveals that both the economical as well as ecological assessment of refill strategies are especially sensitive to the relative valuation of virgin and recycled GAC. Since recycling results in economic and ecological benefits, optimized systems thus may differ only slightly.

  1. Early Child Care Teachers' Socialization Goals and Preferred Behavioral Strategies: A Cross-Cultural Comparison

    Science.gov (United States)

    Gernhardt, Ariane; Lamm, Bettina; Keller, Heidi; Döge, Paula

    2014-01-01

    This study investigated early child care teachers' culturally shaped socialization goals and preferred behavioral strategies. The participants were 183 female teachers and trainees, 93 from Osnabrück, Germany, representing an urban Western context, which can be characterized by a primary cultural orientation toward psychological autonomy and a…

  2. Comparison of acceptance and distraction strategies in coping with experimentally induced pain

    Directory of Open Access Journals (Sweden)

    Moore H

    2015-03-01

    Full Text Available Hazel Moore,1 Ian Stewart,1 Dermot Barnes-Holmes,2 Yvonne Barnes-Holmes,2 Brian E McGuire1,31School of Psychology, National University of Ireland, Galway, 2Department of Psychology, National University of Ireland, Maynooth, 3Centre for Pain Research, National University of Ireland, Galway, IrelandBackground: This study compared an acceptance-based strategy with a control-based strategy (distraction in terms of the ability of participants to tolerate a painful stimulus, across two experiments. In addition, participants were either actively encouraged, or not, to link pain tolerance with pursuit of valued goals to examine the impact of pursuing a personally meaningful goal or value on the extent to which pain will be tolerated.Methods: Participants in experiment 1 (n=41 and experiment 2 (n=52 were equally assigned to acceptance or distraction protocols. Further, half the participants in each group generated examples from their own lives in which they had pursued a valued objective, while the other half did not. In experiment 2, the values focus was enhanced to examine the impact on pain tolerance.Results: There were no significant differences overall between the acceptance and distraction groups on pain tolerance in either experiment. However, in experiment 2, individuals classified as accepting in terms of general coping style and who were assigned to the acceptance strategy showed significantly better pain tolerance than accepting individuals who were in the distraction condition. Across both experiments, those with strong goal-driven values in both protocols were more tolerant of pain. Participants appeared to have more difficulty adhering to acceptance than to distraction as a strategy.Conclusion: Acceptance may be associated with better tolerance of pain, but may also be more difficult to operationalize than distraction in experimental studies. Matching coping style and coping strategy may be most effective, and enhancement of goal

  3. The comparison of the performance of two screening strategies identifying newly-diagnosed HIV during pregnancy.

    Science.gov (United States)

    Boer, Kees; Smit, Colette; van der Flier, Michiel; de Wolf, Frank

    2011-10-01

    In the Netherlands, a non-selective opt-out instead of a selective opt-in antenatal HIV screening strategy was implemented in 2004. In case of infection, screening was followed by prevention of mother-to-child-transmission (PMTCT). We compared the performance of the two strategies in terms of detection of new cases of HIV and vertical transmission. HIV-infected pregnant women were identified retrospectively from the Dutch HIV cohort ATHENA January 2000 to January 2008. Apart from demographic, virological and immunological data, the date of HIV infection in relation to the index pregnancy was established. Separately, all infants diagnosed with HIV born following implementation of the screening program were identified by a questionnaire via the paediatric HIV centres. 162/481 (33.7%) HIV-positive pregnant women were diagnosed with HIV before 2004 and 172/214 (80.3%) after January 2004. Multivariate analysis showed an 8-fold (95% confidence interval 5.47-11.87) increase in the odds of HIV detection during pregnancy after the national introduction of the opt-out strategy. Still, three children born during a 5-year period after July 2004 were infected due to de novo infection in pregnancy. Implementation of a nation-wide screening strategy based upon non-selective opt-out screening followed by effective PMTCT appeared to detect more HIV-infected women for the first time in pregnancy and to reduce vertical transmission of HIV substantially. Nonetheless, still few children are infected because of maternal infection after the first trimester. We propose the introduction of partner screening on HIV as part of the antenatal screening strategy.

  4. Therapeutic cloning: The ethical limits

    International Nuclear Information System (INIS)

    Whittaker, Peter A.

    2005-01-01

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

  5. Strategy for communicating benefit-risk decisions: a comparison of regulatory agencies' publicly available documents.

    Science.gov (United States)

    Leong Wai Yeen, James; Salek, Sam; Walker, Stuart

    2014-01-01

    The assessment report formats of four major regulatory reference agencies, US Food and Drug Administration, European Medicines Agency, Health Canada, and Australia's Therapeutic Goods Administration were compared to a benefit-risk (BR) documentation template developed by the Centre for Innovation in Regulatory Science and a four-member Consortium on Benefit-Risk Assessment. A case study was also conducted using a US FDA Medical Review, the European Public Assessment Report and Australia's Public Assessment Report for the same product. Compared with the BR Template, existing regulatory report formats are inadequate regarding the listing of benefits and risks, the assigning of relative importance and values, visualization and the utilization of a detailed, systematic, standardized structure. The BR Template is based on the principles of BR assessment common to major regulatory agencies. Given that there are minimal differences among the existing regulatory report formats, it is timely to consider the feasibility of a universal template.

  6. Logical network of genotoxic stress-induced NF-kappaB signal transduction predicts putative target structures for therapeutic intervention strategies

    Directory of Open Access Journals (Sweden)

    Rainer Poltz

    2009-12-01

    Full Text Available Rainer Poltz1, Raimo Franke1,#, Katrin Schweitzer1, Steffen Klamt2, Ernst-Dieter Gilles2, Michael Naumann11Institute of Experimental Internal Medicine, Otto von Guericke University, Magdeburg, Germany; 2Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany; #Present address: Department of Chemical Biology, Helmholtz Centre for Infection Research, Braunschweig, GermanyAbstract: Genotoxic stress is induced by a broad range of DNA-damaging agents and could lead to a variety of human diseases including cancer. DNA damage is also therapeutically induced for cancer treatment with the aim to eliminate tumor cells. However, the effectiveness of radio- and chemotherapy is strongly hampered by tumor cell resistance. A major reason for radio- and chemotherapeutic resistances is the simultaneous activation of cell survival pathways resulting in the activation of the transcription factor nuclear factor-kappa B (NF-κB. Here, we present a Boolean network model of the NF-κB signal transduction induced by genotoxic stress in epithelial cells. For the representation and analysis of the model, we used the formalism of logical interaction hypergraphs. Model reconstruction was based on a careful meta-analysis of published data. By calculating minimal intervention sets, we identified p53-induced protein with a death domain (PIDD, receptor-interacting protein 1 (RIP1, and protein inhibitor of activated STAT y (PIASy as putative therapeutic targets to abrogate NF-κB activation resulting in apoptosis. Targeting these structures therapeutically may potentiate the effectiveness of radio- and chemotherapy. Thus, the presented model allows a better understanding of the signal transduction in tumor cells and provides candidates as new therapeutic target structures.Keywords: apoptosis, Boolean network, cancer therapy, DNA-damage response, NF-κB

  7. Avidin-conjugated polymers with monobiotinylated antibody fragments: a new strategy for the noncovalent attachment of recombinant proteins for polymer therapeutics

    Czech Academy of Sciences Publication Activity Database

    Laga, Richard; Pola, Robert; Ulbrich, Karel; Hořejší, Magdalena; Sieglová, Irena; Král, Vlastimil; Fábry, Milan; Pechar, Michal

    2013-01-01

    Roč. 28, č. 3 (2013), s. 289-299 ISSN 0883-9115 R&D Projects: GA ČR GCP207/12/J030; GA AV ČR IAAX00500803 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:61389013 ; RVO:68378050 Keywords : avidin-biotin complex * polymer therapeutics * drug targeting Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.500, year: 2013

  8. Evaluation and comparison of New 4DCT based strategies for proton treatment planning for lung tumors

    International Nuclear Information System (INIS)

    Wang, Ning; Patyal, Baldev; Ghebremedhin, Abiel; Bush, David

    2013-01-01

    To evaluate different strategies for proton lung treatment planning based on four-dimensional CT (4DCT) scans. Twelve cases, involving only gross tumor volumes (GTV), were evaluated. Single image sets of (1) maximum intensity projection (MIP3) of end inhale (EI), middle exhale (ME) and end exhale (EE) images; (2) average intensity projection (AVG) of all phase images; and (3) EE images from 4DCT scans were selected as primary images for proton treatment planning. Internal target volumes (ITVs) outlined by a clinician were imported into MIP3, AVG, and EE images as planning targets. Initially, treatment uncertainties were not included in planning. Each plan was imported into phase images of 4DCT scans. Relative volumes of GTVs covered by 95% of prescribed dose and mean ipsilateral lung dose of a phase image obtained by averaging the dose in inspiration and expiration phases were used to evaluate the quality of a plan for a particular case. For comparing different planning strategies, the mean of the averaged relative volumes of GTVs covered by 95% of prescribed dose and its standard deviation for each planning strategy for all cases were used. Then, treatment uncertainties were included in planning. Each plan was recalculated in phase images of 4DCT scans. Same strategies were used for plan evaluation except dose-volume histograms of the planning target volumes (PTVs) instead of GTVs were used and the mean and standard deviation of the relative volumes of PTVs covered by 95% of prescribed dose and the ipsilateral lung dose were used to compare different planning strategies. MIP3 plans without treatment uncertainties yielded 96.7% of the mean relative GTV covered by 95% of prescribed dose (standard deviations of 5.7% for all cases). With treatment uncertainties, MIP3 plans yielded 99.5% of mean relative PTV covered by 95% of prescribed dose (standard deviations of 0.7%). Inclusion of treatment uncertainties improved PTV dose coverage but also increased the ipsilateral

  9. Identifying quality improvement intervention publications - A comparison of electronic search strategies

    Directory of Open Access Journals (Sweden)

    Rubenstein Lisa V

    2011-08-01

    Full Text Available Abstract Background The evidence base for quality improvement (QI interventions is expanding rapidly. The diversity of the initiatives and the inconsistency in labeling these as QI interventions makes it challenging for researchers, policymakers, and QI practitioners to access the literature systematically and to identify relevant publications. Methods We evaluated search strategies developed for MEDLINE (Ovid and PubMed based on free text words, Medical subject headings (MeSH, QI intervention components, continuous quality improvement (CQI methods, and combinations of the strategies. Three sets of pertinent QI intervention publications were used for validation. Two independent expert reviewers screened publications for relevance. We compared the yield, recall rate, and precision of the search strategies for the identification of QI publications and for a subset of empirical studies on effects of QI interventions. Results The search yields ranged from 2,221 to 216,167 publications. Mean recall rates for reference publications ranged from 5% to 53% for strategies with yields of 50,000 publications or fewer. The 'best case' strategy, a simple text word search with high face validity ('quality' AND 'improv*' AND 'intervention*' identified 44%, 24%, and 62% of influential intervention articles selected by Agency for Healthcare Research and Quality (AHRQ experts, a set of exemplar articles provided by members of the Standards for Quality Improvement Reporting Excellence (SQUIRE group, and a sample from the Cochrane Effective Practice and Organization of Care Group (EPOC register of studies, respectively. We applied the search strategy to a PubMed search for articles published in 10 pertinent journals in a three-year period which retrieved 183 publications. Among these, 67% were deemed relevant to QI by at least one of two independent raters. Forty percent were classified as empirical studies reporting on a QI intervention. Conclusions The presented

  10. COMPARISON OF CLASSICAL AND INTERACTIVE MULTI-ROBOT EXPLORATION STRATEGIES IN POPULATED ENVIRONMENTS

    Directory of Open Access Journals (Sweden)

    Nassim Kalde

    2015-06-01

    Full Text Available Multi-robot exploration consists in coordinating robots for mapping an unknown environment. It raises several issues concerning task allocation, robot control, path planning and communication. We study exploration in populated environments, in which pedestrian flows can severely impact performances. However, humans have adaptive skills for taking advantage of these flows while moving. Therefore, in order to exploit these human abilities, we propose a novel exploration strategy that explicitly allows for human-robot interactions. Our model for exploration in populated environments combines the classical frontier-based strategy with our interactive approach. We implement interactions where robots can locally choose a human guide to follow and define a parametric heuristic to balance interaction and frontier assignments. Finally, we evaluate to which extent human presence impacts our exploration model in terms of coverage ratio, travelled distance and elapsed time to completion.

  11. Comparison of image quality in head CT studies with different dose-reduction strategies

    DEFF Research Database (Denmark)

    Johansen, Jeppe; Nielsen, Rikke; Fink-Jensen, Vibeke

    The number of multi-detector CT examinations is increasing rapidly. They allow high quality reformatted images providing accurate and precise diagnosis at maximum speed. Brain examinations are the most commonly requested studies, and although they come at a lower effective dose than body CT, can...... account to a considerable radiation dose as many patients undergo repeated studies. Therefore, various dose-reduction strategies are applied such as automated tube current and voltage modulation and recently different iterative reconstruction algorithms. However, the trade-off of all dose......-reduction maneuvers is reduction of image quality due to image noise or artifacts. The aim of our study was therefore to find the best diagnostic images with lowest possible dose. We present results of dose- and image quality optimizing strategies of brain CT examinations at our institution. We compare sequential...

  12. Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    DEFF Research Database (Denmark)

    Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

    2012-01-01

    The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

  13. Empathy and perspective-taking: Examination and comparison of strategies to reduce weight stigma

    OpenAIRE

    Gloor Jamie Lee; Puhl Rebecca M.

    2016-01-01

    Considerable evidence indicates that individuals with obesity are vulnerable to stigma and discrimination. However comparably less research has examined strategies to reduce weight bias and the existing evidence is mixed. To help clarify these findings and incorporate prejudice reduction interventions that have been successfully applied to other stigmatized groups (i.e. empathy induction and perspective taking) we experimentally tested and compared 4 different brief stigma reduction intervent...

  14. Comparison of additional costs for several replacement strategies of randomly ageing reinforced concrete pipes

    OpenAIRE

    SCHOEFS , Franck; Aduriz , X.; Bernard , Olivier; Capra , Bruno

    2009-01-01

    International audience; One of the uses of reinforced concrete pipes (RCPs) is the distribution of aggressive water in industrial systems, for example, in water-cooling systems of nuclear power plants. Some of them carry seawater and can deteriorate with time because of internal corrosion. Because of the low O(2) content of aggressive water, slow corrosion is expected for such applications. If the RCPs are not periodically replaced, they will eventually fail. Replacement strategies for these ...

  15. Methodological notes on model comparisons and strategy classification: A falsificationist proposition

    OpenAIRE

    Morten Moshagen; Benjamin E. Hilbig

    2011-01-01

    Taking a falsificationist perspective, the present paper identifies two major shortcomings of existing approaches to comparative model evaluations in general and strategy classifications in particular. These are (1) failure to consider systematic error and (2) neglect of global model fit. Using adherence measures to evaluate competing models implicitly makes the unrealistic assumption that the error associated with the model predictions is entirely random. By means of simple schematic example...

  16. Comparison in Measuring Effectiveness of Momentum and Contrarian Trading Strategy in Indonesian Stock Exchange

    Directory of Open Access Journals (Sweden)

    Rizky Luxianto

    2014-08-01

    Full Text Available This  paper  wants  to  explore  the  effectiveness  of  momentum  or  contrarian  strategy  in Indonesian  Stock  Exchange  using  different  methods  in  measuring  the  performance.  The point of momentum or contrarian strategy is selecting winner (stocks with highest gain or loser stocks (stocks with highest loss and then buy or sell it based on the research result. This research employed three methods in measuring performance to select winner and loser stocks.  The  irst  method  used  cross  section  relative  return,  while  the  second  method  used cross section relative return plus risk component (return divided by standard deviation, and the  third  method  employed  historical  relative  return  instead  of  cross  section.  The  result  is that,  all  of  those  three  methods  prove  that  momentum  strategy  is  effectively applicable  for winner stock, so in the next period winner stock will continue to make profit, while for loser stock, it is more effective to use contrarian strategy because in the next period, loser stock will rebound and make proit after suffering from high loss. ";} // -->activate javascript

  17. Increasing College Students' Interest and Engagement in STEM: A Comparison of Strategies for Challenging STEM Stereotypes

    Science.gov (United States)

    Shin, Jiyun Elizabeth L.

    Increasing science, technology, engineering, and mathematics (STEM) graduates has become an important part of the education agenda in the U.S. in recent years. Stereotypes about STEM (i.e., belief that STEM abilities are innate, and that European American men are best suited for STEM) have been identified as one of the critical factors that may contribute to low recruitment and retention of STEM students. Drawing from the literatures on biological essentialism and role models, this study compared different strategies for challenging STEM stereotypes among undergraduate students in STEM and non-STEM fields. STEM stereotypes were challenged directly with research articles that provided non-biological explanations for STEM success and interest (a strategy used in the essentialism research) and indirectly with biographies of successful STEM role models who are underrepresented in their field and who succeeded through hard work (a strategy used in the role model research). Contrary to the predictions, exposure to the role model biographies, research articles, or combination of both did not have statistically significant effects on participants' reported STEM interest and academic intentions. Possible explanations for the lack of significant findings as well as suggestions for developing effective interventions to promote STEM engagement among students are discussed.

  18. Comparison of mixotrophic to cyclic autotrophic/heterotrophic growth strategies to optimize productivity of Chlorella sorokiniana

    DEFF Research Database (Denmark)

    van Wagenen, Jonathan Myerson; De Francisci, Davide; Angelidaki, Irini

    2015-01-01

    In addition to providing cheap or free mineral nutrients, wastewaters may contain organic carbon compounds that could increase productivity of algal cultures. This study defined a strategy for the addition of organic carbon to photobioreactors in order to improve their productivity compared...... for acetate addition. Acetate was added during the light period for the mixotrophic strategy and during the dark one for the cyclic autotrophic/heterotrophic strategy. Autotrophic productivity of up to 0.99 g L−1 day−1 was obtained using the optimal tested dilution rate of 0.031 h−1. The highest mixotrophic...... productivity was 1.04 g L−1 day−1. When a constant dilution rate was applied throughout the day, cyclic heterotrophy/autotrophy (1.2 g L−1 day−1) showed higher productivity than during mixotrophic growth, while using only half as much acetate. By diluting and adding acetate only during the eight dark hours...

  19. Potential Targets' Analysis Reveals Dual PI3K/mTOR Pathway Inhibition as a Promising Therapeutic Strategy for Uterine Leiomyosarcomas-an ENITEC Group Initiative

    NARCIS (Netherlands)

    Cuppens, T.; Annibali, D.; Coosemans, A.; Trovik, J.; Haar, N. Ter; Colas, E.; Garcia-Jimenez, A.; Vijver, K. van der; Kruitwagen, R.P.; Brinkhuis, M.; Zikan, M.; Dundr, P.; Huvila, J.; Carpen, O.; Haybaeck, J.; Moinfar, F.; Salvesen, H.B.; Stukan, M.; Mestdagh, C.; Zweemer, R.P.; Massuger, L.F.A.G.; Mallmann, M.R.; Wardelmann, E.; Mints, M.; Verbist, G.; Thomas, D; Gomme, E.; Hermans, E; Moerman, P.; Bosse, T.; Amant, F.

    2017-01-01

    Purpose: Uterine sarcomas are rare and heterogeneous tumors characterized by an aggressive clinical behavior. Their high rates of recurrence and mortality point to the urgent need for novel targeted therapies and alternative treatment strategies. However, no molecular prognostic or predictive

  20. Investigation and Comparison of Separate Meter-In Separate Meter-Out Control Strategies

    DEFF Research Database (Denmark)

    Pedersen, Henrik C.; Andersen, Torben Ole; Skoubo, Tobias

    2014-01-01

    In the later years, there has been an increased focus on new valve types, which yield the possibility to do Separate Meter-In Separate Meter-Out (SMISMO) control. This includes both digital valves, but proportional valves with separate metering spools and build in pressure sensors are also emerging....... The possibility to independently control the meter-in and meter-out side not only increase the functionality of the system, but also opens up for better performance and/or lowered energy consumption. The focus of the current paper is therefore on investigation and comparison of what may be obtained using...

  1. Comparison of different strategies in prenatal screening for Down's syndrome: cost effectiveness analysis of computer simulation.

    Science.gov (United States)

    Gekas, Jean; Gagné, Geneviève; Bujold, Emmanuel; Douillard, Daniel; Forest, Jean-Claude; Reinharz, Daniel; Rousseau, François

    2009-02-13

    To assess and compare the cost effectiveness of three different strategies for prenatal screening for Down's syndrome (integrated test, sequential screening, and contingent screenings) and to determine the most useful cut-off values for risk. Computer simulations to study integrated, sequential, and contingent screening strategies with various cut-offs leading to 19 potential screening algorithms. The computer simulation was populated with data from the Serum Urine and Ultrasound Screening Study (SURUSS), real unit costs for healthcare interventions, and a population of 110 948 pregnancies from the province of Québec for the year 2001. Cost effectiveness ratios, incremental cost effectiveness ratios, and screening options' outcomes. The contingent screening strategy dominated all other screening options: it had the best cost effectiveness ratio ($C26,833 per case of Down's syndrome) with fewer procedure related euploid miscarriages and unnecessary terminations (respectively, 6 and 16 per 100,000 pregnancies). It also outperformed serum screening at the second trimester. In terms of the incremental cost effectiveness ratio, contingent screening was still dominant: compared with screening based on maternal age alone, the savings were $C30,963 per additional birth with Down's syndrome averted. Contingent screening was the only screening strategy that offered early reassurance to the majority of women (77.81%) in first trimester and minimised costs by limiting retesting during the second trimester (21.05%). For the contingent and sequential screening strategies, the choice of cut-off value for risk in the first trimester test significantly affected the cost effectiveness ratios (respectively, from $C26,833 to $C37,260 and from $C35,215 to $C45,314 per case of Down's syndrome), the number of procedure related euploid miscarriages (from 6 to 46 and from 6 to 45 per 100,000 pregnancies), and the number of unnecessary terminations (from 16 to 26 and from 16 to 25 per 100

  2. Comparison of operating strategies for increased biogas production from thin stillage.

    Science.gov (United States)

    Moestedt, Jan; Nordell, Erik; Schnürer, Anna

    2014-04-10

    The effect of increasing organic loading rate (OLR) and simultaneously decreasing hydraulic retention time (HRT) during anaerobic digestion of sulphur- and nitrogen-rich thin stillage was investigated during operation of continuously stirred tank laboratory reactors at two different temperatures. The operating strategies and substrate were set in order to mimic an existing full-scale commercial biogas plant in Sweden. The reactors were operated for 554-570 days with a substrate mixture of thin stillage and milled grain, resulting in high ammonium concentrations (>4.5gL(-1)). Initially, one reactor was operated at 38°C, as in the full-scale plant, while in the experimental reactor the temperature was raised to 44°C. Both reactors were then subjected to increasing OLR (from 3.2 to 6.0gVSL(-1)d(-1)) and simultaneously decreasing HRT (from 45 to 24 days) to evaluate the effects of these operational strategies on process stability, hydrogen sulphide levels and microbial composition. The results showed that operation at 44°C was the most successful strategy, resulting in up to 22% higher methane yield compared with the mesophilic reactor, despite higher free ammonia concentration. Furthermore, kinetic studies revealed higher biogas production rate at 44°C compared with 38°C, while the level of hydrogen sulphide was not affected. Quantitative PCR analysis of the microbiological population showed that methanogenic archaea and syntrophic acetate-oxidising bacteria had responded to the new process temperature while sulphate-reducing bacteria were only marginally affected by the temperature-change. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. A comparison of stable caesium uptake by six grass species of contrasting growth strategy

    International Nuclear Information System (INIS)

    Willey, N.J.; Martin, M.H.

    1997-01-01

    Six plants in the family Gramineae were used to investigate the relationship between Cs uptake, nutrient regime and plant growth strategy sensu Grime (1979: Plant Growth Strategies and Vegetation Processes, John Wiley). The roots of 66 day old Elymus repens (L.) Gould., Bromus sterilis L., Agrostis stolonifera L., Anthoxanthum odoratum L., Festuca ovina L. and Nardus stricta L. plants grown in acid-washed sand at high and low nutrient levels were exposed to a 96 h pulse of stable Cs at 0.05 mM, 0.15 mM, 0.3 mM, 1.0 mM and 3.0 mM concentrations. Different nutrient regimes induced large differences in dry wt in E. repens, B. sterilis and A. stolonifera plants but only small differences in N. stricta and F. ovina plants. At high nutrient concentrations, A. stolonifera, A. odoratum, F. ovina and N. stricta shoots showed significantly greater increases in internal Cs concentration with rising external Cs concentrations than did E. repens and B. sterilis shoots. The relationship between increases in shoot and external Cs concentrations was statistically indistinguishable between species in plants grown at the low nutrient concentration. These patterns of Cs uptake ensured that with long-term high K concentrations the more competitive plants (E. repens and B. sterilis) accumulated higher concentrations of Cs from low external concentrations than did non-competitive plants or competitive plants grown at low nutrient levels. It is suggested that the relationship between plant growth strategy sensu Grime (1979) and Cs accumulation patterns may help to explain the different concentrations to which species accumulate radiocaesium from the soil. (author)

  4. A comparison of three strategies for reducing the public stigma associated with stuttering.

    Science.gov (United States)

    Boyle, Michael P; Dioguardi, Lauren; Pate, Julie E

    2016-12-01

    The effects of three anti-stigma strategies for stuttering-contact (hearing personal stories from an individual who stutters), education (replacing myths about stuttering with facts), and protest (condemning negative attitudes toward people who stutter)-were examined on attitudes, emotions, and behavioral intentions toward people who stutter. Two hundred and twelve adults recruited from a nationwide survey in the United States were randomly assigned to one of the three anti-stigma conditions or a control condition. Participants completed questionnaires about stereotypes, negative emotional reactions, social distance, discriminatory intentions, and empowerment regarding people who stutter prior to and after watching a video for the assigned condition, and reported their attitude changes about people who stutter. Some participants completed follow-up questionnaires on the same measures one week later. All three anti-stigma strategies were more effective than the control condition for reducing stereotypes, negative emotions, and discriminatory intentions from pretest to posttest. Education and protest effects for reducing negative stereotypes were maintained at one-week follow-up. Contact had the most positive effect for increasing affirming attitudes about people who stutter from pretest to posttest and pretest to follow-up. Participants in the contact and education groups, but not protest, self-reported significantly more positive attitude change about people who stutter as a result of watching the video compared to the control group. Advocates in the field of stuttering can use education and protest strategies to reduce negative attitudes about people who stutter, and people who stutter can increase affirming attitudes through interpersonal contact with others. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Comparison of different reliability improving investment strategies of Finnish medium-voltage distribution systems

    Energy Technology Data Exchange (ETDEWEB)

    Laagland, H.

    2012-07-01

    The electricity distribution sector in Finland is highly regulated and the return on investments in distribution networks is low. Low profits don't make the electricity distribution sector attractive to outside investors. During the second regulatory period of 2008-2011 incentives are included into the Finnish regulation model which allows higher profits for the network owners for right allocated network investments leading to lower operation and interruption costs. The goal of the thesis is to find cost-effective medium-voltage distribution system investment strategies for the Finnish power distribution companies with respect to the incentives of the second regulatory period. In this work the sectionalisation concept is further developed by deriving equations for a homogeneous electricity distribution system for the economical and reliability indices as a function of the number of sectionalisation zones. The cost-effective medium-voltage distribution system investment strategies are found by studying the technical and economic interaction of feeder automation on different network structures. Ten feeder automation schemes have been applied to six urban/rural area generic feeders and two real rural area feeders of a distribution company in western Finland. The analytical approach includes modelling of the feeders and feeder functions and calculation of the economical and reliability indices. The following investment areas are included: different electricity distribution systems, new substation, new switching station, central earth-fault current compensation, cabling and feeder automation. The value of the results of this work is that they reveal the influence that feeder automation has on the reliability and economy of different distribution structures. This created transparency enables a national and/or distribution company network investment strategy to optimise the economic benefits of investments. (orig.)

  6. Radioiodine therapy of Graves' disease - a dosimetric comparison of different strategies concerning antithyroid drugs

    International Nuclear Information System (INIS)

    Urbannek, V.; Voth, E.; Moka, D.; Schicha, H.

    2001-01-01

    Aim: Premedication with antithyroid drugs (ATD) compared to patients not pretreated with ATD causes a higher failure rate of radioiodine therapy (RITh) or demands higher therapeutical dosage of radioiodine (RI). For clinical reasons and because of accelerated iodine metabolism in hyperthyreosis a compensated thyroid metabolism is desirable. Aim of this study was to investigate the influence of ATD on the biokinetics of RI in case of Graves' disease in order to improve RITh of patients pre-treated with ATD. Methods: 385 consecutive patients who underwent RITh because of Graves' disease for the first time were included: Group A (n = 74): RITh under continuous medication with ATD; Group B (n = 111): Application of RI under continuous medication with ATD, in case of insufficient RI-uptake or shortened effective RI-half-life ATD were stopped 1-5 days after RITh; Group C (n = 200): ATD were stopped 2 days prior to RITh in all patients. We examined the influence of ATD on RI-uptake and effective RI-half-life as well as the absorbed dose achieved on the thyroid in dependence of thyroid volume and applied RI-dosage [TEQ - therapy efficiency quotient, (2)]. Results: In the RI-pretest (all patients under ATD) the RI-uptake was comparable in all three groups. During RITh-RI-uptake, effective RI-half-life and therefore the TEQ were significantly higher in Group C as compared to Groups A and B (p [de

  7. Comparison of Strategies for Signaling of Scheduling Assignments in Wireless OFDMA

    OpenAIRE

    Moosavi, Reza; Eriksson, Jonas; Larsson, Erik G.; Wiberg, Niclas; Frenger, Pål; Gunnarsson, Fredrik

    2010-01-01

    This paper considers transmission of scheduling information in  OFDMA-based cellular communication systems such as 3GPP long-term  evolution (LTE). These systems provide efficient usage of radio  resources by allowing users to be scheduled dynamically in both  frequency and time. This requires considerable amounts of scheduling  information to be sent to the users.  The paper compares two basic transmission strategies: transmitting a  separate scheduling message to each user versus broadcasti...

  8. Natural gas–biomass dual fuelled microturbines: Comparison of operating strategies in the Italian residential sector

    International Nuclear Information System (INIS)

    Pantaleo, Antonio M.; Camporeale, Sergio; Shah, Nilay

    2014-01-01

    This paper compares different operating strategies for small scale (100 kWe) combined heat and power (CHP) plants fired by natural gas and solid biomass to serve a residential energy demand. The focus is on a dual fuel micro gas turbine (MGT) cycle. Various biomass/natural gas energy input ratios are modelled, in order to assess the trade-offs between: (i) lower energy conversion efficiency and higher investment cost when increasing the biomass input rate; (ii) higher primary energy savings and revenues from feed-in tariff available for biomass electricity fed into the grid. The strategies of baseload (BL), heat driven (HD) and electricity driven (ED) plant operation are compared, for an aggregate of residential end-users in cold, average and mild climate conditions. On the basis of the results from thermodynamic assessment and simulation at partial load operation, CAPEX and OPEX estimates, and Italian energy policy scenario (incentives available for biomass electricity, on-site and high efficiency CHP), the maximum global energy efficiency, primary energy savings and investment profitability is found, as a function of biomass/natural gas ratio, plant operating strategy and energy demand typology. The thermal and electric conversion efficiency ranged respectively between 46 and 38% and 30 and 19% for the natural gas and biomass fired case studies. The IRR of the investment was highly influenced by the load/CHP thermal power ratio and by the operation mode. The availability of high heat demand levels was also a key factor, to avoid wasted cogenerated heat and maximize CHP sales revenues. BL operation presented the highest profitability because of the higher revenues from electricity sales. Climate area was another important factor, mainly in case of low load/CHP ratios. Moreover, at low load/CHP power ratio and for the BL operation mode, the dual fuel option presented the highest profitability. This is due to the lower cost of biomass fuel in comparison to natural

  9. A Comparison of the Habitual Landing Strategies from Differing Drop Heights of Parkour Practitioners (Traceurs and Recreationally Trained Individuals

    Directory of Open Access Journals (Sweden)

    Regan J. Standing, Peter S. Maulder

    2015-12-01

    Full Text Available Parkour is an activity that encompasses methods of jumping, climbing and vaulting. With landing being a pertinent part of this practise, Parkour participants (traceurs have devised their own habitual landing strategies, which are suggested to be a safer and more effective style of landing. The purpose of this study was to compare the habitual landing strategies of traceurs and recreationally trained individuals from differing drop heights. Comparisons between landing sound and mechanical parameters were also assessed to gauge the level of landing safety. Ten recreationally trained participants and ten traceurs performed three landings from 25% and 50% body height using their own habitual landing strategies. Results at 25% showed significantly lower maximal vertical force (39.9%, p < 0.0013, ES = -1.88, longer times to maximal vertical force (68.6%, p < 0.0015, ES = 1.72 and lower loading rates (65.1%, p < 0.0002, ES = -2.22 in the traceur group. Maximal sound was also shown to be lower (3.6%, with an effect size of -0.63, however this was not statistically significant (p < 0.1612. At 50%, traceurs exhibited significantly different values within all variables including maximal sound (8.6%, p < 0.03, ES = -1.04, maximal vertical force (49.0%, p < 0.0002, ES = -2.38, time to maximal vertical force (65.9%, p < 0.0067, ES = 1.32 and loading rates (66.3%, p < 0.0002, ES = -2.00. Foot strike analysis revealed traceurs landed using forefoot or forefoot-midfoot strategies in 93.2% of trials; whereas recreationally trained participants used these styles in only 8.3% of these landings. To conclude, the habitual landings of traceurs are more effective at lowering the kinetic landing variables associated with a higher injury risk in comparison to recreationally trained individuals. Sound as a measure of landing effectiveness and safety holds potential significance; however requires further research to confirm.

  10. Comparison of search strategies in systematic reviews of adverse effects to other systematic reviews.

    Science.gov (United States)

    Golder, Su; Loke, Yoon K; Zorzela, Liliane

    2014-06-01

    Research indicates that the methods used to identify data for systematic reviews of adverse effects may need to differ from other systematic reviews. To compare search methods in systematic reviews of adverse effects with other reviews. The search methodologies in 849 systematic reviews of adverse effects were compared with other reviews. Poor reporting of search strategies is apparent in both systematic reviews of adverse effects and other types of systematic reviews. Systematic reviews of adverse effects are less likely to restrict their searches to MEDLINE or include only randomised controlled trials (RCTs). The use of other databases is largely dependent on the topic area and the year the review was conducted, with more databases searched in more recent reviews. Adverse effects search terms are used by 72% of reviews and despite recommendations only two reviews report using floating subheadings. The poor reporting of search strategies in systematic reviews is universal, as is the dominance of searching MEDLINE. However, reviews of adverse effects are more likely to include a range of study designs (not just RCTs) and search beyond MEDLINE. © 2014 Crown Copyright.

  11. Comparison among monitoring strategies to assess water flow dynamic and soil hydraulic properties in agricultural soils

    Energy Technology Data Exchange (ETDEWEB)

    Valdes-Abellan, J.; Jiménez-Martínez, J.; Candela, L.; Tamoh, K.

    2015-07-01

    Irrigated agriculture is usually performed in semi-arid regions despite scarcity of water resources. Therefore, optimal irrigation management by monitoring the soil is essential, and assessing soil hydraulic properties and water flow dynamics is presented as a first measure. For this purpose, the control of volumetric water content, θ, and pressure head, h, is required. This study adopted two types of monitoring strategies in the same experimental plot to control θ and h in the vadose zone: i) non-automatic and more time-consuming; ii) automatic connected to a datalogger. Water flux was modelled with Hydrus-1D using the data collected from both acquisition strategies independently (3820 daily values for the automatic; less than 1000 for the non-automatic). Goodness-of-fit results reported a better adjustment in case of automatic sensors. Both model outputs adequately predicted the general trend of θ and h, but with slight differences in computed annual drainage (711 mm and 774 mm). Soil hydraulic properties were inversely estimated from both data acquisition systems. Major differences were obtained in the saturated volumetric water content, θs, and the n and α van Genuchten model shape parameters. Saturated hydraulic conductivity, Ks, shown lower variability with a coefficient of variation range from 0.13 to 0.24 for the soil layers defined. Soil hydraulic properties were better assessed through automatic data acquisition as data variability was lower and accuracy was higher. (Author)

  12. Comparison of individual pitch and smart rotor control strategies for load reduction

    Science.gov (United States)

    Plumley, C.; Leithead, W.; Jamieson, P.; Bossanyi, E.; Graham, M.

    2014-06-01

    Load reduction is increasingly seen as an essential part of controller and wind turbine design. On large multi-MW wind turbines that experience high levels of wind shear and turbulence across the rotor, individual pitch control and smart rotor control are being considered. While individual pitch control involves adjusting the pitch of each blade individually to reduce the cyclic loadings on the rotor, smart rotor control involves activating control devices distributed along the blades to alter the local aerodynamics of the blades. Here we investigate the effectiveness of using a DQ-axis control and a distributed (independent) control for both individual pitch and trailing edge flap smart rotor control. While load reductions are similar amongst the four strategies across a wide range of variables, including blade root bending moments, yaw bearing and shaft, the pitch actuator requirements vary. The smart rotor pitch actuator has reduced travel, rates, accelerations and power requirements than that of the individual pitch controlled wind turbines. This benefit alone however would be hard to justify the added design complexities of using a smart rotor, which can be seen as an alternative to upgrading the pitch actuator and bearing. In addition, it is found that the independent control strategy is apt at roles that the collective pitch usually targets, such as tower motion and speed control, and it is perhaps here, in supplementing other systems, that the future of the smart rotor lies.

  13. A comparison of integrated river basin management strategies: A global perspective

    Science.gov (United States)

    Zhao, Chunhong; Wang, Pei; Zhang, Guanghong

    In order to achieve the integrated river basin management in the arid and rapid developing region, the Heihe River Basin (HRB) in Northwestern China, one of critical river basins were selected as a representative example, while the Murray-Darling Basin (MDB) in Australia and the Colorado River Basin (CRB) in the USA were selected for comparative analysis in this paper. Firstly, the comparable characters and hydrological contexts of these three watersheds were introduced in this paper. Then, based on comparative studies on the river basin challenges in terms of the drought, intensive irrigation, and rapid industrialization, the hydrological background of the MDB, the CRB and the HRB was presented. Subsequently, the river management strategies were compared in three aspects: water allocation, water organizations, and water act and scientific projects. Finally, we proposed recommendations for integrated river basin management for the HRB: (1) Water allocation strategies should be based on laws and markets on the whole basin; (2) Public participation should be stressed by the channels between governance organizations and local communities; (3) Scientific research should be integrated into river management to understand the interactions between the human and nature.

  14. Comparison of individual pitch and smart rotor control strategies for load reduction

    International Nuclear Information System (INIS)

    Plumley, C; Leithead, W; Jamieson, P; Bossanyi, E; Graham, M

    2014-01-01

    Load reduction is increasingly seen as an essential part of controller and wind turbine design. On large multi-MW wind turbines that experience high levels of wind shear and turbulence across the rotor, individual pitch control and smart rotor control are being considered. While individual pitch control involves adjusting the pitch of each blade individually to reduce the cyclic loadings on the rotor, smart rotor control involves activating control devices distributed along the blades to alter the local aerodynamics of the blades. Here we investigate the effectiveness of using a DQ-axis control and a distributed (independent) control for both individual pitch and trailing edge flap smart rotor control. While load reductions are similar amongst the four strategies across a wide range of variables, including blade root bending moments, yaw bearing and shaft, the pitch actuator requirements vary. The smart rotor pitch actuator has reduced travel, rates, accelerations and power requirements than that of the individual pitch controlled wind turbines. This benefit alone however would be hard to justify the added design complexities of using a smart rotor, which can be seen as an alternative to upgrading the pitch actuator and bearing. In addition, it is found that the independent control strategy is apt at roles that the collective pitch usually targets, such as tower motion and speed control, and it is perhaps here, in supplementing other systems, that the future of the smart rotor lies

  15. Learning outcomes of "The Oncology Patient" study among nursing students: A comparison of teaching strategies.

    Science.gov (United States)

    Roca, Judith; Reguant, Mercedes; Canet, Olga

    2016-11-01

    Teaching strategies are essential in order to facilitate meaningful learning and the development of high-level thinking skills in students. To compare three teaching methodologies (problem-based learning, case-based teaching and traditional methods) in terms of the learning outcomes achieved by nursing students. This quasi-experimental research was carried out in the Nursing Degree programme in a group of 74 students who explored the subject of The Oncology Patient through the aforementioned strategies. A performance test was applied based on Bloom's Revised Taxonomy. A significant correlation was found between the intragroup theoretical and theoretical-practical dimensions. Likewise, intergroup differences were related to each teaching methodology. Hence, significant differences were estimated between the traditional methodology (x-=9.13), case-based teaching (x-=12.96) and problem-based learning (x-=14.84). Problem-based learning was shown to be the most successful learning method, followed by case-based teaching and the traditional methodology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. COMMUNICATION TOPICS AND STRATEGIES IN E-MAIL CONSULTATION: COMPARISON BETWEEN AMERICAN AND INTERNATIONAL UNIVERSITY STUDENTS

    Directory of Open Access Journals (Sweden)

    Sigrun Biesenbach-Lucas

    2005-05-01

    Full Text Available On today's "wired" college campuses, students avail themselves in increasing numbers of electronic channels, most notably e-mail, as a means to consult with their professors. While some research has investigated the purposes for which university students communicate with their instructors via e-mail, little research has examined differences in e-mail use between American and international students. In the present study, e-mail messages sent by American and international students enrolled in a teacher-preparation program to their professor were collected over the course of one semester. The messages were examined for three major communication topics (facilitative, substantive, relational and communication strategies (requesting, negotiating, reporting. Results indicate quantitative and qualitative differences in American and international students' e-mail topics and strategies, suggesting, similar to findings for face-to-face academic advising sessions, that American students demonstrate greater initiative and ability to adapt to the spatial and temporal remoteness between interlocutors in e-mail interaction, especially when using e-mail to solicit face-to-face appointments and input on projects. Findings also show that messages from both groups of students contained substantial relational communication, perhaps in an attempt to compensate for the lack of visual and paralinguistic clues in the e-mail medium.

  17. Urban shrinkage in Germany and the USA: a comparison of transformation patterns and local strategies.

    Science.gov (United States)

    Wiechmann, Thorsten; Pallagst, Karina M

    2012-01-01

    Many American and European cities have to deal with demographic and economic trajectories leading to urban shrinkage. According to official data, 13% of urban regions in the US and 54% of those in the EU have lost population in recent years. However, the extent and spatial distribution of declining populations differ significantly between Europe and the US. In Germany, the situation is driven by falling birth rates and the effects of German reunification. In the US, shrinkage is basically related to long-term industrial transformation. But the challenges of shrinking cities seldom appeared on the agendas of politicians and urban planners until recently. This article provides a critical overview of the development paths and local strategies of four shrinking cities: Schwedt and Dresden in eastern Germany; Youngstown and Pittsburgh in the US. A typology of urban growth and shrinkage, from economic and demographic perspectives, enables four types of city to be differentiated and the differences between the US and eastern Germany to be discussed. The article suggests that a new transatlantic debate on policy and planning strategies for restructuring shrinking cities is needed to overcome the dominant growth orientation that in most cases intensifies the negative consequences of shrinkage.

  18. Experiential avoidance as a generalized psychological vulnerability: comparisons with coping and emotion regulation strategies.

    Science.gov (United States)

    Kashdan, Todd B; Barrios, Velma; Forsyth, John P; Steger, Michael F

    2006-09-01

    Extending previous work, we conducted two studies concerning the toxic influences of experiential avoidance (EA) as a core mechanism in the development and maintenance of psychological distress, and disruption of pleasant, engaging, and spontaneous activity. Of particular interest was whether EA accounted for relationships between coping and emotion regulation strategies on anxiety-related pathology (Study 1) and psychological distress and hedonic functioning over the course of a 21-day monitoring period (Study 2). In Study 1, EA mediated the effects of maladaptive coping, emotional responses styles, and uncontrollability on anxiety-related distress (e.g., anxiety sensitivity, trait anxiety, suffocation fears, and body sensation fears). In Study 2, EA completely mediated the effects of two emotion regulation strategies (i.e., suppression and reappraisal) on daily negative and positive experiences and was associated with diminished daily positive affective experiences and healthy life appraisals, diminished frequency of positive events and more frequent negative life events, and greater negative affective experiences. The present data show that cognitive reappraisal, a primary process of traditional cognitive-behavior therapy, was much less predictive of the quality of psychological experiences and events in everyday life compared with EA. Further consideration of experiential avoidance as a generalized diathesis and toxic process will be useful in improving our understanding of the etiology, phenomenology, and treatment of anxiety conditions, general human suffering, and disruptions in hedonic capacity.

  19. Comparison among monitoring strategies to assess water flow dynamic and soil hydraulic properties in agricultural soils

    Directory of Open Access Journals (Sweden)

    Javier Valdes-Abellan

    2015-03-01

    Full Text Available Abstract Irrigated agriculture is usually performed in semi-arid regions despite scarcity of water resources. Therefore, optimal irrigation management by monitoring the soil is essential, and assessing soil hydraulic properties and water flow dynamics is presented as a first measure. For this purpose, the control of volumetric water content, θ, and pressure head, h, is required. This study adopted two types of monitoring strategies in the same experimental plot to control θ and h in the vadose zone: i non-automatic and more time-consuming; ii automatic connected to a datalogger. Water flux was modelled with Hydrus-1D using the data collected from both acquisition strategies independently (3820 daily values for the automatic; less than 1000 for the non-automatic. Goodness-of-fit results reported a better adjustment in case of automatic sensors. Both model outputs adequately predicted the general trend of θ and h, but with slight differences in computed annual drainage (711 mm and 774 mm. Soil hydraulic properties were inversely estimated from both data acquisition systems. Major differences were obtained in the saturated volumetric water content, θs, and the n and α van Genuchten model shape parameters. Saturated hydraulic conductivity, Ks, shown lower variability with a coefficient of variation range from 0.13 to 0.24 for the soil layers defined. Soil hydraulic properties were better assessed through automatic data acquisition as data variability was lower and accuracy was higher.

  20. On the comparison of stochastic model predictive control strategies applied to a hydrogen-based microgrid

    Science.gov (United States)

    Velarde, P.; Valverde, L.; Maestre, J. M.; Ocampo-Martinez, C.; Bordons, C.

    2017-03-01

    In this paper, a performance comparison among three well-known stochastic model predictive control approaches, namely, multi-scenario, tree-based, and chance-constrained model predictive control is presented. To this end, three predictive controllers have been designed and implemented in a real renewable-hydrogen-based microgrid. The experimental set-up includes a PEM electrolyzer, lead-acid batteries, and a PEM fuel cell as main equipment. The real experimental results show significant differences from the plant components, mainly in terms of use of energy, for each implemented technique. Effectiveness, performance, advantages, and disadvantages of these techniques are extensively discussed and analyzed to give some valid criteria when selecting an appropriate stochastic predictive controller.

  1. microRNAs as a New Mechanism Regulating Adipose Tissue Inflammation in Obesity and as a Novel Therapeutic Strategy in the Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Qian Ge

    2014-01-01

    Full Text Available Obesity is associated closely with the metabolic syndrome (MS. It is well known that obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of MS. White adipose tissue (AT is the primary site for the initiation and exacerbation of obesity-associated inflammation. Exploring the mechanisms of white AT inflammation and resetting the immunological balance in white AT could be crucial for the management of MS. Several prominent molecular mechanisms have been proposed to mediate inflammation in white AT, including hypoxia, endoplasmic reticulum stress, lipotoxicity, and metabolic endotoxemia. Recently, a growing body of evidence supports the role of miRNAs as a new important inflammatory mediator by regulating both the adaptive and innate immunity. This review will focus on the implication of miRNAs in white AT inflammation in obesity, and will also highlight the potential of miRNAs as targets for therapeutic intervention in MS as well as the challenges lying in miRNA-targeting therapeutics.

  2. microRNAs as a new mechanism regulating adipose tissue inflammation in obesity and as a novel therapeutic strategy in the metabolic syndrome.

    Science.gov (United States)

    Ge, Qian; Brichard, Sonia; Yi, Xu; Li, QiFu

    2014-01-01

    Obesity is associated closely with the metabolic syndrome (MS). It is well known that obesity-induced chronic inflammation plays a fundamental role in the pathogenesis of MS. White adipose tissue (AT) is the primary site for the initiation and exacerbation of obesity-associated inflammation. Exploring the mechanisms of white AT inflammation and resetting the immunological balance in white AT could be crucial for the management of MS. Several prominent molecular mechanisms have been proposed to mediate inflammation in white AT, including hypoxia, endoplasmic reticulum stress, lipotoxicity, and metabolic endotoxemia. Recently, a growing body of evidence supports the role of miRNAs as a new important inflammatory mediator by regulating both the adaptive and innate immunity. This review will focus on the implication of miRNAs in white AT inflammation in obesity, and will also highlight the potential of miRNAs as targets for therapeutic intervention in MS as well as the challenges lying in miRNA-targeting therapeutics.

  3. Targeting the intrinsically disordered structural ensemble of α-synuclein by small molecules as a potential therapeutic strategy for Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Gergely Tóth

    Full Text Available The misfolding of intrinsically disordered proteins such as α-synuclein, tau and the Aβ peptide has been associated with many highly debilitating neurodegenerative syndromes including Parkinson's and Alzheimer's diseases. Therapeutic targeting of the monomeric state of such intrinsically disordered proteins by small molecules has, however, been a major challenge because of their heterogeneous conformational properties. We show here that a combination of computational and experimental techniques has led to the identification of a drug-like phenyl-sulfonamide compound (ELN484228, that targets α-synuclein, a key protein in Parkinson's disease. We found that this compound has substantial biological activity in cellular models of α-synuclein-mediated dysfunction, including rescue of α-synuclein-induced disruption of vesicle trafficking and dopaminergic neuronal loss and neurite retraction most likely by reducing the amount of α-synuclein targeted to sites of vesicle mobilization such as the synapse in neurons or the site of bead engulfment in microglial cells. These results indicate that targeting α-synuclein by small molecules represents a promising approach to the development of therapeutic treatments of Parkinson's disease and related conditions.

  4. Comparison of DNA testing strategies in monitoring human papillomavirus infection prevalence through simulation.

    Science.gov (United States)

    Lin, Carol Y; Li, Ling

    2016-11-07

    HPV DNA diagnostic tests for epidemiology monitoring (research pur