Therapeutic Success of the Ketogenic Diet as a Treatment Option for Epilepsy: a Meta-analysis

PubMed Central

Li, Hai-feng; Zou, Yan; Ding, Gangqiang

2013-01-01

Objective To systematically evaluate therapeutic success of the ketogenic diet (KD) as a treatment option for epilepsy. Methods Using MEDLINE and Google Scholar search, we searched for studies investigating the therapeutic success of ketogenic diet for epilepsy. We estimated therapeutic success rate for ketogenic diet as a treatment option for epilepsy and its 95% CIs using generic inverse variance method. Findings A total of 38 studies met the inclusion criteria. In retrospective studies, the weighted success rate of the patients who take the KD as a treatment option for epilepsy was 58.4% (95% confidence interval (95%CI)=48.7% – 69.9%) at 3 months (n=336); 42.8% (95%CI =36.3% – 50.3%) at 6 months (n=492), and 30.1% (95%CI =24.3% – 37.2%) at 12 months (n=387); in prospective studies, weighted success rate was 53.9% (95%CI 45.5% – 63.8%) at 3 months (n=474); 53.2% (95%CI =44.0% – 64.2%) at 6 months (n=321), and 55.0% (95%CI =45.9% – 65.9%) at 12 months (n=347). Conclusion This meta-analysis provides formal statistical support for the efficacy of the ketogenic diet in the treatment of epileptic patients. PMID:24910737

Amyloidosis: Pathogenesis and New Therapeutic Options

PubMed Central

Merlini, Giampaolo; Seldin, David C.; Gertz, Morie A.

2011-01-01

The systemic amyloidoses are a group of complex diseases caused by tissue deposition of misfolded proteins that results in progressive organ damage. The most common type, immunoglobulin light chain amyloidosis (AL), is caused by clonal plasma cells that produce misfolded light chains. The purpose of this review is to provide up-to-date information on diagnosis and treatment options for AL amyloidosis. Early, accurate diagnosis is the key to effective therapy, and unequivocal identification of the amyloidogenic protein may require advanced technologies and expertise. Prognosis is dominated by the extent of cardiac involvement, and cardiac staging directs the choice of therapy. Treatment for AL amyloidosis is highly individualized, determined on the basis of age, organ dysfunction, and regimen toxicities, and should be guided by biomarkers of hematologic and cardiac response. Alkylator-based chemotherapy is effective in almost two thirds of patients. Novel agents are also active, and trials are ongoing to establish their optimal use. Treatment algorithms will continue to be refined through controlled trials. Advances in basic research have led to the identification of new drug targets and therapeutic approaches, which will be integrated with chemotherapy in the future. PMID:21483018

Nuclear Fuel Cycle Options Catalog: FY16 Improvements and Additions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Price, Laura L.; Barela, Amanda Crystal; Schetnan, Richard Reed

2016-08-31

The United States Department of Energy, Office of Nuclear Energy, Fuel Cycle Technology Program sponsors nuclear fuel cycle research and development. As part of its Fuel Cycle Options campaign, the DOE has established the Nuclear Fuel Cycle Options Catalog. The catalog is intended for use by the Fuel Cycle Technologies Program in planning its research and development activities and disseminating information regarding nuclear energy to interested parties. The purpose of this report is to document the improvements and additions that have been made to the Nuclear Fuel Cycle Options Catalog in the 2016 fiscal year.

Herbal Medicine Offered as an Initiative Therapeutic Option for the Management of Hepatocellular Carcinoma.

PubMed

Chen, Shao-Ru; Qiu, Hong-Cong; Hu, Yang; Wang, Ying; Wang, Yi-Tao

2016-06-01

Hepatocellular carcinoma (HCC) is a common malignant cancer and is the third leading cause of death worldwide. Effective treatment of this disease is limited by the complicated molecular mechanism underlying HCC pathogenesis. Thus, therapeutic options for HCC management are urgently needed. Targeting the Wnt/β-catenin, Hedgehog, Notch, and Hippo-YAP signaling pathways in cancer stem cell development has been extensively investigated as an alternative treatment. Herbal medicine has emerged as an initiative therapeutic option for HCC management because of its multi-level, multi-target, and coordinated intervention effects. In this article, we summarized the recent progress and clinical benefits of targeting the above mentioned signaling pathways and using natural products such as herbal medicine formulas to treat HCC. Proving the clinical success of herbal medicine is expected to deepen the knowledge on herbal medicine efficiency and hasten the adoption of new therapies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Therapeutic options to treat sulfur mustard poisoning--the road ahead.

PubMed

Smith, William J

2009-09-01

For the past 15 years the international research community has conducted a basic and applied research program aimed at identifying a medical countermeasure against chemical threat vesicant, or blistering, agents. The primary emphasis of this program has been the development of therapeutic protection against sulfur mustard and its cutaneous pathology-blister formation. In addition to the work on a medical countermeasures, significant research has been conducted on the development of topical skin protectants and medical strategies for wound healing. This review will focus on the pharmacological strategies investigated, novel therapeutic targets currently under investigation and therapeutic approaches being considered for transition to advanced development. Additionally, we will review the expansion of our understanding of the pathophysiological mechanisms of mustard injury that has come from this research. While great strides have been made through these investigations, the complexity of the mustard insult demands that further studies extend the inroads made and point the way toward better understanding of cellular and tissue disruptions caused by sulfur mustard.

Stress urinary incontinence in women: Current and emerging therapeutic options

PubMed Central

Shamout, Samer; Campeau, Lysanne

2017-01-01

Surgical management of stress urinary incontinence (SUI) is most commonly achieved by midurethral synthetic sling (MUS) insertion as a first-line surgical option. A great deal of research continues to evolve new management strategies to reach an optimal balance of high efficacy and minimal adverse events. This expert opinion review provides a brief and comprehensive discussion of recent advances and ongoing research in the management of SUI, with an emphasis on single-incision mini-slings, vaginal laser treatment, and cell-based therapy. It is based on data obtained from numerous published meta-analyses and original studies identified through literature search. Single-incision mini-slings appear equally effective initially compared with standard MUS (retropubic or transobturator) for the treatment of female SUI; however, this efficacy lacks durability evidence beyond one-year followup. There is a lack of sufficient clinical evidence to currently confirm long-term safety and effectiveness of cell-therapy and non-ablative vaginal laser therapy, besides suggestion of apparent initial safety. There are still significant challenges to overcome before widespread clinical practice of the latter two modalities. Future research should be aimed at identifying groups of patients who might benefit from these minimally invasive therapeutic options. PMID:28616118

Inner ear symptoms and disease: Pathophysiological understanding and therapeutic options

PubMed Central

Ciuman, Raphael R.

2013-01-01

In recent years, huge advances have taken place in understanding of inner ear pathophysiology causing sensorineural hearing loss, tinnitus, and vertigo. Advances in understanding comprise biochemical and physiological research of stimulus perception and conduction, inner ear homeostasis, and hereditary diseases with underlying genetics. This review describes and tabulates the various causes of inner ear disease and defines inner ear and non-inner ear causes of hearing loss, tinnitus, and vertigo. The aim of this review was to comprehensively breakdown this field of otorhinolaryngology for specialists and non-specialists and to discuss current therapeutic options in distinct diseases and promising research for future therapies, especially pharmaceutic, genetic, or stem cell therapy. PMID:24362017

Hyperhidrosis: review of recent advances and new therapeutic options for primary hyperhidrosis.

PubMed

Brown, Ashley L; Gordon, Jennifer; Hill, Samantha

2014-08-01

Primary focal hyperhidrosis is a common condition that negatively impacts quality of life for many pediatric patients and can be challenging to treat. Standard treatments for hyperhidrosis can be used with success in many patients, and newer therapies and techniques offer options that have demonstrated efficacy and safety. This review highlights standard therapies for primary focal hyperhidrosis as well as the most recent technique advancements and alternative treatment options. The standard approach to treating primary focal hyperhidrosis remains initiation of topical preparations, followed by advancement to systemic medications, local administration of medication and/or surgical procedures. Recent studies focus on enhancing tolerability of topical preparations as well as evaluating the efficacy of neuromodulator injections, oral anticholinergic medications and laser therapy. Microwave technology has also been introduced for the treatment of focal hyperhidrosis with promising results. Many therapies exist for hyperhidrosis, and each treatment plan must be evaluated on a patient-by-patient basis. Advances in standard therapies and emergence of new treatment techniques are the main emphases of current published literature on hyperhidrosis. This article presents recent therapeutic options as well as updates on more established strategies to help practitioners treat this challenging condition.

[Usher syndrome: clinical features, diagnostic options, and therapeutic prospects].

PubMed

Seeliger, M W; Fischer, M D; Pfister, M

2009-06-01

Usher syndrome denotes a clinically and genetically heterogeneous combination of retinitis pigmentosa and sensorineural deafness. The division into subtypes I, II, and III is based on the degree of hearing loss: Type I is characterized by deafness from birth together with ataxia and retarded motor development, type II by a stationary deafness of a moderate degree, and type III by a progressive deafness with adult onset. In Germany, Usher syndrome currently bears particular relevance because in January 2009 a new compulsory screening of auditory function in newborn infants was introduced. Consequently, it can be expected that a higher number of patients with Usher syndrome will be identified in early childhood and referred to ophthalmologists. The focus of this work is to introduce the typical clinical picture of Usher syndrome, summarize diagnostic options, and give an overview of therapeutic strategies.

Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma

PubMed Central

Chua, Vivian; Lapadula, Dominic; Randolph, Clinita; Benovic, Jeffrey L.; Wedegaertner, Philip; Aplin, Andrew E.

2017-01-01

Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults and arises from the transformation of melanocytes in the uveal tract. Even after treatment of the primary tumor, up to 50% of patients succumb to metastatic disease. The liver is the predominant organ of metastasis. There is an important need to provide effective treatment options for advanced stage UM. In order to provide the preclinical basis for new treatments, it is important to understand the molecular underpinnings of the disease. Recent genomic studies have shown that mutations within components of G protein-coupled receptor (GPCR) signaling are early events associated with ~98% of UMs. Implications This review discusses the alterations in GPCR signaling components (GNAQ and GNA11), dysregulated GPCR signaling cascades, and viable targeted therapies with the intent to provide insight into new therapeutic strategies in UM. PMID:28223438

Achalasia: current therapeutic options

PubMed Central

Arora, Zubin; Thota, Prashanthi N.; Sanaka, Madhusudhan R.

2017-01-01

Achalasia is a chronic incurable esophageal motility disorder characterized by impaired lower esophageal sphincter (LES) relaxation and loss of esophageal peristalsis. Although rare, it is currently the most common primary esophageal motility disorder, with an annual incidence of around 1.6 per 100,000 persons and prevalence of around 10.8/100,000 persons. Symptoms of achalasia include dysphagia to both solids and liquids, regurgitation, aspiration, chest pain and weight loss. As the underlying etiology of achalasia remains unclear, there is currently no curative treatment for achalasia. Management of achalasia mainly involves improving the esophageal outflow in order to provide symptomatic relief to patients. The most effective treatment options for achalasia include pneumatic dilation, Heller myotomy and peroral endoscopic myotomy (POEM), with the latter increasingly emerging as the treatment of choice for many patients. This review focusses on evidence for current and emerging treatment options for achalasia with a particular emphasis on POEM. PMID:28717439

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 4 2013-10-01 2013-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Additional Head Start program option variations. 1306.36 Section 1306.36 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN...

Addition of flexible body option to the TOLA computer program, part 1

NASA Technical Reports Server (NTRS)

Dick, J. W.; Benda, B. J.

1975-01-01

This report describes a flexible body option that was developed and added to the Takeoff and Landing Analysis (TOLA) computer program. The addition of the flexible body option to TOLA allows it to be used to study essentially any conventional type airplane in the ground operating environment. It provides the capability to predict the total motion of selected points on the analytical methods incorporated in the program and operating instructions for the option are described. A program listing is included along with several example problems to aid in interpretation of the operating instructions and to illustrate program usage.

The nitric oxide pathway and possible therapeutic options in pre-eclampsia.

PubMed

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-08-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide-soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3',5'-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. © 2013 The British Pharmacological Society.

The nitric oxide pathway and possible therapeutic options in pre-eclampsia

PubMed Central

Johal, Tamanrit; Lees, Christoph C; Everett, Thomas R; Wilkinson, Ian B

2014-01-01

Pre-eclampsia is a serious multisystem disorder with diverse clinical manifestations. Although not causal, endothelial dysfunction and reduced nitric oxide bioavailability are likely to play an important role in the maternal and fetal pathophysiology of this condition. Lack of treatment modalities that can target the underlying pathophysiological changes and reverse the endothelial dysfunction frequently leads to iatrogenic preterm delivery of the fetus, causing neonatal morbidity and mortality, and the condition itself is associated with short- and longer term maternal morbidity and mortality. Drugs that target various components of the nitric oxide–soluble guanylyl cyclase pathway can help to increase NO bioavailability. The purpose of this review is to outline the current status of clinical research involving these therapeutic modalities in the context of pre-eclampsia, with the focus being on the following: nitric oxide donors, including organic nitrates and S-nitrosothiols; l-arginine, the endogenous precursor of NO; inhibitors of cyclic guanosine 3′,5′-monophosphate breakdown, including sildenafil; and other novel inhibitors of NO donor metabolism. The advantages and limitations of each modality are outlined, and scope for development into established therapeutic options for pre-eclampsia is explored. PMID:24313856

Neuroendocrine tumors: insights into innovative therapeutic options and rational development of targeted therapies.

PubMed

Barbieri, Federica; Albertelli, Manuela; Grillo, Federica; Mohamed, Amira; Saveanu, Alexandru; Barlier, Anne; Ferone, Diego; Florio, Tullio

2014-04-01

Neuroendocrine tumors (NETs) are heterogeneous neoplasms with respect to molecular characteristics and clinical outcome. Although slow-growing, NETs are often late diagnosed, already showing invasion of adjacent tissues and metastases. Precise knowledge of NET biological and molecular features has opened the door to the identification of novel pharmacological targets. Therapeutic options include somatostatin analogs, alone or in combination with interferon-α, multi-targeted tyrosine kinase inhibitors (e.g. sunitinib) or mammalian target of rapamycin (mTOR) inhibitors (e.g. everolimus). Antiangiogenic approaches and anti insulin-like growth factor receptor (IGFR) compounds have been also proposed as combination therapies with the aforementioned compounds. This review will focus on recent studies that have improved therapeutic strategies in NETs, discussing management challenges such as drug resistance development as well as focusing on the need for predictive biomarkers to design distinct drug combinations and optimize pharmacological control. Copyright © 2013 Elsevier Ltd. All rights reserved.

Transcatheter device closure of pseudoaneurysms of the left ventricular wall: An emerging therapeutic option.

PubMed

Madan, Tarun; Juneja, Manish; Raval, Abhishek; Thakkar, Bhavesh

2016-02-01

Left ventricular pseudoaneurysm is a rare but serious complication of acute myocardial infarction and cardiac surgery. While surgical intervention is the conventional therapeutic option, transcatheter closure can be considered in selected patients with suitable morphology of the pseudoaneurysm. We report a case of successful transcatheter closure of a left ventricular pseudoaneurysm orifice and isolation of the sac using an Amplatzer septal occluder. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Alternative therapeutic options for medical management of epilepsy in apes.

PubMed

Gerlach, Trevor; Clyde, Victoria L; Morris, George L; Bell, Barbara; Wallace, Roberta S

2011-06-01

Phenobarbital has been the primary antiepileptic drug used in primates, but the dosage required for seizure control is frequently associated with significant side effects. Newer antiepileptic drugs and adjunctive therapies currently being used in human medicine provide additional options for treatment of nonhuman primates. This report describes different drug regimes used for control of epileptic seizures in apes at the Milwaukee County Zoo (Milwaukee, Wisconsin, U.S.A.), including the addition of acetazolamide to phenobarbital, levetiracetam, carbamazepine, and the use of extended cycle oral contraceptives to assist seizure control in female apes with catamenial epilepsy.

Studies on nonsense mediated decay reveal novel therapeutic options for genetic diseases.

PubMed

Bashyam, Murali D

2009-01-01

Scientific breakthroughs have often led to commercially viable patents mainly in the field of engineering. Commercialization in the field of medicine has been restricted mostly to machinery and engineering on the one hand and therapeutic drugs for common chronic ailments such as cough, cold, headache, etc, on the other. Sequencing of the human genome has attracted the attention of pharmaceutical companies and now biotechnology has become a goldmine for commercialization of products and processes. Recent advances in our understanding of basic biological processes have resulted in the opening of new avenues for treatment of human genetic diseases, especially single gene disorders. A significant proportion of human genetic disorders have been shown to be caused due to degradation of transcripts for specific genes through a process called nonsense mediated decay (NMD). The modulation of NMD provides a viable therapeutic option for treatment of several genetic disorders and therefore has been a good prospect for patenting and commercialization. In this review the molecular basis for NMD and attempts to treat genetic diseases which result from NMD are discussed.

Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options.

PubMed

Iglesias, Pedro; Carrero, Juan J; Díez, Juan J

2012-01-01

Gonadal dysfunction is a frequent finding in men with chronic kidney disease and with end-stage renal disease. Testosterone deficiency, usually accompanied by elevation of serum gonadotropin concentrations, is present in 26-66% of men with different degrees of renal failure. Uremia-associated hypogonadism is multifactorial in its origin, and rarely improves with initiation of dialysis, although it usually normalizes after renal transplantation. Experimental and clinical evidence suggests that testosterone may have important clinical implications with regards to kidney disease progression, derangements in sexual drive, libido and erectile dysfunction, development of anemia, impairment of muscle mass and strength, and also progression of atherosclerosis and cardiovascular disease. Additionally, low testosterone levels in hemodialysis patients have been associated with increased mortality risk in some studies. Currently, we count with available therapeutic options in the management of uremic hypogonadism, from optimal delivery of dialysis and adequate nutritional intake, to hormone replacement therapy with different testosterone preparations. Other potential options for treatment include the use of antiestrogens, dopamine agonists, erythropoiesis-stimulating factors, vitamins, essential trace elements, chorionic gonadotropin and renal transplantation. Potential adverse effects of androgen replacement therapy in patients with kidney disease comprise, however, erythrocytosis, prostate and breast cancer growth, reduced fertility, gynecomastia, obstructive sleep apnea and fluid retention. Androgen preparations should be used with caution with stringent monitoring in uremic men. Although there are encouraging data suggesting plausible benefits from testosterone replacement therapy, further studies are needed with regards to safety and effectiveness of this therapy.

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

PubMed

Zerbib, Frank; Roman, Sabine

2015-07-01

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

[Therapeutic options for pressure ulcers].

PubMed

Damert, H-G; Meyer, F; Altmann, S

2015-04-01

The aim of this overview is based on remarks on the pathogenesis of and therapy for pressure ulcers and selected but representative cases to demonstrate current options of plastic coverage. As a consequence of the demographic developments, in particular, with regard to the increasing proportion of older patients as well as the advances in modern medicine, the number of multimorbid, geriatric and bedridden patients and of those with prolonged sickbed periods has been steadily growing. Therefore, partly severe manifestations of pressure ulcers at various exposed body regions can be observed in spite of the best preventive intention of care. While in the early stages rather conservative treatment is adequate, surgical intervention might become important and indispensable for a sufficient treatment in advanced stages. To facilitate basic care and to appropriately treat the infectious focus, the methods and procedures of plastic surgery can become relevant. Although there are several options and approaches existing to sanitise and cover defects of pressure ulcers, which are described within the article based on representative cases, preventive measures can still be considered the best approach. Georg Thieme Verlag KG Stuttgart · New York.

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

PubMed

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.

Recurrent pericarditis: new and emerging therapeutic options.

PubMed

Imazio, Massimo; Lazaros, George; Brucato, Antonio; Gaita, Fiorenzo

2016-02-01

Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition.

Conclusions of the expert panel: importance of erlotinib as a second-line therapeutic option

PubMed Central

Castagnari, Aldo

2008-01-01

During the Experts Meeting on Lung Cancer, participants emphasized the usefulness of erlotinib as second-line therapy for lung cancer. They noted that, although there are no comparative studies, erlotinib could be as effective as docetaxel and pemetrexed in second-line therapy. Regarding the toxicity profile of each of these drugs – one of the key issues considered in the meeting – specialists pointed out how important it is to clearly identify existing differences in this issue. Each drug has different degrees of toxicity, and this information is crucial at the time of choosing the therapeutic regimen. Erlotinib treatment could be an effective option for second-line therapy. PMID:18831720

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

PubMed

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 ( <15 h including sequential concentration/diafiltration step), and clarification ( <6 NTU). However, the three options differ in terms of process development time required, capital cost, consumable cost, ease of scale-ability and process robustness. It is recommended that these be kept under consideration when making a final decision on a harvesting approach.

Novel Therapeutic Options for the Treatment of Mineral Metabolism Abnormalities in End Stage Renal Disease.

PubMed

Kendrick, Jessica; Chonchol, Michel

2015-01-01

Abnormalities in mineral metabolism are a universal complication in dialysis patients and are associated with an increased risk of cardiovascular disease and mortality. Hyperphosphatemia, increased fibroblast growth factor 23 levels and secondary hyperparathyroidism are all strongly associated with adverse outcomes in end stage renal disease (ESRD) and most treatment strategies target these parameters. Over the past few years, new therapies have emerged for the treatment of abnormalities of mineral metabolism in ESRD and many are promising. This article will review these new therapeutic options including the potential advantages and disadvantages compared to existing therapies. © 2015 Wiley Periodicals, Inc.

Novel Therapeutic Options for the Treatment of Mineral Metabolism Abnormalities in End Stage Renal Disease

PubMed Central

Kendrick, Jessica; Chonchol, Michel

2015-01-01

Abnormalities in mineral metabolism are a universal complication in dialysis patients and are associated with an increased risk of cardiovascular disease and mortality. Hyperphosphatemia, increased fibroblast growth factor 23 levels and secondary hyperparathyroidism are all strongly associated with adverse outcomes in end stage renal disease (ESRD) and most treatment strategies target these parameters. Over the past few years, new therapies have emerged for the treatment of abnormalities of mineral metabolism in ESRD and many are promising. This article will review these new therapeutic options including the potential advantages and disadvantages compared to existing therapies. PMID:26278462

[Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options].

PubMed

Martos-Moreno, Gabriel A; Calzada, Joan; Couce, María L; Argente, Jesús

2018-06-01

Hypophosphatasia is a very rare bone metabolism disorder caused by a deficiency in alkaline phosphatase activity, due to mutations in the ALPL gene. Its clinical hallmark is the impairment of skeletal and teeth mineralisation, although extra-skeletal manifestations are frequent. Its phenotypic spectrum is widely variable from a subtype with exclusive odontological impairment (odontohypophosphatasia) to five subtypes with systemic involvement, classified according to the age at the onset of the first symptoms (four of them in the paediatric age range: perinatal lethal, perinatal benign, infant and childhood hypophosphatasia). Those subtypes of hypophosphatasia with an earliest onset usually involve a worse prognosis, due to the risk of developing potentially lethal complications, such as seizures or severe respiratory insufficiency, secondary to rib cage malformations. Due to the extremely low prevalence of the severe forms of hypophosphatasia, its clinical variability and overlapping phenotypic features with several more prevalent conditions, the diagnosis of hypophosphatasia in the clinical setting is challenging. However, its potential lethality and impact on the patient's quality of life, along with the recent availability of an enzyme replacement therapy, increases the relevance of the early and accurate identification of patients affected with hypophosphatasia. On the basis of published evidence and clinical experience, this article suggests an algorithm with practical recommendations for the differential diagnosis of childhood hypophosphatasia, as well as an updated review of current therapeutic options. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Immunotherapy for Head and Neck Squamous Cell Carcinoma: A Review of Current and Emerging Therapeutic Options

PubMed Central

Moskovitz, Jessica M.; Moy, Jennifer; Seiwert, Tanguy Y.

2017-01-01

Abstract Advances in the field of cancer immunotherapy have occurred rapidly over the past decade. Exciting results from clinical trials have led to new treatment options and improved survival for patients with a myriad of solid tumor pathologies. However, questions remain unanswered regarding duration and timing of therapy, combination regimens, appropriate biomarkers of disease, and optimal monitoring of therapeutic response. This article reviews emerging immunotherapeutic agents and significant clinical trials that have led to advancements in the field of immuno‐oncology for patients with head and neck squamous cell carcinoma. Implications for Practice. This review article summarizes recently developed agents that harness the immune system to fight head and neck squamous cell carcinoma. A brief review of the immune system and its role in cancer development is included. Recently completed and emerging therapeutic trials centering on the immune system and head and neck cancer are reviewed. PMID:28507203

Passive solar addition to therapeutic pre-school. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1983-10-01

This project consisted of designing and constructing a passive solar system on a new classroom addition to the Peanut Butter and Jelly Therapeutic Pre-School in Albuquerque, NM. The purpose of this project was to demonstrate the applicability of solar space heating systems to large institutional buildings, and to demonstrate the energy and cost savings available through the use of such systems. Preliminary estimates indicated that the passive solar systems will provide about 90 percent of the heating and cooling needs for the new classroom addition to the school.

Attention deficit and hyperactivity disorder: a therapeutic option

PubMed Central

Topczewski, Abram

2014-01-01

Objective To evaluate the use of a therapeutic regimen to treat attention deficit hyperactivity disorder patients. Methods A total of 140 patients initially underwent physical, neurological and laboratory evaluation. Thereafter, treatment was initiated with a compounding product consisting of a tricyclic antidepressant and an anxiolytic. Results The response was positive in 71.43% of patients in controlling hyperactivity and improving dispersion and attention deficit. Conclusion The therapeutic regimen utilized proved to be an effective therapeutic alternative, especially for patients who do not adapt to psychostimulant drugs. PMID:25295451

Could Notch signaling pathway be a potential therapeutic option in renal diseases?

PubMed

Marquez-Exposito, Laura; Cantero-Navarro, Elena; Lavoz, Carolina; Fierro-Fernández, Marta; Poveda, Jonay; Rayego-Mateos, Sandra; Rodrigues-Diez, Raúl R; Morgado-Pascual, José Luis; Orejudo, Macarena; Mezzano, Sergio; Ruiz-Ortega, Marta

2018-02-10

Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Technical options for processing additional light tight oil volumes within the United States

EIA Publications

2015-01-01

This report examines technical options for processing additional LTO volumes within the United States. Domestic processing of additional LTO would enable an increase in petroleum product exports from the United States, already the world’s largest net exporter of petroleum products. Unlike crude oil, products are not subject to export limitations or licensing requirements. While this is one possible approach to absorbing higher domestic LTO production in the absence of a relaxation of current limitations on crude exports, domestic LTO would have to be priced at a level required to encourage additional LTO runs at existing refinery units, debottlenecking, or possible additions of processing capacity.

Metabolic syndrome: nature, therapeutic solutions and options.

PubMed

Onat, Altan

2011-08-01

Metabolic syndrome (MetS) defines the clustering in an individual of multiple metabolic abnormalities, based on central obesity and insulin resistance. In addition to its five components, prothrombotic and proinflammatory states are essential features. The significance of MetS lies in its close association with the risk of type 2 diabetes and cardiovascular disease (CVD). This field being an evolving one necessitated the current review. The areas covered in this review include the so far unproven concept that enhanced low-grade inflammation often leads to dysfunction of the anti-inflammatory and atheroprotective properties of apolipoprotein A-I (apoA-I) and HDL particles, which further increases the risk of diabetes and CVD. It was emphasized that lifestyle modification is essential in the prevention and management of MetS, which includes maintenance of optimal weight by caloric restriction, adherence to a diet that minimizes postprandial glucose and triglyceride fluctuations, restricting alcohol consumption, smoking cessation and engaging in regular exercise. Drug therapy should target the dyslipoproteinemia and the often associated hypertension or dysglycemia.Statins are the drugs of first choice, to be initiated in patients with MetS at high 10-year cardiovascular risk. Such treatment is inadequate if fasting serum triglycerides remain at > 150 mg/dl, when niacin should be combined. Fibrates, omega 3 fatty acids, metformin, angiotensin-converting enzyme inhibitors and pioglitazone are additional options in drug therapy. Research on MetS in subpopulations prone to impaired glucose tolerance and insulin resistance has indicated that proinflammatory state and oxidative stress are often prominently involved in MetS, to the extent that evidence of impaired function of HDL and apo A-I particles is discernible by biological evidence of functional defectiveness via outcomes studies and/or correlations with inflammatory and anti-inflammatory biomarkers. A sex difference

Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

PubMed

Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

2011-01-01

Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

Therapeutic options for carotid in-stent restenosis: review of the literature.

PubMed

van Haaften, Anne C; Bots, Michiel L; Moll, Frans L; de Borst, Gert J

2010-10-01

To critically evaluate published evidence on therapeutic options for in-stent restenosis (ISR) after carotid artery stent (CAS) placement, a systematic analysis of studies reporting interventions for ISR after CAS placement was conducted. In total 20 studies were found, describing 100 interventions after carotid ISR in 96 patients. The interventions most performed were repeat percutaneous transluminal angioplasty (PTA; n = 54), repeat CAS placement (n = 31), and carotid endarterectomy with stent removal (n = 9). No periprocedural complications were identified in any of the studies evaluated. Recurrent restenosis after intervention for ISR occurred in 12 of 84 cases (14%). All 12 patients received tertiary treatment. Two patients developed a third recurrence and eventually disabling stroke, one of whom died. In the other 10 interventions, no further follow-up was described. In conclusion, several treatment strategies for ISR after CAS placement have been reported, with acceptable short-term results. The quality of the currently available data is still limited by the variability of results and study designs. Therefore, no recommendation can be made for any specific therapy. This argues for better study design and more consistency of reporting standards. Copyright © 2010 SIR. Published by Elsevier Inc. All rights reserved.

Mitochondrial Neurogastrointestinal Encephalomyopathy Caused by Thymidine Phosphorylase Enzyme Deficiency: From Pathogenesis to Emerging Therapeutic Options

PubMed Central

Yadak, Rana; Sillevis Smitt, Peter; van Gisbergen, Marike W.; van Til, Niek P.; de Coo, Irenaeus F. M.

2017-01-01

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a progressive metabolic disorder caused by thymidine phosphorylase (TP) enzyme deficiency. The lack of TP results in systemic accumulation of deoxyribonucleosides thymidine (dThd) and deoxyuridine (dUrd). In these patients, clinical features include mental regression, ophthalmoplegia, and fatal gastrointestinal complications. The accumulation of nucleosides also causes imbalances in mitochondrial DNA (mtDNA) deoxyribonucleoside triphosphates (dNTPs), which may play a direct or indirect role in the mtDNA depletion/deletion abnormalities, although the exact underlying mechanism remains unknown. The available therapeutic approaches include dialysis and enzyme replacement therapy, both can only transiently reverse the biochemical imbalance. Allogeneic hematopoietic stem cell transplantation is shown to be able to restore normal enzyme activity and improve clinical manifestations in MNGIE patients. However, transplant related complications and disease progression result in a high mortality rate. New therapeutic approaches, such as adeno-associated viral vector and hematopoietic stem cell gene therapy have been tested in Tymp-/-Upp1-/- mice, a murine model for MNGIE. This review provides background information on disease manifestations of MNGIE with a focus on current management and treatment options. It also outlines the pre-clinical approaches toward future treatment of the disease. PMID:28261062

Human and rodent aryl hydrocarbon receptor (AHR): from mediator of dioxin toxicity to physiologic AHR functions and therapeutic options.

PubMed

Bock, Karl Walter

2017-04-01

Metabolism of aryl hydrocarbons and toxicity of dioxins led to the discovery of the aryl hydrocarbon receptor (AHR). Tremendous advances have been made on multiplicity of AHR signaling and identification of endogenous ligands including the tryptophan metabolites FICZ and kynurenine. However, human AHR functions are still poorly understood due to marked species differences as well as cell-type- and cell context-dependent AHR functions. Observations in dioxin-poisoned individuals may provide hints to physiologic AHR functions in humans. Based on these observations three human AHR functions are discussed: (1) Chemical defence and homeostasis of endobiotics. The AHR variant Val381 in modern humans leads to reduced AHR affinity to aryl hydrocarbons in comparison with Neanderthals and primates expressing the Ala381 variant while affinity to indoles remains unimpaired. (2) Homeostasis of stem/progenitor cells. Dioxins dysregulate homeostasis in sebocyte stem cells. (3) Modulation of immunity. In addition to microbial defence, AHR may be involved in a 'disease tolerance defence pathway'. Further characterization of physiologic AHR functions may lead to therapeutic options.

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

PubMed Central

Bruketa, Tomislav; Majerovic, Matea; Augustin, Goran

2015-01-01

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

SGLT2 inhibitors: a promising new therapeutic option for treatment of type 2 diabetes mellitus.

PubMed

Misra, Monika

2013-03-01

Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose reabsorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications. Sodium glucose cotransporter 2 (SGLT2) has a key role in reabsorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes. To discuss the therapeutic potential of SGLT2 inhibitors currently in clinical development. A number of preclinical and clinical studies of SGLT2 inhibitors have demonstrated a good safety profile and beneficial effects in lowering plasma glucose levels, diminishing glucotoxicity, improving glycemic control and reducing weight in diabetes. Of all the SGLT2 inhibitors, dapagliflozin is a relatively advanced compound with regards to clinical development. SGLT2 inhibitors are emerging as a promising therapeutic option for the treatment of diabetes. Their unique mechanism of action offers them the potential to be used in combination with other oral anti-diabetic drugs as well as with insulin. © 2012 The Author. JPP © 2012 Royal Pharmaceutical Society.

Menstrual Migraine: Therapeutic Approaches

PubMed Central

2009-01-01

The development of diagnostic criteria has enabled greater recognition of menstrual migraine as a highly prevalent and disabling condition meriting specific treatment. Although few therapeutic trials have yet been undertaken in accordance with the criteria, the results of those published to date confirm the efficacy of acute migraine drugs for symptomatic treatment. If this approach is insufficient, the predictability of attacks provides the opportunity for perimenstrual prophylaxis. Continuous contraceptive strategies provide an additional option for management, although clinical trial data are limited. Future approaches to treatment could explore the genomic and nongenomic actions of sex steroids. PMID:21180623

Emerging treatment options for the management of pemphigus vulgaris

PubMed Central

Kridin, Khalaf

2018-01-01

Pemphigus vulgaris (PV) is a life-threatening disease belonging to the pemphigus group of autoimmune intra-epidermal bullous diseases of the skin and mucosae. The therapeutic management of PV remains challenging and, in some cases, conventional therapy is not adequate to induce clinical remission. The cornerstone of PV treatment remains systemic corticosteroids. Although very effective, long-term corticosteroid administration is characterized by substantial adverse effects. Corticosteroid-sparing adjuvant therapies have been employed in the treatment of PV, aiming to reduce the necessary cumulative dose of corticosteroids. Specifically, immunosuppressive agents such as azathioprine and mycophenolate mofetil are widely used in PV. More recently, high-dose intravenous immunoglobulins, immunoadsorption, and rituximab have been established as additional successful therapeutic options. This review covers both conventional and emerging therapies in PV. In addition, it sheds light on potential future treatment strategies for this disease. PMID:29740210

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

PubMed

Haque, Azizul; Hober, Didier; Blondiaux, Joel

2015-10-01

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

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

PubMed Central

Hober, Didier; Blondiaux, Joel

2015-01-01

Ebola virus can cause severe hemorrhagic disease with high fatality rates. Currently, no specific therapeutic agent or vaccine has been approved for treatment and prevention of Ebola virus infection of humans. Although the number of Ebola cases has fallen in the last few weeks, multiple outbreaks of Ebola virus infection and the likelihood of future exposure highlight the need for development and rapid evaluation of pre- and postexposure treatments. Here, we briefly review the existing and future options for anti-Ebola therapy, based on the data coming from rare clinical reports, studies on animals, and results from in vitro models. We also project the mechanistic hypotheses of several potential drugs against Ebola virus, including small-molecule-based drugs, which are under development and being tested in animal models or in vitro using various cell types. Our paper discusses strategies toward identifying and testing anti-Ebola virus properties of known and medically approved drugs, especially those that can limit the pathological inflammatory response in Ebola patients and thereby provide protection from mortality. We underline the importance of developing combinational therapy for better treatment outcomes for Ebola patients. PMID:26248374

Current Therapeutic Approach to Hypertrophic Scars

PubMed Central

Mokos, Zrinka Bukvić; Jović, Anamaria; Grgurević, Lovorka; Dumić-Čule, Ivo; Kostović, Krešimir; Čeović, Romana; Marinović, Branka

2017-01-01

Abnormal scarring and its accompanying esthetic, functional, and psychological sequelae still pose significant challe nges. To date, there is no satisfactory prevention or treatment option for hypertrophic scars (HSs), which is mostly due to not completely comprehending the mechanisms underlying their formation. That is why the apprehension of regular and controlled physiological processes of scar formation is of utmost importance when facing hypertrophic scarring, its pathophysiology, prevention, and therapeutic approach. When treating HSs and choosing the best treatment and prevention modality, physicians can choose from a plethora of therapeutic options and many commercially available products, among which currently there is no efficient option that can successfully overcome impaired skin healing. This article reviews current therapeutic approach and emerging therapeutic strategies for the management of HSs, which should be individualized, based on an evaluation of the scar itself, patients’ expectations, and practical, evidence-based guidelines. Clinicians are encouraged to combine various prevention and treatment modalities where combination therapy that includes steroid injections, 5-fluorouracil, and pulsed-dye laser seems to be the most effective. On the other hand, the current therapeutic options are usually empirical and their results are unreliable and unpredictable. Therefore, there is an unmet need for an effective, targeted therapy and prevention, which would be based on an action or a modulation of a particular factor with clarified mechanism of action that has a beneficial effect on wound healing. As the extracellular matrix has a crucial role in cellular and extracellular events that lead to pathological scarring, targeting its components mostly by regulating bone morphogenetic proteins may throw up new therapeutic approach for reduction or prevention of HSs with functionally and cosmetically acceptable outcome. PMID:28676850

Chronobiology of epilepsy: diagnostic and therapeutic implications of chrono-epileptology.

PubMed

Loddenkemper, Tobias; Lockley, Steven W; Kaleyias, Joseph; Kothare, Sanjeev V

2011-04-01

The combination of chronobiology and epilepsy offers novel diagnostic and therapeutic management options. Knowledge of the interactions between circadian periodicity, entrainment, sleep patterns, and epilepsy may provide additional diagnostic options beyond sleep deprivation and extended release medication formulations. It may also provide novel insights into the physiologic, biochemical, and genetic regulation processes of epilepsy and the circadian clock, rendering new treatment options. Temporal fluctuations of seizure susceptibility based on sleep homeostasis and circadian phase in selected epilepsies may provide predictability based on mathematical models. Chrono-epileptology offers opportunities for individualized patient-oriented treatment paradigms based on chrono-pharmacology, differential medication dosing, chrono-drug delivery systems, and utilization of "zeitgebers" such as chronobiotics or light-therapy and desynchronization strategies among others.

Current status of renin-aldosterone angiotensin system-targeting anti-hypertensive drugs as therapeutic options for Alzheimer's disease.

PubMed

Ashby, Emma Louise; Kehoe, Patrick G

2013-10-01

Hypertension is a modifiable risk factor for Alzheimer's disease (AD) and other dementias. Yet, despite this well-documented association, few of the current strategies to treat AD are directed at this possible target. The renin-aldosterone angiotensin system (RAAS) is a centrally active modifiable pathway that is involved in cerebral blood flow regulation. Currently, three classes of RAAS-targeting drugs are licensed for treatment of peripheral hypertension--angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin II receptor blockers (ARBs) and direct renin inhibitors (DRIs). All of these are generally well tolerated and have been shown to offer varying degrees of protection on aspects of cognition and dementia, thus making them an attractive therapeutic option for AD. This review summarises existing evidence regarding the plausibility of using RAAS-targeting drugs as a strategy to treat AD and highlights unresolved aspects to such approaches, namely the potential impact of altering angiotensin II-mediated processes in the central nervous system. Continued biochemical research of the RAAS pathway in combination with formal investigation of current RAAS-modifying drugs in randomised clinical trials is now necessary to determine their therapeutic value in AD.

[Cannabis and cannabinoid receptors: from pathophysiology to therapeutic options].

PubMed

Derkinderen, P; Valjent, E; Darcel, F; Damier, P; Girault, J-A

2004-07-01

Although cannabis has been used as a medicine for several centuries, the therapeutic properties of cannabis preparations (essentially haschich and marijuana) make them far most popular as a recreational drugs. Scientific studies on the effects of cannabis were advanced considerably by the identification in 1964 of cannabinoid D9-tetrahydrocannadinol (THC), recognized as the major active constituent of cannabis. Cloning of the centrally located CB1 receptor in 1990 and the identification of the first endogenous ligand of the CB1 receptor, anandamide, in 1992 further advanced our knowledge. Progress has incited further research on the biochemistry and pharmacology of the cannabinoids in numerous diseases of the central nervous system. In the laboratory animal, cannabinoids have demonstrated potential in motion disorders, demyelinizing disease, epilepsy, and as anti-tumor and neuroprotector agents. Several clinical studies are currently in progress, but therapeutic use of cannabinoids in humans couls be hindered by undesirable effects, particularly psychotropic effects. CB1 receptor antagonists also have interesting therapeutic potential.

The renaissance of complement therapeutics

PubMed Central

Ricklin, Daniel; Mastellos, Dimitrios C.; Reis, Edimara S.; Lambris, John D.

2018-01-01

The increasing number of clinical conditions that involve a pathological contribution from the complement system — many of which affect the kidneys — has spurred a regained interest in therapeutic options to modulate this host defence pathway. Molecular insight, technological advances, and the first decade of clinical experience with the complement-specific drug eculizumab, have contributed to a growing confidence in therapeutic complement inhibition. More than 20 candidate drugs that target various stages of the complement cascade are currently being evaluated in clinical trials, and additional agents are in preclinical development. Such diversity is clearly needed in view of the complex and distinct involvement of complement in a wide range of clinical conditions, including rare kidney disorders, transplant rejection and haemodialysis-induced inflammation. The existing drugs cannot be applied to all complement-driven diseases, and each indication has to be assessed individually. Alongside considerations concerning optimal points of intervention and economic factors, patient stratification will become essential to identify the best complement-specific therapy for each individual patient. This Review provides an overview of the therapeutic concepts, targets and candidate drugs, summarizes insights from clinical trials, and reflects on existing challenges for the development of complement therapeutics for kidney diseases and beyond. PMID:29199277

Hepatocellular carcinoma in a large medical center of China over a 10-year period: evolving therapeutic option and improving survival.

PubMed

Zhu, Qianqian; Li, Na; Zeng, Xiaoyan; Han, Qunying; Li, Fang; Yang, Cuiling; Lv, Yi; Zhou, Zhihua; Liu, Zhengwen

2015-02-28

Hepatocellular carcinoma (HCC) is among the most common and lethal cancers worldwide, especially in China. We retrospectively analyzed data from patients who were diagnosed and treated HCC between 2002 and 2011 in a large hospital in northwest China and compared the data between periods 2002-2006 (P1) and 2007-2011 (P2). 2045 patients were included in analysis. The HCC stages at diagnosis according to the Barcelona clinic liver cancer staging system had no significant change. Treatment options of liver transplantation, transcatheter arterial chemoembolization and other therapy decreased while percutaneous local ablation and supportive care increased from P1 to P2. Options of surgical resection and systematic therapy had no significant change. Patient survival rates at 1, 3 and 5 years significantly improved from P1 to P2. The treatments with increasing option trend had a higher magnitude of survival increase and vise versa. Over the last 10 years, the patient survival had a significant increase which was mainly a result of the optimal therapeutic selections according to disease stages in this center. However, the proportion of patients diagnosed at early stages of HCC remained low and did not increase, a result calling for implementing surveillance system for at risk patients.

Promising personalized therapeutic options for diffuse large B-cell Lymphoma Subtypes with oncogene addictions.

PubMed

Steinhardt, James J; Gartenhaus, Ronald B

2012-09-01

Currently, two major classification systems segregate diffuse large B-cell lymphoma (DLBCL) into subtypes based on gene expression profiles and provide great insights about the oncogenic mechanisms that may be crucial for lymphomagenesis as well as prognostic information regarding response to current therapies. However, these current classification systems primarily look at expression and not dependency and are thus limited to inductive or probabilistic reasoning when evaluating alternative therapeutic options. The development of a deductive classification system that identifies subtypes in which all patients with a given phenotype require the same oncogenic drivers, and would therefore have a similar response to a rational therapy targeting the essential drivers, would significantly advance the treatment of DLBCL. This review highlights the putative drivers identified as well as the work done to identify potentially dependent populations. These studies integrated genomic analysis and functional screens to provide a rationale for targeted therapies within defined populations. Personalizing treatments by identifying patients with oncogenic dependencies via genotyping and specifically targeting the responsible drivers may constitute a novel approach for the treatment of DLBCL. ©2012 AACR.

Proteases as therapeutics

PubMed Central

Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

2015-01-01

Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

Gold Nanostructures as a Platform for Combinational Therapy in Future Cancer Therapeutics

PubMed Central

Jelveh, Salomeh; Chithrani, Devika B.

2011-01-01

The field of nanotechnology is currently undergoing explosive development on many fronts. The technology is expected to generate innovations and play a critical role in cancer therapeutics. Among other nanoparticle (NP) systems, there has been tremendous progress made in the use of spherical gold NPs (GNPs), gold nanorods (GNRs), gold nanoshells (GNSs) and gold nanocages (GNCs) in cancer therapeutics. In treating cancer, radiation therapy and chemotherapy remain the most widely used treatment options and recent developments in cancer research show that the incorporation of gold nanostructures into these protocols has enhanced tumor cell killing. These nanostructures further provide strategies for better loading, targeting, and controlling the release of drugs to minimize the side effects of highly toxic anticancer drugs used in chemotherapy and photodynamic therapy. In addition, the heat generation capability of gold nanostructures upon exposure to UV or near infrared light is being used to damage tumor cells locally in photothermal therapy. Hence, gold nanostructures provide a versatile platform to integrate many therapeutic options leading to effective combinational therapy in the fight against cancer. In this review article, the recent progress in the development of gold-based NPs towards improved therapeutics will be discussed. A multifunctional platform based on gold nanostructures with targeting ligands, therapeutic molecules, and imaging contrast agents, holds an array of promising directions for cancer research. PMID:24212654

Nitroglycerin patch for the treatment of chondrodermatitis nodularis helicis: a new therapeutic option.

PubMed

Garrido Colmenero, Cristina; Martínez García, Eliseo; Blasco Morente, Gonzalo; Tercedor Sánchez, Jesús

2014-01-01

Chondrodermatitis nodularis helicis (CNH) is an inflammatory process that affects the skin and cartilage of the ear. At present, there are many treatment options, although they are not always effective. Based on previous studies where nitroglycerin 2% gel was used, we propose the use of nitroglycerin patches. The purpose of this study was to evaluate the effectiveness of nitroglycerin patches in treating CNH. We performed a prospective study in 11 patients diagnosed with CNH treated with nitroglycerin patches 5 mg, 12 hours a day for 2 months. The therapeutic effectivity was determined by the improvement in the appearance and symptoms of the lesion. Seven of 11 patients (63.6%) had a complete response. One of 11 patients (9%) did not respond completely and surgical treatment was performed. Two of 11 patients (18.1%) stopped the treatment because of headache. One of 11 patients (9%) did not complete the treatment because the said patient forgot to apply the patch every night. Transdermal nitroglycerin has demonstrated efficacy in the treatment of the symptoms and lesional appearance of CNH noninvasive manner. The success rate is comparable with other published methods and the rate of adverse effects is acceptable. © 2014 Wiley Periodicals, Inc.

Bulky Polar Additives That Greatly Reduce the Viscosity of Concentrated Solutions of Therapeutic Monoclonal Antibodies.

PubMed

Larson, Alyssa M; Weight, Alisha K; Love, Kevin; Bonificio, Amanda; Wescott, Charles R; Klibanov, Alexander M

2017-05-01

The viscosity of concentrated aqueous solutions of 3 clinical monoclonal antibodies (mAbs), Erbitux®, Herceptin®, and Rituxan®, has been reduced up to over 10-fold by adding certain bulky polar additives instead of saline at isotonic levels. Because these additives are also found not to compromise mAbs' stability against aggregation induced by stresses, a drug-delivery modality switch from intravenous infusions to more convenient and inexpensive parenteral options like subcutaneous injections may become possible. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Why calpain inhibitors are interesting leading compounds to search for new therapeutic options to treat leishmaniasis?

PubMed

Ennes-Vidal, Vitor; Menna-Barreto, Rubem Figueiredo Sadock; Branquinha, Marta Helena; Dos Santos, André Luis Souza; D'Avila-Levy, Claudia Masini

2017-02-01

Leishmaniasis is a neglected disease, which needs improvements in drug development, mainly due to the toxicity, parasite resistance and low compliance of patients to treatment. Therefore, the development of new chemotherapeutic compounds is an urgent need. This opinion article will briefly highlight the feasible use of calpain inhibitors as leading compounds to search for new therapeutic options to treat leishmaniasis. The milestone of this approach is to take advantage on the myriad of inhibitors developed against calpains, some of which are in advanced clinical trials. The deregulated activity of these enzymes is associated with several pathologies, such as strokes, diabetes and Parkinson's disease, to name a few. In Leishmania, calpain upregulation has been associated to drug resistance and virulence. Whereas the difficulties in developing new drugs for neglected diseases are more economical than biotechnological, repurposing approach with compounds already approved for clinical use by the regulatory agencies can be an interesting shortcut to a successful chemotherapeutic treatment for leishmaniasis.

Cyclic peptides as potential therapeutic agents for skin disorders.

PubMed

Namjoshi, Sarika; Benson, Heather A E

2010-01-01

There is an increasing understanding of the role of peptides in normal skin function and skin disease. With this knowledge, there is significant interest in the application of peptides as therapeutics in skin disease or as cosmeceuticals to enhance skin appearance. In particular, antimicrobial peptides and those involved in inflammatory processes provide options for the development of new therapeutic directions in chronic skin conditions such as psoriasis and dermatitis. To exploit their potential, it is essential that these peptides are delivered to their site of action in active form and in sufficient quantity to provide the desired effect. Many polymers permeate the skin poorly and are vulnerable to enzymatic degradation. Synthesis of cyclic peptide derivatives can substantially alter the physicochemical characteristics of the peptide with the potential to improve its skin permeation. In addition, cyclization can stabilize the peptide structure and thereby increase its stability. This review describes the role of cyclic peptides in the skin, examples of current cyclic peptide therapeutic products, and the potential for cyclic peptides as dermatological therapeutics and cosmeceuticals.

Integration of a Community Pharmacy Simulation Program into a Therapeutics Course.

PubMed

Shin, Jaekyu; Tabatabai, Daryush; Boscardin, Christy; Ferrone, Marcus; Brock, Tina

2018-02-01

Objective. To demonstrate the feasibility of integrating the computer simulation, MyDispense, into a therapeutics course and to measure its effects on student perception and learning. Methods. We conducted a prospective study with an experimental phase and an implementation phase. In the first phase, students were randomized to complete a therapeutics case using MyDispense or traditional paper methods in class. In the second phase, all students completed two therapeutic cases using MyDispense in class with the option to complete four additional outside-of-class cases using MyDispense. Students completed pre- and post-tests in class and three surveys. Results. In the experimental phase, mean test scores increased from pre- to post-test for both MyDispense and traditional paper groups, but the difference between the groups was not statistically significant. Students in the traditional paper group reported statistically significant gains in confidence compared to the MyDispense group. In the implementation phase, mean test scores again increased, however, student perception of the use of MyDispense for therapeutics was negative. Completing the optional outside-of-class cases, however, was positively and significantly correlated with the midterm and final examination scores. Conclusion. Implementation of MyDispense in therapeutics may be feasible and has positive effects (eg, correlation with exam scores, capacity for immediate feedback, and potential for effective self-study). With short-term use and in the absence of assessment methods that also require seeking information from patients, students prefer to learn via traditional paper cases.

Intestinal ischemia-reperfusion injury in horses: pathogenesis and therapeutics.

PubMed

Wong, David M; Moore, Rustin M; Brockus, Charles W

2012-08-01

This article discusses the potential role of oxidative injury to the intestinal tract of horses and the therapeutic approaches that have been investigated to decrease cellular damage secondary to ischemia-reperfusion (IR) injury. Equine colic is a major concern for horse owners and veterinary practitioners. Strangulating and obstructive lesions of the small and large intestines commonly require intervention in patients via exploratory celiotomy. However, the application of information from experimentally induced IR injury in horses to clinical cases of naturally occurring equine colic is not clear. Thus, while the exact mechanisms and clinical significance of intestinal IR are being defined and may be matters of academic debate, a review of the available information may provide knowledge of potential underlying pathophysiologic mechanisms contributing to intestinal injury in equine colic. This information may allow clinicians to offer additional therapeutic strategies for horses with strangulating obstruction of the small or large intestine. Further clinical study of the therapeutic options for horses with naturally occurring disease is warranted.

A Review and Update of Treatment Options and Controversies in the Management of Hepatocellular Carcinoma.

PubMed

Dhir, Mashaal; Melin, Alyson A; Douaiher, Jeffrey; Lin, Chi; Zhen, Weining Ken; Hussain, Shahid M; Geschwind, Jean-Francois H; Doyle, Maria B Majella; Abou-Alfa, Ghassan K; Are, Chandrakanth

2016-06-01

To review the current management, outline recent advances and address controversies in the management of hepatocellular carcinoma (HCC). The treatment of HCC is multidisciplinary involving hepatologists, surgeons, medical oncologists, radiation oncologists, radiologists, interventional radiologists, and other disciplines. Each of these disciplines brings its unique perspective and differing opinions that add to controversies in the management of HCC. A focused literature review was performed to identify recent studies on the management of HCC and thereby summarize relevant information on the various therapeutic modalities and controversies involved in the treatment of HCC. The main treatment algorithms continue to rely on hepatic resection or transplantation with controversies involving patients harboring early stage disease and borderline hepatic function. The other treatment strategies include locoregional therapies, radiation, and systemic therapy used alone or in combination with other treatment modalities. Recent advances in locoregional therapies, radiation, and systemic therapies have provided better therapeutic options with curative intent potential for some locoregional therapies. Further refinements in combination therapies such as algorithms consisting of locoregional therapies and systemic or radiation therapies are likely to add additional options and improve survival. The management of HCC has witnessed significant strides with advances in existing options and introduction of several new treatment modalities of various combinations. Further refinements in these treatment options combined with enrollment in clinical trials are essential to improve the management and outcomes of patients with HCC.

Current treatment options for vulvovaginal candidiasis caused by azole-resistant Candida species.

PubMed

Sobel, J D; Sobel, R

2018-06-22

Clinicians are increasingly challenged by patients with refractory vulvovaginal candidiasis (VVC) caused by azole-resistant Candida species. Fluconazole resistant C.albicans is a growing and perplexing problem following years of indiscriminate drug prescription and unnecessary drug exposure and for which there are few therapeutic alternatives. Regrettably, although the azole class of drugs has expanded, new classes of antifungal drugs have not been forthcoming, limiting effective treatment options in patients with azole resistant Candida vaginitis. Areas covered: This review covers published data on epidemiology, pathophysiology and treatment options for women with azole-resistant refractory VVC. Expert opinion: Fluconazole resistant C.albicans adds to the challenge of azole resistant non-albicans Candida spp. Both issues follow years of indiscriminate drug prescription and unnecessary fluconazole exposure. Although an understanding of azole resistance in yeast has been established, this knowledge has not translated into useful therapeutic advantage. Treatment options for such women with refractory symptoms are extremely limited. New therapeutic options and strategies are urgently needed to meet this challenge of azole drug resistance.

Therapeutic options for the management of hot flashes in breast cancer survivors: an evidence-based review.

PubMed

Bordeleau, Louise; Pritchard, Kathleen; Goodwin, Pamela; Loprinzi, Charles

2007-02-01

Women with breast cancer may experience treatment-induced menopausal symptoms or natural menopause. Menopausal symptoms, particularly hot flashes, are reported at a high frequency in this group and tend to be more severe, distressing, and of greater duration than in controls. Because of the contribution of sex hormones to breast cancer, the use of hormonal agents for the control of hot flashes is problematic in these women. Safer nonhormonal alternatives are recommended for this patient group. This was a systematic review of the therapeutic options for the treatment of hot flashes in breast cancer survivors. MEDLINE was searched from 1990 to July 2006 using the disease-specific term breast neoplasms and the subheadings menopause and hot flashes. EMBASE was searched from 1990 to March 2006 using the disease-specific subject headings breast tumor/ breast cancer and menopause and the key word hot flashes. The reference lists of the identified articles and relevant review articles were examined for additional publications. Pertinent articles and abstracts of large randomized controlled trials focusing on the treatment of hot flashes in breast cancer survivors were selected for review. Pilot studies were excluded. A number of nonpharmacologic approaches are available for the treatment of hot flashes in breast cancer survivors, although they appear to be of limited effectiveness. Complementary alternative medicine therapies and vitamin E have been found to have modest effectiveness at best, and data on their long-term safety are not available. Centrally active agents such as the antidepressants venlafaxine and paroxetine and the anti seizure agent gabapentin have shown clinical effectiveness and appear to be reasonably well tolerated in this population. Centrally active agents (eg, venlafaxine, paroxetine, gabapentin) are regarded as the most promising nonhormonal treatments for hot flashes in breast cancer survivors. Nonpharmacologic and complementary alternative

Biopharmaceuticals from plants: a multitude of options for posttranslational modifications.

PubMed

Warzecha, Heribert

2008-01-01

In 1982 the first recombinant therapeutic, human insulin, was introduced into the market and started a new branch of pharmaceutical development, manufacture, and therapy options. To date, more than 130 recombinant protein therapeutics have been approved by the US Food and Drug Administration (FDA) and many more are being developed world wide. With the increasing number of protein therapeutics the number of potential production organisms is also expanding, and posttranslational modification of proteins has become a topic of special focus. One major difference between small-molecule drugs and protein therapeutics is that the latter are reliant on a host organism for their production and this can have a large influence on the final structure and can ultimately affect the pharmacokinetics, immunogenicity, and the function of the protein depending on the production process. Plants can be efficiently used as production systems for recombinant proteins thereby offering a variety of options for transgene targeting and modification. This review is intended to give an overview about the potential of plants to serve as a production system for therapeutic and prophylactic biopharmaceuticals with respect to posttranslational modifications.

Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities.

PubMed

Pircher, Andreas; Treps, Lucas; Bodrug, Natalia; Carmeliet, Peter

2016-10-01

Atherosclerosis is a leading cause of morbidity and mortality in Western society. Despite improved insight into disease pathogenesis and therapeutic options, additional treatment strategies are required. Emerging evidence highlights the relevance of endothelial cell (EC) metabolism for angiogenesis, and indicates that EC metabolism is perturbed when ECs become dysfunctional to promote atherogenesis. In this review, we overview the latest insights on EC metabolism and discuss current knowledge on how atherosclerosis deregulates EC metabolism, and how maladaptation of deregulated EC metabolism can contribute to atherosclerosis progression. We will also highlight possible therapeutic avenues, based on targeting EC metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Eosinophilic pustular folliculitis: A proposal of diagnostic and therapeutic algorithms.

PubMed

Nomura, Takashi; Katoh, Mayumi; Yamamoto, Yosuke; Miyachi, Yoshiki; Kabashima, Kenji

2016-11-01

Eosinophilic pustular folliculitis (EPF) is a sterile inflammatory dermatosis of unknown etiology. In addition to classic EPF, which affects otherwise healthy individuals, an immunocompromised state can cause immunosuppression-associated EPF (IS-EPF), which may be referred to dermatologists in inpatient services for assessments. Infancy-associated EPF (I-EPF) is the least characterized subtype, being observed mainly in non-Japanese infants. Diagnosis of EPF is challenging because its lesions mimic those of other common diseases, such as acne and dermatomycosis. Furthermore, there is no consensus regarding the treatment for each subtype of EPF. Here, we created procedure algorithms that facilitate the diagnosis and selection of therapeutic options on the basis of published work available in the public domain. Our diagnostic algorithm comprised a simple flowchart to direct physicians toward proper diagnosis. Recommended regimens were summarized in an easy-to-comprehend therapeutic algorithm for each subtype of EPF. These algorithms would facilitate the diagnostic and therapeutic procedure of EPF. © 2016 Japanese Dermatological Association.

Effectiveness of the addition of therapeutic alliance with minimal intervention in the treatment of patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors: a study protocol for a randomized controlled trial (TalkBack trial).

PubMed

Fagundes, Felipe Ribeiro Cabral; de Melo do Espírito Santo, Caique; de Luna Teixeira, Francine Mendonça; Tonini, Thaís Vanelli; Cabral, Cristina Maria Nunes

2017-01-31

The stratified model of care has been an effective approach for the treatment of low back pain. However, the treatment of patients with low risk of psychosocial-factor involvement is unclear. The addition of the therapeutic alliance to a minimal intervention may be an option for the treatment of low back pain. This paper reports on the rationale, design and protocol for a randomized controlled trial with blind assessor to assess the effectiveness of the addition of therapeutic alliance with minimal intervention on pain and disability in patients with chronic, nonspecific low back pain. Two hundred and twenty-two patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors will be assessed and randomly allocated into three groups (n = 74 patients per group). The Positive Therapeutic Alliance group will receive counseling and guidance with an emphasis on therapeutic alliance and empathy. The Usual Treatment group will receive the same information and counseling with limited interaction with the therapist. The Control group will not receive any intervention. The treatment will be composed by two intervention sessions with a 1-week interval. A blinded assessor will collect the following outcomes at baseline, 1 month, 6 months and 12 months after randomization: pain intensity (Pain Numerical Rating Scale), specific disability (Patient-specific Functional Scale), general disability (Oswestry Disability Index), global perceived effect (Global Perceived Effect Scale), empathy (Consultation and Relational Empathy Measure), credibility and expectations related to treatment. The analysis will be performed using linear mixed models. This will be the first study to understand the effect of combining enhanced therapeutic alliance to a treatment based on counseling, information and advice (minimal intervention). The addition of the therapeutic alliance to minimal intervention may improve the treatment of chronic, nonspecific low back

Tadalafil - a therapeutic option in the management of BPH-LUTS.

PubMed

Carson, C C; Rosenberg, M; Kissel, J; Wong, D G

2014-01-01

Men with signs of benign prostatic hyperplasia (BPH) may experience lower urinary tract symptoms (LUTS) such as urinary frequency, urgency, intermittence, nocturia, straining, incomplete emptying or a weak urinary stream. The effective management of LUTS suggestive of BPH (BPH-LUTS) requires careful consideration of several factors, including the severity of a patient's symptoms, concurrent or other coexisting medical conditions, the ability to improve symptoms and impact quality of life (QOL), as well as the potential side effects of available treatment options. Several clinical studies have assessed phosphodiesterase type 5 (PDE5) inhibitors in reducing LUTS; however, tadalafil is the only PDE5 inhibitor approved for the treatment of signs and symptoms of BPH, as well as in men with both erectile dysfunction (ED) and the signs and symptoms of BPH. This review examined articles that assessed tadalafil in patients with signs and symptoms of BPH, with or without erectile dysfunction (ED), which led to regulatory approval in the United States and Europe. In dose-ranging and confirmatory studies, results demonstrate that tadalafil significantly improved total International Prostate Symptom Score (IPSS) following 12 weeks of treatment with once daily tadalafil 5 mg. Statistically significant improvements in Benign Prostatic Hyperplasia Impact Index (BII), IPSS subscores, IPSS QOL and International Index of Erectile Function (IIEF) were also observed. Improvement in urinary symptoms occurred regardless of age, previous treatment with an α1 -adrenergic blocker, BPH-LUTS severity at baseline or ED status. While tadalafil is most frequently recognised as a standard treatment option for men with ED, it also represents a well-tolerated and effective treatment option in men with moderate to severe BPH-LUTS. © 2013 John Wiley & Sons Ltd.

Update on Huntington's disease: advances in care and emerging therapeutic options.

PubMed

Zielonka, Daniel; Mielcarek, Michal; Landwehrmeyer, G Bernhard

2015-03-01

Huntington's disease (HD) is the most common hereditary neurodegenerative disorder. Despite the fact that both the gene and the mutation causing this monogenetic disorder were identified more than 20 years ago, disease-modifying therapies for HD have not yet been established. While intense preclinical research and large cohort studies in HD have laid foundations for tangible improvements in understanding HD and caring for HD patients, identifying targets for therapeutic interventions and developing novel therapeutic modalities (new chemical entities and advanced therapies using DNA and RNA molecules as therapeutic agents) continues to be an ongoing process. The authors review recent achievements in HD research and focus on approaches towards disease-modifying therapies, ranging from huntingtin-lowering strategies to improving huntingtin clearance that may be promoted by posttranslational HTT modifications. The nature and number of upcoming clinical studies/trials in HD is a reason for hope for HD patients and their families. Copyright © 2014 Elsevier Ltd. All rights reserved.

Traumatic aortic injury: CT findings, mimics, and therapeutic options

PubMed Central

Lantz, Eric J.; Johnson, C. Michael; Young, Philip M.

2014-01-01

Objective Traumatic aortic injury (TAI) is rare, but frequently lethal. However, with prompt diagnosis, patients can undergo life-saving open or endovascular repair. Unfortunately, because these injuries are relatively rare, subtle forms of these injuries may be missed, and normal variants may mimic TAI leading to misdiagnosis. Conclusions We will discuss computed tomography findings of typical injury patterns of traumatic aortic injuries as well as treatment options, diagnostic pitfalls and injury mimics. These are highlighted with clinical case examples. PMID:25009793

Quantitative Analysis of Therapeutic Drugs in Dried Blood Spot Samples by Paper Spray Mass Spectrometry: An Avenue to Therapeutic Drug Monitoring

NASA Astrophysics Data System (ADS)

Manicke, Nicholas Edward; Abu-Rabie, Paul; Spooner, Neil; Ouyang, Zheng; Cooks, R. Graham

2011-09-01

A method is presented for the direct quantitative analysis of therapeutic drugs from dried blood spot samples by mass spectrometry. The method, paper spray mass spectrometry, generates gas phase ions directly from the blood card paper used to store dried blood samples without the need for complex sample preparation and separation; the entire time for preparation and analysis of blood samples is around 30 s. Limits of detection were investigated for a chemically diverse set of some 15 therapeutic drugs; hydrophobic and weakly basic drugs, such as sunitinib, citalopram, and verapamil, were found to be routinely detectable at approximately 1 ng/mL. Samples were prepared by addition of the drug to whole blood. Drug concentrations were measured quantitatively over several orders of magnitude, with accuracies within 10% of the expected value and relative standard deviation (RSD) of around 10% by prespotting an internal standard solution onto the paper prior to application of the blood sample. We have demonstrated that paper spray mass spectrometry can be used to quantitatively measure drug concentrations over the entire therapeutic range for a wide variety of drugs. The high quality analytical data obtained indicate that the technique may be a viable option for therapeutic drug monitoring.

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

PubMed Central

Yu, Beiqin; Xie, Jingwu

2016-01-01

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

45 CFR 1306.36 - Additional Head Start program option variations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN..., home-based, combination programs, and family child care options defined in this part, the Director of the Office of Head Start retains the right to fund alternative program variations to meet the unique...

Intermittent Massage as a Therapeutic Option for Compartment Syndrome after Embolectomy of the Lower Limbs.

PubMed

Pereira de Godoy, José Maria; de Fátima Guerreiro Godoy, Maria

2018-01-01

The case of a 54-year-old cardiac patient is reported, who was admitted to hospital with a complaint of sudden pain in the legs associated with edema, paresthesia, and coldness. Arterial embolism of the lower limbs was diagnosed and the patient was submitted to bilateral embolectomy. The patient evolved with a burning sensation, hypersensitivity in the right leg, swelling, and difficulty bending and stretching the sole of the foot and the knee. A physical examination detected edema and increased tension in the anterior, lateral, and posterior compartments. Treatment using intermittent massage of the leg during the evaluation of the patient was chosen in an attempt to stimulate lymphatic and venous drainage. After a few minutes of stimulation, there was significant improvement in the pain and edema. In 40 minutes, there was total reduction of the pain in the posterior and lateral compartments and improvement of over 50% in the anterior compartment. After this, the patient started to bend the knee without pain and bend the sole of the foot with slight pain. On the following day, the patient was walking around the hospital ward without difficulty. It seems that intermittent massage is a therapeutic option in selected cases of compartment syndrome.

Emerging treatments in neurogastroenterology: eluxadoline - a new therapeutic option for diarrhea-predominant IBS.

PubMed

Lacy, B E

2016-01-01

Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder worldwide. The global prevalence of IBS is estimated to be as high as 15%. For many patients, IBS is a chronic disorder which can significantly reduce quality of life. Just as important as the effects on any one individual, IBS also places a significant impact on the population as a whole with its negative effects on the health care system. Irritable bowel syndrome is categorized into one of three main categories: IBS with diarrhea, IBS with constipation, and IBS with mixed bowel habits. Patients with diarrhea-predominant IBS (IBS-D) comprise a substantial proportion of the overall IBS population. A number of therapeutic options exist to treat the symptoms of abdominal pain, bloating, diarrhea, and fecal urgency, including non-pharmacologic therapies such as dietary changes and probiotics, or pharmacologic therapies such as loperamide and alosetron. However, many patients have persistent symptoms despite these therapies. This unmet need led to the development of eluxadoline, a mu-opioid receptor agonist/delta-opioid receptor antagonist/kappa-receptor agonist. Approved by the FDA in May 2015, this medication shows promise in the treatment of diarrhea-predominant IBS for both men and women. This monograph will briefly review the impact of IBS, discuss current treatments for IBS-D, and then focus on the pharmacology, clinical efficacy and safety of eluxadoline. Potential mechanisms related to rare events of acute pancreatitis or elevated liver tests will be discussed. © 2015 John Wiley & Sons Ltd.

[Recurrent vulvovaginitis: diagnostic assessment and therapeutic management].

PubMed

Ramírez-Santos, A; Pereiro, M; Toribio, J

2008-04-01

Recurrent vulvovaginitis is a common problem in clinical practice. Management is often complicated by a long history of inappropriate treatments based on tentative diagnoses after an incomplete diagnostic workup. We review the most common causes of recurrent vulvovaginitis; the appropriate steps with which to establish a diagnosis, from the medical history through to the additional tests needed; and, finally, the best therapeutic options. We will focus on infectious, irritant, allergic, and hormonal causes as the ones of most interest to the dermatologist. Given that infection is the most frequent cause of these processes and also a common reason for inopportune treatment, we will pay particular attention to infectious etiologies and their differential diagnosis.

Intravaginal boric acid: is it an alternative therapeutic option for vaginal trichomoniasis?

PubMed

Thorley, Nicola; Ross, Jonathan

2017-12-09

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common curable sexually transmitted infection worldwide. Current guidance in the UK is to treat TV with a nitroimidazole antibiotic. The high prevalence of TV, high rate of antibiotic resistance and limited tolerability to nitroimidazoles suggest that alternative treatment regimens are needed. Intravaginal boric acid (BA) has been used safely for the treatment of candida vulvovaginitis and bacterial vaginosis, and in vitro studies suggest BA is active against TV. We review the evidence for the efficacy of BA in patients with TV. MEDLINE, EMBASE, CINAHL, AMED, HMIC and BNI and Grey literature databases, The Cochrane Library, Trial Registers, conference abstracts and proceedings were searched. Inclusion criteria were women aged 16 years or over with microbiological confirmation of TV infection and using BA as treatment. There were no restrictions on language, publication date or study design. The in vitro evidence for BA activity against TV was also reviewed. No randomised controlled trials or case series were found. Four case reports demonstrated TV clearance with BA using a variety of dose regimens (dose 600 mg alternate nights to 600 mg two times per day; duration 1-5 months). In vitro studies suggest that BA has activity against TV which is independent of its effect on pH. Further evaluation of BA for the treatment of uncomplicated TV is required, but it may be useful when therapeutic options are limited. If shown to be safe and effective, intravaginal BA might provide a well-tolerated alternative anti-infective treatment which reduces community exposure to systemic antibiotics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Experimental Treatment Options in Absence Epilepsy.

PubMed

Luijtelaar, Gilles van; Zobeiri, Mehrnoush; Lüttjohann, Annika; Depaulis, Antoine

2017-01-01

The benign character of absence epilepsy compared to other genetic generalized epilepsy syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does allow to search for new treatment options not only for absence epilepsy per se but also for other genetic - previously called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models is considered as a new therapeutic target area. Here, we provide an overview regarding the search for new therapeutical options as has been investigated in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be achieved, various types of electrical and optogenetical invasive stimulations, different types of noninvasive stimulation and finally whether absence seizures can be predicted and prevented. Many factors determine either the cortical and or thalamic excitability or the interaction between cortex and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread consequences seems feasible, although its mechanisms remain obscure and seems different from the antiabsence action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron- generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spikeand- wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with

New innovations: therapeutic opportunities for intellectual disabilities.

PubMed

Picker, Jonathan D; Walsh, Christopher A

2013-09-01

Intellectual disability is common and is associated with significant morbidity. Until the latter half of the 20th century, there were no efficacious treatments. Following initial breakthroughs associated with newborn screening and metabolic corrections, little progress was made until recently. With improved understanding of genetic and cellular mechanisms, novel treatment options are beginning to appear for a number of specific conditions. Fragile X and tuberous sclerosis offer paradigms for the development of targeted therapeutics, but advances in understanding of other disorders such as Down syndrome and Rett syndrome, for example, are also resulting in promising treatment directions. In addition, better understanding of the underlying neurobiology is leading to novel developments in enzyme replacement for storage disorders and adjunctive therapies for metabolic disorders, as well as potentially more generalizable approaches that target dysfunctional cell regulation via RNA and chromatin. Physiologic therapies, including deep brain stimulation and transcranial magnetic stimulation, offer yet another direction to enhance cognitive functioning. Current options and evolving opportunities for the intellectually disabled are reviewed and exemplified. Copyright © 2013 American Neurological Association.

Phytotherapy: emerging therapeutic option in urologic disease

PubMed Central

2012-01-01

Phytotherapy belongs to the area of complementary and alternative medicine (CAM) and the definition of phytotherapy is the use of plants or plant extracts for medicinal uses. Interest in phytotherapy is growing in both Asian and western countries for its use in the prevention and management of disease, improvement of general health and anti-aging. And also, there are several studies about the efficacy of phytotherapy in urologic diseases like benign prostatic hyperplasia (BPH), erectile dysfunction (ED), late-onset hypogonadism (LOH) and infertility in males. Phytotherapy for BPH including saw palmetto, pygeum, and nettles, is under vigorous research for the therapeutic effect. No solid evidence showing better effective treatment modality for ED than placebo has been found yet for phytotherapy. Recently, a potent NO donor, L-arginine is under research with promising results. Phytotherapy is used by a number of patients with urological disease, and urologists need to have accurate knowledge about phytotherapy as well as keep a cautious approach. The possible effects and side effects should be defined and related to urologic patients by urologists. PMID:26816707

Therapeutic potential of medicinal marijuana: an educational primer for health care professionals.

PubMed

Mouhamed, Yara; Vishnyakov, Andrey; Qorri, Bessi; Sambi, Manpreet; Frank, Sm Signy; Nowierski, Catherine; Lamba, Anmol; Bhatti, Umrao; Szewczuk, Myron R

2018-01-01

With the proposed Canadian July 2018 legalization of marijuana through the Cannabis Act, a thorough critical analysis of the current trials on the efficacy of medicinal marijuana (MM) as a treatment option is necessary. This review is particularly important for primary care physicians whose patients may be interested in using MM as an alternative therapy. In response to increased interest in MM, Health Canada released a document in 2013 for general practitioners (GPs) as an educational tool on the efficacy of MM in treating some chronic and acute conditions. Although additional studies have filled in some of the gaps since the release of the Health Canada document, conflicting and inconclusive results continue to pose a challenge for physicians. This review aims to supplement the Health Canada document by providing physicians with a critical yet concise update on the recent advancements made regarding the efficacy of MM as a potential therapeutic option. An update to the literature of 2013 is important given the upcoming changes in legislation on the use of marijuana. Also, we briefly highlight the current recommendations provided by Canadian medical colleges on the parameters that need to be considered prior to authorizing MM use, routes of administration as well as a general overview of the endocannabinoid system as it pertains to cannabis. Lastly, we outline the appropriate medical conditions for which the authorization of MM may present as a practical alternative option in improving patient outcomes as well as individual considerations of which GPs should be mindful. The purpose of this paper is to offer physicians an educational tool that provides a necessary, evidence-based analysis of the therapeutic potential of MM and to ensure physicians are making decisions on the therapeutic use of MM in good faith.

Therapeutic potential of medicinal marijuana: an educational primer for health care professionals

PubMed Central

Frank, SM Signy; Nowierski, Catherine; Lamba, Anmol; Bhatti, Umrao; Szewczuk, Myron R

2018-01-01

With the proposed Canadian July 2018 legalization of marijuana through the Cannabis Act, a thorough critical analysis of the current trials on the efficacy of medicinal marijuana (MM) as a treatment option is necessary. This review is particularly important for primary care physicians whose patients may be interested in using MM as an alternative therapy. In response to increased interest in MM, Health Canada released a document in 2013 for general practitioners (GPs) as an educational tool on the efficacy of MM in treating some chronic and acute conditions. Although additional studies have filled in some of the gaps since the release of the Health Canada document, conflicting and inconclusive results continue to pose a challenge for physicians. This review aims to supplement the Health Canada document by providing physicians with a critical yet concise update on the recent advancements made regarding the efficacy of MM as a potential therapeutic option. An update to the literature of 2013 is important given the upcoming changes in legislation on the use of marijuana. Also, we briefly highlight the current recommendations provided by Canadian medical colleges on the parameters that need to be considered prior to authorizing MM use, routes of administration as well as a general overview of the endocannabinoid system as it pertains to cannabis. Lastly, we outline the appropriate medical conditions for which the authorization of MM may present as a practical alternative option in improving patient outcomes as well as individual considerations of which GPs should be mindful. The purpose of this paper is to offer physicians an educational tool that provides a necessary, evidence-based analysis of the therapeutic potential of MM and to ensure physicians are making decisions on the therapeutic use of MM in good faith. PMID:29928146

Anaplastic Thyroid Carcinoma: Current Treatments and Potential New Therapeutic Options with Emphasis on TfR1/CD71

PubMed Central

Salvatorelli, Lucia; Magro, Gaetano

2014-01-01

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers. Actually, ATC is refractory to conventional therapies, including surgery, chemotherapy, radiotherapy, and radioiodine (131I) therapy. Accordingly, genetic and molecular characterizations of ATC have been frequently and periodically reviewed in order to identify potential biological markers exploitable for target therapy. This review briefly focuses on main molecular events that characterize ATC and provides an update about preclinical studies. In addition, the overexpression of transferrin receptor 1 (TfR1/CD71) by neoplastic cells of ATC is emphasized in that it could represent a potential therapeutic target. In this regard, new therapeutic approaches based on the use of monoclonal or recombinant antibodies, or transferrin-gallium-TfR1/CD71 molecular complexes, or lastly small interfering RNAs (siRNAs) are proposed. PMID:25097549

Psychosocial factors and therapeutic approaches in the context of sexual history taking in men: a study conducted among Swiss general practitioners and urologists.

PubMed

Platano, Giacomo; Margraf, Jürgen; Alder, Judith; Bitzer, Johannes

2008-11-01

Male sexual dysfunction is a common medical condition, which is addressed mainly from a biomedical perspective by Swiss general practitioners (GPs) and urologists as the results of part I of our study showed. A psychosocial orientation in sexual history taking (SHT) leads to a truly patient-centered approach and is crucial for improving therapy decisions related to sexual dysfunction. To analyze to what extent Swiss GPs and urologists have a psychosocial orientation in SHT, and what therapeutic options they focus on when confronted with male sexual dysfunction. A semistructured interview was developed and used in face-to-face encounters with 25 GPs and 25 urologists. Content and frequency of interview responses. The GPs and urologists differed significantly from each other in 5 out of 22 psychosocial factors. Summarizing these psychosocial factors in four domains showed a difference between the GPs and urologists in only one domain. Both groups focus on an open conversation as their approach in SHT. No GP and only a minority of urologists based their diagnosis on criteria of the International Classification of Diseases (10th edition) (ICD-10) or Diagnostic and Statistical Manual of Mental Disorders (4th edition) (DSM-IV). The GPs and urologists differed significantly from each other in 4 out of 16 combinations resulting from the given therapeutic options and form of sexual dysfunction. The urologists focus more strongly on medication as a therapeutic option. The results of part II additionally justify establishing guidelines and training resources related to SHT in Switzerland. Swiss physicians should be encouraged to apply a more psychosocial orientation in SHT. This will contribute to a better patient-centered approach with positive consequences on physicians' therapeutic decisions. Optimizing the approach in SHT and the choice of therapeutic options may better facilitate real sexual satisfaction for the patient and ultimately result in fewer health insurance

Indications and interventional options for non-resectable tracheal stenosis

PubMed Central

Bacon, Jenny Louise; Patterson, Caroline Marie

2014-01-01

Non-specific presentation and normal examination findings in early disease often result in tracheal obstruction being overlooked as a diagnosis until patients present acutely. Once diagnosed, surgical options should be considered, but often patient co-morbidity necessitates other interventional options. Non-resectable tracheal stenosis can be successfully managed by interventional bronchoscopy, with therapeutic options including airway dilatation, local tissue destruction and airway stenting. There are common aspects to the management of tracheal obstruction, tracheomalacia and tracheal fistulae. This paper reviews the pathogenesis, presentation, investigation and management of tracheal disease, with a focus on tracheal obstruction and the role of endotracheal intervention in management. PMID:24624290

48 CFR 317.207 - Exercise of options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Exercise of options. 317... METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 317.207 Exercise of options. (h) Before exercising an option for a subsequent performance period/additional quantity under a multiple-year contract...

[Weighing use and safety of therapeutic agents and feed additives (author's transl)].

PubMed

van der Wal, P

1982-02-01

(1) The pros and cons of using feed additives and therapeutic agents may be successfully weighed in the light of carefully considered consumer requirements. (2) The socio-economic interests of the producer and the welfare of the animal will also determine the response of the production apparatus to consumer requirements. (3) Consumption of the current amounts of products of animal origin and maintenance of price and quality will only be feasible in the event of rational large-scale production in which constituents used in nutrition, prophylaxis and therapeutics are highly important factors. (4) Using these ingredients should be preceded by accurate evaluation of their use and safety. Testing facilities, conduct of studies and reporting should be such as to make the results nationally and internationally acceptable to all those concerned. (5) In deciding whether feed constituents are acceptable in view of the established use and safety, compliance will have to be sought with those standards which are accepted in other fields of society. Measures which result in raising the price of food without actually helping to reduce the risks to the safety of man, animals and environment, are likely to be rejected by any well-informed consumer who is aware of the facts. (6) For accurate weighing of use and safety at a national level, possibilities are hardly adequate in Europe. Decisions reached within the framework of the European Community, also tuned to U.S.A.- conditions are rightly encouraged. A centrally managed professionally staffed and equipped test system in the European Community would appear to be indispensable.

Emerging therapeutic options in GERD.

PubMed

Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

2013-06-01

Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. Copyright © 2013 Elsevier Ltd. All rights reserved.

Lung cancer: biology and treatment options

PubMed Central

Hassan, Omer; Yang, Yi-Wei; Buchanan, Petra

2015-01-01

Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLC) and non-small cell lung carcinomas (NSCLC). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation. PMID:26297204

48 CFR 217.207 - Exercise of options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Exercise of options. 217..., DEPARTMENT OF DEFENSE CONTRACTING METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 217.207 Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

Ghrelin, MicroRNAs, and Critical Limb Ischemia: Hungering for a Novel Treatment Option.

PubMed

Neale, Joshua P H; Pearson, James T; Katare, Rajesh; Schwenke, Daryl O

2017-01-01

Critical limb ischemia (CLI) is the most severe manifestation of peripheral artery disease. It is characterized by chronic pain at rest, skin ulcerations, and gangrene tissue loss. CLI is a highly morbid condition, resulting in a severely diminished quality of life and a significant risk of mortality. The primary goal of therapy for CLI is to restore blood flow to the affected limb, which is only possible by surgery, but is inadvisable in up to 50% of patients. This subset of patients who are not candidates for revascularisation are referred to as "no-option" patients and are the focus of investigation for novel therapeutic strategies. Angiogenesis, arteriogenesis and vasculogenesis are the processes whereby new blood vessel networks form from the pre-existing vasculature and primordial cells, respectively. In therapeutic angiogenesis, exogenous stimulants are administered to promote angiogenesis and augment limb perfusion, offering a potential treatment option for "no option" patients. However, to date, very few clinical trials of therapeutic angiogenesis in patients with CLI have reported clinically significant results, and it remains a major challenge. Ghrelin, a 28-amino acid peptide, is emerging as a potential novel therapeutic for CLI. In pre-clinical models, exogenous ghrelin has been shown to induce therapeutic angiogenesis, promote muscle regeneration, and reduce oxidative stress via the modulation of microRNAs (miRs). miRs are endogenous, small, non-coding ribonucleic acids of ~20-22 nucleotides which regulate gene expression at the post-transcriptional level by either translational inhibition or by messenger ribonucleic acid cleavage. This review focuses on the mounting evidence for the use of ghrelin as a novel therapeutic for CLI, and highlights the miRs which orchestrate these physiological events.

Therapeutics for Equine Endocrine Disorders.

PubMed

Durham, Andy E

2017-04-01

Equine endocrine disease is commonly encountered by equine practitioners. Pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS) predominate. The most logical therapeutic approach in PPID uses dopamine agonists; pergolide mesylate is the most common. Bromocryptine and cabergoline are alternative drugs with similar actions. Drugs from other classes have a poor evidence basis, although cyproheptadine and trilostane might be considered. EMS requires management changes as the primary approach; reasonable justification for use of drugs such as levothyroxine and metformin may apply. Therapeutic options exist in rare cases of diabetes mellitus, diabetes insipidus, hyperthyroidism, and critical illness-related corticosteroid insufficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic options in locally advanced thyroid carcinoma. Our experience.

PubMed

Avenia, Nicola; Monacelli, Massimo; Sanguinetti, Alessandro; Santoprete, Stefano; Pecoriello, Roberta; Ragusa, Mark; Puma, Francesco

2012-01-01

Thyroid cancer is the most common endocrine malignancy with an incidence equal to 1% of all malignant tumors. Prognostic factors affecting survival are manifold, including in several classifications (AMES, AGES, CORN and TNM). In this sense, the invasion of adjacent structures is one of the most important variables. The authors describe the experience of a single center in surgical treatment of advanced thyroid cancer. Between 1986 and 2010 , 1565 patients were undergoing surgery with thyroid cancer. In particular, 1403 interventions were made for differentiated cancer, 97 for medullary carcinoma, 25 for insular carcinoma, 29 for anaplastic carcinoma, 2 for plasmacytoma, and 7 for lymphoma and 2 for angiosarcoma. Among these 896 showed invasion of adjacent structures and / or distant metastases. There were no perioperative deaths or major complications. Surgical procedures consisted of: 13 loboistmectomy, 519 total thyroidectomy (TT), 325 TT with lymphadenectomy of the central compartment, 7 TT with radical lymphectomy, 621 TT with functional lymphectomy, 6 TT with breast lumpectomy, 5 TT with with video-assisted lung metastasectomy, 16-TT with resection and tracheal anastomosis, 6 TT with laryngotracheal resection, 3 TT with laryngectomy, 4 TT with trachetomy, 28 TT with respiratory stent placement, 12 tracheotomy. At present, 1328 patients were free of disease, while 104 showed recurrence. Total of 133 deaths were recorded, all linked to disease relapse. The role of surgery in the treatment of advanced thyroid cancer is still undeniable. In the presence of extracapsular trespassing, in fact, the adoption of interventions demolition permits long-term survival, given the lack of aggressiveness of the tumor differentiated representing the majority of cases. The aim of surgical radicalization addition, even in the presence of distant metastases, it is justified by the possibilities offered by the therapeutic radioiodine treatment, which is not feasible in the

Therapeutic decisions in ALS patients: cross-cultural differences and clinical implications.

PubMed

Andersen, Peter M; Kuzma-Kozakiewicz, Magdalena; Keller, Jürgen; Aho-Oezhan, Helena E A; Ciecwierska, Katarzyna; Szejko, Natalia; Vázquez, Cynthia; Böhm, Sarah; Badura-Lotter, Gisela; Meyer, Thomas; Petri, Susanne; Linse, Katharina; Hermann, Andreas; Semb, Olof; Stenberg, Erica; Nackberg, Simona; Dorst, Johannes; Uttner, Ingo; Häggström, Ann-Cristin; Ludolph, Albert C; Lulé, Dorothée

2018-05-04

Quantitative analysis of decision-making on therapeutic options in different sociocultural context in amyotrophic lateral sclerosis (ALS). ALS patients (n = 244) were consecutively recruited in Germany (n = 83), Poland (n = 83), and Sweden (n = 78) in a prospective cross-cultural study ( www.NEEDSinALS.com ). They were interviewed on preferences for therapeutic techniques including invasive (IV) and non-invasive ventilation (NIV), as well as percutaneous endoscopic gastrostomy (PEG) and on hypothetical termination of these using quantitative questions. Using standardized questionnaires, religiousness, personal values, quality of life, and depressiveness were assessed. NIV was most frequently used in Germany and PEG in Sweden. Swedish patients were most liberal on initiation and termination of PEG, NIV and IV. Polish patients were mostly undecided and were least likely to consider discontinuing supportive management. Current use was partly associated with age, gender and state of physical function; also, financial support explained some variance. Future preferences on therapeutic options from the patient's perspective were also closely associated with cultural factors. The more oriented towards traditional and conservative values, the less likely patients were to decide for invasive therapeutic devices (IV, PEG), the least likely to have ideations to discontinue any device and the more likely to have an undecided attitude. Current use of therapeutic options is determined by medical condition in analogy to clinical guidelines. For future considerations, other factors such as cultural background are crucial, yielding hurdles to be regarded in the implementation of advanced directives in a multicultural environment.

Novel therapeutic options for relapsed hairy cell leukemia.

PubMed

Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

2015-01-01

The majority of patients with hairy cell leukemia (HCL) achieve a response to therapy with cladribine or pentostatin with or without rituximab. However, late relapses can occur. Treatment of relapsed HCL can be difficult due to a poor tolerance to chemotherapy, increased risk of infections and decreased responsiveness to chemotherapy. The identification of BRAFV600E mutations and the role of aberrant MEK kinase and Bruton's tyrosine kinase (BTK) pathways in the pathogenesis of HCL have helped to develop novel targeted therapies for these patients. Currently, the most promising therapeutic strategies for relapsed or refractory HCL include recombinant immunoconjugates targeting CD22 (e.g. moxetumomab pasudotox), BRAF inhibitors such as vemurafenib and B cell receptor signaling kinase inhibitors such as ibrutinib. Furthermore, the VH4-34 molecular variant of classic HCL has been identified to be less responsive to chemotherapy. Herein, we review the results of the ongoing clinical trials and potential future therapies for relapsed/refractory HCL.

New therapeutic options for allergic rhinitis: back to the future with intranasal corticosteroid aerosols.

PubMed

Carr, Warner W

2013-01-01

Under current guidelines, intranasal corticosteroids (INSs) are considered the most effective first-line therapy to improve allergic rhinitis (AR) symptoms and burden of disease. In the late 1980s-1990s, chlorofluorocarbon (CFC)-propelled corticosteroid aerosol nasal sprays formed the standard of care for the treatment of AR. Because of environmental concerns, CFC aerosols were gradually phased out, and aqueous INS formulations of nasal sprays became the standard of care. Although many aqueous INS sprays are available, specific product-related factors can reduce patient adherence to an INS and subsequently reduce treatment efficacy. The purpose of this paper was to review the evolution of AR therapeutics and drug devices and how it may have an effect on patient adherence/compliance and patient satisfaction with current available therapies and show the unmet need to improve INS delivery systems. Although aqueous INSs are effective and well tolerated, use in some patients may be compromised because of patient sensory perception and device preference. A historical review of the evolution of intranasal delivery of INSs was undertaken to provide further insight into improving treatment options for patients with AR. Although the various approved INSs appear to be equivalent in terms of reducing AR disease burden, the method in which an INS is delivered to a patient has significant bearing on the overall success of each specific drug product. Hydrofluoroalkane-propelled INS drug products offer a back-to-the-future delivery approach that may be further tailored to the individual patient's needs. Past experiences and the development of new devices are paving the way toward further therapy choices, ultimately affording health care providers access to the most effective treatments for patients with AR.

The state-of-play and future of antibody therapeutics.

PubMed

Elgundi, Zehra; Reslan, Mouhamad; Cruz, Esteban; Sifniotis, Vicki; Kayser, Veysel

2017-12-01

It has been over four decades since the development of monoclonal antibodies (mAbs) using a hybridoma cell line was first reported. Since then more than thirty therapeutic antibodies have been marketed, mostly as oncology, autoimmune and inflammatory therapeutics. While antibodies are very efficient, their cost-effectiveness has always been discussed owing to their high costs, accumulating to more than one billion dollars from preclinical development through to market approval. Because of this, therapeutic antibodies are inaccessible to some patients in both developed and developing countries. The growing interest in biosimilar antibodies as affordable versions of therapeutic antibodies may provide alternative treatment options as well potentially decreasing costs. As certain markets begin to capitalize on this opportunity, regulatory authorities continue to refine the requirements for demonstrating quality, efficacy and safety of biosimilar compared to originator products. In addition to biosimilars, innovations in antibody engineering are providing the opportunity to design biobetter antibodies with improved properties to maximize efficacy. Enhancing effector function, antibody drug conjugates (ADC) or targeting multiple disease pathways via multi-specific antibodies are being explored. The manufacturing process of antibodies is also moving forward with advancements relating to host cell production and purification processes. Studies into the physical and chemical degradation pathways of antibodies are contributing to the design of more stable proteins guided by computational tools. Moreover, the delivery and pharmacokinetics of antibody-based therapeutics are improving as optimized formulations are pursued through the implementation of recent innovations in the field. Copyright © 2016 Elsevier B.V. All rights reserved.

A parasitic helminth-derived peptide that targets the macrophage lysosome is a novel therapeutic option for autoimmune disease.

PubMed

Alvarado, Raquel; O'Brien, Bronwyn; Tanaka, Akane; Dalton, John P; Donnelly, Sheila

2015-02-01

Parasitic worms (helminths) reside in their mammalian hosts for many years. This is attributable, in part, to their ability to skew the host's immune system away from pro-inflammatory responses and towards anti-inflammatory or regulatory responses. This immune modulatory ability ensures helminth longevity within the host, while simultaneously minimises tissue destruction for the host. The molecules that the parasite releases clearly exert potent immune-modulatory actions, which could be exploited clinically, for example in the prophylactic and therapeutic treatment of pro-inflammatory and autoimmune diseases. We have identified a novel family of immune-modulatory proteins, termed helminth defence molecules (HDMs), which are secreted by several medically important helminth parasites. These HDMs share biochemical and structural characteristics with mammalian cathelicidin-like host defence peptides (HDPs), which are significant components of the innate immune system. Like their mammalian counterparts, parasite HDMs block the activation of macrophages via toll like receptor (TLR) 4 signalling, however HDMs are significantly less cytotoxic than HDPs. HDMs can traverse the cell membrane of macrophages and enter the endolysosomal system where they reduce the acidification of lysosomal compartments by inhibiting vacuolar (v)-ATPase activity. In doing this, HDMs can modulate critical cellular functions, such as cytokine secretion and antigen processing/presentation. Here, we review the role of macrophages, specifically their lysosomal mediated activities, in the initiation and perpetuation of pro-inflammatory immune responses. We also discuss the potential of helminth defence molecules (HDMs) as therapeutics to counteract the pro-inflammatory responses underlying autoimmune disease. Given the current lack of effective, non-cytotoxic treatment options to limit the progression of autoimmune pathologies, HDMs open novel treatment avenues. Crown Copyright © 2014. Published by

Precision cut lung slices as test system for candidate therapeutics in organophosphate poisoning.

PubMed

Herbert, Julia; Thiermann, Horst; Worek, Franz; Wille, Timo

2017-08-15

Standard therapeutic options in organophosphate (OP) poisoning are limited to the administration of atropine and oximes, a regimen often lacking in efficacy and applicability. Treatment alternatives are needed, preferably covering a broad spectrum of OP intoxications. Although recent research yielded several promising compounds, e.g. bioscavengers, modulators of the muscarinic acetylcholine (ACh) receptor or bispyridinium non-oximes, these substances still need further evaluation, especially regarding effects on the potentially lethal respiratory symptoms of OP poisoning. Aim of this study was the development of an applicable and easy method to test the therapeutic efficiency of such substances. For this purpose, airway responsiveness in viable precision cut lung slices (PCLS) from rats was analysed. We showed that ACh-induced airway contractions were spontaneously reversible in non-poisoned PCLS, whereas in OP poisoned PCLS, contractions were irreversible. This effect could be antagonized by addition of the standard therapeutic atropine, thereby presenting a clear indication for treatment efficiency. Now, candidate therapeutic compounds can be evaluated, based on their ability to counteract the irreversible airway contraction in OP poisoned PCLS. Copyright © 2017 Elsevier B.V. All rights reserved.

[Orophagyngeal Dysphagia in Older Persons - Evaluation and Therapeutic Options].

PubMed

Wirth, Rainer; Lueg, Gero; Dziewas, Rainer

2018-02-01

The prevalence of oropharyngeal dysphagia in older persons is high. Because it is frequently undetected, screening tests should be applied in risk groups. If the screening test is positive or typical risk factors are present, an instrumental assessment should be utilized. Objective diagnostic tools such as endoscopic evaluation and videofluoroscopy allow the description of the individual dysphagia pattern, which is the basis for an individualized treatment. The endoscopic evaluation of swallowing is increasingly used because it includes several advantages. Potential therapeutic strategies are multifaceted. The evidence for the effectiveness of adaptive, compensatory and rehabilitative strategies is growing, supporting the evolution of dysphagia therapy to an evidence based treatment. © Georg Thieme Verlag KG Stuttgart · New York.

An Update on Clinical Burden, Diagnostic Tools, and Therapeutic Options of Staphylococcus aureus

PubMed Central

Reddy, Prakash Narayana; Srirama, Krupanidhi; Dirisala, Vijaya R

2017-01-01

Staphylococcus aureus is an important pathogen responsible for a variety of diseases ranging from mild skin and soft tissue infections, food poisoning to highly serious diseases such as osteomyelitis, endocarditis, and toxic shock syndrome. Proper diagnosis of pathogen and virulence factors is important for providing timely intervention in the therapy. Owing to the invasive nature of infections and the limited treatment options due to rampant spread of antibiotic-resistant strains, the trend for development of vaccines and antibody therapy is increasing at rapid rate than development of new antibiotics. In this article, we have discussed elaborately about the host-pathogen interactions, clinical burden due to S aureus infections, status of diagnostic tools, and treatment options in terms of prophylaxis and therapy. PMID:28579798

FGFR-targeted therapeutics for the treatment of breast cancer.

PubMed

De Luca, Antonella; Frezzetti, Daniela; Gallo, Marianna; Normanno, Nicola

2017-03-01

Breast cancer is a complex disease and several molecular drivers regulate its progression. Fibroblast growth factor receptor (FGFR) signaling is frequently deregulated in many cancers, including breast cancer. Due the involvement of the FGFR/FGF axis in the pathogenesis and progression of tumors, FGFR-targeted agents might represent a potential therapeutic option for breast cancer patients. Areas covered: This review offers an overview of targeted agents against FGFRs and their clinical development in breast cancer. The most relevant literature and the latest studies in the Clinicaltrial.com database have been discussed. Expert opinion: FGFR inhibition has been recently considered as a promising therapeutic option for different tumor types. However, preliminary results of clinical trials of FGFR inhibitors in breast cancer have been quite disappointing. In order to increase the clinical benefit of FGFR therapies in breast cancer, future studies should focus on: understanding the role of the various FGFR aberrations in cancer progression; identifying potential biomarkers to select patients that could benefit of FGFR inhibitors and developing therapeutic strategies that improve the efficacy of these agents and minimize toxicities.

Automated (Centrifugal) therapeutic plasma exchange option for guillain-barre syndrome: A report from Calabar, Nigeria.

PubMed

Iheanacho, O E; Chimeziem, C; Sachais, B S; Shi, P A

2017-10-01

Therapeutic plasma exchange (TPE) is performed frequently and effectively in developed countries, whereas the reverse is the case in developing countries. Guillain-Barre syndrome (GBS), synonymous with acute inflammatory demyelinating polyneuropathy, is an important indication for TPE, but this is rarely administered in the treatment of such patients in Nigeria due to lack of such automated facility, limited expertise, and high cost. This report therefore presents an uncommon case of GBS in which automated TPE was utilized in the management, with the aims of highlighting the current status and challenges of therapeutic apheresis services in Nigeria. A 42-year-old male presented with rapidly progressive (in an ascending fashion) paralysis of all four limbs within 24 h without any preceding history of fever or other symptoms. Clinical examination revealed a young man, afebrile, not pale, and also not dehydrated. Central nervous system examination showed a conscious man, alert, and oriented in time, person, and place. There were no signs of meningeal irritation and the cranial nerves were grossly intact. There was no power in the limbs: global hypotonia and areflexia were noted on examination. However, he had intact sensory perceptions to touch and pain. Following a diagnosis of GBS, he was treated with four sessions of plasmapheresis and TPE. The TPE session was done using a discontinuous flow apheresis machine which exchanged one plasma volume (3 L of plasma) and 5% albumin used for replacement. The patient made gradual but steady recovery as return of power to the upper limbs and trunk started by the 2nd week of treatment. TPE is an important treatment modality in the management of GBS as well as several other conditions, and it is becoming increasingly available in Nigeria. However, it is still grossly underutilized, thus the need for more therapeutic apheresis facilities and trained personnel, in addition to concerted efforts to subsidize the cost of accessing

Addition of flexible body option to the TOLA computer program. Part 2: User and programmer documentation

NASA Technical Reports Server (NTRS)

Dick, J. W.; Benda, B. J.

1975-01-01

User and programmer oriented documentation for the flexible body option of the Takeoff and Landing Analysis (TOLA) computer program are provided. The user information provides sufficient knowledge of the development and use of the option to enable the engineering user to successfully operate the modified program and understand the results. The programmer's information describes the option structure and logic enabling a programmer to make major revisions to this part of the TOLA computer program.

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

PubMed

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.

Stem cell-based therapies in Parkinson's disease: future hope or current treatment option?

PubMed

Loewenbrück, Kai; Storch, Alexander

2011-05-01

Parkinson's disease (PD) is one of the most frequent neurodegenerative diseases and represents a major therapeutic challenge because of the so far missing therapeutic means to influence the ongoing loss of dopaminergic innervation to the striatum. Cell replacement has raised hope to offer the first restorative treatment option. Clinical trials have provided "proof of principle" that transplantation of dopamine-producing neurons into the striatum of PD patients can achieve symptomatic relief given that the striatum is sufficiently re-innervated. Various cell sources have been tested, including fetal ventral midbrain tissue, embryonic stem cells, fetal and adult neural stem cells and, after a ground-breaking discovery, induced pluripotent stem cells. Although embryonic and induced pluripotent stem cells have emerged as the most promising candidates to overcome most of the obstacles to clinical successful cell replacement, each cell source has its unique drawbacks. This review does not only provide a comprehensive overview of the different cellular candidates, including their assets and drawbacks, but also of the various additional issues that need to be addressed in order to convert cellular replacement therapies from an experimental to a clinically relevant therapeutic alternative.

48 CFR 217.207 - Exercise of options.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

48 CFR 217.207 - Exercise of options.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

48 CFR 217.207 - Exercise of options.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

48 CFR 217.207 - Exercise of options.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Exercise of options. 217.207 Section 217.207 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Exercise of options. (c) In addition to the requirements at FAR 17.207(c), exercise an option only after...

[Adipose-derived stromal cells (ASC) - basics and therapeutic approaches in otorhinolaryngology].

PubMed

Frölich, K; Hagen, R; Kleinsasser, N

2014-06-01

Adipose-derived Stromal Cells (ASC) - Basics and Therapeutic Approaches in Otorhinolaryngology Mesenchymal stem cells from adipose tissue can be easily harvested with less discomfort, low donor-site morbidity and high amount compared to bone marrow-derived stem cells. Due to their multilineage differentiation potential in various cell types, immunmodulatory properties and their capability to enhance wound healing, ASC are a promising cell source for tissue engineering approaches and regenerative medicine. They are characterized by the expression of specific surface marker proteins and their differentiation potential into the mesenchymal lineages. Whereas only preclinical studies are published for otorhinolaryngology-related therapeutic options using ASC, various diseases, for instance graft-versus-host disease, have already been treated with ASC in single cases or clinical trials. Safety and genomic stability of ASC as well as the risk of spontaneous malignant transformation are still disputed. This review summarizes the current literature on characterization and anatomic localization of ASC. In addition, beside the presentation of preclinical studies concerning therapeutic approaches in otorhinolaryngology as well as of current clinical applications, the issue of safety of ASC in human stem cell therapy is discussed. © Georg Thieme Verlag KG Stuttgart · New York.

Neuron-directed autoimmunity in the central nervous system: entities, mechanisms, diagnostic clues, and therapeutic options.

PubMed

Melzer, Nico; Meuth, Sven G; Wiendl, Heinz

2012-06-01

The human central nervous system (CNS) can mistakenly be the target of adaptive cellular and humoral immune responses causing both functional and structural impairment. We here provide an overview of neuron-directed autoimmunity as a novel class of inflammatory CNS disorders, their differential diagnoses, clinical hallmarks, imaging features, characteristic laboratory, electrophysiological, cerebrospinal fluid and neuropathological findings, cellular and molecular disease mechanisms, as well as therapeutic options. A growing number of immune-mediated CNS disorders of both autoimmune and paraneoplastic origin have emerged, in which neurons seem to be the target of the immune response. Antibodies binding to a variety of synaptic and extrasynaptic antigens located on the neuronal surface membrane can define distinct entities. Clinically, these disorders are characterized by subacute CNS-related [and sometimes peripheral nervous system (PNS)-related] symptoms involving a variety of cortical and subcortical gray matter areas, which often reflect the expression pattern and function of the respective target antigen. Antibodies seem to be pathogenic and cause (reversible) disturbance of synaptic transmission and neuronal excitability by selective functional inhibition or crosslinking and internalization of their antigen in the absence of overt cytotoxicity, at least at early disease stages. Whether at later disease stages antibody-mediated cytotoxicity, cytotoxic CD8+ T cells, or other detrimental immune mechanisms contribute to neuronal impairment is unclear at present. Adaptive humoral autoimmunity directed to neuronal cell-surface antigens offers first and unique insights and provokes further investigation into the systemic, cellular, and molecular consequences of immune-mediated disruption of distinct neuronal signaling pathways within the living human CNS.

Sleep Physiology, Abnormal States, and Therapeutic Interventions

PubMed Central

Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

2012-01-01

Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

40 CFR 80.163 - Detergent certification options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Detergent certification options. 80... options. To be used to satisfy the detergency requirements under § 80.161(a), a detergent additive must be certified in accordance with the requirements of one or more of the options and suboptions described in this...

Multiple Administrations of 64Cu-ATSM as a Novel Therapeutic Option for Glioblastoma: a Translational Study Using Mice with Xenografts.

PubMed

Yoshii, Yukie; Matsumoto, Hiroki; Yoshimoto, Mitsuyoshi; Zhang, Ming-Rong; Oe, Yoko; Kurihara, Hiroaki; Narita, Yoshitaka; Jin, Zhao-Hui; Tsuji, Atsushi B; Yoshinaga, Keiichiro; Fujibayashi, Yasuhisa; Higashi, Tatsuya

2018-02-01

Glioblastoma is the most aggressive malignant brain tumor in humans and is difficult to cure using current treatment options. Hypoxic regions are frequently found in glioblastoma, and increased levels of hypoxia are associated with poor clinical outcomes of glioblastoma patients. Hypoxia plays important roles in the progression and recurrence of glioblastoma because of drug delivery deficiencies and induction of hypoxia-inducible factor-1α in tumor cells, which lead to poor prognosis. We focused on a promising hypoxia-targeted internal radiotherapy agent, 64 Cu-diacetyl-bis (N 4 -methylthiosemicarbazone) ( 64 Cu-ATSM), to address the need for additional treatment for glioblastoma. This compound can target the overreduced state under hypoxic conditions within tumors. Clinical positron emission tomography studies using radiolabeled Cu-ATSM have shown that Cu-ATSM accumulates in glioblastoma and its uptake is associated with high hypoxia-inducible factor-1α expression. To evaluate the therapeutic potential of this agent for glioblastoma, we examined the efficacy of 64 Cu-ATSM in mice bearing U87MG glioblastoma tumors. Administration of single dosage (18.5, 37, 74, 111, and 148 MBq) and multiple dosages (37 MBq × 4) of 64 Cu-ATSM was investigated. Single administration of 64 Cu-ATSM in high-dose groups dose-dependently inhibited tumor growth and prolonged survival, with slight and reverse signs of adverse events. Multiple dosages of 64 Cu-ATSM remarkably inhibited tumor growth and prolonged survival. By splitting the dose of 64 Cu-ATSM, no adverse effects were observed. Our findings indicate that multiple administrations of 64 Cu-ATSM have effective antitumor effects in glioblastoma without side effects, indicating its potential for treating this fatal disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

New therapeutic options for the metabolic syndrome: what's next?

PubMed

Flordellis, Christodoulos S; Ilias, Ioannis; Papavassiliou, Athanasios G

2005-08-01

The metabolic syndrome (MSX), characterized by obesity, insulin resistance, dyslipidemia and hypertension, increases the risk of cardiovascular morbidity and mortality. It has recently been hypothesized that MSX and type 2 diabetes are caused by triglyceride and long-chain fatty acid accumulation in liver, muscle, pancreatic islets and selected brain areas. This lipocentric approach is integrated with analysis of inflammation associated with end-organ damage, including the vascular wall. Genes and proteins contributing to insulin resistance, beta cell dysfunction and vascular wall damage have been identified. Transcription factors and coactivators, including peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator-1 are crucial in mediating insulin resistance and accelerating vascular wall inflammation, and represent promising therapeutic targets. New pharmacological strategies include dual PPARalpha/gamma agonists, drugs with pleiotropic effects or combination therapies.

Novel treatment options for portal hypertension

PubMed Central

Laleman, Wim

2017-01-01

Abstract Portal hypertension is most frequently associated with cirrhosis and is a major driver for associated complications, such as variceal bleeding, ascites or hepatic encephalopathy. As such, clinically significant portal hypertension forms the prelude to decompensation and impacts significantly on the prognosis of patients with liver cirrhosis. At present, non-selective β-blockers, vasopressin analogues and somatostatin analogues are the mainstay of treatment but these strategies are far from satisfactory and only target splanchnic hyperemia. In contrast, safe and reliable strategies to reduce the increased intrahepatic resistance in cirrhotic patients still represent a pending issue. In recent years, several preclinical and clinical trials have focused on this latter component and other therapeutic avenues. In this review, we highlight novel data in this context and address potentially interesting therapeutic options for the future. PMID:28533907

Therapeutic cloning and tissue engineering.

PubMed

Koh, Chester J; Atala, Anthony

2004-01-01

A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

Treatment options for moderate-to-very severe chronic obstructive pulmonary disease.

PubMed

Cazzola, Mario; Rogliani, Paola; Ora, Josuel; Matera, Maria Gabriella

2016-01-01

The appropriate drug management of COPD is still based on the use of bronchodilators, possibly associated with an anti-inflammatory agent. However, there are still fundamental questions that require clarification to optimise their use and major unmet clinical needs that must be addressed. The advances obtained with the pharmacological options currently consolidated and the different approaches that are often used in an attempt to respond to unmet therapeutic needs are reviewed Expert opinion: In view of the unsatisfactory status of current treatments for COPD, there is an urgent need for alternative and more effective therapeutic approaches that will help to relieve patient symptoms and affect the natural course of COPD, inhibiting chronic inflammation and reversing the disease process or preventing its progression. However, new pharmacologic options have proved difficult to develop. Therefore, it is mandatory to optimize the use of the treatment options at our disposal. However, there are still fundamental questions regarding their use, including the step-up and step-down pharmacological approach, that require clarification to optimise the use of these drugs. It is likely that phenotyping COPD patients would help in identifying the right treatment for each COPD patient and improve the effectiveness of therapies.

Early invasive cervical cancer during pregnancy: different therapeutic options to preserve fertility.

PubMed

Ferraioli, Domenico; Ferriaoli, Domenico; Buenerd, Annie; Marchiolè, Pierangelo; Constantini, Sergio; Venturini, Pier Luigi; Mathevet, Patrice

2012-06-01

Cervical cancer is the second most common cancer diagnosed during pregnancy. Conservative management is possible, and different options should be discussed with patients. The main decision parameters are stage of disease, lymph node status, trimester of pregnancy and wishes of the patient. We reviewed our experience on cases of early-stage cervical cancer discovered during pregnancy and treated with different options of fertility-sparing management. Between 1990 and 2010, 5 patients with early-stage cervical cancer diagnosed during pregnancy were referred to our department for fertility-sparing treatment. The mean age at diagnosis was 28.6 years (range, 26-30 years). The stages of the tumors according to the International Federation of Gynecology and Obstetrics were IA2 in 2 women and IB1 in 3 women. The histological type was squamous carcinoma in 3 cases and adenocarcinoma in 2 cases. All patients willing to preserve their fertility were treated with vaginal radical trachelectomy (VRT) and pelvic lymph nodes dissection (PLN-D). Three procedures were performed in the first trimester: 1 patient was treated with medical abortion and then VRT and PLN-D, 2 patients were submitted to VRT and PLN-D during the first trimester, and 1 patient's case was complicated by spontaneous abortion. One patient was observed during the second trimester (20 weeks of gestation) and treated with VRT and PLN-D during pregnancy. Because this patient had pelvic lymph nodes positive for cancer, a cesarean delivery (CD) with radical hysterectomy and para-aortic lymph nodes dissection was performed followed by chemoradiotherapy. The last patient was evaluated during the third trimester of her pregnancy. Treatment included CD followed by VRT and PLN-D, which was delayed, to allow fetal maturity. Diagnosis of cervical cancer can occur during pregnancy. Different options of fertility-sparing treatment can be discussed on the basis of several factors: tumor stage, gestational age, and the patient

Clinical research and the development of medical therapeutics.

PubMed

Antman, Elliott M

2014-01-01

Clinical research plays a central role in the development of medical therapeutics, but the current system is estimated to take 10-15 years from initial discovery to regulatory approval, at a cost of approximately US$1 billion. Contrast the paths by which 2 anticoagulant options for atrial fibrillation were discovered and ultimately established as treatment options in clinical medicine. Warfarin was discovered by serendipity and compared with placebo in relatively small trials; this was associated with a low cost of development. The new oral anticoagulants were synthesized to provide highly specific, targeted inhibition of critical steps in the coagulation system. They were compared with warfarin for prevention of stroke and systemic embolic events in large, phase 3 trials; this resulted in very expensive development programs. Neither of these paths is desirable for future development of therapeutics. We need to focus on innovative approaches at the preclinical level (systems approach, greater use of inducible pluripotent stem cells, use of novel bioengineering platforms) and clinical trial level (adaptive design, greater use of new and emerging technology). Focusing on disruptive innovations for development of medical therapeutics has the potential to bring us closer to the goal of precision medicine where safer, more effective treatments are discovered in a more efficient system.

Therapeutic potential of the original incretin hormone glucose-dependent insulinotropic polypeptide: diabetes, obesity, osteoporosis and Alzheimer's disease?

PubMed

Irwin, Nigel; Gault, Victor; Flatt, Peter R

2010-09-01

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that potentiates nutrient-induced insulin release. To date, the physiological importance of GIP has received much less attention than its younger sister incretin hormone glucagon-like peptide-1. Thus, it is worthwhile to refocus on this important and somewhat neglected incretin hormone. The potential role of GIP as a treatment option for type 2 diabetes is highlighted. Furthermore, the use of GIP as a new therapeutic option for obesity, osteoporosis and cognitive impairment is also considered. Long-acting GIP receptor agonists offer a potential new class of antidiabetic drugs. Furthermore, recent observations suggest an as yet untapped potential for GIP agonists in the treatment of osteoporosis and cognitive impairment. In addition, GIP is known to play a role in lipid metabolism and fat deposition. Accordingly, both genetic and chemical ablation of GIP signalling in mice with obesity-diabetes can protect against, or reverse, many of the obesity-associated metabolic disturbances. This review focuses on preclinical data generated to date. GIP-based therapeutics have potential for the treatment of type 2 diabetes and obesity, with the possibility of further beneficial actions in osteoporosis and cognitive decline.

Intuition, subjectivity, and Le bricoleur: cancer patients' accounts of negotiating a plurality of therapeutic options.

PubMed

Broom, Alex

2009-08-01

Cancer patients are now combining complementary and alternative medicine (CAM) with biomedical cancer treatments, reflecting an increasingly pluralistic health care environment. However, there has been little research done on the ways in which cancer patients juggle multiplicity in claims to expertise, models of disease, and therapeutic practice. Drawing on the accounts of cancer patients who use CAM, in this article I develop a conceptualization of therapeutic decision making, utilizing the notion of bricolage as a key point of departure. The patient accounts illustrate the "piecing together" (or bricolage) of therapeutic trajectories, drawing on intuitive, embodied knowledge, as well as formalized "objective" scientific expertise. Le bricoleur, as characterized here, actively mediates, rather than accepts or rejects CAM or biomedicine, and utilizes a combination of scientific expertise, embodied physicality, and social knowledge to make decisions and assess therapeutic effectiveness. Although these "border crossings" are potentially subversive of established biomedical expertise, the analysis also illustrates the structural constraints (and penalties) associated with bricolage, and furthermore, the interplay of a repositioning of responsibility with neoliberal forms of self-governance.

78 FR 38843 - Single Application Option

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-28

... Application Option AGENCY: U.S. Copyright Office, Library of Congress. ACTION: Interim final rule. SUMMARY: The U.S. Copyright Office is amending its regulations on an interim basis in order to establish a new... an additional option for individual authors/claimants registering a single (one) work that is not a...

Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

PubMed Central

Li, Qi; Wang, Wei; Machino, Yusuke; Yamada, Tadaaki; Kita, Kenji; Oshima, Masanobu; Sekido, Yoshitaka; Tsuchiya, Mami; Suzuki, Yui; Nan-ya, Ken-ichiro; Iida, Shigeru; Nakamura, Kazuyasu; Iwakiri, Shotaro; Itoi, Kazumi; Yano, Seiji

2015-01-01

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. PMID:25421609

New therapeutic solutions for Behçet's syndrome.

PubMed

Vitale, Antonio; Rigante, Donato; Lopalco, Giuseppe; Emmi, Giacomo; Bianco, Maria Teresa; Galeazzi, Mauro; Iannone, Florenzo; Cantarini, Luca

2016-07-01

Behçet's syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of potential clinical manifestations with no gold-standard therapy. However, the recent classification of BS at a crossroads between autoimmune and autoinflammatory syndromes has paved the way to new further therapeutic opportunities in addition to anti-tumor necrosis factor agents. This review provides a digest of all current experience and evidence about pharmacological agents recently described as having a role in the treatment of BS, including interleukin (IL)-1 inhibitors, tocilizumab, rituximab, alemtuzumab, ustekinumab, interferon-alpha-2a, and apremilast. IL-1 inhibitors currently represent the most studied agents among the latest treatment options for BS, proving to be effective, safe and with an acceptable retention on treatment. However, since BS is a peculiar disorder with clinical features responding to certain treatments that in turn can worsen other manifestations, identifying new treatment options for patients unresponsive to the current drug armamentarium is of great relevance. A number of agents have been studied in the last decade showing changing fortunes in some cases and promising results in others. The latter will potentially provide their contribution for better clinical management of BS, improving patients' quality of life and long-term outcome.

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases.

PubMed

Frentzas, Sophia; Simoneau, Eve; Bridgeman, Victoria L; Vermeulen, Peter B; Foo, Shane; Kostaras, Eleftherios; Nathan, Mark; Wotherspoon, Andrew; Gao, Zu-Hua; Shi, Yu; Van den Eynden, Gert; Daley, Frances; Peckitt, Clare; Tan, Xianming; Salman, Ayat; Lazaris, Anthoula; Gazinska, Patrycja; Berg, Tracy J; Eltahir, Zak; Ritsma, Laila; Van Rheenen, Jacco; Khashper, Alla; Brown, Gina; Nystrom, Hanna; Sund, Malin; Van Laere, Steven; Loyer, Evelyne; Dirix, Luc; Cunningham, David; Metrakos, Peter; Reynolds, Andrew R

2016-11-01

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.

Inhalation delivery of protein therapeutics.

PubMed

Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

2013-04-01

Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

Constipation: Pathophysiology and Current Therapeutic Approaches.

PubMed

Sharma, Amol; Rao, Satish

2017-01-01

addition of sensory retraining. Our understanding of the pathophysiology of STC is evolving. The advent of high-resolution colonic manometry allows for the improved identification of colonic motor patterns and may provide further insight into pathophysiological mechanisms. In a minority of cases of STC, identification of colonic neuropathy suggests a medically refractory condition, warranting consideration of colectomy. The pathophysiology of IBS-C is poorly understood with multiple etiological factors implicated. Pharmacological advances in the treatment of primary constipation have added therapeutic options to the armamentarium of this disorder. Drug development in the secretagogue, serotonergic prokinetic, and ileal bile acid transporter inhibition pathways has yielded current and future medical treatment options for primary chronic constipation.

Avian Diagnostic and Therapeutic Antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bradley, David Sherman

2012-12-31

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

Nanotechnology—novel therapeutics for CNS disorders

PubMed Central

Srikanth, Maya; Kessler, John A.

2013-01-01

Research into treatments for diseases of the CNS has made impressive strides in the past few decades, but therapeutic options are limited for many patients with CNS disorders. Nanotechnology has emerged as an exciting and promising new means of treating neurological disease, with the potential to fundamentally change the way we approach CNS-targeted therapeutics. Molecules can be nanoengineered to cross the blood–brain barrier, target specific cell or signalling systems, respond to endogenous stimuli, or act as vehicles for gene delivery, or as a matrix to promote axon elongation and support cell survival. The wide variety of available nanotechnologies allows the selection of a nanoscale material with the characteristics best suited to the therapeutic challenges posed by an individual CNS disorder. In this Review, we describe recent advances in the development of nanotechnology for the treatment of neurological disorders—in particular, neurodegenerative disease and malignant brain tumours—and for the promotion of neuroregeneration. PMID:22526003

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction.

PubMed

Inatomi, Osamu; Bamba, Shigeki; Shioya, Makoto; Mochizuki, Yosuke; Ban, Hiromitsu; Tsujikawa, Tomoyuki; Saito, Yasuharu; Andoh, Akira; Fujiyama, Yoshihide

2013-02-14

Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy.

Periprosthetic Joint Infection of Shoulder Arthroplasties: Diagnostic and Treatment Options

PubMed Central

Sevelda, Florian

2017-01-01

Periprosthetic joint infection (PJI) is one of the most frequent reasons for painful shoulder arthroplasties and revision surgery of shoulder arthroplasties. Cutibacterium acnes (Propionibacterium acnes) is one of the microorganisms that most often causes the infection. However, this slow growing microorganism is difficult to detect. This paper presents an overview of different diagnostic test to detect a periprosthetic shoulder infection. This includes nonspecific diagnostic tests and specific tests (with identifying the responsible microorganism). The aspiration can combine different specific and nonspecific tests. In dry aspiration and suspected joint infection, we recommend a biopsy. Several therapeutic options exist for the treatment of PJI of shoulder arthroplasties. In acute infections, the options include leaving the implant in place with open debridement, septic irrigation with antibacterial fluids like octenidine or polyhexanide solution, and exchange of all removable components. In late infections (more than four weeks after implantation) the therapeutic options are a permanent spacer, single-stage revision, and two-stage revision with a temporary spacer. The functional results are best after single-stage revisions with a success rate similar to two-stage revisions. For single-stage revisions, the microorganism should be known preoperatively so that specific antibiotics can be mixed into the cement for implantation of the new prosthesis and specific systemic antibiotic therapy can be applied to support the surgery. PMID:29423407

Future therapeutic directions; new medications and insulin delivery in a changing world for effective diabetes management.

PubMed

Modi, Pankaj

2009-09-01

Insulin remains a key to the management of diabetes. The early addition of insulin to oral therapy in type-2 patients is recognized as an effective option that can help improve glycemic control and reduces the complications and contribute to more favorable outcomes. Controlling blood glucose levels within acceptable limits is crucial to the long-term health of patients with diabetes. The benefits of patient education and chronic disease management tools cannot be underestimated as many patients will require education and help in initiation of insulin therapy to achieve glycemic targets. The wide choice of insulin formulations and the ever-expanding range of delivery methods are now available. These methods made insulin administration easier, less painful, more discreet, and more accurate than ever before thus providing important tools to overcome barriers to insulin initiation and improve achievement of glycemic goals. In addition, exciting developments in newer therapeutics have increased the potential for optimal glycemic control. This review discusses how these approaches can help patients manage their diabetes effectively by considering new insulin formulations and delivery devices and newer therapeutics.

Tissue engineering applications of therapeutic cloning.

PubMed

Atala, Anthony; Koh, Chester J

2004-01-01

Few treatment options are available for patients suffering from diseased and injured organs because of a severe shortage of donor organs available for transplantation. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for replacement therapy. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure.

An antidote approach to reduce risk and broaden utility of antibody-based therapeutics.

PubMed

Portnoff, Alyse D; Gao, Cuihua; Borrok, M Jack; Gao, Xizhe; Gao, Changshou; Rainey, G Jonah

2017-05-19

Antibody therapeutics offer effective treatment options for a broad range of diseases. One of the greatest benefits of antibody therapeutics is their extraordinarily long serum half-life, allowing infrequent dosing with long-lasting effects. A characteristic of antibodies that drives long half-life is the ability to interact with the recycling receptor, FcRn, in a pH-dependent manner. The benefit of long half-life, however, carries with it liabilities. Although the positive effects of antibody therapeutics are long-lasting, any acute adverse events or chronic negative impacts, such as immunosuppression in the face of an infection, are also long-lasting. Therefore, we sought to develop antibodies with a chemical handle that alone would enjoy the long half-life of normal antibodies but, upon addition of a small-molecule antidote, would interact with the chemical handle and inhibit the antibody recycling mechanism, thus leading to rapid degradation and shortened half-life in vivo Here we present a proof of concept study where we identify sites to incorporate a non-natural amino acid that can be chemically modified to modulate FcRn interaction in vitro and antibody half-life in vivo This is an important first step in developing safer therapeutics, and the next step will be development of technology that can perform the modifying chemistry in vivo . © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Pharmacological treatment options for cryopyrin-associated periodic syndromes.

PubMed

Landmann, Emmanuelle C; Walker, Ulrich A

2017-08-01

Cryopyrin-associated periodic syndromes (CAPS) are rare monogenic autoinflammatory diseases, comprising a spectrum of phenotypes of varying severity. CAPS are associated with gain-of-function mutations in the NLRP3 inflammasome, a multiprotein complex critical for the activation of IL-1ß, and are characterized by episodes of fever, urticaria-like rash, musculoskeletal, ocular, and neurological symptoms. Areas covered: Accounting for the pivotal role of IL-1ß in the pathogenesis of CAPS, three therapeutic options, all blocking the action of IL-1ß, are currently approved: anakinra, a recombinant IL-1 receptor antagonist, the IL-1 trap rilonacept and canakinumab, a monoclonal anti-IL-1ß antibody. All agents reduce or even resolve clinical symptoms, biochemical activity markers and improve quality of life in CAPS. This review also covers pharmacokinetic, pharmacodynamic and safety aspects of the approved drugs and the potential utility of IL-1β blockers in a wide range of other conditions with an autoinflammatory component. Expert commentary: Due to the success story of current pharmaceutics, the therapeutic options in CAPS are not expected to expand in the near future. Prospective observational studies are needed to confirm long-term efficacy and sustained benefit. New IL-1ß blockers will likely address unmet clinical needs in other autoinflammatory conditions.

Context-dependent decisions among options varying in a single dimension.

PubMed

Morgan, Kate V; Hurly, T Andrew; Bateson, Melissa; Asher, Lucy; Healy, Susan D

2012-02-01

Contrary to theories of rational choice, adding alternatives to a choice set can change the choices made by both humans and animals. This is usually done by adding an inferior decoy to a choice set of two favoured options that are characterized on two distinct dimensions. We presented wild, free-living rufous hummingbirds (Selasphorus rufus) with choices between two or three options that varied in a single dimension only. The options varied in concentration, in volume or in corolla length. When the options varied in concentration, the addition of a medium option to a choice set of a low and a high concentration caused birds to increase their preference for the high option. However, they decreased their preference for the high concentration option when a low option was added to a choice set of high and medium concentrations. When the options varied only in volume, the addition of a high volume option to a choice set of low and medium options decreased the birds' preference for the medium option. We saw no effects of adding a third option when the options varied in corolla length alone. Hummingbirds, then, make context-dependent decisions even when the options vary in only a single dimension although which effect occurs seems to depend on the dimension being manipulated. None of the current theories alone adequately explain these results. Copyright © 2011 Elsevier B.V. All rights reserved.

The potential for emerging therapeutic options for Clostridium difficile infection

PubMed Central

Mathur, Harsh; Rea, Mary C; Cotter, Paul D; Ross, R Paul; Hill, Colin

2014-01-01

Clostridium difficile is mainly a nosocomial pathogen and is a significant cause of antibiotic-associated diarrhea. It is also implicated in the majority of cases of pseudomembranous colitis. Recently, advancements in next generation sequencing technology (NGS) have highlighted the extent of damage to the gut microbiota caused by broad-spectrum antibiotics, often resulting in C. difficile infection (CDI). Currently the treatment of choice for CDI involves the use of metronidazole and vancomycin. However, recurrence and relapse of CDI, even after rounds of metronidazole/vancomycin administration is a problem that must be addressed. The efficacy of alternative antibiotics such as fidaxomicin, rifaximin, nitazoxanide, ramoplanin and tigecycline, as well as faecal microbiota transplantation has been assessed and some have yielded positive outcomes against C. difficile. Some bacteriocins have also shown promising effects against C. difficile in recent years. In light of this, the potential for emerging treatment options and efficacy of anti-C. difficile vaccines are discussed in this review. PMID:25564777

Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma.

PubMed

Li, Qi; Wang, Wei; Machino, Yusuke; Yamada, Tadaaki; Kita, Kenji; Oshima, Masanobu; Sekido, Yoshitaka; Tsuchiya, Mami; Suzuki, Yui; Nan-Ya, Ken-ichiro; Iida, Shigeru; Nakamura, Kazuyasu; Iwakiri, Shotaro; Itoi, Kazumi; Yano, Seiji

2015-01-01

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics

PubMed Central

Puchalska, Patrycja; Crawford, Peter A.

2017-01-01

Ketone body metabolism is a central node in physiological homeostasis. In this review, we discuss how ketones serve discrete fine-tuning metabolic roles that optimize organ and organism performance in varying nutrient states, and protect from inflammation and injury in multiple organ systems. Traditionally viewed as metabolic substrates enlisted only in carbohydrate restriction, recent observations underscore the importance of ketone bodies as vital metabolic and signaling mediators when carbohydrates are abundant. Complementing a repertoire of known therapeutic options for diseases of the nervous system, prospective roles for ketone bodies in cancer have arisen, as have intriguing protective roles in heart and liver, opening therapeutic options in obesity-related and cardiovascular disease. Controversies in ketone metabolism and signaling are discussed to reconcile classical dogma with contemporary observations. PMID:28178565

Amelogenesis imperfecta: therapeutic strategy from primary to permanent dentition across case reports.

PubMed

Toupenay, Steve; Fournier, Benjamin Philippe; Manière, Marie-Cécile; Ifi-Naulin, Chantal; Berdal, Ariane; de La Dure-Molla, Muriel

2018-06-15

Hereditary enamel defect diseases are regrouped under the name "Amelogenesis Imperfecta" (AIH). Both dentitions are affected. Clinical expression is heterogeneous and varies between patients. Mutations responsible for this multigene disease may alter various genes and the inheritance can be either autosomal dominant or recessive, or X-linked. Until now, no therapeutic consensus has emerged for this rare disease. The purpose of this article was to report treatments of AIH patients from childhood to early adulthood. Treatment of three patients of 3, 8 16 years old are described. Each therapeutic option was discussed according to patients' age and type of enamel alteration. Paediatric crowns and resin based bonding must be preferred in primary teeth. In permanent teeth, non-invasive or minimally invasive dentistry should be the first choice in order to follow a therapeutic gradient from the less invasive options to prosthodontic treatments. Functional and aesthetic issues require patients to be treated; this clinical care should be provided as early as possible to enable a harmonious growth of the maxillofacial complex and to prevent pain.

The expanding spectrum of paroxysmal movement disorders: update from clinical features to therapeutics.

PubMed

McGovern, Eavan M; Roze, Emmanuel; Counihan, Timothy J

2018-05-15

This review will discuss the expanding clinical spectrum of paroxysmal movement disorders and therapeutic options in light of emerging genotypic heterogeneity in these conditions. Paroxysmal movement disorders comprise a heterogeneous group of rare neurological conditions characterized by intermittent episodes of abnormal movement associated with various triggers. As the clinical and genotypic spectrum of these disorders evolves, so also has the range of therapeutic options. Triheptanoin has recently been shown to be a very promising alternative to the ketogenic diet in paroxysmal exercise-induced dyskinesia. Four-aminopyridine is now considered first-line symptomatic therapy for episodic ataxia type-2, with pre-clinical findings indicating cerebellar neuroprotection. In light of the newly emerging therapies, careful clinical phenotyping is needed to ensure diagnostic precision and timely initiation of appropriate therapies.

Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases?

PubMed

Abreu, Soraia C; Weiss, Daniel J; Rocco, Patricia R M

2016-04-14

Extracellular vesicles (EVs) are plasma membrane-bound fragments released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. EVs derived from MSCs and other cell types transfer molecules (such as DNA, proteins/peptides, mRNA, microRNA, and lipids) and/or organelles with reparative and anti-inflammatory properties to recipient cells. The paracrine anti-inflammatory effects promoted by MSC-derived EVs have attracted significant interest in the regenerative medicine field, including for potential use in lung injuries. In the present review, we describe the characteristics, biological activities, and mechanisms of action of MSC-derived EVs. We also review the therapeutic potential of EVs as reported in relevant preclinical models of acute and chronic respiratory diseases, such as pneumonia, acute respiratory distress syndrome, asthma, and pulmonary arterial hypertension. Finally, we discuss possible approaches for potentiating the therapeutic effects of MSC-derived EVs so as to enable use of this therapy in clinical practice.

Therapeutic cloning applications for organ transplantation.

PubMed

Koh, Chester J; Atala, Anthony

2004-04-01

A severe shortage of donor organs available for transplantation in the United States leaves patients suffering from diseased and injured organs with few treatment options. Scientists in the field of tissue engineering apply the principles of cell transplantation, material science, and engineering to construct biological substitutes that will restore and maintain normal function in diseased and injured tissues. Therapeutic cloning, where the nucleus from a donor cell is transferred into an enucleated oocyte in order to extract pluripotent embryonic stem cells, offers a potentially limitless source of cells for tissue engineering applications. The present chapter reviews recent advances that have occurred in therapeutic cloning and tissue engineering and describes applications of these new technologies that may offer novel therapies for patients with end-stage organ failure. Copyright 2004 Elsevier B.V.

Threaded biliary inside stents are a safe and effective therapeutic option in cases of malignant hilar obstruction

PubMed Central

2013-01-01

Background Although endoscopic biliary stents have been accepted as part of palliative therapy for cases of malignant hilar obstruction, the optimal endoscopic management regime remains controversial. In this study, we evaluated the safety and efficacy of placing a threaded stent above the sphincter of Oddi (threaded inside plastic stents, threaded PS) and compared the results with those of other stent types. Methods Patients with malignant hilar obstruction, including those requiring biliary drainage for stent occlusion, were selected. Patients received either one of the following endoscopic indwelling stents: threaded PS, conventional plastic stents (conventional PS), or metallic stents (MS). Duration of stent patency and the incident of complication were compared in these patients. Results Forty-two patients underwent placement of endoscopic indwelling stents (threaded PS = 12, conventional PS = 17, MS = 13). The median duration of threaded PS patency was significantly longer than that of conventional PS patency (142 vs. 32 days; P = 0.04, logrank test). The median duration of threaded PS and MS patency was not significantly different (142 vs. 150 days, P = 0.83). Stent migration did not occur in any group. Among patients who underwent threaded PS placement as a salvage therapy after MS obstruction due to tumor ingrowth, the median duration of MS patency was significantly shorter than that of threaded PS patency (123 vs. 240 days). Conclusions Threaded PS are safe and effective in cases of malignant hilar obstruction; moreover, it is a suitable therapeutic option not only for initial drainage but also for salvage therapy. PMID:23410217

Targeted disruption of FANCC and FANCG in human cancer provides a preclinical model for specific therapeutic options.

PubMed

Gallmeier, Eike; Calhoun, Eric S; Rago, Carlo; Brody, Jonathan R; Cunningham, Steven C; Hucl, Tomas; Gorospe, Myriam; Kohli, Manu; Lengauer, Christoph; Kern, Scott E

2006-06-01

How specifically to treat pancreatic and other cancers harboring Fanconi anemia gene mutations has raised great interest recently, yet preclinical studies have been hampered by the lack of well-controlled human cancer models. We endogenously disrupted FANCC and FANCG in a human adenocarcinoma cell line and determined the impact of these genes on drug sensitivity, irradiation sensitivity, and genome maintenance. FANCC and FANCG disruption abrogated FANCD2 monoubiquitination, confirming an impaired Fanconi anemia pathway function. On treatment with DNA interstrand-cross-linking agents, FANCC and FANCG disruption caused increased clastogenic damage, G2/M arrest, and decreased proliferation. The extent of hypersensitivity varied among agents, with ratios of inhibitory concentration 50% ranging from 2-fold for oxaliplatin to 14-fold for melphalan, a drug infrequently used in solid tumors. No hypersensitivity was observed on gemcitabine, etoposide, 3-aminobenzamide, NU1025, or hydrogen peroxide. FANCC and FANCG disruption also resulted in increased clastogenic damage on irradiation, but only FANCG disruption caused a subsequent decrease in relative survival. Finally, FANCC and FANCG disruption increased spontaneous chromosomal breakage, supporting the role of these genes in genome maintenance and likely explaining why they are mutated in sporadic cancer. Our human cancer cell model provides optimal controls to elucidate fundamental biologic features of individual Fanconi anemia gene defects and facilitates preclinical studies of therapeutic options. The impact of Fanconi gene defects on drug and irradiation sensitivity renders these genes promising targets for a specific, genotype-based therapy for individual cancer patients, providing a strong rationale for clinical trials.

Targeting IFN-λ: therapeutic implications.

PubMed

Eslam, Mohammed; George, Jacob

2016-12-01

Type-III interferons (IFN-λ), the most recently discovered family of IFNs, shares common features with other family members, but also has many distinctive activities. IFN-λ uniquely has a different receptor complex, and a more focused pattern of tissue expression and signaling effects, from other classes of IFNs. Multiple genome-wide association studies (GWAS) and subsequent validation reports suggest a pivotal role for polymorphisms near the IFNL3 gene in hepatitis C clearance and control, as also for several other epithelial cell tropic viruses. Apart from its antiviral activity, IFN-λ possesses anti-tumor, immune-inflammatory and homeostatic functions. The overlapping effects of IFN-λ with type I IFN, with a restricted tissue expression pattern renders IFN-λ an attractive therapeutic target for viral infection, cancer and autoimmune diseases, with limited side effects. Areas covered: This review will summarize the current and future therapeutic opportunities offered by this most recently discovered family of interferons. Expert opinion: Our knowledge on IFN-λ is rapidly expanding. Though there are many remaining questions and challenges that require elucidation, the unique characteristics of IFN-λ increases enthusiasm that multiple therapeutic options will emerge.

Therapeutic Vaccination for HPV Induced Cervical Cancers

PubMed Central

Brinkman, Joeli A.; Hughes, Sarah H.; Stone, Pamela; Caffrey, Angela S.; Muderspach, Laila I.; Roman, Lynda D.; Weber, Jeffrey S.; Kast, W. Martin

2007-01-01

Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence. PMID:17627067

[LifeVest - a novel treatment option prior to implantable cardioverter defibrillator].

PubMed

Mustafić, Hazrije; Karimzadeh, Soran; Park, Chan-Il

2017-03-01

Implantable cardioverter defibrillation has taken a predominant place in secondary and primary preventions of sudden rhythmic cardiac death in high-risk patients. However, in certain clinical situations, the implantation of definitive system should be postponed. The LifeVest, a portable external cardiac defibrillator system, has emerged as a novel therapeutic option before a final decision.

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

PubMed

Johnston, Atholl

2010-04-01

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

Therapeutic applications of hydrogels in oral drug delivery

PubMed Central

Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

2015-01-01

Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

Recent developments in emerging therapeutic targets of osteoarthritis.

PubMed

Sun, Margaret Man-Ger; Beier, Frank; Pest, Michael A

2017-01-01

Despite the tremendous individual suffering and socioeconomic burden caused by osteoarthritis, there are currently no effective disease-modifying treatment options. This is in part because of our incomplete understanding of osteoarthritis disease mechanism. This review summarizes recent developments in therapeutic targets identified from surgical animal models of osteoarthritis that provide novel insight into osteoarthritis pathology and possess potential for progression into preclinical studies. Several candidate pathways and processes that have been identified include chondrocyte autophagy, growth factor signaling, inflammation, and nociceptive signaling. Major strategies that possess therapeutic potential at the cellular level include inhibiting autophagy suppression and decreasing reactive oxygen species (ROS) production. Cartilage anabolism and prevention of cartilage degradation has been shown to result from growth factor signaling modulation, such as TGF-β, TGF-α, and FGF; however, the results are context-dependent and require further investigation. Pain assessment studies in rodent surgical models have demonstrated potential in employing anti-NGF strategies for minimizing osteoarthritis-associated pain. Studies of potential therapeutic targets in osteoarthritis using animal surgical models are helping to elucidate osteoarthritis pathology and propel therapeutics development. Further studies should continue to elucidate pathological mechanisms and therapeutic targets in various joint tissues to improve overall joint health.

To be targeted: is the magic bullet concept a viable option for synthetic nucleic acid therapeutics?

PubMed

Ogris, Manfred; Wagner, Ernst

2011-07-01

Nucleic acids offer the possibility of tailor-made, individualized treatments for genetic disorders, infectious diseases, and cancer. As an alternative to viral vectors, synthetic delivery systems have a potentially improved safety profile, but often lack sufficient efficiency especially when applied in vivo. Receptor targeting of synthetic vectors can improve the specificity of the vector and increase the efficiency of nucleic acid delivery to the target site. This review covers recent concepts for targeted DNA and RNA delivery to organs like liver and lung, and also to solid cancers. Syntheses and applications of delivery systems targeted with proteins, peptides, and small molecules as ligands coupled to polymeric or lipidic nucleic acid carriers are reviewed. Therapeutic concepts for treatment of genetic and infectious diseases are explained. Systemic treatment regimens of metastasized malignancies in combination with chemotherapy and radiation have already been successfully applied in preclinical studies. In addition, a first clinical study in the human application of a targeted synthetic carrier has been performed.

48 CFR 552.217-71 - Notice Regarding Option(s).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Notice Regarding Option(s... Notice Regarding Option(s). As prescribed in 517.208(b), insert the following provision: Notice Regarding Option(s) (NOV 1992) The General Services Administration (GSA) has included an option to [Insert...

Current and Novel Therapeutic Options for Irritable Bowel Syndrome Management

PubMed Central

Camilleri, Michael; Andresen, Viola

2009-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder affecting up to 3-15% of the general population in western countries. It is characterized by unexplained abdominal pain, discomfort, and bloating in association with altered bowel habits. The pathophysiology of IBS is multifactorial involving disturbances of the brain-gut-axis. The pathophysiology provides the rationale for pharmacotherapy: abnormal gastrointestinal motor functions, visceral hypersensitivity, psychosocial factors, autonomic dysfunction, and mucosal immune activation. Understanding the mechanisms, and their mediators or modulators including neurotransmitters and receptors have led to several therapeutic approaches including agents acting on the serotonin receptor or serotonin transporter system, antidepressants, novel selective anticholinergics, α-adrenergic agonists, opioid agents, cholecystokinin-antagonists, neurokinin-antagonists, somatostatin receptor agonists, corticotropin releasing factor antagonists, chloride-channel activators, guanylate-cyclase-c agonists, melatonin, atypical benzodiazepines, antibiotics, immune modulators and probiotics. The mechanisms and current evidence regarding efficacy of these agents are reviewed. PMID:19665953

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

Shukla, Prashant; Rao, G Madhava; Pandey, Gitu; Sharma, Shweta; Mittapelly, Naresh; Shegokar, Ranjita; Mishra, Prabhat Ranjan

2014-01-01

Sepsis is a clinical syndrome characterized by a multisystem response to a pathogenic assault due to underlying infection that involves a combination of interconnected biochemical, cellular and organ–organ interactive networks. After the withdrawal of recombinant human-activated protein C (rAPC), researchers and physicians have continued to search for new therapeutic approaches and targets against sepsis, effective in both hypo- and hyperinflammatory states. Currently, statins are being evaluated as a viable option in clinical trials. Many agents that have shown favourable results in experimental sepsis are not clinically effective or have not been clinically evaluated. Apart from developing new therapeutic molecules, there is great scope for for developing a variety of drug delivery strategies, such as nanoparticulate carriers and phospholipid-based systems. These nanoparticulate carriers neutralize intracorporeal LPS as well as deliver therapeutic agents to targeted tissues and subcellular locations. Here, we review and critically discuss the present status and new experimental and clinical approaches for therapeutic intervention in sepsis. PMID:24977655

Delirium and Antipsychotics: A Systematic Review of Epidemiology and Somatic Treatment Options

PubMed Central

2008-01-01

Delirium is a very common medical condition encountered throughout the world and, undoubtedly, is one of the most frequent reasons psychiatrists are consulted by primary care physicians. Recognizing delirium and treating the underlying medical cause are the first steps in the management of this potentially fatal syndrome. The selection of an appropriate medication to target the perceptual, behavioral, and cognitive abnormalities is crucial. In addition to several of the older, typical antipsychotics, which have been found to be effective for the treatment of delirium, some of the newer, atypical antipsychotic agents have been demonstrated to be efficacious. This paper will review both the typical and atypical antipsychotics with the best evidence for efficacy and safety in the treatment of delirium. Finally, environmental treatments are discussed to present the full armamentarium of therapeutic options available to the practicing clinician. PMID:19724721

Imaging enabled platforms for development of therapeutics

NASA Astrophysics Data System (ADS)

Celli, Jonathan; Rizvi, Imran; Blanden, Adam R.; Evans, Conor L.; Abu-Yousif, Adnan O.; Spring, Bryan Q.; Muzikansky, Alona; Pogue, Brian W.; Finkelstein, Dianne M.; Hasan, Tayyaba

2011-03-01

Advances in imaging and spectroscopic technologies have enabled the optimization of many therapeutic modalities in cancer and noncancer pathologies either by earlier disease detection or by allowing therapy monitoring. Amongst the therapeutic options benefiting from developments in imaging technologies, photodynamic therapy (PDT) is exceptional. PDT is a photochemistry-based therapeutic approach where a light-sensitive molecule (photosensitizer) is activated with light of appropriate energy (wavelength) to produce reactive molecular species such as free radicals and singlet oxygen. These molecular entities then react with biological targets such as DNA, membranes and other cellular components to impair their function and lead to eventual cell and tissue death. Development of PDT-based imaging also provides a platform for rapid screening of new therapeutics in novel in vitro models prior to expensive and labor-intensive animal studies. In this study we demonstrate how an imaging platform can be used for strategizing a novel combination treatment strategy for multifocal ovarian cancer. Using an in vitro 3D model for micrometastatic ovarian cancer in conjunction with quantitative imaging we examine dose and scheduling strategies for PDT in combination with carboplatin, a chemotherapeutic agent presently in clinical use for management of this deadly form of cancer.

Current options for the treatment of pathological scarring.

PubMed

Poetschke, Julian; Gauglitz, Gerd G

2016-05-01

Scarring is the consequence of surgery, trauma or different skin diseases. Apart from fresh, immature scars,that transform into mature scars over the course of would healing and that do not require further treatment,linear hypertrophic scars, widespread hypertrophic scars, keloids and atrophic scars exist. Symptoms like pruritusand pain, stigmatization as well as functional and aesthetic impairments that are very disturbing for the affected patients can bethe basis for the desire for treatment. Today, a multitude of options for the treatment and prevention of scars exists. Topical agents based on silicone or onion extract, intralesional injections of cristalline glucocorticoids (oftentimes in combinationwith cryotherapy) or 5-Fluorouracil as well as ablative and nonablative laser treatment are used. Current guidelines summarize the multitude of available treatment options and the currently available datafor the treating physicians, allowing them to make clear therapy recommendations for every single scar type. Relieving patients of their discomfort and doing their aesthetic demands justice is thus possible. Apart from scar prevention becoming more and more important, the increased use of modernlaser treatment options constitutes a key point in clinical scar treatment. At the same time the attention is turned to evaluating current therapeutic options with the help of contemporary study designs so as to graduallyimprove the level of evidence in scar treatment. © 2016 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.

78 FR 68983 - Cotton Futures Classification: Optional Classification Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

...-AD33 Cotton Futures Classification: Optional Classification Procedure AGENCY: Agricultural Marketing... regulations to allow for the addition of an optional cotton futures classification procedure--identified and known as ``registration'' by the U.S. cotton industry and the Intercontinental Exchange (ICE). In...

Management of hypertriglyceridemia induced acute pancreatitis and therapeutic plasmapheresis : Report of nine cases and review of literature.

PubMed

Uyar, S; Harmandar, F; Kök, M; Taș, Z; Dolu, S; Tokuç, A; Köker, G; Görar, S; Çekin, A H

2017-01-01

Hypertriglyceridemia is one of the rare causes of the acute pancreatitis. The prevalance of hypertriglyceridemia has increased recently due to the changing eating habits, sedentary lifestyle, alcohol consumption, obesity and concomitant diabetes mellitus. Therefore, the frequency of the acute pancreatitis due to hypertriglyceridemia may increase in coming years. Diagnosis of the acute pancreatitis by hypertriglyceridemia can be overlooked easily and may be very severe if untreated accurately on time. In addition to the standard management of pancreatitis, specific treatment for hypertriglyceridemia that is insulin, heparin and anti-hypertriglyceridemic drugs are used. Therapeutic plasmapheresis is the last treatment option and seems the most effective one in this subject through developing device and membrane technologies when we review the current literature. Not only triglycerides but also proinflammatory cytokines and adhesion molecules that play an active role in pathogenesis are removed by plasmapheresis. So, the effectiveness of treatment appears promising. However, the exact pathophysiology of hypertriglyceridemia-induced pancreatitis could not be fully understood and the majority of published experience comes from the case reports and the benefit of randomized clinical trials is not available. Therefore, there are no data about what are the exact indications and when we start therapeutic plasmapheresis in literature. This manuscript describes our hospital experience with treatment options and analyzes reports published recently about plasmapheresis as a treatment modality for hypertriglyceridemia induced acute pancreatitis. © Acta Gastro-Enterologica Belgica.

Anti-diabetic potential of peptides: Future prospects as therapeutic agents.

PubMed

Marya; Khan, Haroon; Nabavi, Seyed Mohammad; Habtemariam, Solomon

2018-01-15

Diabetes mellitus is a metabolic disorder in which the glucose level in blood exceeds beyond the normal level. Persistent hyperglycemia leads to diabetes late complication and obviously account for a large number of morbidity and mortality worldwide. Numerous therapeutic options are available for the treatment of diabetes including insulin for type I and oral tablets for type II, but its effective management is still a dream. To date, several options are under investigation in various research laboratories for efficacious and safer agents. Of them, peptides are currently amongst the most widely investigated potential therapeutic agents whose design and optimal uses are under development. A number of natural and synthetic peptides have so far been found with outstanding antidiabetic effect mediated through diverse mechanisms. The applications of new emerging techniques and drug delivery systems further offer opportunities to achieve the desired target outcomes. Some outstanding peptides in preclinical and clinical studies with better efficacy and safety profile have already been identified. Further detail studies on these peptides may therefore lead to significant clinically useful antidiabetic agents. Copyright © 2017. Published by Elsevier Inc.

Next-Generation Therapeutics for Inflammatory Bowel Disease.

PubMed

Dulai, Parambir S; Sandborn, William J

2016-09-01

Tumor necrosis factor (TNF) antagonists are the cornerstone of therapy for moderately to severely active inflammatory bowel disease (IBD). Although our understanding of pharmacokinetics, pharmacodynamics, and treatment optimization for these agents has evolved considerably over the past decade, a substantial majority of individuals fail to respond or lose response to TNF-antagonists over time. A need therefore remains for efficacious treatment options in these patients. Alternative immunological targets have now been identified, and several novel therapeutic agents are in development for IBD. In this review article, we discuss these novel therapeutic agents, with a particular focus on those demonstrated to be efficacious in phase 2 and 3 clinical trials. We further discuss considerations to be made when integrating these agents into routine practice over the next decade.

Next generation therapeutics for inflammatory bowel disease

PubMed Central

Dulai, Parambir S.; Sandborn, William J.

2018-01-01

Tumor necrosis factor (TNF)-antagonists are the cornerstone of therapy for moderately-severely active inflammatory bowel disease (IBD). Although our understanding of pharmacokinetics, pharmacodynamics, and treatment optimization for these agents has evolved considerably over the past decade, a substantial majority of individuals fail to respond or lose response to TNF-antagonists over time. A need therefore remains for efficacious treatment options in these patients. Alternative immunological targets have now been identified, and several novel therapeutic agents are in development for IBD. In this review article we discuss these novel therapeutic agents, with a particular focus on those demonstrated to be efficacious in phase 2 and 3 clinical trials. We further discuss considerations to be made when integrating these agents into routine practice over the next decade. PMID:27461274

Misremembrance of options past: source monitoring and choice.

PubMed

Mather, M; Shafir, E; Johnson, M K

2000-03-01

This study reveals that when remembering past decisions, people engage in choice-supportive memory distortion. When asked to make memory attributions of options' features, participants made source-monitoring errors that supported their decisions. They tended to attribute, both correctly and incorrectly, more positive features to the option they had selected than to its competitor. In addition, they sometimes attributed, both correctly and incorrectly, more negative features to the nonselected option. This pattern of distortion may be beneficial to people's general well-being, reducing regret for options not taken. At the same time, it is problematic for memory accuracy, for accountability, and for learning from past experience.

Off Label Antiviral Therapeutics for Henipaviruses: New Light Through Old Windows

PubMed Central

Aljofan, Mohamad; Lo, Michael K.; Rota, Paul A.; Michalski, Wojtek P.; Mungall, Bruce A.

2010-01-01

Hendra and Nipah viruses are recently emerged zoonotic paramyxoviruses for which there is no vaccine or protective therapy available. While a number of experimental therapeutics and vaccines have recently been reported, all of these will require lengthy approval processes, limiting their usefulness in the short term. To address the urgent need for henipavirus therapeutics, a number of currently licensed pharmaceuticals have been evaluated for off label efficacy against henipavirus replication in vitro. Initially it was observed that compounds which released intracellular calcium stores induced a potent inhibition of henipaviruses replication, prompting the evaluation of known drugs with a similar effect on calcium mobilisation. Of the eight compounds randomly selected based on existing literature, seven inhibited virus replication in the micromolar range while the remaining compound also inhibited virus replication but only at millimolar concentrations. Pretreatment experiments with various calcium chelators, channel antagonists or endoplasmic reticulum release inhibitors supported a calcium mediated mechanism of action for five of these compounds. The mechanism of antiviral action for the remaining three compounds is currently unknown. Additionally, a number of other modulators of calcium flux, including calcium channel and calmodulin antagonists also exhibited potent antiviral activity in vitro providing a broad range of potential therapeutic options for the treatment of henipavirus infections. Importantly, as many of these compounds are currently licensed drugs, regulatory approval should be a much more streamlined process, with the caveat that appropriate in vivo efficacy can be demonstrated in animal models. PMID:20668647

Potential Therapeutics for Vascular Cognitive Impairment and Dementia.

PubMed

Sun, Miao-Kun

2017-10-16

As the human lifespan increases, the number of people affected by age-related dementia is growing at an epidemic pace. Vascular pathology dramatically affects cognitive profiles, resulting in dementia and cognitive impairment. While vascular dementia itself constitutes a medical challenge, hypoperfusion/vascular risk factors enhance amyloid toxicity and other memory-damaging factors and hasten Alzheimer's disease (AD) and other memory disorders' progression, as well as negatively affect treatment outcome. Few therapeutic options are, however, currently available to improve the prognosis of patients with vascular dementia and cognitive impairment, mixed AD dementia with vascular pathology, or other memory disorders. Emerging evidence, however, indicates that, like AD and other memory disorders, synaptic impairment underlies much of the memory impairment in the cognitive decline of vascular cognitive impairment and vascular dementia. Effective rescues of the memory functions might be achieved through synaptic and memory therapeutics, targeting distinct molecular signaling pathways that support the formation of new synapses and maintaining their connections. Potential therapeutic agents include: 1) memory therapeutic agents that rescue synaptic and memory functions after the brain insults; 2) anti-pathologic therapeutics and an effective management of vascular risk factors; and 3) preventative therapeutic agents that achieve memory therapy through functional enhancement. Their development and potential as clinically effective memory therapeutics for vascular cognitive impairment and dementia are discussed in this review. These therapeutic agents are also likely to benefit patients with AD and/or other types of memory disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention.

PubMed

Cougnoux, Antony; Drummond, Rebecca A; Collar, Amanda L; Iben, James R; Salman, Alexander; Westgarth, Harrison; Wassif, Christopher A; Cawley, Niamh X; Farhat, Nicole Y; Ozato, Keiko; Lionakis, Michail S; Porter, Forbes D

2018-06-15

Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative disorder with limited treatment options. NPC1 is associated with neuroinflammation; however, attempts to therapeutically target neuroinflammation in NPC1 have had mixed success. We show here that NPC1 neuroinflammation is characterized by an atypical microglia activation phenotype. Specifically, Npc1-/- microglia demonstrated altered morphology, reduced levels of lineage markers and a shift toward glycolytic metabolism. Treatment with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a drug currently being studied in a phase 2b/3 clinical trial, reversed all microglia-associated defects in Npc1-/- animals. In addition, impairing microglia mediated neuroinflammation by genetic deletion of IRF8 led to decreased symptoms and increased lifespan. We identified CD22 as a marker of dysregulated microglia in Npc1 mutant mice and subsequently demonstrated that elevated cerebrospinal fluid levels of CD22 in NPC1 patients responds to HPβCD administration. Collectively, these data provide the first in-depth analysis of microglia function in NPC1 and suggest possible new therapeutic approaches.

[Extracorporeal shockwave therapy (ESWT) as therapeutic option in supraspinatus tendon syndrome? One year results of a placebo controlled study].

PubMed

Schmitt, J; Tosch, A; Hünerkopf, M; Haake, M

2002-07-01

Extracorporeal shock wave therapy (ESWT) is seen as a therapeutic option in the treatment of chronic supraspinatus tendinitis by some authors. To test whether ESWT comprising 3 x 2000 pulses with the positive energy flux density ED+ of 0.33 mJ/mm2 is clinically superior to a sham ESWT treatment, a prospective, randomized, single-blinded, placebo-controlled study with an independent observer was performed. Forty patients were treated either by verum ESWT or sham ESWT under local anesthesia. Target criteria were the age-corrected Constant score, pain at rest and during activity on a visual analogue scale, and subjective improvement. Patients who reported no subjective improvement after 12 weeks were deblinded and received verum ESWT if they had belonged to the placebo group (partial crossover). The results of the verum group lie within the range of results for ESWT published by other authors. Patients in the placebo group with local anesthetic showed equally good results. At 12 weeks, and 1 year after intervention, no difference could be found between the verum and placebo groups regarding Constant score, pain, shoulder function, or subjective improvement. The nonresponders to the placebo ESWT continued to show no improvement after receiving verum ESWT. This contradicts a specific ESWT effect. Based on the results of this placebo-controlled study, ESWT appears to have no clinically relevant effect on supraspinatus tendinitis. The study underlines the importance of a control group in evaluating new treatment methods for diseases with unknown natural history.

Language Patterns and Therapeutic Change.

ERIC Educational Resources Information Center

Phoenix, Valdemar G.; Lindeman, Mary L.

Noting that the mental health practitioner needs highly developed linguistic and communicative skills in order to precipitate therapeutic changes, this paper discusses the nature of the contexts of therapeutic interaction. It examines verb tense as a linguistic context marker and shows how various schools of therapy can use it. In addition, it…

Therapeutic relevance of ozone therapy in degenerative diseases: Focus on diabetes and spinal pain.

PubMed

Braidy, Nady; Izadi, Morteza; Sureda, Antoni; Jonaidi-Jafari, Nematollah; Banki, Abdolali; Nabavi, Seyed F; Nabavi, Seyed M

2018-04-01

Ozone, one of the most important air pollutants, is a triatomic molecule containing three atoms of oxygen that results in an unstable form due to its mesomeric structure. It has been well-known that ozone has potent ability to oxidize organic compounds and can induce respiratory irritation. Although ozone has deleterious effects, many therapeutic effects have also been suggested. Since last few decades, the therapeutic potential of ozone has gained much attention through its strong capacity to induce controlled and moderated oxidative stress when administered in precise therapeutic doses. A plethora of scientific evidence showed that the activation of hypoxia inducible factor-1α (HIF-1a), nuclear factor of activated T-cells (NFAT), nuclear factor-erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE), and activated protein-1 (AP-1) pathways are the main molecular mechanisms underlying the therapeutic effects of ozone therapy. Activation of these molecular pathways leads to up-regulation of endogenous antioxidant systems, activation of immune functions as well as suppression of inflammatory processes, which is important for correcting oxidative stress in diabetes and spinal pain. The present study intended to review critically the available scientific evidence concerning the beneficial properties of ozone therapy for treatment of diabetic complications and spinal pain. It finds benefit for integrating the therapy with ozone into pharmacological procedures, instead of a substitutive or additional option to therapy. © 2017 Wiley Periodicals, Inc.

Active targeted delivery of immune therapeutics to lymph nodes.

PubMed

Bahmani, Baharak; Vohra, Ishaan; Kamaly, Nazila; Abdi, Reza

2018-02-01

Organ transplantation is a life-saving procedure and the only option for patients with end-organ failure. Immune therapeutics have been key to the success of organ transplantation. However, immune therapeutics are still unable to eliminate graft rejection and their toxicity has been implicated in poorer long-term transplant outcomes. Targeted nanodelivery has the potential to enhance not only the therapeutic index but also the bioavailability of the immune therapeutics. One of the key sites of immune therapeutics delivery is lymph node where the priming of immune cells occur. The focus of this review is on nanomedicine research to develop the targeted delivery of immune therapeutics to lymph nodes for controlling immune activation. As nanomedicine creates its niche in clinical care, it provides novel immunotherapy platforms for transplant recipients. Draining lymph nodes are the primary loci of immune activation and represent a formidable site for delivery of wide variety of immune therapeutics. There have been relentless efforts to improve the properties of nanomedicines, to have in-depth knowledge of antigen and drug loading, and, finally, to explore various routes of passive and active targeted delivery to lymph nodes. The application of nanotechnology principles in the delivery of immune therapeutics to the lymph node has created enormous excitement as a paradigm shifting approach that enables targeted delivery of a gamut of molecules to achieve a desired immune response. Therefore, innovative strategies that improve their efficacy while reducing their toxicity are among the highest unmet needs in transplantation.

75 FR 29893 - Business Reply Mail Online Application Option

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-28

... POSTAL SERVICE 39 CFR Part 111 Business Reply Mail Online Application Option AGENCY: Postal Service TM . ACTION: Final rule. SUMMARY: The Postal Service TM will revise the Mailing Standards of the... option to obtain a Business Reply Mail[supreg] (BRM) permit online. Additionally, the electronic version...

Impact of Absorption and Transport on Intelligent Therapeutics and Nano-scale Delivery of Protein Therapeutic Agents

PubMed Central

Peppas, Nicholas A.; Carr, Daniel A

2009-01-01

The combination of materials design and advances in nanotechnology has led to the development of new therapeutic protein delivery systems. The pulmonary, nasal, buccal and other routes have been investigated as delivery options for protein therapy, but none result in improved patient compliances and patient quality of life as the oral route. For the oral administration of these new systems, an understanding of protein transport is essential because of the dynamic nature of the gastrointestinal tract and the barriers to transport that exist. Models have been developed to describe the transport between the gastrointestinal lumen and the bloodstream, and laboratory techniques like cell culture provide a means to investigate the absorption and transport of many therapeutic agents. Biomaterials, including stimuli-sensitive complexation hydrogels, have been investigated as promising carriers for oral delivery. However, the need to develop models that accurately predict protein blood concentration as a function of the material structure and properties still exists. PMID:20161384

Therapeutic Options for Controlling Fluids in the Visual System

NASA Technical Reports Server (NTRS)

Curry, Kristina M.; Wotring, Virginia E.

2014-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

ROCK as a therapeutic target for ischemic stroke.

PubMed

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

2017-12-01

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

Management of stage IV rectal cancer: Palliative options

PubMed Central

Ronnekleiv-Kelly, Sean M; Kennedy, Gregory D

2011-01-01

Approximately 30% of patients with rectal cancer present with metastatic disease. Many of these patients have symptoms of bleeding or obstruction. Several treatment options are available to deal with the various complications that may afflict these patients. Endorectal stenting, laser ablation, and operative resection are a few of the options available to the patient with a malignant large bowel obstruction. A thorough understanding of treatment options will ensure the patient is offered the most effective therapy with the least amount of associated morbidity. In this review, we describe various options for palliation of symptoms in patients with metastatic rectal cancer. Additionally, we briefly discuss treatment for asymptomatic patients with metastatic disease. PMID:21412493

Possibility of Exosome-Based Therapeutics and Challenges in Production of Exosomes Eligible for Therapeutic Application.

PubMed

Yamashita, Takuma; Takahashi, Yuki; Takakura, Yoshinobu

2018-01-01

Exosomes are cell-derived vesicles with a diameter 30-120 nm. Exosomes contain endogenous proteins and nucleic acids; delivery of these molecules to exosome-recipient cells causes biological effects. Exosomes derived from some types of cells such as mesenchymal stem cells and dendritic cells have therapeutic potential and may be biocompatible and efficient agents against various disorders such as organ injury. However, there are many challenges for the development of exosome-based therapeutics. In particular, producing exosomal formulations is the major barrier for therapeutic application because of their heterogeneity and low productivity. Development and optimization of producing methods, including methods for isolation and storage of exosome formulations, are required for realizing exosome-based therapeutics. In addition, improvement of therapeutic potential and delivery efficiency of exosomes are important for their therapeutic application. In this review, we summarize current knowledge about therapeutic application of exosomes and discuss some challenges in their successful use.

Age Differences in Consumer Decision Making under Option Framing: From the Motivation Perspective

PubMed Central

Peng, Huamao; Xia, Shiyong; Ruan, Fanglin; Pu, Bingyan

2016-01-01

Option framing effect is the phenomena that participants often accept more options when they are asked to delete undesired options from a full model (subtractive framing) than they do when they are instructed to add desired options to a base model (additive framing). Whether the same effect exists in different age groups is less well known. To explore the roles of age and purchase motivations on the option framing effect for automobiles purchases, this study adopted a 3 (age group: younger, middle-aged, vs. older) × 2 (option framing: additive vs. subtractive) × 2 (focus condition: information vs. emotion) mixed design. To manipulate purchase motivations, participants in the three age groups were instructed to focus on the ratio of utility and price of options (information-focus) or the extent of pleasure induced by the options (emotion-focus) when they made purchase decisions in two framing conditions. The results revealed similar option framing effect across all age groups in the information-focus condition regarding the total price paid for accepted options. In contrast, the framing effect was not found in the emotion-focus condition. In addition, older adults accepted more options and an overall higher price than younger and middle-aged adults in both focus conditions. This difference was more obvious in the emotion-focus condition than in the information-focus condition. Moreover, both the number of accepted options and the total accepted price of the younger group in the information-focus condition were higher than those in the emotion-focus condition, whereas the older and middle-aged groups accepted same number of options and price between two focus conditions. These results imply that purchase motivation is a moderator of the option framing effect and age characteristics linked with motivations must be considered in sales. PMID:27872603

Age Differences in Consumer Decision Making under Option Framing: From the Motivation Perspective.

PubMed

Peng, Huamao; Xia, Shiyong; Ruan, Fanglin; Pu, Bingyan

2016-01-01

Option framing effect is the phenomena that participants often accept more options when they are asked to delete undesired options from a full model (subtractive framing) than they do when they are instructed to add desired options to a base model (additive framing). Whether the same effect exists in different age groups is less well known. To explore the roles of age and purchase motivations on the option framing effect for automobiles purchases, this study adopted a 3 (age group: younger, middle-aged, vs. older) × 2 (option framing: additive vs. subtractive) × 2 (focus condition: information vs. emotion) mixed design. To manipulate purchase motivations, participants in the three age groups were instructed to focus on the ratio of utility and price of options (information-focus) or the extent of pleasure induced by the options (emotion-focus) when they made purchase decisions in two framing conditions. The results revealed similar option framing effect across all age groups in the information-focus condition regarding the total price paid for accepted options. In contrast, the framing effect was not found in the emotion-focus condition. In addition, older adults accepted more options and an overall higher price than younger and middle-aged adults in both focus conditions. This difference was more obvious in the emotion-focus condition than in the information-focus condition. Moreover, both the number of accepted options and the total accepted price of the younger group in the information-focus condition were higher than those in the emotion-focus condition, whereas the older and middle-aged groups accepted same number of options and price between two focus conditions. These results imply that purchase motivation is a moderator of the option framing effect and age characteristics linked with motivations must be considered in sales.

NASA's EOSDIS: options for data providers

NASA Astrophysics Data System (ADS)

Khalsa, Siri J.; Ujhazy, John E.

1995-12-01

EOSDIS, the data and information system being developed by NASA to support interdisciplinary earth science research into the 21st century, will do more than manage and distribute data from EOS-era satellites. It will also promote the exchange of data, tools, and research results across disciplinary, agency, and national boundaries. This paper describes the options that data providers will have for interacting with the EOSDIS Core System (ECS), the infrastructure of EOSDIS. The options include: using the ECS advertising service to announce the availability of data at the provider's site; submitting a candidate data set to one of the Distributed Active Archive Centers (DAACs); establishing a data server that will make the data accessible via ECS and establishing Local Information Manager (LIM) which would make the data available for multi-site searches. One additional option is through custom gateway interfaces which would provide access to existing data archives. The gateway, data server, and LIM options require the implementation of ECS code at the provider site to insure proper protocols. The advertisement and ingest options require no part of ECS design to reside at the provider site.

Biomimetic Particles as Therapeutics

PubMed Central

Green, Jordan J.

2015-01-01

In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

Controlling the spread of carbapenemase-producing Gram-negatives: therapeutic approach and infection control.

PubMed

Carmeli, Y; Akova, M; Cornaglia, G; Daikos, G L; Garau, J; Harbarth, S; Rossolini, G M; Souli, M; Giamarellou, H

2010-02-01

Although the rapid spread of carbapenemase-producing Gram-negatives (CPGNs) is providing the scientific community with a great deal of information about the molecular epidemiology of these enzymes and their genetic background, data on how to treat multidrug-resistant or extended drug-resistant carbapenemase-producing Enterobacteriaceae and how to contain their spread are still surprisingly limited, in spite of the rapidly increasing prevalence of these organisms and of their isolation from patients suffering from life-threatening infections. Limited clinical experience and several in vitro synergy studies seem to support the view that antibiotic combinations should be preferred to monotherapies. But, in light of the data available to date, it is currently impossible to quantify the real advantage of drug combinations in the treatment of these infections. Comprehensive clinical studies of the main therapeutic options, broken down by pathogen, enzyme and clinical syndrome, are definitely lacking and, as carbapenemases keep spreading, are urgently needed. This spread is unveiling the substantial unpreparedness of European public health structures to face this worrisome emergency, although experiences from different countries-chiefly Greece and Israel-have shown that CPGN transmission and cross-infection can cause a substantial threat to the healthcare system. This unpreparedness also affects the treatment of individual patients and infection control policies, with dramatic scarcities of both therapeutic options and infection control measures. Although correct implementation of such measures is presumably cumbersome and expensive, the huge clinical and public health problems related to CPGN transmission, alongside the current scarcity of therapeutic options, seem to fully justify this choice.

Optional games on cycles and complete graphs.

PubMed

Jeong, Hyeong-Chai; Oh, Seung-Yoon; Allen, Benjamin; Nowak, Martin A

2014-09-07

We study stochastic evolution of optional games on simple graphs. There are two strategies, A and B, whose interaction is described by a general payoff matrix. In addition, there are one or several possibilities to opt out from the game by adopting loner strategies. Optional games lead to relaxed social dilemmas. Here we explore the interaction between spatial structure and optional games. We find that increasing the number of loner strategies (or equivalently increasing mutational bias toward loner strategies) facilitates evolution of cooperation both in well-mixed and in structured populations. We derive various limits for weak selection and large population size. For some cases we derive analytic results for strong selection. We also analyze strategy selection numerically for finite selection intensity and discuss combined effects of optionality and spatial structure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Acquired hemophilia A: a review of recent data and new therapeutic options.

PubMed

Franchini, Massimo; Vaglio, Stefania; Marano, Giuseppe; Mengoli, Carlo; Gentili, Sara; Pupella, Simonetta; Liumbruno, Giancarlo Maria

2017-10-01

Acquired hemophilia A (AHA) is a rare, but potentially life-threatening, bleeding disorder caused by an autoantibody against factor VIII that interferes with its coagulant function. We performed a narrative review focusing on the diagnostic aspects of AHA and on the current treatment strategies with particular regard to new data and therapeutic developments. The management of this severe hemorrhagic disorder is based on the control of bleeding with the use of bypassing agents and on the utilization of a variety of immunosuppressant agents with the goal of eliminating the autoantibody permanently. The optimal management of AHA should be multidisciplinary and requires a close collaboration between physicians from various specialties.

Therapeutic Contraindications in Exotic Pets.

PubMed

Petritz, Olivia A; Chen, Sue

2018-05-01

The selection and dosing of medications for exotic pets are often challenging because most drugs are used in an extralabel manner without pharmacokinetic and pharmacodynamic studies. Doses are often extrapolated from common domestic animals and safety data are often lacking in exotic species. Just as the bioavailability and therapeutic levels are different for each species, what may be a safe and commonly used medication in one species can be deadly in another. Various drugs with documented contraindications in certain exotic pet species are outlined in this review and the pathophysiology, clinical signs, and treatment options are described when applicable. Copyright © 2018 Elsevier Inc. All rights reserved.

Comparison between three option, four option and five option multiple choice question tests for quality parameters: A randomized study.

PubMed

Vegada, Bhavisha; Shukla, Apexa; Khilnani, Ajeetkumar; Charan, Jaykaran; Desai, Chetna

2016-01-01

Most of the academic teachers use four or five options per item of multiple choice question (MCQ) test as formative and summative assessment. Optimal number of options in MCQ item is a matter of considerable debate among academic teachers of various educational fields. There is a scarcity of the published literature regarding the optimum number of option in each item of MCQ in the field of medical education. To compare three options, four options, and five options MCQs test for the quality parameters - reliability, validity, item analysis, distracter analysis, and time analysis. Participants were 3 rd semester M.B.B.S. students. Students were divided randomly into three groups. Each group was given one set of MCQ test out of three options, four options, and five option randomly. Following the marking of the multiple choice tests, the participants' option selections were analyzed and comparisons were conducted of the mean marks, mean time, validity, reliability and facility value, discrimination index, point biserial value, distracter analysis of three different option formats. Students score more ( P = 0.000) and took less time ( P = 0.009) for the completion of three options as compared to four options and five options groups. Facility value was more ( P = 0.004) in three options group as compared to four and five options groups. There was no significant difference between three groups for the validity, reliability, and item discrimination. Nonfunctioning distracters were more in the four and five options group as compared to three option group. Assessment based on three option MCQs is can be preferred over four option and five option MCQs.

RNAi therapeutics for brain cancer: current advancements in RNAi delivery strategies.

PubMed

Malhotra, Meenakshi; Toulouse, André; Godinho, Bruno M D C; Mc Carthy, David John; Cryan, John F; O'Driscoll, Caitriona M

2015-10-01

Malignant primary brain tumors are aggressive cancerous cells that invade the surrounding tissues of the central nervous system. The current treatment options for malignant brain tumors are limited due to the inability to cross the blood-brain barrier. The advancements in current research has identified and characterized certain molecular markers that are essential for tumor survival, progression, metastasis and angiogenesis. These molecular markers have served as therapeutic targets for the RNAi based therapies, which enable site-specific silencing of the gene responsible for tumor proliferation. However, to bring about therapeutic success, an efficient delivery carrier that can cross the blood-brain barrier and reach the targeted site is essential. The current review focuses on the potential of targeted, non-viral and viral particles containing RNAi therapeutic molecules as delivery strategies specifically for brain tumors.

Lunar Cube Transfer Trajectory Options

NASA Technical Reports Server (NTRS)

Folta, David; Dichmann, Donald James; Clark, Pamela E.; Haapala, Amanda; Howell, Kathleen

2015-01-01

Numerous Earth-Moon trajectory and lunar orbit options are available for Cubesat missions. Given the limited Cubesat injection infrastructure, transfer trajectories are contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these transfers can be restricted by the selection or designs of Cubesat subsystems such as propulsion or communication. Nonetheless, many trajectory options can b e considered which have a wide range of transfer duration, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several options including deployment from low Earth orbit (LEO) geostationary transfer orbits (GTO) and higher energy direct lunar transfer and the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory.

Lunar Cube Transfer Trajectory Options

NASA Technical Reports Server (NTRS)

Folta, David; Dichmann, Donald J.; Clark, Pamela; Haapala, Amanda; Howell, Kathleen

2015-01-01

Numerous Earth-Moon trajectory and lunar orbit options are available for Cubesat missions. Given the limited Cubesat injection infrastructure, transfer trajectories are contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these transfers can be restricted by the selection or designs of Cubesat subsystems such as propulsion or communication. Nonetheless, many trajectory options can be considered which have a wide range of transfer durations, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several options including deployment from low Earth orbit (LEO), geostationary transfer orbits (GTO), and higher energy direct lunar transfers and the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory.

Emerging molecular therapeutic targets for cholangiocarcinoma.

PubMed

Rizvi, Sumera; Gores, Gregory J

2017-09-01

Cholangiocarcinomas (CCAs) are diverse epithelial tumors arising from the liver or large bile ducts with features of cholangiocyte differentiation. CCAs are classified anatomically into intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). Each subtype has distinct risk factors, molecular pathogenesis, therapeutic options, and prognosis. CCA is an aggressive malignancy with a poor overall prognosis and median survival of less than 2years in patients with advanced disease. Potentially curative surgical treatment options are limited to the subset of patients with early-stage disease. Presently, the available systemic medical therapies for advanced or metastatic CCA have limited therapeutic efficacy. Molecular alterations define the differences in biological behavior of each CCA subtype. Recent comprehensive genetic analysis has better characterized the genomic and transcriptomic landscape of each CCA subtype. Promising candidates for targeted, personalized therapy have emerged, including potential driver fibroblast growth factor receptor (FGFR) gene fusions and somatic mutations in isocitrate dehydrogenase (IDH)1/2 in iCCA, protein kinase cAMP-activated catalytic subunit alpha (PRKACA) or beta (PRKACB) gene fusions in pCCA, and ELF3 mutations in dCCA/ampullary carcinoma. A precision genomic medicine approach is dependent on an enhanced understanding of driver mutations in each subtype and stratification of patients according to their genetic drivers. We review the current genomic landscape of CCA, the potentially actionable molecular aberrations in each CCA subtype, and the role of immunotherapy in CCA. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

How collaboration in therapy becomes therapeutic: the therapeutic collaboration coding system.

PubMed

Ribeiro, Eugénia; Ribeiro, António P; Gonçalves, Miguel M; Horvath, Adam O; Stiles, William B

2013-09-01

The quality and strength of the therapeutic collaboration, the core of the alliance, is reliably associated with positive therapy outcomes. The urgent challenge for clinicians and researchers is constructing a conceptual framework to integrate the dialectical work that fosters collaboration, with a model of how clients make progress in therapy. We propose a conceptual account of how collaboration in therapy becomes therapeutic. In addition, we report on the construction of a coding system - the therapeutic collaboration coding system (TCCS) - designed to analyse and track on a moment-by-moment basis the interaction between therapist and client. Preliminary evidence is presented regarding the coding system's psychometric properties. The TCCS evaluates each speaking turn and assesses whether and how therapists are working within the client's therapeutic zone of proximal development, defined as the space between the client's actual therapeutic developmental level and their potential developmental level that can be reached in collaboration with the therapist. We applied the TCCS to five cases: a good and a poor outcome case of narrative therapy, a good and a poor outcome case of cognitive-behavioural therapy, and a dropout case of narrative therapy. The TCCS offers markers that may help researchers better understand the therapeutic collaboration on a moment-to-moment basis and may help therapists better regulate the relationship. © 2012 The British Psychological Society.

Therapeutic inertia amongst general practitioners with interest in diabetes.

PubMed

Seidu, Samuel; Than, Tun; Kar, Deb; Lamba, Amrit; Brown, Pam; Zafar, Azhar; Hussain, Rizwan; Amjad, Ahmed; Capehorn, Mathew; Martin, Elizabeth; Fernando, Kevin; McMoran, Jim; Millar-Jones, David; Kahn, Shahzada; Campbell, Nigel; Brice, Richard; Mohan, Rahul; Mistry, Mukesh; Kanumilli, Naresh; St John, Joan; Quigley, Richard; Kenny, Colin; Khunti, Kamlesh

2018-02-01

As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p=0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Date Palm Tree (Phoenix dactylifera L.): Natural Products and Therapeutic Options.

PubMed

Al-Alawi, Reem A; Al-Mashiqri, Jawhara H; Al-Nadabi, Jawaher S M; Al-Shihi, Badria I; Baqi, Younis

2017-01-01

Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans ( Coffea ), shows biological activity in the treatment of the central nervous system (CNS) disorders, indole-3-carbinol, and 3,3'-diindolylmethane are both broccoli ( Brassica oleracea ) derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape ( Vitis vinifera ), is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products.

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis

PubMed Central

Blakeley, Jaishri O.; Plotkin, Scott R.

2016-01-01

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded by NF1) and merlin (encoded by NF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1 and LZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations in NF1 (ie, glioblastoma, breast cancer, melanoma), NF2 (ie, meningioma, mesothelioma) and SMARCB1 (ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID:26851632

Update in feline therapeutics: clinical use of 10 emerging therapies.

PubMed

Whitehouse, William; Viviano, Katrina

2015-03-01

The field of veterinary medicine is constantly evolving. New medications are being introduced into clinical practice, and novel uses for established medications are frequently being discovered as new information comes to light. Therapeutic options for our feline patients can be restricted based on inadequate clinical evidence, adverse effects and patient compliance concerns. Additionally, with the reduced availability of commonly used medications in some regions, clinicians are forced to utilize alternatives with which they may have limited experience. This review article is directed towards primary care veterinarians working with feline patients. The selection of medications discussed is based on many of the clinical challenges commonly encountered in practice. The evidence for use of some of these medications is limited due to their novelty. Known mechanisms of action, pharmacokinetic and pharmacodynamics data, adverse effects and clinical uses are reviewed where possible, with clinical recommendations made based on the evidence of data available. © ISFM and AAFP 2015.

Immune checkpoints PVR and PVRL2 are prognostic markers in AML and their blockade represents a new therapeutic option.

PubMed

Stamm, Hauke; Klingler, Felix; Grossjohann, Eva-Maria; Muschhammer, Jana; Vettorazzi, Eik; Heuser, Michael; Mock, Ulrike; Thol, Felicitas; Vohwinkel, Gabi; Latuske, Emily; Bokemeyer, Carsten; Kischel, Roman; Dos Santos, Cedric; Stienen, Sabine; Friedrich, Matthias; Lutteropp, Michael; Nagorsen, Dirk; Wellbrock, Jasmin; Fiedler, Walter

2018-05-31

Immune checkpoints are promising targets in cancer therapy. Recently, poliovirus receptor (PVR) and poliovirus receptor-related 2 (PVRL2) have been identified as novel immune checkpoints. In this investigation we show that acute myeloid leukemia (AML) cell lines and AML patient samples highly express the T-cell immunoreceptor with Ig and ITIM domains (TIGIT) ligands PVR and PVRL2. Using two independent patient cohorts, we could demonstrate that high PVR and PVRL2 expression correlates with poor outcome in AML. We show for the first time that antibody blockade of PVR or PVRL2 on AML cell lines or primary AML cells or TIGIT blockade on immune cells increases the anti-leukemic effects mediated by PBMCs or purified CD3 + cells in vitro. The cytolytic activity of the BiTE® antibody construct AMG 330 against leukemic cells could be further enhanced by blockade of the TIGIT-PVR/PVRL2 axis. This increased immune reactivity is paralleled by augmented secretion of Granzyme B by immune cells. Employing CRISPR/Cas9-mediated knockout of PVR and PVRL2 in MV4-11 cells, the cytotoxic effects of antibody blockade could be recapitulated in vitro. In NSG mice reconstituted with human T cells and transplanted with either MV4-11 PVR/PVRL2 knockout or wildtype cells, prolonged survival was observed for the knockout cells. This survival benefit could be further extended by treating the mice with AMG 330. Therefore, targeting the TIGIT-PVR/PVRL2 axis with blocking antibodies might represent a promising future therapeutic option in AML.

Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics

PubMed Central

Rath, Timo; Baker, Kristi; Dumont, Jennifer A.; Peters, Robert T.; Jiang, Haiyan; Qiao, Shuo-Wang; Lencer, Wayne I.; Pierce, Glenn F.; Blumberg, Richard S.

2016-01-01

Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn–Fc interaction can generate longer-lasting and more effective therapeutics. PMID:24156398

HER2-positive breast cancer: Current and new therapeutic strategies.

PubMed

Escrivá-de-Romaní, Santiago; Arumí, Miriam; Bellet, Meritxell; Saura, Cristina

2018-06-01

Since the identification of the HER2 receptor amplification as an adverse prognostic factor that defined a special subtype of metastatic breast cancer, there has been a substantial improvement in survival of patients affected with this disease due to the development of anti-HER2 targeted therapies. The approval of trastuzumab and pertuzumab associated to a taxane in first line and subsequent treatment with the antibody-drug conjugate T-DM1 has certainly contributed to achieve these outcomes. The Tyrosine Kinase Inhibitor lapatinib was also approved in the basis of an improvement in progression free survival, becoming another commonly used treatment in combination with capecitabine. Inevitably, despite these therapeutic advances most patients progress on therapy due to primary or acquired resistance or because of an incorrect HER2 positivity assessment. Hence, it is crucial to correctly categorize HER2 amplified tumors and define mechanisms of resistance to design effective new treatment approaches. In addition, identifying biomarkers of response or resistance permits to tailor the therapeutic options for each patient sparing them from unnecessary toxicity as well as improving their outcomes. The aim of this review is to examine new strategies in development to treat HER2-positive metastatic breast cancer referring to the mechanisms of action of new drugs and new combinations including results reported so far. Copyright © 2018 Elsevier Ltd. All rights reserved.

Redox Control of Leukemia: From Molecular Mechanisms to Therapeutic Opportunities

PubMed Central

Irwin, Mary E.; Rivera-Del Valle, Nilsa

2013-01-01

Abstract Reactive oxygen species (ROS) play both positive and negative roles in the proliferation and survival of a cell. This dual nature has been exploited by leukemia cells to promote growth, survival, and genomic instability—some of the hallmarks of the cancer phenotype. In addition to altered ROS levels, many antioxidants are dysregulated in leukemia cells. Together, the production of ROS and the expression and activity of antioxidant enzymes make up the primary redox control of leukemia cells. By manipulating this system, leukemia cells gain proliferative and survival advantages, even in the face of therapeutic insults. Standard treatment options have improved leukemia patient survival rates in recent years, although relapse and the development of resistance are persistent challenges. Therapies targeting the redox environment show promise for these cases. This review highlights the molecular mechanisms that control the redox milieu of leukemia cells. In particular, ROS production by the mitochondrial electron transport chain, NADPH oxidase, xanthine oxidoreductase, and cytochrome P450 will be addressed. Expression and activation of antioxidant enzymes such as superoxide dismutase, catalase, heme oxygenase, glutathione, thioredoxin, and peroxiredoxin are perturbed in leukemia cells, and the functional consequences of these molecular alterations will be described. Lastly, we delve into how these pathways can be potentially exploited therapeutically to improve treatment regimens and promote better outcomes for leukemia patients. Antioxid. Redox Signal. 18, 1349–1383. PMID:22900756

Therapeutic options for acute cough due to upper respiratory infections in children.

PubMed

Paul, Ian M

2012-02-01

Cough due to upper respiratory tract infections (URIs) is one of the most frequent complaints encountered by pediatric health-care providers, and one of the most disruptive symptoms for children and families. Despite the frequency of URIs, there is limited evidence to support the few therapeutic agents currently available in the United States (US) to treat acute cough due to URI. Published, well-designed, contemporary research supporting the efficacy of narcotics (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over-the-counter (OTC) oral antitussives and expectorants (dextromethorphan, diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated pediatric cough. Alternatively, honey and topically applied vapor rubs may be effective antitussives.

Treatment options for demodex blepharitis: patient choice and efficacy.

PubMed

Hirsch-Hoffmann, S; Kaufmann, C; Bänninger, P B; Thiel, M A

2015-04-01

Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis. Georg Thieme Verlag KG Stuttgart · New York.

Therapeutic options for lymphangioleiomyomatosis (LAM): where we are and where we are going

PubMed Central

Steagall, Wendy K; Moss, Joel

2009-01-01

Lymphangioleiomyomatosis (LAM), a multisystem disease affecting predominantly premenopausal and middle-aged women, causes progressive respiratory failure due to cystic lung destruction and is associated with lymphatic and kidney tumors. In the past, the treatment of LAM comprised exclusively anti-estrogen and related hormonal therapies. These treatments, however, have not been proven effective. In this article, we discuss new findings regarding the molecular mechanisms involved in the regulation of LAM cell growth, which may offer opportunities to develop effective and targeted therapeutic agents. PMID:20948684

Surgical Options for the Refractive Correction of Keratoconus: Myth or Reality

PubMed Central

Zaldivar, R.; Aiello, F.; Madrid-Costa, D.

2017-01-01

Keratoconus provides a decrease of quality of life to the patients who suffer from it. The treatment used as well as the method to correct the refractive error of these patients may influence on the impact of the disease on their quality of life. The purpose of this review is to describe the evidence about the conservative surgical treatment for keratoconus aiming to therapeutic and refractive effect. The visual rehabilitation for keratoconic corneas requires addressing three concerns: halting the ectatic process, improving corneal shape, and minimizing the residual refractive error. Cross-linking can halt the disease progression, intrastromal corneal ring segments can improve the corneal shape and hence the visual quality and reduce the refractive error, PRK can correct mild-moderate refractive error, and intraocular lenses can correct from low to high refractive error associated with keratoconus. Any of these surgical options can be performed alone or combined with the other techniques depending on what the case requires. Although it could be considered that the surgical option for the refracto-therapeutic treatment of the keratoconus is a reality, controlled, randomized studies with larger cohorts and longer follow-up periods are needed to determine which refractive procedure and/or sequence are most suitable for each case. PMID:29403662

CDK4/6 dual inhibitor abemaciclib demonstrates compelling preclinical activity against esophageal adenocarcinoma: a novel therapeutic option for a deadly disease.

PubMed

Kosovec, Juliann E; Zaidi, Ali H; Omstead, Ashten N; Matsui, Daisuke; Biedka, Mark J; Cox, Erin J; Campbell, Patrick T; Biederman, Robert W W; Kelly, Ronan J; Jobe, Blair A

2017-11-21

Esophageal adenocarcinoma (EAC) is a deadly disease with limited therapeutic options. In the present study, we determined the preclinical efficacy of CDK4/6 inhibitor abemaciclib for treatment of EAC. In vitro , apoptosis, proliferation, and pathway regulation were evaluated in OE19, OE33, and FLO1 EAC cell lines. In vivo , esophagojejunostomy was performed on rats to induce EAC. At 36 weeks post-surgery, MRI and endoscopic biopsy established baseline tumor volume and molecular correlates, respectively. Next, the study animals were randomized to 26mg/kg intraperitoneal abemaciclib treatment or vehicle control for 28 days. Pre and post treatment MRIs, histopathology, and qRT-PCR were utilized to determine response. Our results demonstrated treatment with abemaciclib lead to increased apoptosis, and decreased proliferation in OE19 (p=0.185), OE33 (p=0.048), and FLO1 (p=0.043) with anticipated downstream molecular inhibition. In vivo , 78.9% of treatment animals demonstrated >20% tumor volume decrease (placebo 0%). Mean tumor volume changed in the treatment arm by -65.5% (placebo +133.5%) (p<0.01), and prevalence changed by -37.5% (placebo +16.7%) (p<0.01). Pre vs post treatment qRT-PCR demonstrated significant inhibition of all downstream molecular correlates. Overall our findings suggest potent antitumor efficacy of abemaciclib against EAC with evident molecular pathway inhibition and reasonable safety, establishing the rationale for future clinical development.

Date Palm Tree (Phoenix dactylifera L.): Natural Products and Therapeutic Options

PubMed Central

Al-Alawi, Reem A.; Al-Mashiqri, Jawhara H.; Al-Nadabi, Jawaher S. M.; Al-Shihi, Badria I.; Baqi, Younis

2017-01-01

Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans (Coffea), shows biological activity in the treatment of the central nervous system (CNS) disorders, indole-3-carbinol, and 3,3′-diindolylmethane are both broccoli (Brassica oleracea) derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape (Vitis vinifera), is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products. PMID:28588600

Suppressing ghost beams: Backlink options for LISA

NASA Astrophysics Data System (ADS)

Isleif, K.-S.; Gerberding, O.; Penkert, D.; Fitzsimons, E.; Ward, H.; Robertson, D.; Livas, J.; Mueller, G.; Reiche, J.; Heinzel, G.; Danzmann, K.

2017-05-01

In this article we discuss possible design options for the optical phase reference system, the so called backlink, between two moving optical benches in a LISA satellite. The candidates are based on two approaches: Fiber backlinks, with additional features like mode cleaning cavities and Faraday isolators, and free beam backlinks with angle compensation techniques. We will indicate dedicated ghost beam mitigation strategies for the design options and we will point out critical aspects in case of an implementation in LISA.

Options for the Future of the US National Strong-Motion Program

USGS Publications Warehouse

,

1997-01-01

This report constitutes the requested 'Options Document'. This report considers three options. Option I assumes a constant level of financial support for Operating Expenses (OE) with not additional personnel support. Option II assumes a slight increase in OE support of $150K for FY 99 and beyond. Option III considers the role that a NSMP must play if the nation's urgent need to record the main earthquake at locations of significance for society is to be met. Two parts of Option III are considered. The first part of this option, termed Option III A, considers the role that strong-motion recording in and near man-made structures must play if a near-real time hazard initiative is to be implemented in the United States; The second part of Option III; termed Option III B, considers the scope of a NSMP needed to address society's needs to record the main earthquake in locations of significance for future public earthquake safety.

Transdermal delivery of therapeutic agent

NASA Technical Reports Server (NTRS)

Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

2008-01-01

A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

[Extemporaneous magistral formulas for the topical treatment of pruritus : Proven and new options].

PubMed

Staubach, P; Weisshaar, E

2016-08-01

The treatment of pruritus, primarily chronic pruritus, is often difficult and must be treated simultaneously with the cause of pruritus and the individual demands of the skin. Due to the chronicity, a combination of systemic therapies, different active ingredients and basic formulas must be used in local therapies and adjusted during the course of the treatment. There are still therapeutic gaps, which can be closed by the use of extemporaneous preparations. Magistral formulas, which are already checked for plausibility, should be preferred over individual prescriptions. In the following, different therapeutic options in daily practice by using extemporaneous formulas from the NRF (New German Pharmacopoeia for compounded medications) are presented.

Tackling obesity: new therapeutic agents for assisted weight loss

PubMed Central

Karam, JG; McFarlane, SI

2010-01-01

The pandemic of overweight and obesity continues to rise in an alarming rate in western countries and around the globe representing a major public health challenge in desperate need for new strategies tackling obesity. In the United States nearly two thirds of the population is overweight or obese. Worldwide the number of persons who are overweight or obese exceeded 1.6 billion. These rising figures have been clearly associated with increased morbidity and mortality. For example, in the Framingham study, the risk of death increases with each additional pound of weight gain even in the relatively younger population between 30 and 42 years of age. Overweight and obesity are also associated with increased co-morbid conditions such as diabetes, hypertension and cardiovascular disease as well as certain types of cancer. In this review we discuss the epidemic of obesity, highlighting the pathophysiologic mechanisms of weight gain. We also provide an overview of the assessment of overweight and obese individuals discussing possible secondary causes of obesity. In a detailed section we discuss the currently approved therapeutic interventions for obesity highlighting their mechanisms of action and evidence of their efficacy and safety as provided in clinical trials. Finally, we discuss novel therapeutic interventions that are in various stages of development with a special section on the weight loss effects of anti-diabetic medications. These agents are particularly attractive options for our growing population of obese diabetic individuals. PMID:21437080

Endothelin therapeutics in cancer: Where are we?

PubMed

Rosanò, Laura; Bagnato, Anna

2016-03-15

In human cancers, the autocrine and paracrine loop mediated by the aberrantly activation of endothelin-1 (ET-1) receptor (ET-1R) elicits pleiotropic effects, preferentially mediated by the scaffold protein β-arrestin 1 (β-arr1), on tumor cells and on the host microenvironment, providing a strong rationale for targeting ET-1 receptors. This review describes the most up-to-date preclinical and clinical results obtained by using ET-1 therapeutics. The previous negative clinical results of ET-1 therapeutics should not prevent us from setting the standard of this class of drugs for future well-designed clinical trials. The preclinical data obtained with the dual ETAR and ETBR antagonist macitentan indicate that this molecule, which targets cancer cells and tumor-associated microenvironmental elements, could be a cancer therapeutic option. The field of ET-1 therapeutics will be improved in the next decade, facilitated by the new knowledge on the genomic landscape of the human stroma and tumor, and by the low invasive approaches based on liquid biopsies for the discovery of predictive biomarkers. The information obtained from preclinical studies in patient-derived models and from the Cancer Genome Atlas will set the scene of precision medicine for cancer. Results from these studies are expected to open the possibility that ET-1R antagonists might be more efficacious as molecular cancer therapeutics, able to hamper the functional β-arr1-dependent signaling complexes, either alone or coupled with new targeted approaches. Copyright © 2016 the American Physiological Society.

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel therapeutic approaches in chondrosarcoma.

PubMed

Polychronidou, Genovefa; Karavasilis, Vasilios; Pollack, Seth M; Huang, Paul H; Lee, Alex; Jones, Robin L

2017-03-01

Chondrosarcoma is a malignant tumor of bones, characterized by the production of cartilage matrix. Due to lack of effective treatment for advanced disease, the clinical management of chondrosarcomas is exceptionally challenging. Current research focuses on elucidating the molecular events underlying the pathogenesis of this rare bone malignancy, with the goal of developing new molecularly targeted therapies. Signaling pathways suggested to have a role in chondrosarcoma include Hedgehog, Src, PI3k-Akt-mTOR and angiogenesis. Mutations in IDH1/2, present in more than 50% of primary conventional chondrosarcomas, make the development of IDH inhibitors a promising treatment option. The present review discusses the preclinical and early clinical data on novel targeted therapeutic approaches in chondrosarcoma.

78 FR 75395 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... series expire (``Short Term Option Expiration Dates'') at one time; and (ii) state that additional series... Rule Change, as Modified by Amendment No. 1, Relating to the Short Term Option Series Program December... Exchange's Short Term Option Series Program (``Weeklys Program''). The proposed rule change was published...

Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options.

PubMed

Teschke, Rolf

2018-06-01

Clinicians caring for patients with alcoholic hepatitis (AH) are often confronted with the question of the best pharmacotherapy to be used. Areas covered: This article covers metabolic aspects of alcohol as the basis of understanding pharmacotherapy and to facilitate choosing the drug therapeutic options for patients with severe AH. Expert opinion: Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH) as terms are often used interchangeably in scientific literature but a stringent differentiation is recommended for proper clarity. As opposed to ASH, the clinical course of AH is often severe and requires an effective drug treatment strategy, in addition to absolute alcohol abstinence and nutritional support. Drug options include corticosteroids as a first choice and pentoxifylline, an inhibitor of phosphodiesterase, as a second line therapy, especially in patients with contraindications for a corticosteroid therapy such as infections or sepsis. At seven days under corticosteroids, treatment should be terminated in non-responders, and patients must then be evaluated for liver transplantation. Pentoxifylline is not effective as a rescue therapy for these patients. Other treatments such as infliximab, propylthiouracil, N-acetylcysteine, silymarin, colchicine, insulin and glucagon, oxandrolone, testosterone, and polyunsaturated lecithin are not effective in severe AH. For liver transplantation, few patients will be eligible.

Split high-dose oral levothyroxine treatment as a successful therapy option in myxedema coma.

PubMed

Charoensri, Suranut; Sriphrapradang, Chutintorn; Nimitphong, Hataikarn

2017-10-01

High-dose intravenous thyroxine (T4) is the preferable treatment for myxedema coma. We describe the clinical course of a 69-year-old man who presented with myxedema coma and received oral levothyroxine (LT4) therapy (1 mg) in a split dose. This suggests split high-dose oral LT4 as a therapeutic option in myxedema coma.

Cyanobacterial Treatment Options: Permanganate and ...

EPA Pesticide Factsheets

This presentation will begin with a brief overview of drinking water treatment options for cyanobacteria and their toxins. The treatment discussion will focus on the impacts of permanganate addition to suspensions of toxin-producing Microcystis aeruginosa, followed by powdered activated carbon (PAC) addition. Results will be presented that show changes in toxin concentrations, chlorophyll-a concentrations and cell membrane integrity. The EPA Small Systems Webinar Presentations allow the dissemination of the latest Agency guidance and research to a large geographically dispersed audience while minimizing taxpayer expense

[Hemoglobinopathies. Current therapeutic possibilities].

PubMed

Birgens, H S; Karle, H

1995-05-29

In recent years, the number of immigrants has increased considerably in Denmark. Consequently, a series of new clinical pictures has appeared in the Danish health care system. Typical examples are the genetic diseases, the haemoglobinopathies. Most of the immigrants come from areas, where the gene frequency of these disorders is widely distributed, for instance the Mediterranean countries, the Middle East, Southeast Asia and Africa. Most frequent are the heterozygous thalassaemias, but also the number of patients with severe thalassaemia and other clinically important haemoglobinopathies such as sickle cell anaemia has also increased in recent years. The clinical problems concerning these patients focus on two important topics, namely genetic counselling of heterozygous individuals (in some cases combined with prenatal diagnostics) and the treatment of patients with clinically severe haemoglobinopathy. The only curative treatment of the haemoglobinopathies is allogeneic bone marrow transplantation, but this treatment can only be offered to a few of these patients. However, a variety of therapeutic options exist which can improve their prognosis and quality of life. Since the number of patients with these diseases will probably increase over the next years we find it relevant, based on typical case stories, to give a review of the present therapeutic possibilities for these disorders.

The central nervous system--an additional consideration in 'rotator cuff tendinopathy' and a potential basis for understanding response to loaded therapeutic exercise.

PubMed

Littlewood, Chris; Malliaras, Peter; Bateman, Marcus; Stace, Richmond; May, Stephen; Walters, Stephen

2013-12-01

Tendinopathy is a term used to describe a painful tendon disorder but despite being a well-recognised clinical presentation, a definitive understanding of the pathoaetiology of rotator cuff tendinopathy remains elusive. Current explanatory models, which relate to peripherally driven nocioceptive mechanisms secondary to structural abnormality, or failed healing, appear inadequate on their own in the context of current literature. In light of these limitations this paper presents an extension to current models that incorporates the integral role of the central nervous system in the pain experience. The role of the central nervous system (CNS) is described and justified along with a potential rationale to explain the favourable response to loaded therapeutic exercises demonstrated by previous studies. This additional consideration has the potential to offer a useful way to explain pain to patients, for clinicians to prescribe appropriate therapeutic management strategies and for researchers to advance knowledge in relation to this clinically challenging problem. Copyright © 2013 Elsevier Ltd. All rights reserved.

[CANNABIS AND GLAUCOMA: AN ANCIENT LEGEND OR A NOVEL THERAPEUTIC HORIZON?].

PubMed

Mathalone, Nurit; Wolf, Alvit; Geyer, Orna

2015-06-01

Glaucoma causes damage to the optic nerve and compromises the visual field. The main risk factor of the disease is the level of the intra-ocular pressure. Therapeutic options include medical and surgical treatment, aimed to lower the intra-ocular pressure. Consumption of the cannabis plant (Cannabis Satival has been known since ancient times. It can be consumed orally, topically, intra-venous or by inhalation. The main active ingredient of cannabis is THC (Tetra-Hydro-Cannabinol). One of THC's reported effects is the reduction of intra-ocular pressure. Several studies have demonstrated temporary intra-ocular pressure decrease in both healthy subjects and glaucoma patients following topical application or systemic consumption. The effect was a short term one. It was followed by the development of resistance to the drug after prolonged intake and it was also accompanied by topical and systemic side effects. Cannabis may be considered as a therapeutic option in glaucoma. Its limited effect, development of resistance, acquired side effects and the accompanying psycho-active influence limit its advantage and cause its efficacy to be dubious. Therefore, cannabis treatment for glaucoma currently seems impractical and is not recommended by either the Israeli or the American glaucoma societies.

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

PubMed

Huard, J; Mu, X; Lu, A

2016-08-01

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

Ocular toxocariasis: new diagnostic and therapeutic perspectives.

PubMed

Martínez-Pulgarín, Dayron F; Muñoz-Urbano, Marcela; Gomez-Suta, Luz D; Delgado, Olinda M; Rodriguez-Morales, Alfonso J

2015-01-01

To provide an updated insight of concepts regarding the overview, epidemiology, risk factors, clinical manifestations, diagnosis, treatment and prevention of ocular toxocariasis. Perspective of literature review. Review and synthesis of literature about toxocariasis, with interpretation and perspective. A literature search for "ocular toxocariasis" was performed using PubMed, ScienceDirect, Scopus, SciELO and LILACS databases. Mild to moderate infections are frequently reported in ocular toxocariasis which usually occurs in children and typically presents as unilateral vision impairment, blindness is common and could present invasion of the retina. There are three groups of presentation of toxocariasis (according to the physical examination): chronic endophthalmitis, posterior granuloma and peripheral granuloma. Standard diagnosis of ocular toxocariasis is based on the identification of clinical signs, supported by additional diagnostic methods. Regarding treatment, there is no commonly accepted regimen but most of the authors prefer to use steroids and anthelminthic agents, but nowadays there are no standardized parameters in terms of dosage, duration and route of administration. Surgery has been recommended in some cases. Toxocariasis is still a problem of public health, particularly in developing countries with an increasing epidemiological burden in terms of morbidity and mortality and most of the authors agree on the utmost relevance of its prevention. Clinical experience and suspicion of ophthalmologists make an important role in its diagnosis, but always with supportive diagnostic methods. Additional studies should explore new therapeutic options for toxocariasis.

Dry eye syndrome. Etiological and therapeutic aspects.

PubMed

Apostol, Silvia; Filip, M; Dragne, Carmen; Filip, A

2003-01-01

"Dry eye syndrome" is a common disorder of the tear film that results from inadequate tear production, excessive tear evaporation or abnormality in mucin or lipid components of the tear film. A number of 53 patients suffering from dry eye syndrome were followed up for a period of 18 months. The study group was heterogeneous, including a lot of conditions accompanied by dry eye syndrome: Syogren's syndrome, lupus erythematous, ocular rosacea, patients with systemic treatments with antidepressants, betablockers, diuretics, oral contraceptives, glaucomatous patients with topical beta-blockers, postmenopausal women, aging people, computer users and long-term contact lens wearers. The therapeutical options were dictated by the severity of the syndrome: substitution therapy, treatment of the underlying eyelid diseases, modifying of the environmental conditions and treatment of the complications in the most severe cases. The new pathological approach is innovative and it may provide a real therapeutical measure for this condition: topical A Cyclosporine and androgen drops.

Medical therapeutics: from induction to scientific evolution.

PubMed

Nunes, José Pedro Lopes

2013-01-01

The field of medical therapeutics may be characterized as having suffered major scientific evolution in the last decades. The publication of landmark studies has been important enough to produce shifts in patient care. However, the scientific evolution in this field does not necessarily imply a progressively greater degree of certitude. In fact, it is not uncommon for new knowledge, when reflected in clinical practice, to weaken previous knowledge. In medical therapeutics, strict inductive reasoning implies the existence of empirical intervention data, typically clinical trial data. In many instances, however, such data does not exist-leaving room for a mixture of inductive and "pseudo-deductive" reasoning. It is often necessary to establish treatment on the basis of incomplete and inconclusive information, more so when the clinical situation is grave, but when no valid information exists, no treatment may be an option. In many instances, the rule "I wish not to impose on others" has superseded the concept "Do not impose on others what you yourself do not desire."

Novel unconventional therapeutic approaches to atopic eczema.

PubMed

Worm, M; Henz, B M

2000-01-01

Atopic eczema is a chronic, recurrent, multifactorial skin disease, and, accordingly, there are numerous therapeutic options for its symptomatic treatment. Conventional medications are however often unsatisfactory for many patients because of adverse effects on long-term use. For this reason, patients often readily welcome unconventional therapeutic approaches. We present here a selected number of such treatment modalities, namely gamma-linolenic acid, Chinese herbal tea, diets eliminating allergens, pseudoallergens, metal salts and sodium, and bioresonance. When stringent scientific criteria are applied in the evaluation of such study results, none of the reviewed alternative treatments provides unequivocal, convincing evidence of its efficacy, even when double-blind, placebo-controlled studies are available. With Chinese herbal tea, potentially serious adverse effects should be considered as well. Any new type of unconventional therapy should thus be thoroughly evaluated and shown to be equal or superior to conventional treatments with regard to both efficacy and tolerability before it is recommended for use in clinical practice. Copyright 2000 S. Karger AG, Basel.

Achieving the Promise of Therapeutic Extracellular Vesicles: The Devil is in Details of Therapeutic Loading.

PubMed

Sutaria, Dhruvitkumar S; Badawi, Mohamed; Phelps, Mitch A; Schmittgen, Thomas D

2017-05-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics.

SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies.

PubMed

Hayashi, Akinori; Takano, Koji; Kawai, Sayuki; Shichiri, Masayoshi

2016-01-01

Diabetes mellitus complicated with insulin antibodies is rare in clinical practice but usually difficult to control. A high amount of insulin antibodies, especially with low affinity and high binding capacity, leads to unstable glycemic control characterized by hyperglycemia unresponsive to large volume of insulin and unanticipated hypoglycemia. There are several treatment options, such as changing insulin preparation, immunosupression with glucocorticoids, and plasmapheresis, most of which are of limited efficacy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drug which decrease renal glucose reabsorption and lowers plasma glucose level independent of insulin action. We report here a case with diabetes complicated with insulin antibodies who was effectively controlled by an SGLT2 inhibitor. A 47-year-old man with type 2 diabetes treated with insulin had very poor glycemic control characterized by postprandial hyperglycemia unresponsive to insulin therapy and repetitive hypoglycemia due to insulin antibodies. Treatment with ipragliflozin, an SGLT2 inhibitor, improved HbA1c from 8.4% to 6.0% and glycated albumin from 29.4% to 17.9%. Continuous glucose monitoring revealed improvement of glycemic profile (average glucose level from 212 mg/dL to 99 mg/dL and glycemic standard deviation from 92 mg/dL to 14 mg/dL) with disappearance of hypoglycemic events. This treatment further ameliorated the characteristics of insulin antibodies and resulted in reduced insulin requirement. SGLT2 inhibitors may offer an effective treatment option for managing the poor glycemic control in diabetes complicated with insulin antibodies.

[Therapeutic nursing: a systematic review].

PubMed

Lautenschläger, S; Müller, C; Immenschuh, U; Muser, J; Behrens, J

2014-08-01

For some years therapeutic service catalogues have been established in medical rehabilitation which have broadened our previous understanding of nursing actions. Currently, therapeutic nursing plays a prominent role in neurological early rehabilitation because the operations and procedures coding system (OPS) 8-552 within the DRG-System (Diagnosis Related Groups) states that therapeutic nursing must be carried out by specially trained nursing personnel. This requirement leads to inconsistencies in nursing practice and the medical service of the health insurance (MDK) since a definition of therapeutic nursing is lacking. A previous review of therapeutic nursing in 2003 focused primarily on the development of the therapeutic nursing role, but not on therapeutic nursing itself. The following article contains the first systematic review of the current state of research regarding a definition of therapeutic nursing. For this purpose, a systematic study was conducted to examine if there are, nationally or internationally, any definitions of therapeutic nursing and to identify what the therapeutic aspects of nursing are. The research included following database; Medline, Cinahl and Embase. Additionally, a research by hand of several German journals as well as textbooks and specialized literature was carried out. 5 studies were selected which define the term "therapeutic nursing". Among these are one review, one primary study, one theoretical discussion and one dissertation. Further twenty four studies were identified which do not define the term, but are closely related to the subject, and use or characterize the term in various contexts. The publications examined provided indications of duties, interventions and roles nurses should perform, but not how to carry these out, nor what is therapeutic about the nursing. At the same time, the low number of studies reveals that therapeutic nursing has barely been examined and demonstrates the lack of theoretically grounding

Role and Therapeutic Targeting of the HGF/MET Pathway in Glioblastoma

PubMed Central

Cruickshanks, Nichola; Zhang, Ying; Yuan, Fang; Pahuski, Mary; Gibert, Myron; Abounader, Roger

2017-01-01

Glioblastoma (GBM) is a lethal brain tumor with dismal prognosis. Current therapeutic options, consisting of surgery, chemotherapy and radiation, have only served to marginally increase patient survival. Receptor tyrosine kinases (RTKs) are dysregulated in approximately 90% of GBM; attributed to this, research has focused on inhibiting RTKs as a novel and effective therapy for GBM. Overexpression of RTK mesenchymal epithelial transition (MET), and its ligand, hepatocyte growth factor (HGF), in GBM highlights a promising new therapeutic target. This review will discuss the role of MET in cell cycle regulation, cell proliferation, evasion of apoptosis, cell migration and invasion, angiogenesis and therapeutic resistance in GBM. It will also discuss the modes of deregulation of HGF/MET and their regulation by microRNAs. As the HGF/MET pathway is a vital regulator of multiple pro-survival pathways, efforts and strategies for its exploitation for GBM therapy are also described. PMID:28696366

Myocardial Energetics and Heart Failure: a Review of Recent Therapeutic Trials.

PubMed

Bhatt, Kunal N; Butler, Javed

2018-06-01

Several novel therapeutics being tested in patients with heart failure are based on myocardial energetics. This review will provide a summary of the recent trials in this area, including therapeutic options targeting various aspects of cellular and mitochondrial metabolism. Agents that improve the energetic balance in myocardial cells have the potential to improve clinical heart failure status. The most promising therapies currently under investigation in this arena include (1) elamipretide, a cardiolipin stabilizer; (2) repletion of iron deficiency with intravenous ferrous carboxymaltose; (3) coenzyme Q10; and (4) the partial adenosine receptor antagonists capadenoson and neladenosone. Myocardial energetics-based therapeutics are groundbreaking in that they utilize novel mechanisms of action to improve heart failure symptoms, without causing the adverse neurohormonal side effects associated with current guideline-based therapies. The drugs appear likely to be added to the heart failure therapy armamentarium as adjuncts to current regimens in the near future.

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

PubMed

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

2011-03-31

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

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

PubMed Central

2011-01-01

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

Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis.

PubMed

Blakeley, Jaishri O; Plotkin, Scott R

2016-05-01

Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

[Immunotherapy: a therapeutic revolution against prostate cancer?].

PubMed

Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

2013-05-22

The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

Emerging Non-Cancer Applications of Therapeutic Ultrasound

PubMed Central

O’Reilly, Meaghan A.; Hynynen, Kullervo

2015-01-01

Ultrasound therapy has been investigated for over half a century. Ultrasound can act on tissue through a variety of mechanisms, including thermal, shockwave and cavitation mechanisms, and through these can elicit different responses. Ultrasound therapy can provide a non-invasive or minimally invasive treatment option, and ultrasound technology has advanced to the point where devices can be developed to investigate a wide range of applications. This review focuses on non-cancer, clinical applications of therapeutic ultrasound, with an emphasis on treatments that have recently reached clinical investigations, and preclinical research programs that have great potential to impact patient care. PMID:25792225

Treatment options for diabetic foot osteomyelitis.

PubMed

Senneville, Eric; Robineau, Olivier

2017-06-01

Diabetic foot osteomyelitis therapeutical options are based on antibiotic therapy and surgical resection of the infected bone(s). Surgical and medical approaches of patients suffering from a diabetic foot osteomyelitis do not oppose but are complementary and need to be discussed as a tailored manner. Areas covered: The aim of the present article is to discuss data issued from the most recent guidelines of the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot on the management of the diabetic foot infection and from a search in the current literature using the terms diabetic foot osteomyelitis and treatment/therapy/therapeutical in both PubMed and Medline, restricted to the last five years. Expert opinion: Surgical removal of the entire infected bone(s) has been considered in the past as the standard treatment but medical approach of these patients has now proven efficacy in selected situations. The current emergence of bacteria, especially among Gram negative rods, resistant to almost all the available antibiotics gradually augments the complexity of the management of these patients and is likely to decrease the place of the medical approach and to worsen the outcome of these infections in the next future.

78 FR 27271 - Self-Regulatory Organizations; BOX Options Exchange LLC; Order Granting Approval of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-09

... symbols (SPYJ) than the corresponding standard options on SPY.\\8\\ In addition, the Exchange proposes to list Jumbo SPY Options for all expirations applicable to standard options on SPY,\\9\\ and proposes that strike prices for Jumbo SPY Options be set at the same level as standard options on SPY.\\10\\ Bids and...

Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.

PubMed

Bakker, Guido J; Nieuwdorp, Max

2017-08-01

The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.

Refractory pulmonary sarcoidosis - proposal of a definition and recommendations for the diagnostic and therapeutic approach.

PubMed

Korsten, Peter; Strohmayer, Katharina; Baughman, Robert P; Sweiss, Nadera J

2016-03-01

Patients with sarcoidosis undergo spontaneous remission or may be effectively controlled with glucocorticoids alone in many cases. Progressive and refractory pulmonary sarcoidoisis constitute more than 10% of patients seen at specialized centers. Pulmonary fibrosis and associated complications, such as infections and pulmonary hypertension are leading causes of mortality. No universal definition of refractoriness exists, we therefore propose classifying patients as having refractory disease when the following criteria are fulfilled: (1) progressive disease despite at least 10 mg of prednisolone or equivalent for at least three months and need for additional disease-modifying anti-sarcoid drugs due to lack of efficacy, drug toxicity or intolerability and (2) treatment started for significant impairment of life due to progressive pulmonary symptoms. Both criteria should be fulfilled. Treatment options in addition to or instead of glucocorticoids for these patients include second- (methotrexate, azathioprine, leflunomide) and third-line agents (infliximab, adalimumab). Other immunmodulating agents can be used, but the evidence is very limited. Newer agents with anti-fibrotic properties, such as pirfenidone or nintedanib, might hold promise also for the pulmonary fibrosis seen in sarcoidosis. Treating physicians have to actively look for potentially treatable complications, such as pulmonary hypertension, cardiac disease or infections before patients should be classified as treatment-refractory. Ultimately, lung transplantation has to be considered as treatment option for patients not responding to medical therapy. In this review, we aim to propose a new definition of refractoriness, describe the associated clinical features and suggest the therapeutic approach.

Advancing treatment options for chronic idiopathic constipation.

PubMed

Quigley, Eamonn M M; Neshatian, Leila

2016-01-01

Chronic constipation is a global problem affecting all ages and associated with considerable morbidity and significant financial burden for society. Though formerly defined on the basis of a single symptom, infrequent defecation; constipation is now viewed as a syndrome encompassing several complaints such as difficulty with defecation, a sense of incomplete evacuation, hard stools, abdominal discomfort and bloating. The expanded concept of constipation has inevitably led to a significant change in outcomes in clinical trials, as well as in patient expectations from new therapeutic interventions. The past decades have also witnessed a proliferation in therapeutic targets for new agents. Foremost among these have been novel prokinetics, a new category, prosecretory agents and innovative approaches such as inhibitors of bile salt transport. In contrast, relatively few effective therapies exist for the management of those anorectal and pelvic floor problems that result in difficult defecation. Though constipation is a common and often troublesome disorder, many of those affected can resolve their symptoms with relatively simple measures. For those with more resistant symptoms a number of novel, effective and safe options now exist. Those with defecatory difficulty (anismus, pelvic floor dysfunction) continue to represent a significant management challenge.

An update on adjunctive treatment options for bipolar disorder.

PubMed

Dean, Olivia M; Gliddon, Emma; Van Rheenen, Tamsyn E; Giorlando, Francesco; Davidson, Sandra K; Kaur, Manreena; Ngo, Trung T; Williams, Lana J

2018-03-01

Bipolar disorder is a complex illness often requiring combinations of therapies to successfully treat symptoms. In recent years, there have been significant advancements in a number of therapies for bipolar disorder. It is therefore timely to provide an overview of current adjunctive therapeutic options to help treating clinicians to inform their patients and work towards optimal outcomes. Publications were identified from PubMed searches on bipolar disorder and pharmacotherapy, nutraceuticals, hormone therapy, psychoeducation, interpersonal and social rhythm therapy, cognitive remediation, mindfulness, e-Health and brain stimulation techniques. Relevant articles in these areas were selected for further review. This paper provides a narrative review of adjunctive treatment options and is not a systematic review of the literature. A number of pharmacotherapeutic, psychological and neuromodulation treatment options are available. These have varying efficacy but all have shown benefit to people with bipolar disorder. Due to the complex nature of treating the disorder, combination treatments are often required. Adjunctive treatments to traditional pharmacological and psychological therapies are proving useful in closing the gap between initial symptom remission and full functional recovery. Given that response to monotherapy is often inadequate, combination regimens for bipolar disorder are typical. Correspondingly, psychiatric research is working towards a better understanding of the disorder's underlying biology. Therefore, treatment options are changing and adjunctive therapies are being increasingly recognized as providing significant tools to improve patient outcomes. Towards this end, this paper provides an overview of novel treatments that may improve clinical outcomes for people with bipolar disorder. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Therapeutic hypothermia as a bridge to transplantation in patients with fulminant hepatic failure

PubMed Central

Castillo, Luis; Bugedo, Guillermo; Rovegno, Max

2015-01-01

The most important topics in fulminant hepatic failure are cerebral edema and intracranial hypertension. Among all therapeutic options, systemic induced hypothermia to 33 - 34ºC has been reported to reduce the high pressure and increase the time during which patients can tolerate a graft. This review discusses the indications and adverse effects of hypothermia. PMID:25909316

ACHIEVING THE PROMISE OF THERAPEUTIC EXTRACELLULAR VESICLES: THE DEVIL IS IN DETAILS OF THERAPEUTIC LOADING

PubMed Central

Sutaria, Dhruvitkumar S.; Badawi, Mohamed; Phelps, Mitch A.; Schmittgen, Thomas D.

2017-01-01

Extracellular vesicles (EVs) represent a class of cell secreted organelles which naturally contain biomolecular cargo such as miRNA, mRNA and proteins. EVs mediate intercellular communication, enabling the transfer of functional nucleic acids from the cell of origin to the recipient cells. In addition, EVs make an attractive delivery vehicle for therapeutics owing to their increased stability in circulation, biocompatibility, low immunogenicity and toxicity profiles. EVs can also be engineered to display targeting moieties on their surfaces which enables targeting to desired tissues, organs or cells. While much has been learned on the role of EVs as cell communicators, the field of therapeutic EV application is currently under development. Critical to the future success of EV delivery system is the description of methods by which therapeutics can be successfully and efficiently loaded within the EVs. Two methods of loading of EVs with therapeutic cargo exist, endogenous and exogenous loading. We have therefore focused this review on describing the various published approaches for loading EVs with therapeutics. PMID:28315083

Therapeutic touch and post-Hurricane Hugo stress.

PubMed

Olson, M; Sneed, N; Bonadonna, R; Ratliff, J; Dias, J

1992-06-01

This repeated-session design sought to answer questions about the effectiveness of therapeutic touch in reduction of stress for 23 individuals following a natural disaster. In addition, methodological issues related to the average length of time for a therapeutic-touch treatment and a method of documenting the nonverbal interaction between subject and toucher were investigated. Findings indicate that stressed people report themselves to be less stressed following therapeutic touch (p = .05). Time of therapeutic-touch intervention varied significantly between the touchers, with a range of 6.8 to 20 minutes. Qualitative data examining the interaction of toucher and subject raised a number of questions that require further study.

Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease.

PubMed

Freitag, Helma; Christen, Friederike; Lewens, Florentine; Grass, Irina; Briest, Franziska; Iwaszkiewicz, Sara; Siegmund, Britta; Grabowski, Patricia

2017-01-01

The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials. © 2016 The Author(s) Published by S. Karger AG, Basel.

Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease

PubMed Central

Freitag, Helma; Christen, Friederike; Lewens, Florentine; Grass, Irina; Briest, Franziska; Iwaszkiewicz, Sara; Siegmund, Britta; Grabowski, Patricia

2017-01-01

Background The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. Aim We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. Methods We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). Results In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. Conclusion PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials. PMID:27513674

Direct lymphangiography as treatment option of lymphatic leakage: indications, outcomes and role in patient's management.

PubMed

Gruber-Rouh, Tatjana; Naguib, Nagy N N; Lehnert, Thomas; Harth, Marc; Thalhammer, Axel; Beeres, Martin; Tsaur, Igor; Hammersting, Renate; Wichmann, Julian L; Vogl, Thomas J; Jacobi, Volkmar

2014-12-01

To evaluate the effectiveness of lymphography as a minimally invasive treatment option of lymphatic leakage in terms of local control and to investigate which parameters influence the success rate. This retrospective study protocol was approved by the ethic committee. Patient history, imaging data, therapeutic options and follow-up were recorded and retrospectively analyzed. Between June 1998 and February 2013, 71 patients (m:w = 42:29, mean age, 52.4; range 42–75 years) with lymphatic leakage in form of lymphatic fistulas (n = 37), lymphocele (n = 11), chylothorax (n = 13) and chylous ascites (n = 10)underwent lymphography. Sixty-four patients (90.1%) underwent successful lymphography while lymphography failed in 7 cases. Therapeutic success was evaluated and correlated to the volume of lymphatic leakage and to the volume of the applied iodized oil. Signs of leakage or contrast extravasation were directly detected in 64 patients. Of 64 patients, 45 patients (70.3%) were treated and cured after lymphography. Based on the lymphography findings, 19 patients (29.7%) underwent surgical intervention with a completely occlusion of lymphatic leakage. The lymphatic leak could be completely occluded in 96.8% of patients when the lymphatic drainage volume was less than 200 mL/day (n = 33). Even when lymphatic drainage was higher than 200 mL/day (n = 31),therapeutic lymphography was still successful in 58.1% of the patients. Lymphography is an effective, minimally invasive method in the detection and treatment of lymphatic leakage. The volume of lymphatic drainage per day is a significant predictor of the therapeutic success rate. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

Fakhrejahani, Farhad; Madan, Ravi A; Dahut, William L

2017-05-01

monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

Asteroid Redirect Robotic Mission: Robotic Boulder Capture Option Overview

NASA Technical Reports Server (NTRS)

Mazanek, Daniel D.; Merrill, Raymond G.; Belbin, Scott P.; Reeves, David M.; Earle, Kevin D.; Naasz, Bo J.; Abell, Paul A.

2014-01-01

The National Aeronautics and Space Administration (NASA) is currently studying an option for the Asteroid Redirect Robotic Mission (ARRM) that would capture a multi-ton boulder (typically 2-4 meters in size) from the surface of a large (is approximately 100+ meter) Near-Earth Asteroid (NEA) and return it to cislunar space for subsequent human and robotic exploration. This alternative mission approach, designated the Robotic Boulder Capture Option (Option B), has been investigated to determine the mission feasibility and identify potential differences from the initial ARRM concept of capturing an entire small NEA (4-10 meters in size), which has been designated the Small Asteroid Capture Option (Option A). Compared to the initial ARRM concept, Option B allows for centimeter-level characterization over an entire large NEA, the certainty of target NEA composition type, the ability to select the boulder that is captured, numerous opportunities for mission enhancements to support science objectives, additional experience operating at a low-gravity planetary body including extended surface contact, and the ability to demonstrate future planetary defense strategies on a hazardous-size NEA. Option B can leverage precursor missions and existing Agency capabilities to help ensure mission success by targeting wellcharacterized asteroids and can accommodate uncertain programmatic schedules by tailoring the return mass.

Hypochondriasis: treatment options for a diagnostic quagmire.

PubMed

Starcevic, Vladan

2015-08-01

This article presents the conceptual and diagnostic conundrums surrounding hypochondriasis and reviews current treatment options for this disorder. The removal of hypochondriasis from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and its replacement with two new diagnostic entities have been controversial. It appears that the Eleventh Revision of the International Classification of Diseases will take a more cautious approach and emphasise the links between hypochondriasis, obsessive-compulsive disorder and other anxiety disorders. The cornerstone of any treatment approach to hypochondriasis is establishing a good therapeutic relationship with the patient. Psychological treatments, especially cognitive-behavioural therapy, have been more useful than pharmacotherapy, but there is much room for improving treatment outcomes. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Nonlethal weapons as force options for the Army

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, J.B.

This paper suggests that future challenges to US national security will be very different from those previously experienced. In a number of foreseeable circumstances, conventional military force will be inappropriate. The National Command Authority, and other appropriate levels of command, need expanded options available to meet threats for which the application of massive lethal force is counterproductive or inadvisable. It is proposed that nonlethal concepts be developed that provide additional options for military leaders and politicians. Included in this initiative should be exploration of policy, strategy, doctrine, and training issues as well as the development of selected technologies and weapons.more » In addition, civilian law enforcement agencies have similar requirements for less-than-lethal systems. This may be an excellent example for a joint technology development venture.« less

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models

PubMed Central

Rentsch, Jakob; Freitag, Helma; Detjen, Katharina; Briest, Franziska; Möbs, Markus; Weissmann, Victoria; Siegmund, Britta; Auernhammer, Christoph J.; Aristizabal Prada, Elke Tatjana; Lauseker, Michael; Grossman, Ashley; Exner, Samantha; Fischer, Christian; Grötzinger, Carsten

2017-01-01

Background/Aims The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Methods Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. Results BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Conclusion Our results suggest that the agent BYL719 could be a novel

The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.

PubMed

Nölting, Svenja; Rentsch, Jakob; Freitag, Helma; Detjen, Katharina; Briest, Franziska; Möbs, Markus; Weissmann, Victoria; Siegmund, Britta; Auernhammer, Christoph J; Aristizabal Prada, Elke Tatjana; Lauseker, Michael; Grossman, Ashley; Exner, Samantha; Fischer, Christian; Grötzinger, Carsten; Schrader, Jörg; Grabowski, Patricia

2017-01-01

The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA. BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately. Our results suggest that the agent BYL719 could be a novel therapeutic approach to the treatment of NETs

Pricing of swing options: A Monte Carlo simulation approach

NASA Astrophysics Data System (ADS)

Leow, Kai-Siong

We study the problem of pricing swing options, a class of multiple early exercise options that are traded in energy market, particularly in the electricity and natural gas markets. These contracts permit the option holder to periodically exercise the right to trade a variable amount of energy with a counterparty, subject to local volumetric constraints. In addition, the total amount of energy traded from settlement to expiration with the counterparty is restricted by a global volumetric constraint. Violation of this global volumetric constraint is allowed but would lead to penalty settled at expiration. The pricing problem is formulated as a stochastic optimal control problem in discrete time and state space. We present a stochastic dynamic programming algorithm which is based on piecewise linear concave approximation of value functions. This algorithm yields the value of the swing option under the assumption that the optimal exercise policy is applied by the option holder. We present a proof of an almost sure convergence that the algorithm generates the optimal exercise strategy as the number of iterations approaches to infinity. Finally, we provide a numerical example for pricing a natural gas swing call option.

Adolescent depression: clinical features and therapeutic strategies.

PubMed

Nardi, B; Francesconi, G; Catena-Dell'osso, M; Bellantuono, C

2013-06-01

Major depressive disorder (MDD) is a common disorder during adolescence and it is associated with an increased risk of suicide, poor school performance, impaired social skills, social withdrawal and substance abuse. Further, as many depressive episode in adolescents do not reach the diagnostic threshold for MDD, the disorder remains undetected. This review aims to provide an update of clinical features of adolescent MDD and to focus on the most appropriate therapeutic strategies to adopt in clinical practice. We reviewed the international literature to identify studies focusing on clinical features and therapeutic options in adolescents affected by MDD. PubMed, Medline and Cochrane Library databases were searched for English language papers. The clinical picture of depression is variable with sex and age. Somatic complaints, particularly headache and fatigue, are a common presentation in adolescent MDD. Irritability is present most frequently in female and it is related to the severity of MDD. Adolescent MDD is also characterized by a high rates of suicides. The therapeutic strategy in adolescent depression includes psychotropic medications, psychotherapy or a combination of both treatments, with selection of the most appropriate strategy depending on symptom severity. As first-line treatment the traditional cognitive behavioural therapy (CBT), as well as the cognitive Post-Rationalist (PR) approach, are so far considered the goal standard. The therapeutic approach to the adolescent affected by MMD should respect the person in his/her psycho-physical entirety. The intervention may help the subject in seeking a more stable and adaptable identity. It is relevant to have a good knowledge of the peculiar clinical picture of adolescent MDD in order to make an early identification of the disorder and to define an appropriate personalized therapeutic program.

Therapeutic Amenorrhea in Patients at Risk for Thrombocytopenia

PubMed Central

Martin-Johnston, Meredith K.; Okoji, Olanma Y.; Armstrong, Alicia

2016-01-01

To examine the need for and evaluate the method of menses suppression in women at risk for thrombocytopenia. A systematic review of the published literature in MEDLINE using the search terms thrombocytopenia, menorrhagia, therapeutic amenorrhea, progestin intrauterine device, combination oral contraceptive—extended and cyclic, gonadotropin releasing hormone agonist, danazol, and progestins. There are an increased number of reproductive age women at risk for thrombocytopenia who would benefit from menses suppression. A number of effective medical regimens are available. In patients who fail medical therapy, endometrial ablation appears to be effective in women with thrombocytopenia. As a result of the increased number of women at risk for thrombocytopenia, there is a need for therapeutic amenorrhea. The type of regimen selected depends upon the patients need for contraception and the ability to tolerate estrogen-containing medications. For women who fail medical therapy, there are surgical options, which are associated with less morbidity than hysterectomy. PMID:18492296

The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis.

PubMed

Heijman, Jordi; Algalarrondo, Vincent; Voigt, Niels; Melka, Jonathan; Wehrens, Xander H T; Dobrev, Dobromir; Nattel, Stanley

2016-04-01

Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms for arrhythmia initiation and maintenance. However, it has become clear that the clinical factors predisposing to AF and the cellular and molecular mechanisms involved are extremely complex. Moreover, all AF-promoting and maintaining mechanisms are dynamically regulated and subject to remodelling caused by both AF and cardiovascular disease. Accordingly, the initial presentation and clinical progression of AF patients are enormously heterogeneous. An understanding of arrhythmia mechanisms is widely assumed to be the basis of therapeutic innovation, but while this assumption seems self-evident, we are not aware of any papers that have critically examined the practical contributions of basic research into AF mechanisms to arrhythmia management. Here, we review recent insights into the basic mechanisms of AF, critically analyse the role of basic research insights in the development of presently used anti-AF therapeutic options and assess the potential value of contemporary experimental discoveries for future therapeutic innovation. Finally, we highlight some of the important challenges to the translation of basic science findings to clinical application. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

European option pricing under the Student's t noise with jumps

NASA Astrophysics Data System (ADS)

Wang, Xiao-Tian; Li, Zhe; Zhuang, Le

2017-03-01

In this paper we present a new approach to price European options under the Student's t noise with jumps. Through the conditional delta hedging strategy and the minimal mean-square-error hedging, a closed-form solution of the European option value is obtained under the incomplete information case. In particular, we propose a Value-at-Risk-type procedure to estimate the volatility parameter σ such that the pricing error is in accord with the risk preferences of investors. In addition, the numerical results of us show that options are not priced in some cases in an incomplete information market.

Respiratory Syncytial Virus: Infection, Detection, and New Options for Prevention and Treatment

PubMed Central

Griffiths, Cameron

2016-01-01

SUMMARY Respiratory syncytial virus (RSV) infection is a significant cause of hospitalization of children in North America and one of the leading causes of death of infants less than 1 year of age worldwide, second only to malaria. Despite its global impact on human health, there are relatively few therapeutic options available to prevent or treat RSV infection. Paradoxically, there is a very large volume of information that is constantly being refined on RSV replication, the mechanisms of RSV-induced pathology, and community transmission. Compounding the burden of acute RSV infections is the exacerbation of preexisting chronic airway diseases and the chronic sequelae of RSV infection. A mechanistic link is even starting to emerge between asthma and those who suffer severe RSV infection early in childhood. In this article, we discuss developments in the understanding of RSV replication, pathogenesis, diagnostics, and therapeutics. We attempt to reconcile the large body of information on RSV and why after many clinical trials there is still no efficacious RSV vaccine and few therapeutics. PMID:27903593

Preemptive Renal Transplantation-The Best Treatment Option for Terminal Chronic Renal Failure.

PubMed

Arze Aimaretti, L; Arze, S

2016-03-01

Renal transplantation is the best therapeutic option for end-stage chronic renal disease. Assuming that it is more advisable if performed early, we aimed to show the clinical, social, and economic advantages in 70% of our patients who were dialyzed only for a short period. For this purpose, we retrospectively collected data over 28 years in 142 kidney transplants performed in patients with <6 weeks on dialysis. 66% of our patients were 30-60 years old; 98% of the patients had living donors. At transplantation, 64% of our patients had no public support; however, 64% of them returned to work and got health insurance 2 months later. Full rehabilitation was achieved in all cases, including integration to the family, return to full-time work, school and university, sports, and reproduction. Immunosuppression consisted of 3 drugs, including steroids, cyclosporine, and azathioprine or mycophenolate. The cost in the 1st year, including patient and donor evaluation, surgery, immunosuppression, and follow-up, was $13,300 USD versus $22,320 for hemodialysis. We conclude that preemptive renal transplantation with <6 weeks on dialysis is the best therapeutic option for end-stage renal failure, especially in developing countries such as Bolivia, where until last year, full public support for renal replacement therapy was unavailable. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 77191 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... Effectiveness of a Proposed Rule Relating to the Quarterly Option Series Program December 16, 2013. Pursuant to... the Quarterly Options Series (``QOS'') Program to eliminate the cap on the number of additional series... eliminate the cap on the number of additional series that may be listed per expiration month for each QOS in...

78 FR 25112 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-29

... VOLATILITY INDEXES the ``Specified Proprietary Index Options Rate Table--SPX, SPXW, SPXpm, SRO, OEX, XEO, VIX and VOLATILITY INDEXES'' (the ``Specified Index Options Rate Table''). The addition of the word..., SPXpm, SRO, OEX, XEO, VIX and VOLATILITY INDEXES (the ``Other Index Options Rate Table'')). Footnote 20...

Potential new regulatory options for e-cigarettes in New Zealand.

PubMed

Wilson, Nick; Edwards, Richard; Hoek, Janet; Thomson, George; Blakely, Tony; van der Deen, Frederieke Sanne; Crane, Julian

2015-11-20

While e-cigarette usage has grown rapidly in New Zealand and around the world, the scientific evidence base regarding the net benefits and risks of these types of products at the population level remains uncertain. The health-based policy experience is also minimal. Here, we analyse plausible future regulatory options for e-cigarettes that the New Zealand Government could explore, and that further research could help clarify. These options include: (1) a full free market (an option we doubt is desirable for multiple reasons); (2) controlled increased access through: (a) pharmacy only, (b) pharmacy only plus sales by prescription/ to licensed vapers; (c) additional controls through non-profit supply/distribution (eg, public hospital pharmacies); (3) increased restrictions compared with current (eg, adopting a complete ban on self-imports and use). In addition, we consider mechanisms to improve product quality and safety, and argue that policy makers should take great care when regulating e-cigarettes, given the scientific uncertainty and the role of commercial vested interests.

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

PubMed

Ahn, Julie; Bishop, Justin A; Akpeng, Belinda; Pai, Sara I; Best, Simon R A

2015-02-01

Identifying effective treatment for papillomatosis is limited by a lack of animal models, and there is currently no preclinical model for testing potential therapeutic agents. We hypothesized that xenografting of papilloma may facilitate in vivo drug testing to identify novel treatment options. A biopsy of fresh tracheal papilloma was xenografted into a NOD-scid-IL2Rgamma(null) (NSG) mouse. The xenograft began growing after 5 weeks and was serially passaged over multiple generations. Each generation showed a consistent log-growth pattern, and in all xenografts, the presence of the human papillomavirus (HPV) genome was confirmed by polymerase chain reaction (PCR). Histopathologic analysis demonstrated that the squamous architecture of the original papilloma was maintained in each generation. In vivo drug testing with bevacizumab (5 mg/kg i.p. twice weekly for 3 weeks) showed a dramatic therapeutic response compared to saline control. We report here the first successful case of serial xenografting of a tracheal papilloma in vivo with a therapeutic response observed with drug testing. In severely immunocompromised mice, the HPV genome and squamous differentiation of the papilloma can be maintained for multiple generations. This is a feasible approach to identify therapeutic agents in the treatment of recurrent respiratory papillomatosis. © The Author(s) 2014.

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression

PubMed Central

2017-01-01

Background. Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose. One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections. There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion. Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies. PMID:28503571

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression.

PubMed

Lee, Gihyun; Bae, Hyunsu

2017-01-01

Background . Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose . One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections . There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion . Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies.

Rehabilitation Options

MedlinePlus

... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ... Speech Pathology Occupational Therapy Art Therapy Recreational therapy Neuropsychology Home Care Options Advanced Care Planning Palliative Care ...

Preclinical evaluation of potential therapeutic targets in dedifferentiated liposarcoma.

PubMed

Hanes, Robert; Grad, Iwona; Lorenz, Susanne; Stratford, Eva W; Munthe, Else; Reddy, Chilamakuri Chandra Sekhar; Meza-Zepeda, Leonardo A; Myklebost, Ola

2016-08-23

Sarcomas are rare cancers with limited treatment options. Patients are generally treated by chemotherapy and/or radiotherapy in combination with surgery, and would benefit from new personalized approaches. In this study we demonstrate the potential of combining personal genomic characterization of patient tumors to identify targetable mutations with in vitro testing of specific drugs in patient-derived cell lines. We have analyzed three metastases from a patient with high-grade metastatic dedifferentiated liposarcoma (DDLPS) by exome and transcriptome sequencing as well as DNA copy number analysis. Genomic aberrations of several potentially targetable genes, including amplification of KITLG and FRS2, in addition to amplification of CDK4 and MDM2, characteristic of this disease, were identified. We evaluated the efficacy of drugs targeting these aberrations or the corresponding signaling pathways in a cell line derived from the patient. Interestingly, the pan-FGFR inhibitor NVP-BGJ398, which targets FGFR upstream of FRS2, strongly inhibited cell proliferation in vitro and induced an accumulation of cells into the G0 phase of the cell cycle. This study indicates that FGFR inhibitors have therapeutic potential in the treatment of DDLPS with amplified FRS2.

Endoscopy and polyps-diagnostic and therapeutic advances in management

PubMed Central

Steele, Scott R; Johnson, Eric K; Champagne, Bradley; Davis, Brad; Lee, Sang; Rivadeneira, David; Ross, Howard; Hayden, Dana A; Maykel, Justin A

2013-01-01

Despite multiple efforts aimed at early detection through screening, colon cancer remains the third leading cause of cancer-related deaths in the United States, with an estimated 51000 deaths during 2013 alone. The goal remains to identify and remove benign neoplastic polyps prior to becoming invasive cancers. Polypoid lesions of the colon vary widely from hyperplastic, hamartomatous and inflammatory to neoplastic adenomatous growths. Although these lesions are all benign, they are common, with up to one-quarter of patients over 60 years old will develop pre-malignant adenomatous polyps. Colonoscopy is the most effective screening tool to detect polyps and colon cancer, although several studies have demonstrated missed polyp rates from 6%-29%, largely due to variations in polyp size. This number can be as high as 40%, even with advanced (> 1 cm) adenomas. Other factors including sub-optimal bowel preparation, experience of the endoscopist, and patient anatomical variations all affect the detection rate. Additional challenges in decision-making exist when dealing with more advanced, and typically larger, polyps that have traditionally required formal resection. In this brief review, we will explore the recent advances in polyp detection and therapeutic options. PMID:23885138

77 FR 57602 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Proposed...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-18

... options on other indices and on individual equity securities in the future, subject to Commission approval... ``OTC index option'' generically in order to simplify future amendments to provide for additional... proposed Section 6 of Article XVII of the By-Laws. With respect to future OTC options accepted for clearing...

5 CFR 870.705 - Amount and election of Option B and Option C.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Amount and election of Option B and Option C. 870.705 Section 870.705 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED... Compensationers § 870.705 Amount and election of Option B and Option C. (a) The number of multiples of Option B...

Dietary therapy is not the best option for refractory nonsurgical epilepsy.

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

The ketogenic diet (KD) is currently a well-established treatment for patients with medically refractory, nonsurgical epilepsy. However, despite its efficacy, the KD is highly restrictive and constitutes a treatment with serious potential adverse effects, and often with difficulties in its implementation and compliance. Patients on the KD require strict follow-up and constant supervision by a medical team highly experienced in its management in order to prevent complications. Other alternative treatments for patients with refractory epilepsy include vagus nerve stimulation (VNS), new-generation antiepileptic drugs (AEDs), corpus callosotomy (CC), and responsive focal cortical stimulation (RNS). In this review, we explain not only the difficulties of the KD as a therapeutic option for refractory epilepsy but also the benefits of other therapeutic strategies, which, in many cases, have proven to have better efficacy than the KD itself. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Adaptive [theta]-methods for pricing American options

NASA Astrophysics Data System (ADS)

Khaliq, Abdul Q. M.; Voss, David A.; Kazmi, Kamran

2008-12-01

We develop adaptive [theta]-methods for solving the Black-Scholes PDE for American options. By adding a small, continuous term, the Black-Scholes PDE becomes an advection-diffusion-reaction equation on a fixed spatial domain. Standard implementation of [theta]-methods would require a Newton-type iterative procedure at each time step thereby increasing the computational complexity of the methods. Our linearly implicit approach avoids such complications. We establish a general framework under which [theta]-methods satisfy a discrete version of the positivity constraint characteristic of American options, and numerically demonstrate the sensitivity of the constraint. The positivity results are established for the single-asset and independent two-asset models. In addition, we have incorporated and analyzed an adaptive time-step control strategy to increase the computational efficiency. Numerical experiments are presented for one- and two-asset American options, using adaptive exponential splitting for two-asset problems. The approach is compared with an iterative solution of the two-asset problem in terms of computational efficiency.

Space Station redesign option A: Modular buildup concept

NASA Technical Reports Server (NTRS)

1993-01-01

In early 1993, President Clinton mandated that NASA look at lower cost alternatives to Space Station Freedom. He also established an independent advisory committee - the Blue Ribbon Panel - to review the redesign work and evaluate alternatives. Daniel Goldin, NASA Administrator, established a Station Redesign Team that began operating in late March from Crystal City, Virginia. NASA intercenter teams - one each at Marshall Space Flight Center, Johnson Space Center, and Langley Research Center provided engineering and other support. The results of the Option A study done at Marshall Space Flight Center are summarized. Two configurations (A-1 and A-2) are covered. Additional data is provided in the briefing package MSFC SRT-001, Final System Review to SRT-002, Space Station Option A Modular Buildup Concept, Volumes 1-5, Revision B, June 10, 1993. In June 1993, President Clinton decided to proceed with a modular concept consistent with Option A, and asked NASA to provide an Implementation Plan by September. All data from the Option A redesign activity was provided to NASA's Transition Team for use in developing the Implementation Plan.

New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

PubMed Central

Norata, Giuseppe Danilo; Ballantyne, Christie M.; Catapano, Alberico Luigi

2013-01-01

Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. PMID:23509227

Management options for cholestatic liver disease in children.

PubMed

Catzola, Andrea; Vajro, Pietro

2017-11-01

Due to a peculiar age-dependent increased susceptibility, neonatal cholestasis affects the liver of approximately 1 in every 2500 term infants. A high index of suspicion is the key to an early diagnosis, and to implement timely, often life-saving treatments. Even when specific treatment is not available or curative, prompt medical management and optimization of nutrition are of paramount importance to survival and avoidance of complications. Areas covered: The present article will prominently focus on a series of newer diagnostic and therapeutic options of cholestasis in neonates and infants blended with consolidated established paradigms. The overview of strategies for the management reported here is based on a systematic literature search published in English using accessible databases (PubMed, MEDLINE) with the keywords biliary atresia, choleretics and neonatal cholestasis. References lists from retrieved articles were also reviewed. Expert commentary: A large number of uncommon and rare hepatobiliary disorders may present with cholestasis during the neonatal and infantile period. Potentially life-saving disease-specific pharmacological and surgical therapeutic approaches are currently available. Advances in hepatobiliary transport mechanisms have started clarifying fundamental aspects of inherited and acquired cholestasis, laying the foundation for the development of possibly more effective specific therapies.

Ethylene glycol poisoning in three dogs: Importance of early diagnosis and role of hemodialysis as a treatment option.

PubMed

Schweighauser, A; Francey, T

2016-02-01

Poisoning with ethylene glycol as contained in antifreeze can rapidly lead to irreversible acute renal failure and other organ damage. It carries a grave prognosis unless diagnosed early and adequate treatment is initiated within 8 hours of ingestion. Toxicity of ethylene glycol is related to the production of toxic metabolites by the enzyme alcohol dehydrogenase (ADH), leading to early signs of severe polyuria (PU) and polydipsia (PD), gastritis, ataxia and central nervous depression, followed by progressive dehydration, and ultimately oligoanuric renal failure. In addition to general supportive care, therapeutic interventions must include either antidotes blocking ADH-mediated metabolism or blood purification techniques to remove both the parent compound and the toxic metabolites. The goal of this case report is to describe three cases of acute antifreeze intoxication in dogs, and to discuss treatment options available for this poisoning.

Cyanobacterial Treatment Options: Permanganate and Powdered Activated Carbon

EPA Science Inventory

This presentation will begin with a brief overview of drinking water treatment options for cyanobacteria and their toxins. The treatment discussion will focus on the impacts of permanganate addition to suspensions of toxin-producing Microcystis aeruginosa, followed by powdered ac...

Lunar Cube Transfer Trajectory Options

NASA Technical Reports Server (NTRS)

Folta, David C.; Dichman, Don; Clark, Pamela; Haapala, Amanda; Howell, Kathleen

2014-01-01

Contingent upon the modification of an initial condition of the injected or deployed orbit. Additionally, these designs can be restricted by the selection of the Cubesat subsystem design such as propulsion or communication. Nonetheless, many trajectory options can be designed with have a wide range of transfer durations, fuel requirements, and final destinations. Our investigation of potential trajectories highlights several design options including deployment into low Earth orbit (LEO), geostationary transfer orbits (GTO), and higher energy direct lunar transfer orbits. In addition to direct transfer options from these initial orbits, we also investigate the use of longer duration Earth-Moon dynamical systems. For missions with an intended lunar orbit, much of the design process is spent optimizing a ballistic capture while other science locations such as Sun-Earth libration or heliocentric orbits may simply require a reduced Delta-V imparted at a convenient location along the trajectory. In this article we examine several design options that meet the above limited deployment and subsystem drivers. We study ways that both impulsive and low-thrust Solar Electric Propulsion (SEP) engines can be used to place the Cubesat first into a highly eccentric Earth orbit, enter the Moon's Sphere of Influence, and finally achieve a highly eccentric lunar orbit. We show that such low-thrust transfers are feasible with a realistic micro-thruster model, assuming that the Cubesat can generate sufficient power for the SEP. Two examples are shown here: (1) A Cubestat injected by Exploration Mission 1 (EM-1) then employing low thrust; and (2) a CubSat deployed in a GTO, then employing impulsive maneuvers. For the EM-1 injected initial design, we increase the EM-1 targeted lunar flyby distance to reduce the energy of the lunar flyby to match that of a typical lMoon system heteroclinic manifold. Figure 1 presents an option that encompasses the similar dynamics as that of the ARTEMIS

7 CFR 3555.304 - Special servicing options.

Code of Federal Regulations, 2014 CFR

2014-01-01

... consider a mortgage recovery advance under this section in addition to the extended-term loan modification... required for taxes and insurance. (6) The following terms apply to the repayment of mortgage recovery... does not change the terms of the loan note guarantee. (4) Special servicing options shall be used in...

Designing flexible engineering systems utilizing embedded architecture options

NASA Astrophysics Data System (ADS)

Pierce, Jeff G.

This dissertation develops and applies an integrated framework for embedding flexibility in an engineered system architecture. Systems are constantly faced with unpredictability in the operational environment, threats from competing systems, obsolescence of technology, and general uncertainty in future system demands. Current systems engineering and risk management practices have focused almost exclusively on mitigating or preventing the negative consequences of uncertainty. This research recognizes that high uncertainty also presents an opportunity to design systems that can flexibly respond to changing requirements and capture additional value throughout the design life. There does not exist however a formalized approach to designing appropriately flexible systems. This research develops a three stage integrated flexibility framework based on the concept of architecture options embedded in the system design. Stage One defines an eight step systems engineering process to identify candidate architecture options. This process encapsulates the operational uncertainty though scenario development, traces new functional requirements to the affected design variables, and clusters the variables most sensitive to change. The resulting clusters can generate insight into the most promising regions in the architecture to embed flexibility in the form of architecture options. Stage Two develops a quantitative option valuation technique, grounded in real options theory, which is able to value embedded architecture options that exhibit variable expiration behavior. Stage Three proposes a portfolio optimization algorithm, for both discrete and continuous options, to select the optimal subset of architecture options, subject to budget and risk constraints. Finally, the feasibility, extensibility and limitations of the framework are assessed by its application to a reconnaissance satellite system development problem. Detailed technical data, performance models, and cost estimates

Vulvovaginal candidosis: contemporary challenges and the future of prophylactic and therapeutic approaches.

PubMed

Chew, Shu Yih; Than, Leslie Thian Lung

2016-05-01

Vulvovaginal candidosis (VVC) is a common gynaecological disorder that is delineated by the inflammation of vaginal wall and it is caused by the opportunistic fungal pathogen Candida species. In fact, three out of every four women will experience at least one occasion of VVC during some point in their lives. Although uncomplicated VVC is relatively harmless, the complicated VVC such as recurrent attack often creates restlessness and depression in the patients, thus greatly affects their quality of life. Managements of VVC are usually associated with the use of antimycotic suppositories, topical cream or oral agents. These antimycotic agents are either available over-the-counter or prescribed by the clinicians. In recent decades, the rise of clinical challenges such as the increased prevalence of resistant Candida strains, recurrent VVC infection and adverse effects of multidrug interactions have necessitated the development of novel therapeutic or prophylactic options to combat the complicated VVC in the future. In this review, we discuss the current antimycotic treatments available for Candida vaginitis and the problems that exist in these seemingly effective treatments. Besides, we attempt to contemplate some of the future and prospective strategies surrounding the development of alternative therapeutic and prophylactic options in treating and preventing complicated VVC respectively. © 2016 Blackwell Verlag GmbH.

Therapeutic considerations of sarcopenia in heart failure patients.

PubMed

Saitoh, Masakazu; Ebner, Nicole; von Haehling, Stephan; Anker, Stefan D; Springer, Jochen

2018-02-01

Sarcopenia is a common feature, and affects 20-47% of patients with heart failure (HF). Sarcopenia is also an independent predictor of impaired functional capacity, even after adjusting for clinical relevant variables, which is associated with adverse outcome in patients with HF. Areas covered: Several different pathophysiological pathways are involved in sarcopenic processes including altered nutrient intake and absorption, hormonal factor, inflammatory processes, oxidative stress, cellular proteolysis, and unhealthy lifestyle. Nutritional therapy, physical activity and/or exercise training have been associated with improved muscle mass or physical performance in HF. Few studies reported beneficial effects for muscle mass and physical performance, in those who received angiotensin-converting enzyme (ACE) inhibitors, or/and beta-blocker. In addition, testosterone, selective androgen receptor modulators, ghrelin agonist and myostatin inhibitors are currently under study as possible future therapeutic options. Expert commentary: Regular and adequate level of physical activity and/or exercise training, and sufficient nutritional intake or special nutritional supplementation may represent the best strategy for prevention or delay of sarcopenia and worsening physical performance in patients with HF. Maximal tolerated dosages of standard therapies for HF such as ACE-inhibitors or beta-blockers are first-line strategy, however it is difficult to recommend other pharmacological agents as part of routine treatment of sarcopenia.

Realizing the therapeutic potential of rare earth elements in designing nanoparticles to target and treat glioblastoma.

PubMed

Lu, Victor M; McDonald, Kerrie L; Townley, Helen E

2017-10-01

The prognosis of brain cancer glioblastoma (GBM) is poor, and despite intense research, there have been no significant improvements within the last decade. This stasis implicates the need for more novel therapeutic investigation. One such option is the use of nanoparticles (NPs), which can be beneficial due to their ability to penetrate the brain, overcome the blood-brain barrier and take advantage of the enhanced permeation and retention effect of GBM to improve specificity. Rare earth elements possess a number of interesting natural properties due to their unique electronic configuration, which may prove therapeutically advantageous in an NP formulation. The underexplored exciting potential for rare earth elements to augment the therapeutic potential of NPs in GBM treatment is discussed in this review.

Comprehensive Genomic Profiling of Esthesioneuroblastoma Reveals Additional Treatment Options.

PubMed

Gay, Laurie M; Kim, Sungeun; Fedorchak, Kyle; Kundranda, Madappa; Odia, Yazmin; Nangia, Chaitali; Battiste, James; Colon-Otero, Gerardo; Powell, Steven; Russell, Jeffery; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Ali, Siraj M; Stephens, Philip J; Miller, Vincent A; Ross, Jeffrey S

2017-07-01

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neoplasm of the olfactory mucosa. Despite surgical resection combined with radiotherapy and adjuvant chemotherapy, ENB often relapses with rapid progression. Current multimodality, nontargeted therapy for relapsed ENB is of limited clinical benefit. We queried whether comprehensive genomic profiling (CGP) of relapsed or refractory ENB can uncover genomic alterations (GA) that could identify potential targeted therapies for these patients. CGP was performed on formalin-fixed, paraffin-embedded sections from 41 consecutive clinical cases of ENBs using a hybrid-capture, adaptor ligation based next-generation sequencing assay to a mean coverage depth of 593X. The results were analyzed for base substitutions, insertions and deletions, select rearrangements, and copy number changes (amplifications and homozygous deletions). Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in clinical trials. A total of 28 ENBs harbored GA, with a mean of 1.5 GA per sample. Approximately half of the ENBs (21, 51%) featured at least one CRGA, with an average of 1 CRGA per sample. The most commonly altered gene was TP53 (17%), with GA in PIK3CA , NF1 , CDKN2A , and CDKN2C occurring in 7% of samples. We report comprehensive genomic profiles for 41 ENB tumors. CGP revealed potential new therapeutic targets, including targetable GA in the mTOR, CDK and growth factor signaling pathways, highlighting the clinical value of genomic profiling in ENB. Comprehensive genomic profiling of 41 relapsed or refractory ENBs reveals recurrent alterations or classes of mutation, including amplification of tyrosine kinases encoded on chromosome 5q and mutations affecting genes in the mTOR/PI3K pathway. Approximately half of the ENBs (21, 51%) featured at least one clinically relevant genomic alteration (CRGA), with an average of 1 CRGA per sample. The most commonly altered

18 CFR 808.4 - Optional joint hearing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 2 2011-04-01 2011-04-01 false Optional joint hearing. 808.4 Section 808.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION... or exercise any power or duty as a result of such additional designation to decide the merits of any...

18 CFR 808.4 - Optional joint hearing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 2 2014-04-01 2014-04-01 false Optional joint hearing. 808.4 Section 808.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION... or exercise any power or duty as a result of such additional designation to decide the merits of any...

18 CFR 808.4 - Optional joint hearing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 2 2012-04-01 2012-04-01 false Optional joint hearing. 808.4 Section 808.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION... or exercise any power or duty as a result of such additional designation to decide the merits of any...

18 CFR 808.4 - Optional joint hearing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 2 2013-04-01 2012-04-01 true Optional joint hearing. 808.4 Section 808.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION... or exercise any power or duty as a result of such additional designation to decide the merits of any...

18 CFR 808.4 - Optional joint hearing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 2 2010-04-01 2010-04-01 false Optional joint hearing. 808.4 Section 808.4 Conservation of Power and Water Resources SUSQUEHANNA RIVER BASIN COMMISSION... or exercise any power or duty as a result of such additional designation to decide the merits of any...

Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.

PubMed

Kou, Jinghong; Yang, Junling; Lim, Jeong-Eun; Pattanayak, Abhinandan; Song, Min; Planque, Stephanie; Paul, Sudhir; Fukuchi, Ken-Ichiro

2015-02-01

Accumulation of amyloid beta-peptide (Aβ) in the brain is hypothesized to be a causal event leading to dementia in Alzheimer's disease (AD). Aβ vaccination removes Aβ deposits from the brain. Aβ immunotherapy, however, may cause T cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal Aβ deposits to blood vessels leading to cerebral hemorrhages. Because catalytic antibodies do not form stable immune complexes and Aβ fragments produced by catalytic antibodies are less likely to form aggregates, Aβ-specific catalytic antibodies may have safer therapeutic profiles than reversibly-binding anti-Aβ antibodies. Additionally, catalytic antibodies may remove Aβ more efficiently than binding antibodies because a single catalytic antibody can hydrolyze thousands of Aβ molecules. We previously isolated Aβ-specific catalytic antibody, IgVL5D3, with strong Aβ-hydrolyzing activity. Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9) in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the unilateral hemisphere. IgVL5D3 expression was readily detectable in the contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of rAAV9-IgVL5D3 reduced Aβ load in the ipsilateral hippocampus of AD model mice. No evidence of hemorrhages, increased vascular amyloid deposits, increased proinflammatory cytokines, or infiltrating T-cells in the brains was found in the experimental animals. AAV9-mediated anti-Aβ catalytic antibody brain delivery can be prophylactic and therapeutic options for AD.

The origins of options.

PubMed

Smaldino, Paul E; Richerson, Peter J

2012-01-01

Most research on decision making has focused on how human or animal decision makers choose between two or more options, posed in advance by the researchers. The mechanisms by which options are generated for most decisions, however, are not well understood. Models of sequential search have examined the trade-off between continued exploration and choosing one's current best option, but still cannot explain the processes by which new options are generated. We argue that understanding the origins of options is a crucial but untapped area for decision making research. We explore a number of factors which influence the generation of options, which fall broadly into two categories: psycho-biological and socio-cultural. The former category includes factors such as perceptual biases and associative memory networks. The latter category relies on the incredible human capacity for culture and social learning, which doubtless shape not only our choices but the options available for choice. Our intention is to start a discussion that brings us closer toward understanding the origins of options.

The Origins of Options

PubMed Central

Smaldino, Paul E.; Richerson, Peter J.

2012-01-01

Most research on decision making has focused on how human or animal decision makers choose between two or more options, posed in advance by the researchers. The mechanisms by which options are generated for most decisions, however, are not well understood. Models of sequential search have examined the trade-off between continued exploration and choosing one’s current best option, but still cannot explain the processes by which new options are generated. We argue that understanding the origins of options is a crucial but untapped area for decision making research. We explore a number of factors which influence the generation of options, which fall broadly into two categories: psycho-biological and socio-cultural. The former category includes factors such as perceptual biases and associative memory networks. The latter category relies on the incredible human capacity for culture and social learning, which doubtless shape not only our choices but the options available for choice. Our intention is to start a discussion that brings us closer toward understanding the origins of options. PMID:22514515

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Part 90 option; notice of eligibility; exercise of option. 90.3 Section 90.3 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a...

The unsolved cyclosporine-induced kidney injury: is paricalcitol a feasible new renoprotective option?

PubMed

Reis, Flávio N F

2010-06-01

The management of cyclosporine A (CsA)-induced nephrotoxicity remains one of the main challenges in kidney transplantation. The animal study by Park et al. proposes that paricalcitol, a vitamin D analog with renoprotective actions reported in other conditions, attenuates CsA-induced kidney injury via the suppression of inflammatory, fibrotic, and apoptotic factors. Before paricalcitol can be considered a feasible new therapeutic option for post-transplantation nephropathy, these interesting data require further studies assessing other mechanisms of CsA-induced nephrotoxicity.

14 CFR 25.1533 - Additional operating limitations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... and wet), and runway gradients) for smooth, hard-surfaced runways. Additionally, at the option of the... for variable factors (such as altitude, temperature, wind, and runway gradients) are those at which...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

30 CFR 90.3 - Part 90 option; notice of eligibility; exercise of option.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Part 90 option; notice of eligibility; exercise... DEVELOPMENT OF PNEUMOCONIOSIS General § 90.3 Part 90 option; notice of eligibility; exercise of option. (a... meter of air. Each of these miners shall be notified in writing of eligibility to exercise the option...

Option pricing: Stock price, stock velocity and the acceleration Lagrangian

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.; Du, Xin; Bhanap, Jitendra

2014-12-01

The industry standard Black-Scholes option pricing formula is based on the current value of the underlying security and other fixed parameters of the model. The Black-Scholes formula, with a fixed volatility, cannot match the market's option price; instead, it has come to be used as a formula for generating the option price, once the so called implied volatility of the option is provided as additional input. The implied volatility not only is an entire surface, depending on the strike price and maturity of the option, but also depends on calendar time, changing from day to day. The point of view adopted in this paper is that the instantaneous rate of return of the security carries part of the information that is provided by implied volatility, and with a few (time-independent) parameters required for a complete pricing formula. An option pricing formula is developed that is based on knowing the value of both the current price and rate of return of the underlying security which in physics is called velocity. Using an acceleration Lagrangian model based on the formalism of quantum mathematics, we derive the pricing formula for European call options. The implied volatility of the market can be generated by our pricing formula. Our option price is applied to foreign exchange rates and equities and the accuracy is compared with Black-Scholes pricing formula and with the market price.

NASA's asteroid redirect mission: Robotic boulder capture option

NASA Astrophysics Data System (ADS)

Abell, P.; Nuth, J.; Mazanek, D.; Merrill, R.; Reeves, D.; Naasz, B.

2014-07-01

NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (˜4--10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is also examining another option that entails retrieving a boulder (˜1--5 m) via robotic manipulators from the surface of a larger (˜100+ m) pre-characterized NEA. The Robotic Boulder Capture (RBC) option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Japan Aerospace Exploration Agency's (JAXA) Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU_3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. This ARM option reduces mission risk and provides increased benefits for science, human exploration, resource utilization, and planetary defense.

New testing options for diagnosing and grading dry eye disease.

PubMed

Foulks, Gary N; Pflugfelder, Stephen C

2014-06-01

To describe new options for diagnosis and severity grading of dry eye disease. Perspective on technological advancements to identify tear dysfunction and their value in diagnosing and grading dry eye disease. Evidence is presented on new and evolving technologies to measure tear stability, composition, and meniscus height and their role in dry eye diagnosis and therapeutic efficacy grading is assessed. Evolving concepts regarding pathogenesis and new technologies to evaluate the tears and ocular surface have improved the ability to diagnose, classify, and grade the severity of dry eye disease. New technologies include noninvasive imaging of tear stability and tear meniscus height as a measure of tear volume and tear composition (osmolarity, lacrimal factors, inflammatory mediators, growth and differentiation factors). Approved tests, such as tear osmolarity and tear imaging, are being integrated into clinical practice and may eventually supplant certain traditional tests that have greater variability and less sensitivity. Other tests, such as molecular assays of tears and conjunctival cells, are currently being used in studies investigating pathogenesis and therapeutic mechanism of action. They may eventually translate to routine clinical practice. New technologies have emerged that can noninvasively evaluate the tears and measure disease-associated compositional changes. These tests are being integrated into clinical practice and therapeutic trials for diagnosis, classification, and severity grading of dry eye disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Risk profile and treatment options of acute ischemic in-hospital stroke.

PubMed

Schürmann, Kolja; Nikoubashman, Omid; Falkenburger, Björn; Tauber, Simone C; Wiesmann, Martin; Schulz, Jörg B; Reich, Arno

2016-03-01

Despite the potential immediate access to diagnosis and care, in-hospital stroke (IHS) is associated with delay in diagnosis, lower rates of reperfusion treatment, and unfavorable outcome. Endovascular reperfusion therapy has shown promising results in recent trials for community-onset strokes (COS) and is limited by less contraindications than systemic thrombolysis. Thus, endovascular approaches may offer additional acute treatment options for IHS. We performed a retrospective, observational monocentric analysis of patients with acute ischemic stroke between January 2010 and December 2014. Out of 3506 acute ischemic strokes, 331 (9.4%) were IHS. In-hospital mortality (31.4 vs. 8.0%) and duration of stay after stroke (19.5 vs. 12.1 days) were higher in IHS than in COS. Most IHS occurred in cardiologic and cardiosurgical patients after catheterization or surgery. In 111 cases (33.5%) the time of onset could not be established as a result of sedation or delayed referral resulting in delayed symptom recognition. 52 IHS (15.7%) and 828 COS (26.0%, p < 0.001) patients received any kind of reperfusion therapy, of which 59.6% (IHS) and 12.1% (COS) comprised isolated endovascular interventions (p < 0.001). Intra-hospital delays (time to brain imaging, systemic thrombolysis, and angiography) were longer and outcome parameters (mRS d90, in-hospital mortality, length of stay) were worse in IHS, whereas rates of procedural complications and intracranial hemorrhages were similar in both groups. The overall rate of reperfusion treatment is lower in IHS compared to COS, as IHS patients are less likely to be eligible for systemic thrombolysis. Interventional stroke treatment is a safe and feasible therapeutic option for patients who are not eligible for systemic thrombolysis and should be anticipated whenever IHS is diagnosed.

Therapeutic apheresis for severe hypertriglyceridemia in pregnancy.

PubMed

Basar, Rafet; Uzum, Ayse Kubat; Canbaz, Bulent; Dogansen, Sema Ciftci; Kalayoglu-Besisik, Sevgi; Altay-Dadin, Senem; Aral, Ferihan; Ozbey, Nese Colak

2013-05-01

During pregnancy, a progressive increase in serum triglyceride (TG) and cholesterol levels is observed whereas TG levels mostly remain <300 mg/dl. In women with genetic forms of hypertriglyceridemia, pregnancy may cause extremely elevated TG levels leading to potentially life-threatening pancreatitis attacks and chylomicronemia syndrome. The only safe medical treatment option during pregnancy is ω-3 fatty acids, which have moderate TG lowering effects. Therapeutic apheresis could be used as primary treatment approach during pregnancy. We reported the effect of double filtration apheresis in one pregnant women with severe hypertriglyceridemia, therapeutic plasmapheresis and double filtration methods in the other severe hypertriglyceridemic pregnant woman; a 32-year-old pregnant woman (patient 1) with a history of hypertriglyceridemia-induced acute pancreatitis during pregnancy and a 30-year-old pregnant woman with extremely high TG levels (12,000 mg/dl) leading to chylomicronemia syndrome (patient 2). Medical nutrition therapy and ω-3 fatty acids were also provided. Double filtration apheresis (patient 1) and plasmapheresis + double filtration apheresis (patient 2) were used. When we calculated the TG levels before and after therapeutic apheresis, maximum decrease achieved with double filtration apheresis was 46.3 % for patient 1 and 37.3 % for patient 2. However, with plasmapheresis TG level declined by 72 % in patient 2. Plasmapheresis seemed to be more efficient to decrease TG levels. Iron deficiency anemia was the main complication apart from technical difficulties by lipemic obstruction of tubing system. Healthy babies were born. Delivery led to decreases in TG levels. It is concluded that during pregnancy therapeutic apheresis is an effective method to decrease extremely high TG levels and risks of its potentially life-threatening complications.

Pelvic radiation disease: Updates on treatment options

PubMed Central

Frazzoni, Leonardo; La Marca, Marina; Guido, Alessandra; Morganti, Alessio Giuseppe; Bazzoli, Franco; Fuccio, Lorenzo

2015-01-01

Pelvic cancers are among the most frequently diagnosed neoplasms and radiotherapy represents one of the main treatment options. The irradiation field usually encompasses healthy intestinal tissue, especially of distal large bowel, thus inducing gastrointestinal (GI) radiation-induced toxicity. Indeed, up to half of radiation-treated patients say that their quality of life is affected by GI symptoms (e.g., rectal bleeding, diarrhoea). The constellation of GI symptoms - from transient to long-term, from mild to very severe - experienced by patients who underwent radiation treatment for a pelvic tumor have been comprised in the definition of pelvic radiation disease (PRD). A correct and evidence-based therapeutic approach of patients experiencing GI radiation-induced toxicity is mandatory. Therapeutic non-surgical strategies for PRD can be summarized in two broad categories, i.e., medical and endoscopic. Of note, most of the studies have investigated the management of radiation-induced rectal bleeding. Patients with clinically significant bleeding (i.e., causing chronic anemia) should firstly be considered for medical management (i.e., sucralfate enemas, metronidazole and hyperbaric oxygen); in case of failure, endoscopic treatment should be implemented. This latter should be considered the first choice in case of acute, transfusion requiring, bleeding. More well-performed, high quality studies should be performed, especially the role of medical treatments should be better investigated as well as the comparative studies between endoscopic and hyperbaric oxygen treatments. PMID:26677440

Review of Systemic Treatment Options for Adult Atopic Dermatitis.

PubMed

Gooderham, Melinda; Lynde, Charles W; Papp, Kim; Bourcier, Marc; Guenther, Lyn; Gulliver, Wayne; Hong, Chih-Ho; Poulin, Yves; Sussman, Gordon; Vender, Ronald

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease. To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy. A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search. Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence. Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.

Space station needs, attributes and architectural options study

NASA Technical Reports Server (NTRS)

1983-01-01

All the candidate Technology Development missions investigated during the space station needs, attributes, and architectural options study are described. All the mission data forms plus additional information such as, cost, drawings, functional flows, etc., generated in support of these mission is included with a computer generated mission data form.

Additive Manufacturing: From Form to Function

DTIC Science & Technology

2016-01-01

embedded electronics in clothing that could allow additional protective benefits and health monitoring options.13 AM has also enabled proof-of-concept...the International Space Station (ISS) in September 2014 to test plastics . The second 3D printer was delivered to the ISS in April 2016. In addition...was developed by the Innovative Advanced Concepts program. The sensor is essentially a transparent sheet of plastic with printed elec- tronics that

Surgical options for lumbosacral fusion: biomechanical stability, advantage, disadvantage and affecting factors in selecting options.

PubMed

Yoshihara, Hiroyuki

2014-07-01

Numerous surgical procedures and instrumentation techniques for lumbosacral fusion (LSF) have been developed. This is probably because of its high mechanical demand and unique anatomy. Surgical options include anterior column support (ACS) and posterior stabilization procedures. Biomechanical studies have been performed to verify the stability of those options. The options have their own advantage but also disadvantage aspects. This review article reports the surgical options for lumbosacral fusion, their biomechanical stability, advantages/disadvantages, and affecting factors in option selection. Review of literature. LSF has lots of options both for ACS and posterior stabilization procedures. Combination of posterior stabilization procedures is an option. Furthermore, combinations of ACS and posterior stabilization procedures are other options. It is difficult to make a recommendation or treatment algorithm of LSF from the current literature. However, it is important to know all aspects of the options and decision-making of surgical options for LSF needs to be tailored for each patient, considering factors such as biomechanical stress and osteoporosis.

Cachexia and pancreatic cancer: Are there treatment options?

PubMed Central

Mueller, Tara C; Burmeister, Marc A; Bachmann, Jeannine; Martignoni, Marc E

2014-01-01

Cachexia is frequently described in patients with pancreatic ductal adenocarcinoma (PDAC) and is associated with reduced survival and quality of life. Unfortunately, the therapeutic options of this multi-factorial and complex syndrome are limited. This is due to the fact that, despite extensive preclinical and clinical research, the underlying pathological mechanisms leading to PDAC-associated cachexia are still not fully understood. Furthermore, there is still a lack of consensus on the definition of cachexia, which complicates the standardization of diagnosis and treatment as well as the analysis of the current literature. In order to provide an efficient therapy for cachexia, an early and reliable diagnosis and consistent monitoring is required, which can be challenging especially in obese patients. Although many substances have been tested in clinical and preclinical settings, so far none of them have been proven to have a long-term effect in ameliorating cancer-associated cachexia. However, recent studies have demonstrated that multidimensional therapeutic modalities are able to alleviate pancreatic cancer-associated cachexia and ultimately improve patients’ outcome. In this current review, we propose a stepwise and pragmatic approach to facilitate and standardize the treatment of cachexia in pancreatic cancer patients. This strategy consists of nutritional, dietary, pharmacological, physical and psychological methods. PMID:25071331

Morphoproteomics, E6/E7 in-situ hybridization, and biomedical analytics define the etiopathogenesis of HPV-associated oropharyngeal carcinoma and provide targeted therapeutic options.

PubMed

Brown, Robert E; Naqvi, Syed; McGuire, Mary F; Buryanek, Jamie; Karni, Ron J

2017-08-17

biomedical analytics as consistent with published literature. This is significant because the biology lends itself to targeted therapeutic options using metformin, curcumin, celecoxib and sulforaphane as therapeutic strategies to prevent progression or recurrence of disease.

Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization

PubMed Central

Kurup, Shree; Lew, Julie; Byrnes, Gordon; Yeh, Steven; Nussenblatt, Robert; Levy-Clarke, Grace

2010-01-01

Purpose To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization. Methods Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab. Results Significant anatomical and functional recovery was evident in both patients within a few weeks. Conclusion In selected uveitic patients, bevacizumab may be an option for managing neovascularization. PMID:18513266

Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention.

PubMed

Mastellos, D C; Ricklin, D; Hajishengallis, E; Hajishengallis, G; Lambris, J D

2016-02-01

There is increasing appreciation that complement dysregulation lies at the heart of numerous immune-mediated and inflammatory disorders. Complement inhibitors are therefore being evaluated as new therapeutic options in various clinical translation programs and the first clinically approved complement-targeted drugs have profoundly impacted the management of certain complement-mediated diseases. Among the many members of the intricate protein network of complement, the central component C3 represents a 'hot-spot' for complement-targeted therapeutic intervention. C3 modulates both innate and adaptive immune responses and is linked to diverse immunomodulatory systems and biological processes that affect human pathophysiology. Compelling evidence from preclinical disease models has shown that C3 interception may offer multiple benefits over existing therapies or even reveal novel therapeutic avenues in disorders that are not commonly regarded as complement-driven, such as periodontal disease. Using the clinically developed compstatin family of C3 inhibitors and periodontitis as illustrative examples, this review highlights emerging therapeutic concepts and developments in the design of C3-targeted drug candidates as novel immunotherapeutics for oral and systemic inflammatory diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dedifferentiated Liposarcoma: Updates on Morphology, Genetics, and Therapeutic Strategies.

PubMed

Thway, Khin; Jones, Robin L; Noujaim, Jonathan; Zaidi, Shane; Miah, Aisha B; Fisher, Cyril

2016-01-01

Well-differentiated liposarcoma (WDL) and dedifferentiated liposarcoma (DDL) form the largest subgroup of liposarcomas, and represent a morphologic and behavioral spectrum of 1 disease entity, which arises typically in middle to late adult life, most frequently within the retroperitoneum or extremities. DDL is defined as nonlipogenic sarcoma that is juxtaposed to WDL, occurs as a recurrence of WDL or which can arise de novo, and typically has the appearance of undifferentiated pleomorphic or spindle cell sarcoma. DDL have a propensity for local recurrence, whereas distant metastasis is rarer, and behavior is related to anatomic site, with retroperitoneal neoplasms showing a significantly worse prognosis. Surgical resection remains the mainstay of treatment, and medical options for patients with aggressive recurrent or metastatic disease are limited. DDL share similar genetic abnormalities to WDL, with high-level amplifications of chromosome 12q14-15, including the MDM2 and CDK4 cell cycle oncogenes, and DDL harbor additional genetic changes, particularly coamplifications of 6q23 and 1p32. Novel therapies targeted at the gene products of chromosome 12 are being tested in clinical trials. We review the pathology and genetics of DDL, discussing morphologic patterns, immunohistochemical and genetic findings, the differential diagnosis, and future therapeutic strategies.

Treatment Options to Manage Wound Biofilm

PubMed Central

Jones, Curtis E.; Kennedy, John P.

2012-01-01

Background Bioburden is an accepted barrier to chronic wound healing. Defining the significance, phenotype, clinical classification, and treatment guidelines has been historically lacking of evidence and based on paradigms that do not represent the scientific or clinical reality. The Problem Chronic wound bioburden is typically abundant, polymicrobial, and extremely diverse. These microbes naturally adopt biofilm phenotypes, which are quite often viable but not culturable, thereby going undetected. The failures of culture-based detection have led to abandonment of routine bioburden evaluation and aggressive treatment or, worse, to assume bioburden is not a significant barrier. Predictably, treatment regimens to address biofilm phenotypes lagged behind our diagnostic tools and understanding. Basic/Clinical Science Advances Microbial DNA-based diagnostic tools and treatment regimens have emerged, which provide and leverage objective information, resulting in a dramatic impact on outcomes. Relevance to Clinical Care Modern medicine demands decisions based on objective evidence. The diagnostic and treatment protocols reviewed herein empower clinicians to practice modern medicine with regard to bioburden, with DNA level certainty. Conclusion Bioburden is a significant barrier to healing for all chronic wounds. Molecular diagnostics provide the first objective means of assessing wound bioburden. The accuracy and comprehensive data from such diagnostic methodologies provide clinicians with the ability to employ patient-specific treatment options, targeted to each patient's microbial wound census. Based on current outcomes data, the most effective therapeutic options are topical (TPL) antibiofilm agents (ABF) combined with TPL antibiotics (ABX). In specific patients, systemic ABX and selective biocides are also appropriate, but not exclusive of ABF combined with TPL ABX. PMID:24527291

Astroglial networks and implications for therapeutic neuromodulation of epilepsy.

PubMed

Witcher, Mark R; Ellis, Thomas L

2012-01-01

Epilepsy is a common chronic neurologic disorder affecting approximately 1% of the world population. More than one-third of all epilepsy patients have incompletely controlled seizures or debilitating medication side effects in spite of optimal medical management. Medically refractory epilepsy is associated with excess injury and mortality, psychosocial dysfunction, and significant cognitive impairment. Effective treatment options for these patients can be limited. The cellular mechanisms underlying seizure activity are incompletely understood, though we here describe multiple lines of evidence supporting the likely contribution of astroglia to epilepsy, with focus on individual astrocytes and their network functions. Of the emerging therapeutic modalities for epilepsy, one of the most intriguing is the field of neuromodulation. Neuromodulatory treatment, which consists of administering electrical pulses to neural tissue to modulate its activity leading to a beneficial effect, may be an option for these patients. Current modalities consist of vagal nerve stimulation, open and closed-loop stimulation, and transcranial magnetic stimulation. Due to their unique properties, we here present astrocytes as likely important targets for the developing field of neuromodulation in the treatment of epilepsy.

[Pancreatic pseudocyst in children: what is the best therapeutic approach?].

PubMed

Nouira, F; Ben Ahmed, Y; Sarrai, N; Ghorbel, S; Jlidi, S; Chaouachi, B

2011-11-01

Pancreatic pseudocyst is an uncommon disorder in children and the majority of reported cases are secondary to trauma. Treatment options range from medical management to different forms of drainage procedure. The aim of this study was to discuss therapeutic strategies. The authors report herein pancreatic pseudocyst in four children aged 7, 9, 12, and 13 years with non-resolving pancreatic pseudocyst over a 2-year period from January 2006 to July 2008. The etiology of pancreatic pseudocyst was abdominal trauma in two cases and acute pancreatitis in two cases. Ultrasound and computed tomography scans confirmed the diagnosis. Two patients had endoscopic drainage. There were no procedure-related complications, nor was there a recurrence of the cyst. In one case, the pancreatic pseudocyst resolved spontaneously. This report suggests that children with non-spontaneously resolving pancreatic pseudocyst can be treated successfully and safely with endoscopic drainage. Surgical treatment remains an important alternative in the therapeutic armamentarium of this affection. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Clinically advancing and promising polymer-based therapeutics.

PubMed

Souery, Whitney N; Bishop, Corey J

2018-02-01

In this review article, we will examine the history of polymers and their evolution from provisional World War II materials to medical therapeutics. To provide a comprehensive look at the current state of polymer-based therapeutics, we will classify technologies according to targeted areas of interest, including central nervous system-based and intraocular-, gastrointestinal-, cardiovascular-, dermal-, reproductive-, skeletal-, and neoplastic-based systems. Within each of these areas, we will consider several examples of novel, clinically available polymer-based therapeutics; in addition, this review will also include a discussion of developing therapies, ranging from the in vivo to clinical trial stage, for each targeted area of treatment. Finally, we will emphasize areas of patient care in need of more effective, accessible, and targeted treatment approaches where polymer-based therapeutics may offer potential solutions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Discrete choice experiment produced estimates of acceptable risks of therapeutic options in cancer patients with febrile neutropenia.

PubMed

Sung, Lillian; Alibhai, Shabbir M; Ethier, Marie-Chantal; Teuffel, Oliver; Cheng, Sylvia; Fisman, David; Regier, Dean A

2012-06-01

To use a discrete choice experiment (DCE) to describe patient/proxy tolerance for the number of clinic visits, and chances of readmission, intensive care unit admission, and mortality to accept oral outpatient management of low-risk febrile neutropenia. Adults and children aged 12-18 years with cancer and parents of pediatric cancer patients were asked to choose between outpatient oral and inpatient intravenous management of low-risk febrile neutropenia. Using a DCE, we varied the attribute levels with the outpatient option and kept them constant for the inpatient option. Seventy-eight adults, 153 parents, and 43 children provided responses. All four attributes significantly affected choices. The mean tolerance (95% confidence interval) for the number of clinic visits per week was 3.6 (2.2-4.8), 2.1 (1.1-3.2), and 4.3 (2.5-6.0) to accept outpatient management among adults, parents, and children, respectively. With thrice weekly clinic visits and 7.5% chance of readmission, probabilities of accepting the outpatient strategy were 50% (44-54%) for adults, 43% (39-48%) for parents, and 53% (46-59%) for children. Using a DCE, we determined that a 7.5% chance of readmission and clinic visits more frequently than thrice weekly are unlikely to be acceptable. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

PubMed

Cortina, Gerard; McRae, Rosemary; Chiletti, Roberto; Butt, Warwick

2018-02-01

To characterize the clinical indications, procedural safety, and outcome of critically ill children requiring therapeutic plasma exchange. Retrospective observational study based on a prospective registry. Tertiary and quaternary referral 30-bed PICU. Forty-eight critically ill children who received therapeutic plasma exchange during an 8-year period (2007-2014) were included in the study. Therapeutic plasma exchange. A total of 48 patients underwent 244 therapeutic plasma exchange sessions. Of those, therapeutic plasma exchange was performed as sole procedure in 193 (79%), in combination with continuous renal replacement therapy in 40 (16.4%) and additional extracorporeal membrane oxygenation in 11 (4.6%) sessions. The most common admission diagnoses were hematologic disorders (30%), solid organ transplantation (20%), neurologic disorders (20%), and rheumatologic disorders (15%). Complications associated with the procedure occurred in 50 (21.2%) therapeutic plasma exchange sessions. Overall, patient survival from ICU was 82%. Although patients requiring therapeutic plasma exchange alone (n = 31; 64%) had a survival rate of 97%, those with additional continuous renal replacement therapy (n = 13; 27%) and extracorporeal membrane oxygenation (n = 4; 8%) had survival rates of 69% and 50%, respectively. Factors associated with increased mortality were lower Pediatric Index of Mortality 2 score, need for mechanical ventilation, higher number of failed organs, and longer ICU stay. Our results indicate that, in specialized centers, therapeutic plasma exchange can be performed relatively safely in critically ill children, alone or in combination with continuous renal replacement therapy and extracorporeal membrane oxygenation. Outcome in children requiring therapeutic plasma exchange alone is excellent. However, survival decreases with the number of failed organs and the need for continuous renal replacement therapy and extracorporeal membrane oxygenation.

An emerging treatment option for glaucoma: Rho kinase inhibitors

PubMed Central

Wang, Sean K; Chang, Robert T

2014-01-01

Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma. PMID:24872673

SATPdb: a database of structurally annotated therapeutic peptides

PubMed Central

Singh, Sandeep; Chaudhary, Kumardeep; Dhanda, Sandeep Kumar; Bhalla, Sherry; Usmani, Salman Sadullah; Gautam, Ankur; Tuknait, Abhishek; Agrawal, Piyush; Mathur, Deepika; Raghava, Gajendra P.S.

2016-01-01

SATPdb (http://crdd.osdd.net/raghava/satpdb/) is a database of structurally annotated therapeutic peptides, curated from 22 public domain peptide databases/datasets including 9 of our own. The current version holds 19192 unique experimentally validated therapeutic peptide sequences having length between 2 and 50 amino acids. It covers peptides having natural, non-natural and modified residues. These peptides were systematically grouped into 10 categories based on their major function or therapeutic property like 1099 anticancer, 10585 antimicrobial, 1642 drug delivery and 1698 antihypertensive peptides. We assigned or annotated structure of these therapeutic peptides using structural databases (Protein Data Bank) and state-of-the-art structure prediction methods like I-TASSER, HHsearch and PEPstrMOD. In addition, SATPdb facilitates users in performing various tasks that include: (i) structure and sequence similarity search, (ii) peptide browsing based on their function and properties, (iii) identification of moonlighting peptides and (iv) searching of peptides having desired structure and therapeutic activities. We hope this database will be useful for researchers working in the field of peptide-based therapeutics. PMID:26527728

Option price and market instability

NASA Astrophysics Data System (ADS)

Baaquie, Belal E.; Yu, Miao

2017-04-01

An option pricing formula, for which the price of an option depends on both the value of the underlying security as well as the velocity of the security, has been proposed in Baaquie and Yang (2014). The FX (foreign exchange) options price was empirically studied in Baaquie et al., (2014), and it was found that the model in general provides an excellent fit for all strike prices with a fixed model parameters-unlike the Black-Scholes option price Hull and White (1987) that requires the empirically determined implied volatility surface to fit the option data. The option price proposed in Baaquie and Cao Yang (2014) did not fit the data during the crisis of 2007-2008. We make a hypothesis that the failure of the option price to fit data is an indication of the market's large deviation from its near equilibrium behavior due to the market's instability. Furthermore, our indicator of market's instability is shown to be more accurate than the option's observed volatility. The market prices of the FX option for various currencies are studied in the light of our hypothesis.

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

PubMed

Griffith, Gina L; Kasus-Jacobi, Anne; Pereira, H Anne

2017-06-01

Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit.

[Psychological aspects of pruritus and therapy options].

PubMed

Stumpf, A; Schut, C; Schneider, G

2016-08-01

Besides biological factors, which cause or influence chronic pruritus, more and more attention has recently also been paid to psychological and psychoneuroimmunological factors which uphold the symptom. This review article gives an overview of the state of research regarding psychological and psychoneuroimmunological factors and the resulting therapeutic options. The article is based on a literature search in the PubMed database. Under experimental conditions, pruritus can be induced by verbal instructions and modulated by placebo and nocebo effects. Stressful life events can also induce pruritus or its exacerbation. This can also be demonstrated on a cellular level. The knowledge that pruritus intensity is modulated by cognitions, behavioral factors, and stress is important for the development and application of psychological interventions. More research should be done regarding psychological interventions in the treatment of chronic itch and they should be applied clinically more often.

Pectus excavatum: history, hypotheses and treatment options

PubMed Central

Brochhausen, Christoph; Turial, Salmai; Müller, Felix K.P.; Schmitt, Volker H.; Coerdt, Wiltrud; Wihlm, Jean-Marie; Schier, Felix; Kirkpatrick, C. James

2012-01-01

Pectus excavatum and pectus carinatum represent the most frequent chest wall deformations. However, the pathogenesis is still poorly understood and research results remain inconsistent. To focus on the recent state of knowledge, we summarize and critically discuss the pathological concepts based on the history of these entities, beginning with the first description in the sixteenth century. Based on the early clinical descriptions, we review and discuss the different pathogenetic hypotheses. To open new perspectives for the potential pathomechanisms, the embryonic and foetal development of the ribs and the sternum is highlighted following the understanding that the origin of these deformities is given by the disruption in the maturation of the parasternal region. In the second, different therapeutical techniques are highlighted and based on the pathogenetic hypotheses and the embryological knowledge potential new biomaterial-based perspectives with interesting insights for tissue engineering-based treatment options are presented. PMID:22394989

Efficient Trajectory Options Allocation for the Collaborative Trajectory Options Program

NASA Technical Reports Server (NTRS)

Rodionova, Olga; Arneson, Heather; Sridhar, Banavar; Evans, Antony

2017-01-01

The Collaborative Trajectory Options Program (CTOP) is a Traffic Management Initiative (TMI) intended to control the air traffic flow rates at multiple specified Flow Constrained Areas (FCAs), where demand exceeds capacity. CTOP allows flight operators to submit the desired Trajectory Options Set (TOS) for each affected flight with associated Relative Trajectory Cost (RTC) for each option. CTOP then creates a feasible schedule that complies with capacity constraints by assigning affected flights with routes and departure delays in such a way as to minimize the total cost while maintaining equity across flight operators. The current version of CTOP implements a Ration-by-Schedule (RBS) scheme, which assigns the best available options to flights based on a First-Scheduled-First-Served heuristic. In the present study, an alternative flight scheduling approach is developed based on linear optimization. Results suggest that such an approach can significantly reduce flight delays, in the deterministic case, while maintaining equity as defined using a Max-Min fairness scheme.

The costs and benefits of Option B+ for the prevention of mother-to-child transmission of HIV.

PubMed

Gopalappa, Chaitra; Stover, John; Shaffer, Nathan; Mahy, Mary

2014-01-01

Most countries follow WHO 2010 guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV using either Option A or B for women not yet eligible for antiretroviral therapy (ART). Both of these approaches involve the use of antiretrovirals during pregnancy and breastfeeding. Some countries have adopted a new strategy, Option B+, in which HIV-positive pregnant women are started immediately on ART and continued for life. Option B+ is more costly than Options A or B, but provides additional health benefits. In this article, we estimate the additional costs and effectiveness of Option B+. We developed a deterministic model to simulate births, breastfeeding, and HIV infection in women in four countries, Kenya, Zambia, South Africa, and Vietnam that differ in fertility rate, birth interval, age at first birth, and breastfeeding patterns, but have similar age at HIV infection. We estimated the total PMTCT costs and new child infections under Options A, B, and B+, and measured cost-effectiveness as the incremental PMTCT-related costs per child infection averted. We included adult sexual transmissions averted from ART, the corresponding costs saved, and estimated the total incremental cost per transmission (child and adult) averted. When considering PMTCT-related costs and child infections, Option B+ was the most cost-effective strategy costing between $6000 and $23 000 per infection averted compared with Option A. Option B+ averted more child infections compared with Option B in all four countries and cost less than Option B in Kenya and Zambia. When including adult sexual transmissions averted, Option B+ cost less and averted more infections than Options A and B.

Comparing the ability of OPTION(12) and OPTION(5) to assess shared decision-making in genetic counselling.

PubMed

Vortel, Martina A; Adam, Shelin; Port-Thompson, Ashley V; Friedman, Jan M; Grande, Stuart W; Birch, Patricia H

2016-10-01

OPTION(12) is the most widely used tool to measure shared decision-making (SDM) in health care. A newer scale, OPTION(5), has been proposed as a more parsimonious measure that better addresses core concepts of SDM. This study compares OPTION(5) to OPTION(12) in prenatal genetic counselling. Two raters independently used OPTION(12) and OPTION(5) to score 27 clinical encounters between genetic counsellors (GC) and women with pregnancies at increased risk for genetic conditions. Global and item scores on the two instruments were compared to test concurrent validity and to identify usability in this context. Inter-rater reliability was also assessed for both instruments. Mean scores for OPTION(12) were 43.8 (SD=9.7), and for OPTION(5) were=60.6 (SD=12.5). The correlation between OPTION(12) and OPTION(5) scores was r=0.70. Inter-rater reliability was 0.70 and 0.85 for OPTION(12) and OPTION(5) respectively, however mean inter-rater reliability for individual items was 0.31 and 0.63 for OPTION(12) and OPTION(5) respectively. GCs exhibit SDM as measured by both OPTION instruments. OPTION(5) exhibits improved psychometric performance relative to OPTION(12), and more specifically targets the core constructs of SDM. However, refinement of OPTION instruments or manuals is needed to improve reliability and validity in GC assessment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Pawnee Nation Energy Option Analyses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matlock, M.; Kersey, K.; Riding In, C.

2009-07-31

code and introduced two model energy codes Pawnee Nation should consider for adoption. Summary of Current and Expected Future Electricity Usage The research team provided a summary overview of electricity usage patterns in current buildings and included discussion of known plans for new construction. Utility Options Review Pawnee Nation electric utility options were analyzed through a four-phase process, which included: 1) summarizing the relevant utility background information; 2) gathering relevant utility assessment data; 3) developing a set of realistic Pawnee electric utility service options, and 4) analyzing the various Pawnee electric utility service options for the Pawnee Energy Team’s consideration. III. Findings and Recommendations Due to a lack of financial incentives for renewable energy, particularly at the state level, combined mediocre renewable energy resources, renewable energy development opportunities are limited for Pawnee Nation. However, near-term potential exists for development of solar hot water at the gym, and an exterior wood-fired boiler system at the tribe’s main administrative building. Pawnee Nation should also explore options for developing LFGTE resources in collaboration with the City of Pawnee. Significant potential may also exist for development of bio-energy resources within the next decade. Pawnee Nation representatives should closely monitor market developments in the bio-energy industry, establish contacts with research institutions with which the tribe could potentially partner in grant-funded research initiatives. In addition, a substantial effort by the Kaw and Cherokee tribes is underway to pursue wind development at the Chilocco School Site in northern Oklahoma where Pawnee is a joint landowner. Pawnee Nation representatives should become actively involved in these development discussions and should explore the potential for joint investment in wind development at the Chilocco site.« less

Implementation of power barrier option valuation

NASA Astrophysics Data System (ADS)

Cahyani, Agatha C. P.; Sumarti, Novriana

2015-09-01

Options are financial instruments that can be utilized to reduce risk in stock investment. Barrier options are one of the major types of options actively used in financial markets where its life period depends on the path of the underlying stock prices. The features of the barrier option can be used to modify other types of options. In this research, the barrier option will be implemented into power option, so it is called power barrier option. This option is an extension of the vanilla barrier options where the Call payoff being considered is defined as P C =max (STβ-Kβ,0 ) , and the Put payoff being considered is defined as P P =max (Kβ-STβ,0 ) . Here β > 0 and β ≠ 1, K is the strike price of the option, and ST is the price of the underlying stock at time maturity T. In this paper, we generate the prices of stock using binomial method which is adjusted to the power option. In the conclusion, the price of American power barrier option is more expensive than the price of European power barrier option.

An accurate European option pricing model under Fractional Stable Process based on Feynman Path Integral

NASA Astrophysics Data System (ADS)

Ma, Chao; Ma, Qinghua; Yao, Haixiang; Hou, Tiancheng

2018-03-01

In this paper, we propose to use the Fractional Stable Process (FSP) for option pricing. The FSP is one of the few candidates to directly model a number of desired empirical properties of asset price risk neutral dynamics. However, pricing the vanilla European option under FSP is difficult and problematic. In the paper, built upon the developed Feynman Path Integral inspired techniques, we present a novel computational model for option pricing, i.e. the Fractional Stable Process Path Integral (FSPPI) model under a general fractional stable distribution that tackles this problem. Numerical and empirical experiments show that the proposed pricing model provides a correction of the Black-Scholes pricing error - overpricing long term options, underpricing short term options; overpricing out-of-the-money options, underpricing in-the-money options without any additional structures such as stochastic volatility and a jump process.

Update on therapeutic interventions for the management of achalasia.

PubMed

Gunasingam, Nishmi; Perczuk, Adam; Talbot, Michael; Kaffes, Arthur; Saxena, Payal

2016-08-01

Achalasia is a primary esophageal motility disorder. It is the absence of peristalsis in the esophageal body and inability of the lower esophageal sphincter to relax, which characterizes this rare condition. Its features typically include dysphagia, regurgitation, chest pain, and weight loss. The ultimate goal in treating achalasia is to relieve the patient's symptoms, improve esophageal emptying, and prevent further dilatation of the esophagus. Current treatment modalities targeted at achalasia include pharmacological therapy, endoscopic therapy, and surgery. This review focuses on the current therapeutic options and explores the role of peroral endoscopic myotomy in the management armamentarium. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Novel Therapeutics for Therapy-Related Acute Myeloid Leukemia: 2014.

PubMed

Feldman, Eric J

2015-06-01

Effective treatment options for adults with therapy-related AML continues to be an area of unmet need. Genetic and molecular changes within these leukemias confer resistance to standard chemotherapy regimens. Emerging developmental therapeutics in this area has focused on several approaches. These include; novel delivery of chemotherapy as well as newer DNA-damaging agents delivered through antibody-drug conjugates, increased use of hypomethylating agents, and molecularly-directed small molecules against specific mutations commonly occurring in secondary AML. Results of this efforts are encouraging, but to date, no clear improvements have been demonstrated in this most difficult to treat population. Copyright © 2015 Elsevier Inc. All rights reserved.

Recent Progress in Nanomedicine: Therapeutic, Diagnostic and Theranostic Applications

PubMed Central

Rizzo, Larissa Y.; Theek, Benjamin; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2013-01-01

In recent years, the use of nanomedicine formulations for therapeutic and diagnostic applications has increased exponentially. Many different systems and strategies have been developed for drug targeting to pathological sites, as well as for visualizing and quantifying important (patho-) physiological processes. In addition, ever more efforts have been undertaken to combine diagnostic and therapeutic properties within a single nanomedicine formulation. These so-called nanotheranostics are able to provide valuable information on drug delivery, drug release and drug efficacy, and they are considered to be highly useful for personalizing nanomedicine-based (chemo-) therapeutic interventions. PMID:23578464

Selected Energy Conservation Options for Homeowners: Options, Expenses and Payoffs.

ERIC Educational Resources Information Center

Lengyel, Dorothy L.; And Others

This publication is a check list for homeowners and renters to help them reduce energy costs. The list consists of 126 energy conservation options. These options range from "change clothes instead of adjusting thermostat" and "air conditioners turned off when not home" to "use sink stopper" and "weatherstripping…

Cardiac Sarcoidosis: Clinical Manifestations, Imaging Characteristics, and Therapeutic Approach

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

Sarcoidosis is a multi-system disease pathologically characterized by the accumulation of T-lymphocytes and mononuclear phagocytes into the sine qua non pathologic structure of the noncaseating granuloma. Cardiac involvement remains a key source of morbidity and mortality in sarcoidosis. Definitive diagnosis of cardiac sarcoidosis, particularly early enough in the disease course to provide maximal therapeutic impact, has proven a particularly difficult challenge. However, major advancements in imaging techniques have been made in the last decade. Advancements in imaging modalities including echocardiography, nuclear spectroscopy, positron emission tomography, and magnetic resonance imaging all have improved our ability to diagnose cardiac sarcoidosis, and in many cases to provide a more accurate prognosis and thus targeted therapy. Likewise, therapy for cardiac sarcoidosis is beginning to advance past a “steroids-only” approach, as novel immunosuppressant agents provide effective steroid-sparing options. The following focused review will provide a brief discussion of the epidemiology and clinical presentation of cardiac sarcoidosis followed by a discussion of up-to-date imaging modalities employed in its assessment and therapeutic approaches. PMID:25452702

Clinical and therapeutic aspects of childhood kerosene poisoning in Djibouti.

PubMed

Benois, Alain; Petitjeans, Fabrice; Raynaud, Laurent; Dardare, Eric; Sergent, Hervé

2009-10-01

We report a prospective and descriptive study about childhood acute poisoning with kerosene in Djibouti. Acute poisoning is a common and stable occurrence in low socioeconomic groups in Africa, where negligence is the main cause of poisoning. The respiratory system was the main target, with 41% of patients having pneumonia, which may become life-threatening, but with low mortality rate. Asymptomatic patients (35%) can be discharged, while those with pulmonary or neurological signs must be admitted for observation and supportive treatment based on oxygen administration. Our study suggests management and provides a discussion for therapeutic options and emphasizes the importance of prevention.

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

PubMed Central

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

Evaluation of transcranial surgical decompression of the optic canal as a treatment option for traumatic optic neuropathy.

PubMed

He, Zhenhua; Li, Qiang; Yuan, Jingmin; Zhang, Xinding; Gao, Ruiping; Han, Yanming; Yang, Wenzhen; Shi, Xuefeng; Lan, Zhengbo

2015-07-01

Traumatic optic neuropathy (TON) is a serious complication of head trauma, with the incidence rate ranging from 0.5% to 5%. The two treatment options widely practiced for TON are: (i) high-dose corticosteroid therapy and (ii) surgical decompression. However, till date, there is no consensus on the treatment protocol. This study aimed to evaluate the therapeutic efficacy of transcranial decompression of optic canal in TON patients. A total of 39 patients with visual loss resulting from TON between January 2005 and June 2013 were retrospectively reviewed for preoperative vision, preoperative image, visual evoked potential (VEP), surgical approach, postoperative visual acuity, complications, and follow-up results. All these patients underwent transcranial decompression of optic canal. During the three-month follow-up period, among the 39 patients, 21 showed an improvement in their eyesight, 6 recovered to standard logarithmic visual acuity chart "visible," 10 could count fingers, 2 could see hand movement, and 3 regained light sensation. Visual evoked potential could be used as an important preoperative and prognostic evaluation parameter for TON patients. Once TON was diagnosed, surgery is a promising therapeutic option, especially when a VEP wave is detected, irrespective of the HRCT scan findings. Operative time between trauma and operation is not necessary reference to assess the therapeutic effect of surgical decompression. The poor results of this procedure may be related to the severity of optic nerve injury. The patient's age is an important factor affecting the surgical outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Expensing options solves nothing.

PubMed

Sahlman, William A

2002-12-01

The use of stock options for executive compensation has become a lightning rod for public anger, and it's easy to see why. Many top executives grew hugely rich on the back of the gains they made on their options, profits they've been able to keep even as the value they were supposed to create disappeared. The supposed scam works like this: Current accounting regulations let companies ignore the cost of option grants on their income statements, so they can award valuable option packages without affecting reported earnings. Not charging the cost of the grants supposedly leads to overstated earnings, which purportedly translate into unrealistically high share prices, permitting top executives to realize big gains when they exercise their options. If an accounting anomaly is the problem, then the solution seems obvious: Write off executive share options against the current year's revenues. The trouble is, Sahlman writes, expensing option grants won't give us a more accurate view of earnings, won't add any information not already included in the financial statements, and won't even lead to equal treatment of different forms of executive pay. Far worse, expensing evades the real issue, which is whether compensation (options and other-wise) does what it's supposed to do--namely, help a company recruit, retain, and provide the right people with appropriate performance incentives. Any performance-based compensation system has the potential to encourage cheating. Only ethical management, sensible governance, adequate internal control systems, and comprehensive disclosure will save the investor from disaster. If, Sahlman warns, we pass laws that require the expensing of options, thinking that's fixed the fundamental flaws in corporate America's accounting, we will have missed a golden opportunity to focus on the much more extensive defects in the present system.

NASA's Asteroid Redirect Mission: The Boulder Capture Option

NASA Technical Reports Server (NTRS)

Abell, Paul A.; Nuth, J.; Mazanek, D.; Merrill, R.; Reeves, D.; Naasz, B.

2014-01-01

NASA is examining two options for the Asteroid Redirect Mission (ARM), which will return asteroid material to a Lunar Distant Retrograde Orbit (LDRO) using a robotic solar-electric-propulsion spacecraft, called the Asteroid Redirect Vehicle (ARV). Once the ARV places the asteroid material into the LDRO, a piloted mission will rendezvous and dock with the ARV. After docking, astronauts will conduct two extravehicular activities (EVAs) to inspect and sample the asteroid material before returning to Earth. One option involves capturing an entire small (approximately 4-10 m diameter) near-Earth asteroid (NEA) inside a large inflatable bag. However, NASA is examining another option that entails retrieving a boulder (approximately 1-5 m) via robotic manipulators from the surface of a larger (approximately 100+ m) pre-characterized NEA. This option can leverage robotic mission data to help ensure success by targeting previously (or soon to be) well-characterized NEAs. For example, the data from the Hayabusa mission has been utilized to develop detailed mission designs that assess options and risks associated with proximity and surface operations. Hayabusa's target NEA, Itokawa, has been identified as a valid target and is known to possess hundreds of appropriately sized boulders on its surface. Further robotic characterization of additional NEAs (e.g., Bennu and 1999 JU3) by NASA's OSIRIS REx and JAXA's Hayabusa 2 missions is planned to begin in 2018. The boulder option is an extremely large sample-return mission with the prospect of bringing back many tons of well-characterized asteroid material to the Earth-Moon system. The candidate boulder from the target NEA can be selected based on inputs from the world-wide science community, ensuring that the most scientifically interesting boulder be returned for subsequent sampling. This boulder option for NASA's ARM can leverage knowledge of previously characterized NEAs from prior robotic missions, which provides more

Injectable contraception. New and existing options.

PubMed

Kaunitz, A M

2000-12-01

DMPA and MPA/E2C contraception offer women safe, effective, convenient, and reversible birth control choices. The use of DMPA, a 3-month injectable, is characteristically associated with amenorrhea. Lactating women and women in whom contraceptive doses of estrogen are contraindicated can use this progestin-only birth control method. Return of fertility can be delayed in women discontinuing DMPA to become pregnant. In some cases, the use of DMPA also confers important noncontraceptive and therapeutic benefits. A monthly estrogen/progestin injectable contraceptive, MPA/E2C should appeal to women who are concerned about daily pill taking, who prefer regular cycles to amenorrhea, and who find monthly injections acceptable and accessible. As is true for oral contraceptives, MPA/E2C represents an appropriate choice for women who prefer a rapidly reversible contraceptive. Currently, the proposed contraindications for MPA/E2C parallel those for combined oral contraceptives. As MPA/E2C contraception becomes available for American women, clinicians will learn how to best include this new method among the array of contraceptive choices. By individualizing contraceptive selection, counseling, and management approaches based on the relevant behavioral and medical considerations reviewed herein, clinicians can maximize their patients' success with injectable contraceptives. The more innovative that clinicians, family planning agencies, and insurers are in facilitating access to care (including reinjections), the more women will be able to avail themselves of safe, effective, and reversible methods of contraception. In addition to the physician's office or health clinic, other sites at which women might receive contraceptive injections include employee health clinics, college health clinics, or perhaps the pharmacy where the prescription is filled. Self-administration may become an appropriate option for some users of injectable contraception.

Distributed Energy Implementation Options

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shah, Chandralata N

2017-09-13

This presentation covers the options for implementing distributed energy projects. It distinguishes between options available for distributed energy that is government owned versus privately owned, with a focus on the privately owned options including Energy Savings Performance Contract Energy Sales Agreements (ESPC ESAs). The presentation covers the new ESPC ESA Toolkit and other Federal Energy Management Program resources.

Sulfur mustard skin lesions: A systematic review on pathomechanisms, treatment options and future research directions.

PubMed

Rose, Dorothee; Schmidt, Annette; Brandenburger, Matthias; Sturmheit, Tabea; Zille, Marietta; Boltze, Johannes

2018-09-01

Sulfur mustard (SM) is a chemical warfare, which has been used for one hundred years. However, its exact pathomechanisms are still incompletely understood and there is no specific therapy available so far. In this systematic review, studies published between January 2000 and July 2017 involving pathomechanisms and experimental treatments of SM-induced skin lesions were analyzed to summarize current knowledge on SM pathology, to provide an overview on novel treatment options, and to identify promising targets for future research to more effectively counter SM effects. We suggest that future studies should focus on (I) systemic effects of SM intoxication due to its distribution throughout the body, (II) removal of SM depots that continuously release active compound contributing to chronic skin damage, and (III) therapeutic options that counteract the pleiotropic effects of SM. Copyright © 2017 Elsevier B.V. All rights reserved.

Consumer satisfaction with psychiatric services: The role of shared decision making and the therapeutic relationship.

PubMed

Klingaman, Elizabeth A; Medoff, Deborah R; Park, Stephanie G; Brown, Clayton H; Fang, Lijuan; Dixon, Lisa B; Hack, Samantha M; Tapscott, Stephanie L; Walsh, Mary Brighid; Kreyenbuhl, Julie A

2015-09-01

Although dissatisfaction is a primary reason for disengagement from outpatient psychiatric care among consumers with serious mental illnesses, little is known about predictors of their satisfaction with medication management visits. The primary purpose of this study was to explore how dimensions of consumer preferences for shared decision making (i.e., preferences for obtaining knowledge about one's mental illness, being offered and asked one's opinion about treatment options, and involvement in treatment decisions) and the therapeutic relationship (i.e., positive collaboration and type of clinician input) were related to visit satisfaction. Participants were 228 Veterans with serious mental illnesses who completed a 19-item self-report questionnaire assessing satisfaction with visits to prescribers (524 assessments) immediately after visits. In this correlational design, a 3-level mixed model with the restricted maximum likelihood estimation procedure was used to examine shared decision-making preferences and therapeutic alliance as predictors of visit satisfaction. Preferences for involvement in treatment decisions was the unique component of shared decision making associated with satisfaction, such that the more consumers desired involvement, the less satisfied they were. Positive collaboration and prescriber input were associated with greater visit satisfaction. When consumers with serious mental illnesses express preferences to be involved in shared decision making, it may not be sufficient to only provide information and treatment options; prescribers should attend to consumers' interest in involvement in actual treatment decisions. Assessment and tailoring of treatment approaches to consumer preferences for shared decision making should occur within the context of a strong therapeutic relationship. (c) 2015 APA, all rights reserved).

The results of therapeutic plasma exchange in patients with severe hyperthyroidism: a retrospective multicenter study.

PubMed

Keklik, Muzaffer; Kaynar, Leylagul; Yilmaz, Mehmet; Sivgin, Serdar; Solmaz, Musa; Pala, Cigdem; Aribas, Sulbiye; Akyol, Gulsah; Unluhizarci, Kursat; Cetin, Mustafa; Eser, Bulent; Unal, Ali

2013-06-01

Hyperthyroidism characterized by elevated serum levels of circulating thyroid hormones. The aim of hyperthyroidism treatment is to achieve a euthyroid state as soon as possible and to maintain euthyroid status. However, drug withdrawal and utilization of alternative therapies are needed in cases in which leucopenia or impairment in liver functions is observed during medical therapy. In the present study, we aimed to present our cases which underwent therapeutic plasma exchange (TPE) due to severe hyperthyroidism. The results of 22 patients who underwent therapeutic plasma exchange due to hyperthyroidism in Apheresis Units of Erciyes University and Gaziantep University, between 2006 and 2012, were retrospectively reviewed. These cases had severe thyrotoxic values despite anti-thyroid drug use. After TPE, we observed a significant decrease in free thyroxin (FT4) (p<0.001) and free triiodotyhronin (FT3) (p<0.004) levels. There was statistically significant increase in the mean values of TSH levels after TPE (p<0.001). Clinical improvement was achieved in hyperthyroidism by TPE in 20 cases (91%). Both FT3 and FT4 levels remained above the normal limits in two of 22 patients. TPE should be considered as an effective and safe therapeutic option to achieve euthyroid state before surgery or radioactive iodine treatment. TPE is a useful option in cases with severe hyperthyroidism unresponsive to anti-thyroid agents and in those with clinical manifestations of cardiac failure and in patients with severe adverse events during anti-thyroid therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contraceptive options for women living with HIV.

PubMed

Phillips, Sharon; Steyn, Petrus; Temmerman, Marleen

2014-08-01

Women living with HIV are often of reproductive age, and many desire effective contraceptive options to delay or prevent pregnancy. We review the safety of various hormonal and non-hormonal contraceptive methods for women living with human immunodeficiency virus (HIV). Additionally, we discuss drug interactions between contraceptive methods and antiretrovirals and the safety of methods with respect to onward transmission to HIV-negative partners for women in sero-discordant partnerships. In general, most methods are safe for most women living with HIV. An understanding of the reproductive goals of each individual patient, as well as her medical condition and medication, should be taken into account when counselling women on their contraceptive options. Further research is needed to understand drug interactions between contraceptives and antiretrovirals better and how to fulfil the contraceptive needs of HIV-positive women. Copyright © 2014. Published by Elsevier Ltd.

75 FR 6243 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... capacity to handle the additional traffic associated with the listing and trading of $1 strikes (where the... Change, and Amendment No. 1 Thereto, To Establish Strike Price Intervals and Trading Hours for Options on... the commencement of trading options on Index-Linked Securities, CBOE proposes to establish strike...

[Premenstrual dysphoric disorder: diagnosis and therapeutic strategy].

PubMed

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.

Microbiome therapeutics - Advances and challenges.

PubMed

Mimee, Mark; Citorik, Robert J; Lu, Timothy K

2016-10-01

The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. Copyright © 2016. Published by Elsevier B.V.

[Attention deficit hyperactivity disorder: pharmacological options that are not "Ritalin"].

PubMed

Shmueli, Dorit; Gross-Tsur, Varda

2005-08-01

Methylphenidate (Ritalin) is the drug of choice for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). Methylphenidate has been rigorously studied and found to be a safe and effective drug. However, there is a need for pharmacological alternatives since there are patients and therapists who are reluctant to use the drug. In some cases it is ineffective, others suffer from intolerable side effects and still others need treatment extended for the entire day. Recently, new pharmacological agents have been introduced for use in Israel. This article discusses the use of these new psychostimulants as well as other non-psychostimulant options. One of the new psychostimulants is Concerta, a very long acting methylphenidate preparation, that has been shown to be very effective. Adderall, a mixture of amphetamine salts, and Dexedrine (dexamphetamine) are also widely used. This article also presents data on an older psychostimulant, Cylert, Nitan (pemoline), prescribed until recently as a major alternative for Ritalin but, at present, it is rarely used because of its hepatotoxicity. Strattera (atomoxetine), a new non-stimulant drug, is a selective noradrenaline reuptake inhibitor that is a promising therapeutic option for children with ADHD. In summary, it is encouraging that there are multiple pharmacological options for treating children with ADHD. There is no one drug for all children and this is particularly important for children with do not respond to methylphenidate. Last, but not least, the mere fact that the new drugs are not called Ritalin, may play an important role in reducing the irrational opposition to the pharmacological treatment of ADHD.

Biomedical applications of microneedles in therapeutics: recent advancements and implications in drug delivery.

PubMed

Rejinold, N Sanoj; Shin, Ju-Hyung; Seok, Hae Yong; Kim, Yeu-Chun

2016-01-01

The skin, as the largest organ, is a better option for drug delivery in many diseases. However, most transdermal delivery is difficult due to the low permeability of therapeutics across the various skin layers. There have been many innovations in transdermal drug delivery to enhance the therapeutic efficacy of the drugs administered. Microneedles (MN), micron sized needles, are of great interest to scientists as a new therapeutic vehicle through transdermal routes, especially for vaccines, drugs, small molecules, etc. This review covers new insights into different types of MNs such as solid, hollow, coated and dissolving MNs (SMNs, HMNs, CMNs, and DMNs) for selected biomedical applications in detail. Specific focus has been given to CMNs and DMNs for vaccine and drug delivery applications with recent developments in new MNs covered. This review explores the feasibility of innovative MNs used as a drug delivery carrier. Because most of the SMNs and HMNs have many limitations, it is difficult to achieve therapeutic efficacy. Therefore, many scientists are investigating functional modifications of MNs through covalent and non-covalent methods, especially for CMNs and DMNs. The biomedical applications of MNs are growing and new exciting improvements could be achieved, thus resulting in better micro/nano technologies in the near future.

32 CFR 48.201 - Options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 1 2010-07-01 2010-07-01 false Options. 48.201 Section 48.201 National Defense...'S FAMILY PROTECTION PLAN Election of Options § 48.201 Options. As provided in § 48.203, a member may... amount equal to such 121/2 per centum. (a) Option 1 is an annuity payable to or on behalf of his widow...

Gut microbiota role in irritable bowel syndrome: New therapeutic strategies

PubMed Central

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

2016-01-01

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. PMID:26900286

Managing the side effects of multiple sclerosis therapy: pharmacotherapy options for patients.

PubMed

Rommer, Paulus S; Zettl, Uwe K

2018-04-01

Multiple sclerosis (MS) is an immune-mediated and neurodegenerative disease with an unpredictable outcome. Immune-modulatory treatment aims at decreasing long-term disability. With the increasing number of treatment options, it is essential to fully digest the possible side effects of the available therapeutics and to monitor patients is essential. Areas covered: All approved disease-modifying drugs (DMD) for MS are discussed in this review. Mode of action, adverse effects, reported risks for infections and malignancies, and pregnancy related issues are discussed in the review. The authors also provide suggestions for monitoring therapy. For all approved DMDs the pivotal studies have been included for possible side effects, as well as reports by health authorities. For this manuscript, PubMed was checked for reports on side effects for various drugs. Expert opinion: Treatment options in MS are manifold, each carrying different risks. The safety-risk profile for approved agents is favorable. Knowing and monitoring these possible side effects is essential to minimize risks associated with treatment. Presently, the long-term experience for some of these therapies is missing and this must be addressed.

Therapeutic clinical applications of reactor-produced radioisotopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp, F.F. Jr.

1997-12-01

One of the most rapidly growing areas of clinical nuclear medicine is the therapeutic use of radioisotopes for applications in oncology, rheumatology and, more recently, interventional cardiology. With the rapidly increasing development and evaluation of new agents, their introduction into clinical use, and commercialization, the availability of high levels of therapeutic reactor-produced neutron-rich radioisotopes is of increasing importance. The goals of this paper are to discuss the issues associated with optimization of the production and processing of reactor-produced radioisotopes for therapy, with special emphasis on {sup 188}W, and the optimization of the use of the {sup 188}W/{sup 188}Re generator. Inmore » addition, other key examples of therapeutic radioisotopes of current interest and their specific clinical applications are discussed.« less

78 FR 75420 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... To Amend Interpretive Material To Rule 5050 To Eliminate the Cap on the Number of Additional Series... Rule 5050 (Series of Options Contracts Open for Trading) to eliminate the cap on the number of... Rule 5050 (Series of Options Contracts Open for Trading) to eliminate the cap on the number of...

A discontinuous Galerkin method for numerical pricing of European options under Heston stochastic volatility

NASA Astrophysics Data System (ADS)

Hozman, J.; Tichý, T.

2016-12-01

The paper is based on the results from our recent research on multidimensional option pricing problems. We focus on European option valuation when the price movement of the underlying asset is driven by a stochastic volatility following a square root process proposed by Heston. The stochastic approach incorporates a new additional spatial variable into this model and makes it very robust, i.e. it provides a framework to price a variety of options that is closer to reality. The main topic is to present the numerical scheme arising from the concept of discontinuous Galerkin methods and applicable to the Heston option pricing model. The numerical results are presented on artificial benchmarks as well as on reference market data.

Influence of an Intermediate Option on the Description-Experience Gap and Information Search

PubMed Central

Sharma, Neha; Debnath, Shoubhik; Dutt, Varun

2018-01-01

Research shows that people tend to overweight small probabilities in description and underweight them in experience, thereby leading to a different pattern of choices between description and experience; a phenomenon known as the Description-Experience (DE) gap. However, little is known on how the addition of an intermediate option and contextual framing influences the DE gap and people’s search strategies. This paper tests the effects of an intermediate option and contextual framing on the DE gap and people’s search strategies, where problems require search for information before a consequential choice. In the first experiment, 120 participants made choice decisions across investment problems that differed in the absence or presence of an intermediate option. Results showed that adding an intermediate option did not reduce the DE gap on the maximizing option across a majority of problems. There were a large majority of choices for the intermediate option. Furthermore, there was an increase in switching between options due to the presence of the intermediate option. In the second experiment, 160 participants made choice decisions in problems like those presented in experiment 1; however, problems lacked the investment framing. Results replicated findings from the first experiment and showed a similar DE gap on the maximizing option in a majority of problems in both the absence and presence of the intermediate option. Again, there were a large majority of choices for the intermediate option. Also, there was an increase in switching between options due to the presence of the intermediate option. Meta-analyses revealed that the absence or presence of the intermediate option created certain differences in the strength of frequency and recency processes. Also, a single natural-mean heuristic model was able to account for the experimental results across both experiments. We discuss implications of our findings to consequential decisions made after information search

Influence of an Intermediate Option on the Description-Experience Gap and Information Search.

PubMed

Sharma, Neha; Debnath, Shoubhik; Dutt, Varun

2018-01-01

Research shows that people tend to overweight small probabilities in description and underweight them in experience, thereby leading to a different pattern of choices between description and experience; a phenomenon known as the Description-Experience (DE) gap. However, little is known on how the addition of an intermediate option and contextual framing influences the DE gap and people's search strategies. This paper tests the effects of an intermediate option and contextual framing on the DE gap and people's search strategies, where problems require search for information before a consequential choice. In the first experiment, 120 participants made choice decisions across investment problems that differed in the absence or presence of an intermediate option. Results showed that adding an intermediate option did not reduce the DE gap on the maximizing option across a majority of problems. There were a large majority of choices for the intermediate option. Furthermore, there was an increase in switching between options due to the presence of the intermediate option. In the second experiment, 160 participants made choice decisions in problems like those presented in experiment 1; however, problems lacked the investment framing. Results replicated findings from the first experiment and showed a similar DE gap on the maximizing option in a majority of problems in both the absence and presence of the intermediate option. Again, there were a large majority of choices for the intermediate option. Also, there was an increase in switching between options due to the presence of the intermediate option. Meta-analyses revealed that the absence or presence of the intermediate option created certain differences in the strength of frequency and recency processes. Also, a single natural-mean heuristic model was able to account for the experimental results across both experiments. We discuss implications of our findings to consequential decisions made after information search.

The Decoy Effect as a Nudge: Boosting Hand Hygiene With a Worse Option.

PubMed

Li, Meng; Sun, Yan; Chen, Hui

2018-05-01

This article provides the first test of the decoy effect as a nudge to influence real-world behavior. The decoy effect is the phenomenon that an additional but worse option can boost the appeal of an existing option. It has been widely demonstrated in hypothetical choices, but its usefulness in real-world settings has been subject to debate. In three longitudinal experiments in food-processing factories, we tested two decoy sanitation options that were worse than the existing sanitizer spray bottle. Results showed that the presence of a decoy, but not an additional copy of the original sanitizer bottle in a different color, drastically increased food workers' hand sanitizer use from the original sanitizer bottle and, consequently, improved workers' passing rate in hand sanitary tests from 60% to 70% to above 90% for 20 days. These findings indicate that the decoy effect can be a powerful nudge technique to influence real-world behavior.

48 CFR 570.401 - Renewal options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Renewal options. 570.401... Requirements 570.401 Renewal options. (a) Exercise of options. Before exercising an option to renew, follow the... survey. Before exercising an option to renew a lease, review current market information to ensure the...

Co-option of Liver Vessels and Not Sprouting Angiogenesis Drives Acquired Sorafenib Resistance in Hepatocellular Carcinoma.

PubMed

Kuczynski, Elizabeth A; Yin, Melissa; Bar-Zion, Avinoam; Lee, Christina R; Butz, Henriett; Man, Shan; Daley, Frances; Vermeulen, Peter B; Yousef, George M; Foster, F Stuart; Reynolds, Andrew R; Kerbel, Robert S

2016-08-01

The anti-angiogenic Sorafenib is the only approved systemic therapy for advanced hepatocellular carcinoma (HCC). However, acquired resistance limits its efficacy. An emerging theory to explain intrinsic resistance to other anti-angiogenic drugs is 'vessel co-option,' ie, the ability of tumors to hijack the existing vasculature in organs such as the lungs or liver, thus limiting the need for sprouting angiogenesis. Vessel co-option has not been evaluated as a potential mechanism for acquired resistance to anti-angiogenic agents. To study sorafenib resistance mechanisms, we used an orthotopic human HCC model (n = 4-11 per group), where tumor cells are tagged with a secreted protein biomarker to monitor disease burden and response to therapy. Histopathology, vessel perfusion assessed by contrast-enhanced ultrasound, and miRNA sequencing and quantitative real-time polymerase chain reaction were used to monitor changes in tumor biology. While sorafenib initially inhibited angiogenesis and stabilized tumor growth, no angiogenic 'rebound' effect was observed during development of resistance unless therapy was stopped. Instead, resistant tumors became more locally infiltrative, which facilitated extensive incorporation of liver parenchyma and the co-option of liver-associated vessels. Up to 75% (±10.9%) of total vessels were provided by vessel co-option in resistant tumors relative to 23.3% (±10.3%) in untreated controls. miRNA sequencing implicated pro-invasive signaling and epithelial-to-mesenchymal-like transition during resistance development while functional imaging further supported a shift from angiogenesis to vessel co-option. This is the first documentation of vessel co-option as a mechanism of acquired resistance to anti-angiogenic therapy and could have important implications including the potential therapeutic benefits of targeting vessel co-option in conjunction with vascular endothelial growth factor receptor signaling. © The Author 2016. Published by

Nelson Syndrome: Update on Therapeutic Approaches.

PubMed

Azad, Tej D; Veeravagu, Anand; Kumar, Sunny; Katznelson, Laurence

2015-06-01

To review the pathophysiology and therapeutic modalities availble for Nelson syndrome. We reviewed the current literature including managment for Nelson syndrome. For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS. An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic Hypothermia for Neuroprotection

PubMed Central

Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

2014-01-01

The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections

PubMed Central

Griffith, Gina L.; Kasus-Jacobi, Anne; Pereira, H. Anne

2017-01-01

Significance: More than 2 million eye injuries and infections occur each year in the United States that leave civilians and military members with reduced or complete vision loss due to the lack of effective therapeutics. Severe ocular injuries and infections occur in varied settings including the home, workplace, and battlefields. In this review, we discuss the potential of developing antimicrobial peptides (AMPs) as therapeutics for the treatment of corneal wounds and infections for which the current treatment options are inadequate. Recent Advances: Standard-of-care employs the use of fluorescein dye for the diagnosis of ocular defects and is followed by the use of antibiotics and/or steroids to treat the infection and reduce inflammation. Recent advances for treating corneal wounds include the development of amniotic membrane therapies, wound chambers, and drug-loaded hydrogels. In this review, we will discuss an innovative approach using AMPs with the dual effect of promoting corneal wound healing and clearing infections. Critical Issues: An important aspect of treating ocular injuries is that treatments need to be effective and administered expeditiously. This is especially important for injuries that occur during combat and in individuals who demonstrate delayed wound healing. To overcome gaps in current treatment modalities, bioactive peptides based on naturally occurring cationic antimicrobial proteins are being investigated as new therapeutics. Future Directions: The development of new therapeutics that can treat ocular infections and promote corneal wound healing, including the healing of persistent corneal epithelial defects, would be of great clinical benefit. PMID:28616359

[Dendritic cell-based therapeutic cancer vaccines].

PubMed

Rizzo, Manglio; Alaniz, Laura; Mazzolini, Guillermo D

In recent years immunotherapy has revolutionized the treatment of patients with advanced cancer. The increased knowledge in the tumor immune-biology has allowed developing rational treatments by manipulation of the immune system with significant clinical impact. This rapid development has significantly changed the prognosis of many tumors without treatment options up to date. Other strategies have explored the use of therapeutic vaccines based on dendritic cells (DC) by inducing antitumor immunity. DC are cells of hematopoietic origin, constitutively expressing molecules capable to present antigens, that are functionally the most potent inducers of the activation and proliferation of antigen specific T lymphocytes. The CD8+ T cells proliferate and acquire cytotoxic capacity after recognizing their specific antigen presented on the surface of DC, although only some types of DC can present antigens internalized from outside the cell to precursors of cytotoxic T lymphocytes (this function is called cross-presentation) requiring translocation mechanisms of complex antigens. The induction of an effective adaptive immune response is considered a good option given its specificity, and prolonged duration of response. The DC, thanks to its particular ability of antigen presentation and lymphocyte stimulation, are able to reverse the poor antitumor immune response experienced by patients with cancer. The DC can be obtained from various sources, using different protocols to generate differentiation and maturation, and are administered by various routes such as subcutaneous, intravenous or intranodal. The wide variety of protocols resulted in heterogeneous clinical responses.

The Therapeutic School.

ERIC Educational Resources Information Center

Rice, John Steadman

2002-01-01

Contributes to the recent research on specific institutional carriers of the therapeutic culture, such as the state, the corporation, and the self- help movement, defining therapeutic discourse and discussing the therapeutic ethic, the therapeutic school, schools of education and their critics, and disappointing results of therapeutic schooling.…

75 FR 66402 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... necessary systems capacity to handle the additional traffic associated with the expanded range of strike... Effectiveness of Proposed Rule Change To Expand the Range of Strike Price Intervals for VIX Options October 21... amend Rule 24.9.01(e), Terms of Index Option Contracts, to expand the range of strike price intervals...

ATR Spent Fuel Options Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Connolly, Michael James; Bean, Thomas E.; Brower, Jeffrey O.

The Advanced Test Reactor (ATR) is a materials and fuels test nuclear reactor that performs irradiation services for the U.S. Department of Energy (DOE) Office of Nuclear Energy (NE), Naval Reactors, the National Nuclear Security Administration (NNSA), and other research programs. ATR achieved initial criticality in 1967 and is expected to operate in support of needed missions until the year 2050 or beyond. It is anticipated that ATR will generate approximately 105 spent nuclear fuel (SNF) elements per year through the year 2050. Idaho National Laboratory (INL) currently stores 2,008 ATR SNF elements in dry storage, 976 in wet storage,more » and expects to have 1,000 elements in wet storage before January 2017. A capability gap exists at INL for long-term (greater than the year 2050) management, in compliance with the Idaho Settlement Agreement (ISA), of ATR SNF until a monitored retrievable geological repository is open. INL has significant wet and dry storage capabilities that are owned by the DOE Office of Environmental Management (EM) and operated and managed by Fluor Idaho, which include the Idaho Nuclear Technology and Engineering Center’s (INTEC’s) CPP-666, CPP-749, and CPP-603. In addition, INL has other capabilities owned by DOE-NE and operated and managed by Battelle Energy Alliance, LLC (BEA), which are located at the Materials and Fuel Complex (MFC). Additional storage capabilities are located on the INL Site at the Naval Reactors Facility (NRF). Current INL SNF management planning, as defined in the Fluor Idaho contract, shows INTEC dry fuel storage, which is currently used for ATR SNF, will be nearly full after transfer of an additional 1,000 ATR SNF from wet storage. DOE-NE tasked BEA with identifying and analyzing options that have the potential to fulfill this capability gap. BEA assembled a team comprised of SNF management experts from Fluor Idaho, Savannah River Site (SRS), INL/BEA, and the MITRE Corp with an objective of developing and

Microbiome Therapeutics – Advances and Challenges

PubMed Central

Mimee, Mark; Citorik, Robert J.; Lu, Timothy K.

2016-01-01

The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. PMID:27158095

New options in the management of tendinopathy

PubMed Central

Maffulli, Nicola; Longo, Umile Giuseppe; Loppini, Mattia; Spiezia, Filippo; Denaro, Vincenzo

2010-01-01

Tendon injuries can be acute or chronic, and caused by intrinsic or extrinsic factors, either alone or in combination. Tendinopathies are a common cause of disability in occupational medicine and account for a substantial proportion of overuse injuries in sports. Tendinopathy is essentially a failed healing response, with haphazard proliferation of tenocytes, abnormalities in tenocytes, with disruption of collagen fibres and subsequent increase in noncollagenous matrix. The scientific evidence base for managing tendinopathies is limited. What may appear clinically as an “acute tendinopathy” is actually a well advanced failure of a chronic healing response in which there is neither histologic nor biochemical evidence of inflammation. In this review we report the new options for the management of tendinopathy, including eccentric exercises, extracorporeal shockwave therapy, injections (intratendinous injections of corticosteroids, aprotinin, polidocanol platelet-rich plasma, autologous blood injection, high-volume injections) and surgery. Open surgery aims to excise fibrotic adhesions, remove areas of failed healing and make multiple longitudinal incisions in the tendon to detect intratendinous lesions, and to restore vascularity and possibly stimulate the remaining viable cells to initiate cell matrix response and healing. New surgical techniques aim to disrupt the abnormal neoinnervation to interfere with the pain sensation caused by tendinopathy. These procedures are intrinsically different from the classical ones in present use, because they do not attempt to address directly the pathologic lesion, but act only to denervate them. They include endoscopy, electrocoagulation, and minimally invasive stripping. Further randomized controlled trials are necessary to clarify better the best therapeutic options for the management of tendinopathy. PMID:24198540

Using real options analysis to support strategic management decisions

NASA Astrophysics Data System (ADS)

Kabaivanov, Stanimir; Markovska, Veneta; Milev, Mariyan

2013-12-01

Decision making is a complex process that requires taking into consideration multiple heterogeneous sources of uncertainty. Standard valuation and financial analysis techniques often fail to properly account for all these sources of risk as well as for all sources of additional flexibility. In this paper we explore applications of a modified binomial tree method for real options analysis (ROA) in an effort to improve decision making process. Usual cases of use of real options are analyzed with elaborate study on the applications and advantages that company management can derive from their application. A numeric results based on extending simple binomial tree approach for multiple sources of uncertainty are provided to demonstrate the improvement effects on management decisions.

Complex Care Options for Patients With Advanced Heart Failure Approaching End of Life.

PubMed

Wordingham, Sara E; McIlvennan, Colleen K; Dionne-Odom, J Nicholas; Swetz, Keith M

2016-02-01

Care for patients with advanced cardiac disease continues to evolve in a complex milieu of therapeutic options, advanced technological interventions, and efforts at improving patient-centered care and shared decision-making. Despite improvements in quality of life and survival with these interventions, optimal supportive care across the advanced illness trajectory remains diverse and heterogeneous. Herein, we outline challenges in prognostication, communication, and caregiving in advanced heart failure and review the unique needs of patients who experience frequent hospitalizations, require chronic home inotropic support, and who have implantable cardioverter-defibrillators and mechanical circulatory support in situ, to name a few.

Current and future treatment options for esophageal cancer in the elderly.

PubMed

Bollschweiler, Elfriede; Plum, Patrick; Mönig, Stefan P; Hölscher, Arnulf H

2017-07-01

Esophageal cancer is the eighth most common cancer globally and has the sixth worst prognosis because of its aggressiveness and poor survival. Data regarding cancer treatment in older patients is limited because the elderly have been under-represented in clinical trials. Therefore, we reviewed the existing literature regarding treatment results for elderly patients (70+ years). Areas covered: We used pubmed to analyze the actual literature according to elderly esophageal cancer patients with subheading of incidence, esophagectomy, chemoradiation or chemotherapy. The main points of interest were treatment options for patients with Barrett's esophagus or early carcinoma, advanced tumor stages, and inoperable cancer. Expert opinion: The incidence of esophageal cancer has been increasing over the past thirty years, with a rapid increase of esophageal adenocarcinoma in Western industrialized nations. Patients aged over 60 years have been particularly affected. In this review, we have shown that elderly patients with esophageal cancer have various alternatives for adequate treatment. Clinical evaluation of comorbidity is necessary to make treatment decisions. Therapeutic options for early carcinomas are endoscopic or surgical resection. For elderly patients with advanced carcinomas, preoperative chemoradiation or chemotherapy should be discussed.

Bariatric embolization: a new and effective option for the obese patient?

PubMed

Weiss, Clifford R; Kathait, Anjaneya S

2017-04-01

Obesity is a public health epidemic in the United States, which results in significant morbidity, mortality, and cost to the healthcare system. Despite advancements in traditional therapeutic options for the obese patients, there is a treatment gap for patients in whom lifestyle modifications alone have not been successful, but for whom bariatric surgery is not a suitable option. Areas covered: This treatment gap needs to be addressed and thus, complimentary or alternative treatments to lifestyle changes and surgery are urgently needed. Recent evidence suggests that embolization of the gastric fundus ('Bariatric Embolization'), which is predominantly supplied by the left gastric artery, may affect energy homeostasis by decreasing ghrelin production. The purpose of this special report is to discuss the background, rationale and latest data on this topic, as well as provide the latest data from the ongoing BEAT Obesity clinical trial. Expert commentary: A multipronged approach is essential in the treatment of obesity. Bariatric embolization looks to treat the hormonal imbalances which contribute to obesity. If proven successful in the long-term, bariatric embolization represents a potential minimally invasive approach to treat obesity offered by interventional radiologists.

Clinical trials as treatment option: bioethics and health care disparities in substance dependency.

PubMed

Timmermans, Stefan; McKay, Tara

2009-12-01

Bioethicists have warned against the dangers of mixing research with treatment. They are concerned that research priorities may take precedence over individual patient needs and that research subjects tend to misunderstand the purpose of research or overestimate the direct medical benefits of participating in studies. Yet, other work has questioned whether clinical research can always be separated from therapeutic benefit for participants. Using in-depth interviews with participants in two phase III randomized U.S. clinical trials for methamphetamine dependency, we examine the treatment options available to participants, their experiences with participating in the trials, and potential problems of trial participation. We find that while participants have experience with four alternative treatment modalities - quitting alone, support groups, in-patient treatment facilities, and consulting primary care physicians - the randomized clinical trials compare favorably to alternatives because they provide access to evidence-based behavioral treatments, specialized medical professionals, non-judgmental staff, and the possibility of receiving an experimental drug. We conclude that while randomized clinical trials are imperfect substitutes for clinical care, they constitute a fragile and sporadic therapeutic niche in a country with fundamental problems in access to health care, a mixed punitive-therapeutic drug addiction policy, and a profit-driven pharmaceutical development and approval process.

A systematic evaluation of the therapeutic effectiveness of sacroiliac joint interventions.

PubMed

Hansen, Hans; Manchikanti, Laxmaiah; Simopoulos, Thomas T; Christo, Paul J; Gupta, Sanjeeva; Smith, Howard S; Hameed, Haroon; Cohen, Steven P

2012-01-01

The contribution of the sacroiliac joint to low back and lower extremity pain has been a subject of debate with extensive research. It is generally accepted that approximately 10% to 25% of patients with persistent low back pain may have pain arising from the sacroiliac joints. In spite of this, there are currently no definite conservative, interventional, or surgical management options for managing sacroiliac joint pain. In addition, there continue to be significant variations in the application of various techniques as well as a paucity of literature. A systematic review of therapeutic sacroiliac joint interventions. To evaluate the accuracy of therapeutic sacroiliac joint interventions. The available literature on therapeutic sacroiliac joint interventions in managing chronic low back and lower extremity pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria for randomized trials of interventional techniques and the criteria developed by the Newcastle-Ottawa Scale for observational studies. The level of evidence was classified as good, fair, or poor based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature published from 1966 through December 2011 that was identified through searches of PubMed and EMBASE, and manual searches of the bibliographies of known primary and review articles. The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. For this systematic review, 56 studies were considered for inclusion. Of these, 45 studies were excluded and a total of 11 studies met inclusion criteria for methodological quality assessment with 6 randomized trials and 5 non-randomized studies. The evidence for cooled

ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiovascular risk: diagnostic-therapeutic pathway in Italy.

PubMed

Gulizia, Michele Massimo; Colivicchi, Furio; Ricciardi, Gualtiero; Giampaoli, Simona; Maggioni, Aldo Pietro; Averna, Maurizio; Graziani, Maria Stella; Ceriotti, Ferruccio; Mugelli, Alessandro; Rossi, Francesco; Medea, Gerardo; Parretti, Damiano; Abrignani, Maurizio Giuseppe; Arca, Marcello; Perrone Filardi, Pasquale; Perticone, Francesco; Catapano, Alberico; Griffo, Raffaele; Nardi, Federico; Riccio, Carmine; Di Lenarda, Andrea; Scherillo, Marino; Musacchio, Nicoletta; Panno, Antonio Vittorio; Zito, Giovanni Battista; Campanini, Mauro; Bolognese, Leonardo; Faggiano, Pompilio Massimo; Musumeci, Giuseppe; Pusineri, Enrico; Ciaccio, Marcello; Bonora, Enzo; Cantelli Forti, Giorgio; Ruggieri, Maria Pia; Cricelli, Claudio; Romeo, Francesco; Ferrari, Roberto; Maseri, Attilio

2017-05-01

Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia.

Efficient option valuation of single and double barrier options

NASA Astrophysics Data System (ADS)

Kabaivanov, Stanimir; Milev, Mariyan; Koleva-Petkova, Dessislava; Vladev, Veselin

2017-12-01

In this paper we present an implementation of pricing algorithm for single and double barrier options using Mellin transformation with Maximum Entropy Inversion and its suitability for real-world applications. A detailed analysis of the applied algorithm is accompanied by implementation in C++ that is then compared to existing solutions in terms of efficiency and computational power. We then compare the applied method with existing closed-form solutions and well known methods of pricing barrier options that are based on finite differences.

Insights into the Biology and Therapeutic Applications of Neural Stem Cells

PubMed Central

Harris, Lachlan; Zalucki, Oressia; Piper, Michael; Heng, Julian Ik-Tsen

2016-01-01

The cerebral cortex is essential for our higher cognitive functions and emotional reasoning. Arguably, this brain structure is the distinguishing feature of our species, and yet our remarkable cognitive capacity has seemingly come at a cost to the regenerative capacity of the human brain. Indeed, the capacity for regeneration and neurogenesis of the brains of vertebrates has declined over the course of evolution, from fish to rodents to primates. Nevertheless, recent evidence supporting the existence of neural stem cells (NSCs) in the adult human brain raises new questions about the biological significance of adult neurogenesis in relation to ageing and the possibility that such endogenous sources of NSCs might provide therapeutic options for the treatment of brain injury and disease. Here, we highlight recent insights and perspectives on NSCs within both the developing and adult cerebral cortex. Our review of NSCs during development focuses upon the diversity and therapeutic potential of these cells for use in cellular transplantation and in the modeling of neurodevelopmental disorders. Finally, we describe the cellular and molecular characteristics of NSCs within the adult brain and strategies to harness the therapeutic potential of these cell populations in the treatment of brain injury and disease. PMID:27069486

42 CFR 435.232 - Individuals receiving only optional State supplements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Medicaid, in one or more of the following classifications, to individuals who receive only an optional... additional classifications specified by the Secretary for federally administered supplementary payments under... State supplements); and (3) Available to all individuals in each classification in paragraph (a) of this...

42 CFR 435.232 - Individuals receiving only optional State supplements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Medicaid, in one or more of the following classifications, to individuals who receive only an optional... additional classifications specified by the Secretary for federally administered supplementary payments under... State supplements); and (3) Available to all individuals in each classification in paragraph (a) of this...

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

PubMed Central

Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

2016-01-01

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

Therapeutic drug monitoring of antimetabolic cytotoxic drugs

PubMed Central

Lennard, L

1999-01-01

Therapeutic drug monitoring is not routinely used for cytotoxic agents. There are several reasons, but one major drawback is the lack of established therapeutic concentration ranges. Combination chemotherapy makes the establishment of therapeutic ranges for individual drugs difficult, the concentration-effect relationship for a single drug may not be the same as that when the drug is used in a drug combination. Pharmacokinetic optimization protocols for many classes of cytotoxic compounds exist in specialized centres, and some of these protocols are now part of large multicentre trials. Nonetheless, methotrexate is the only agent which is routinely monitored in most treatment centres. An additional factor, especially in antimetabolite therapy, is the existence of pharmacogenetic enzymes which play a major role in drug metabolism. Monitoring of therapy could include assay of phenotypic enzyme activities or genotype in addition to, or instead of, the more traditional measurement of parent drug or drug metabolites. The cytotoxic activities of mercaptopurine and fluorouracil are regulated by thiopurine methyltransferase (TPMT) and dihydropyrimidine dehydrogenase (DPD), respectively. Lack of TPMT functional activity produces life-threatening mercaptopurine myelotoxicity. Very low DPD activity reduces fluorouracil breakdown producing severe cytotoxicity. These pharmacogenetic enzymes can influence the bioavailability, pharmacokinetics, toxicity and efficacy of their substrate drugs. PMID:10190647

Effects of an e-Prescribing interface redesign on rates of generic drug prescribing: exploiting default options.

PubMed

Malhotra, Sameer; Cheriff, Adam D; Gossey, J Travis; Cole, Curtis L; Kaushal, Rainu; Ancker, Jessica S

2016-09-01

Increasing the use of generic medications could help control medical costs. However, educational interventions have limited impact on prescriber behavior, and e-prescribing alerts are associated with high override rates and alert fatigue. Our objective was to evaluate the effect of a less intrusive intervention, a redesign of an e-prescribing interface that provides default options intended to "nudge" prescribers towards prescribing generic drugs. This retrospective cohort study in an academic ambulatory multispecialty practice assessed the effects of customizing an e-prescribing interface to substitute generic equivalents for brand-name medications during order entry and allow a one-click override to order the brand-name medication. Among drugs with generic equivalents, the proportion of generic drugs prescribed more than doubled after the interface redesign, rising abruptly from 39.7% to 95.9% (a 56.2% increase; 95% confidence interval, 56.0-56.4%; P < .001). Before the redesign, generic drug prescribing rates varied by therapeutic class, with rates as low as 8.6% for genitourinary products and 15.7% for neuromuscular drugs. After the redesign, generic drug prescribing rates for all but four therapeutic classes were above 90%: endocrine drugs, neuromuscular drugs, nutritional products, and miscellaneous products. Changing the default option in an e-prescribing interface in an ambulatory care setting was followed by large and sustained increases in the proportion of generic drugs prescribed at the practice. Default options in health information technology exert a powerful effect on user behavior, an effect that can be leveraged to optimize decision making. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dopamine Modulates Option Generation for Behavior.

PubMed

Ang, Yuen-Siang; Manohar, Sanjay; Plant, Olivia; Kienast, Annika; Le Heron, Campbell; Muhammed, Kinan; Hu, Michele; Husain, Masud

2018-05-21

Animals make innumerable decisions every day, each of which involves evaluating potential options for action. But how are options generated? Although much is now known about decision making when a fixed set of potential options is provided, surprisingly little progress has been made on self-generated options. Some researchers have proposed that such abilities might be modulated by dopamine. Here, we used a new measure of option generation that is quantitative, objective, and culture fair to investigate how humans generate different behavioral options. Participants were asked to draw as many different paths (options) as they could between two points within a fixed time. Healthy individuals (n = 96) exhibited a trade-off between uniqueness (how individually different their options were) and fluency (number of options), generating either many similar or few unique options. To assess influence of dopamine, we first examined patients with Parkinson's disease (n = 35) ON and OFF their dopaminergic medication and compared them to elderly healthy controls (n = 34). Then we conducted a double-blind, placebo-controlled crossover study of the D2 agonist cabergoline in healthy older people (n = 29). Across both studies, dopamine increased fluency but diminished overall uniqueness of options generated, due to the effect of fluency trading off with uniqueness. Crucially, however, when this trade-off was corrected for, dopamine was found to increase uniqueness for any given fluency. Three carefully designed control studies showed that performance on our option-generation task was not related to executing movements, planning actions, or selecting between generated options. These findings show that dopamine plays an important role in modulating option generation. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Current Status of Gene Engineering Cell Therapeutics

PubMed Central

Saudemont, Aurore; Jespers, Laurent; Clay, Timothy

2018-01-01

Ex vivo manipulations of autologous patient’s cells or gene-engineered cell therapeutics have allowed the development of cell and gene therapy approaches to treat otherwise incurable diseases. These modalities of personalized medicine have already shown great promises including product commercialization for some rare diseases. The transfer of a chimeric antigen receptor or T cell receptor genes into autologous T cells has led to very promising outcomes for some cancers, and particularly for hematological malignancies. In addition, gene-engineered cell therapeutics are also being explored to induce tolerance and regulate inflammation. Here, we review the latest gene-engineered cell therapeutic approaches being currently explored to induce an efficient immune response against cancer cells or viruses by engineering T cells, natural killer cells, gamma delta T cells, or cytokine-induced killer cells and to modulate inflammation using regulatory T cells. PMID:29459866

Therapeutic approaches to preventing cell death in Huntington disease.

PubMed

Kaplan, Anna; Stockwell, Brent R

2012-12-01

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

Therapeutic approaches to preventing cell death in Huntington disease

PubMed Central

Kaplan, Anna; Stockwell, Brent R.

2012-01-01

Neurodegenerative diseases affect the lives of millions of patients and their families. Due to the complexity of these diseases and our limited understanding of their pathogenesis, the design of therapeutic agents that can effectively treat these diseases has been challenging. Huntington disease (HD) is one of several neurological disorders with few therapeutic options. HD, like numerous other neurodegenerative diseases, involves extensive neuronal cell loss. One potential strategy to combat HD and other neurodegenerative disorders is to intervene in the execution of neuronal cell death. Inhibiting neuronal cell death pathways may slow the development of neurodegeneration. However, discovering small molecule inhibitors of neuronal cell death remains a significant challenge. Here, we review candidate therapeutic targets controlling cell death mechanisms that have been the focus of research in HD, as well as an emerging strategy that has been applied to developing small molecule inhibitors—fragment-based drug discovery (FBDD). FBDD has been successfully used in both industry and academia to identify selective and potent small molecule inhibitors, with a focus on challenging proteins that are not amenable to traditional high-throughput screening approaches. FBDD has been used to generate potent leads, pre-clinical candidates, and has led to the development of an FDA approved drug. This approach can be valuable for identifying modulators of cell-death-regulating proteins; such compounds may prove to be the key to halting the progression of HD and other neurodegenerative disorders. PMID:22967354

Radiation Therapy: Additional Treatment Options

MedlinePlus

... And Anus Cancers Gynecologic Cancers Head And Neck Cancers Lung Cancer Lymphomas Prostate Cancer Skin Cancer Upper GI ... And Anus Cancers Gynecologic Cancers Head And Neck Cancers Lung Cancer Lymphomas Prostate Cancer Skin Cancer Upper GI ...

78 FR 7997 - Noncompensatory Partnership Options

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-05

...) accounting for noncompensatory options; (3) the characterization rule; (4) the convertible bond provision... option would necessitate adjustments to the capital accounting requirements of the regulations, as... the option. 2. Accounting for Noncompensatory Options A. Accounting for the Issuance of a...

Therapeutic potential of cannabinoids in schizophrenia.

PubMed

Kucerova, Jana; Tabiova, Katarina; Drago, Filippo; Micale, Vincenzo

2014-04-01

Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia. The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana's psychoactive principle Δ(9)-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation. It has been suggested to be a pro-homeostatic and pleiotropic signalling system activated in a time- and tissue-specific manner during pathophysiological conditions. In the brain, activation of this system impacts the release of numerous neurotransmitters in various systems and cytokines from glial cells. Hence, the endocannabinoid system is strongly involved in neuropsychiatric disorders, such as schizophrenia. Therefore, adolescence use of Cannabis may alter the endocannabinoid signalling and pose a potential environmental risk to develop psychosis. Consistently, preclinical and clinical studies have found a dysregulation in the endocannabinoid system such as changed expression of CB1 and CB2 receptors or altered levels of AEA and 2-AG . Thus, due to the partial efficacy of actual antipsychotics, compounds which modulate this system may provide a novel therapeutic target for the treatment of schizophrenia. The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology. Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.

Therapeutic Uses of Triphala in Ayurvedic Medicine.

PubMed

Peterson, Christine Tara; Denniston, Kate; Chopra, Deepak

2017-08-01

The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. A search of the PubMed database was conducted. In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development.

Exploring Therapeutic Potential Of Nanocarrier Systems Against Breast Cancer.

PubMed

Kumar, Lalit; Baldi, Ashish; Verma, Shivani; Utreja, Puneet

2018-06-03

Breast cancer is most widely occurring non-cutaneous cancer in women. Treatment options available for breast cancer are limited and there are a number of toxicity concerns associated with them. Therefore, nanocarrier based approaches have been explored for breast cancer treatment. Nanocarriers implemented for breast cancer treatment are nanoliposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, dendrimers, and protein nanocages. Objective of this review was to explore the therapeutic efficacy of various nanocarrier systems against breast cancer. Existing literature regarding nanocarrier systems for breast cancer therapy was reviewed using Pubmed and Google Scholar. Nanocarriers may show prolonged circulation time of chemotherapeutic agent with efficient breast tumor targeting. Both active and passive targeting methodologies can be explored to target breast cancer cells using different nanocarriers. Targeted nanocarriers have the capability to reduce side effects caused by various conventional formulations used to treat breast cancer. Various nanocarriers listed above have shown their therapeutic potential in preclinical studies to treat breast cancer. Satisfactory clinical evaluation and scale up techniques can promote their entry into the pharmaceutical market in greater extent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Options to improve energy efficiency for educational building

NASA Astrophysics Data System (ADS)

Jahan, Mafruha

The cost of energy is a major factor that must be considered for educational facility budget planning purpose. The analysis of energy related issues and options can be complex and requires significant time and detailed effort. One way to facilitate the inclusion of energy option planning in facility planning efforts is to utilize a tool that allows for quick appraisal of the facility energy profile. Once such an appraisal is accomplished, it is then possible to rank energy improvement options consistently with other facility needs and requirements. After an energy efficiency option has been determined to have meaningful value in comparison with other facility planning options, it is then possible to utilize the initial appraisal as the basis for an expanded consideration of additional facility and energy use detail using the same analytic system used for the initial appraisal. This thesis has developed a methodology and an associated analytic model to assist in these tasks and thereby improve the energy efficiency of educational facilities. A detailed energy efficiency and analysis tool is described that utilizes specific university building characteristics such as size, architecture, envelop, lighting, occupancy, thermal design which allows reducing the annual energy consumption. Improving the energy efficiency of various aspects of an educational building's energy performance can be complex and can require significant time and experience to make decisions. The approach developed in this thesis initially assesses the energy design for a university building. This initial appraisal is intended to assist administrators in assessing the potential value of energy efficiency options for their particular facility. Subsequently this scoping design can then be extended as another stage of the model by local facility or planning personnel to add more details and engineering aspects to the initial screening model. This approach can assist university planning efforts to

Targeted Treatment Options in Mastocytosis

PubMed Central

Vaes, Mélanie; Benghiat, Fleur Samantha; Hermine, Olivier

2017-01-01

Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN). While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation) within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN). Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy. PMID:28775983

Therapeutic Use of Filgrastim for Established Febrile Neutropenia Is Cost Effective Among Patients With Solid Tumors and Lymphomas.

PubMed

Wang, Xiao Jun; Tong, Wei Xiang; Chan, Alexandre

2017-06-01

With the emergence of biosimilar filgrastim to the market, there is a gradual decrease in the listed price of the originator product of filgrastim over the years, and this could have an impact on the cost-effectiveness of filgrastim in the treatment of febrile neutropenia (FN). A cost-effectiveness analysis would allow clinicians to make informed decision when considering the therapeutic filgrastim among low-risk FN patients. This study aims to evaluate the cost-effectiveness of adding therapeutic filgrastim to antibiotics in the treatment of established FN among patients with solid tumors and lymphomas. A decision tree model was created to compare two treatment options for established FN as follows: (1) antibiotics alone (standard care) and (2) antibiotics with therapeutic filgrastim (comparator). The target population was a hypothetical cohort of adult cancer patients with solid tumors or lymphomas hospitalized with FN in Singapore. The analysis was performed from a hospital's perspective over a 21-day time horizon. The main outcome measures included costs, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the results. Compared with antibiotics alone, the treatment strategy of antibiotics with therapeutic filgrastim was a dominant choice, incurring a cost saving of US$125 per patient (comparator versus standard care: US$9110 versus US$9235) and additional health benefit of 0.0007 QALY gained per patient (comparator versus standard care: 0.0450 versus 0.0443). Model results were robust against the parameter variations in the one-way sensitivity analyses, but increasing the cost of filgrastim beyond US$87 per injection would increase the ICER to >US$50,000/QALY. Furthermore, the strategy of antibiotics with therapeutic filgrastim was the preferred choice (dominant or cost-effective) in 83.7% of the model iterations at a

Consumer Satisfaction with Psychiatric Services: The Role of Shared Decision-Making and the Therapeutic Relationship

PubMed Central

Klingaman, Elizabeth A.; Medoff, Deborah R.; Park, Stephanie G.; Brown, Clayton H.; Fang, Lijuan; Dixon, Lisa B.; Hack, Samantha M.; Tapscott, Stephanie L.; Walsh, Mary Brighid; Kreyenbuhl, Julie A.

2017-01-01

Objective Although dissatisfaction is a primary reason for disengagement from outpatient psychiatric care among consumers with serious mental illnesses, little is known about predictors of their satisfaction with medication management visits. The primary purpose of the present study was to explore how dimensions of consumer preferences for shared decision-making (i.e., preferences for obtaining knowledge about one’s mental illness, being offered and asked one’s opinion about treatment options, and involvement in treatment decisions) and the therapeutic relationship (i.e., positive collaboration and type of clinician input) were related to visit satisfaction. Methods Participants were 228 Veterans with serious mental illnesses who completed a 19-item self-report questionnaire assessing satisfaction with visits to prescribers (n=524 assessments) immediately after visits. In this correlational design, a 3-level mixed model with the restricted maximum likelihood estimation procedure was used to examine shared decision-making preferences and therapeutic alliance as predictors of visit satisfaction. Results Preferences for involvement in treatment decisions was the unique component of shared decision-making associated with satisfaction, such that the more consumers desired involvement, the less satisfied they were. Positive collaboration and prescriber input were associated with greater visit satisfaction. Conclusions and Implications for Practice When consumers with serious mental illnesses express preferences to be involved in shared decision-making, it may not be sufficient to only provide information and treatment options; prescribers should attend to consumers’ interest in involvement in actual treatment decisions. Assessment and tailoring of treatment approaches to consumer preferences for shared decision-making should occur within the context of a strong therapeutic relationship. PMID:25664755

48 CFR 17.107 - Options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Options. 17.107 Section 17... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multiyear Contracting 17.107 Options. Benefits may accrue by including options in a multiyear contract. In that event, contracting officers must follow the requirements...

48 CFR 2917.207 - Exercising options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exercising options. 2917... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.207 Exercising options. The contracting officer must use a standardized determination and finding before exercising an option in accordance with...

Old and new challenges in Parkinson's disease therapeutics.

PubMed

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

2017-09-01

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

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

PubMed Central

Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

Current issues of RNAi therapeutics delivery and development.

PubMed

Haussecker, D

2014-12-10

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

38 CFR 6.10 - Options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 6.10 Section 6.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS UNITED STATES GOVERNMENT LIFE INSURANCE Optional Settlement § 6.10 Options. Insurance will be payable in one sum only when...

Trajectory options for the DART mission

NASA Astrophysics Data System (ADS)

Atchison, Justin A.; Ozimek, Martin T.; Kantsiper, Brian L.; Cheng, Andrew F.

2016-06-01

This study presents interplanetary trajectory options for the Double Asteroid Redirection Test (DART) spacecraft to reach the near Earth object, Didymos binary system, during its 2022 Earth conjunction. DART represents a component of a joint NASA-ESA mission to study near Earth object kinetic impact deflection. The DART trajectory must satisfy mission objectives for arrival timing, geometry, and lighting while minimizing launch vehicle and spacecraft propellant requirements. Chemical propulsion trajectories are feasible from two candidate launch windows in late 2020 and 2021. The 2020 trajectories are highly perturbed by Earth's orbit, requiring post-launch deep space maneuvers to retarget the Didymos system. Within these windows, opportunities exist for flybys of additional near Earth objects: Orpheus in 2021 or 2007 YJ in 2022. A second impact attempt, in the event that the first impact is unsuccessful, can be added at the expense of a shorter launch window and increased (∼3x) spacecraft ΔV . However, the second impact arrival geometry has poor lighting, high Earth ranges, and would require additional degrees of freedom for solar panel and/or antenna gimbals. A low-thrust spacecraft configuration increases the trajectory flexibility. A solar electric propulsion spacecraft could be affordably launched as a secondary spacecraft in an Earth orbit and spiral out to target the requisite interplanetary departure condition. A sample solar electric trajectory was constructed from an Earth geostationary transfer using a representative 1.5 kW thruster. The trajectory requires 9 months to depart Earth's sphere of influence, after which its interplanetary trajectory includes a flyby of Orpheus and a second Didymos impact attempt. The solar electric spacecraft implementation would impose additional bus design constraints, including large solar arrays that could pose challenges for terminal guidance. On the basis of this study, there are many feasible options for DART to

The valuation of currency options by fractional Brownian motion.

PubMed

Shokrollahi, Foad; Kılıçman, Adem

2016-01-01

This research aims to investigate a model for pricing of currency options in which value governed by the fractional Brownian motion model (FBM). The fractional partial differential equation and some Greeks are also obtained. In addition, some properties of our pricing formula and simulation studies are presented, which demonstrate that the FBM model is easy to use.

Right and left partial iatrogenic injuries of the biliary tree. Therapeutic options.

PubMed

Mercado, Miguel Angel; Domínguez, Ismael; Arriola, Juan Carlos; Ramirez-Del Val, Fernando; Urencio, Miguel; Sánchez-Fernández, Norberto

2010-01-01

Bile duct injuries (BDI) have a wide array of presentation. Left partial injuries (Strasberg D) of the hepatic duct are the result of excessive traction, which dissects the hepatic hilum and provokes medial perforations without continuity loss. Right partial injuries (Strasberg A, B and C) are produced by direct damage to the hepatic duct or isolated injury to the right and accessory ducts. It is important to determine frequency, spectrum and treatment outcome of this BDI in the surgical scenario. Patients with BDI who underwent surgical treatment in our hospital were reviewed, right and left partial injuries were selected. Demographic, clinical and therapeutic data were analyzed. In a 16-year period, 405 patients underwent surgical treatment of BDI. 31 (8%) were classified as a left partial injury (Strasberg D): 23 injuries at the common hepatic duct treated with a Hepatojejunostomy (HJ); four at the confluence level which received a HJ with neoconfluence construction; two partial injuries in the left hepatic duct underwent a selective left HJ; and two complete occlusions of the left hepatic duct, one treated with a partial hepatectomy and the last case underwent a partial HJ. Right partial injuries (Strasberg A, B or C) were identified in 21 cases (5%), their treatment was tailored according to the type of BDI (conservative, selective HJ, or hepatectomy). In our series the frequency of left and right partial BDI injuries was 8% and 5%, respectively. The spectrum of analyzed injuries included four subtypes for the left partial and eight for the right partial lesions. Most BDI in the two analyzed groups presented concomitant devascularization of the extra-hepatic ducts, therefore receiving surgical treatment rather than endoscopic treatment was done.

Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

PubMed

Jeong, Su Jin; Kim, Jie-Hyun; Jung, Da Hyun; Lee, Kyoung Hwa; Park, Soon Young; Song, Yungoo; Kang, Il-Mo; Song, Young Goo

2018-02-12

Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Therapeutic Symptomatic Strategies in the Parasomnias.

PubMed

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.

48 CFR 317.107 - Options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Options. 317.107 Section... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multi-year Contracting 317.107 Options. When used as part of a multi-year contract, options shall not be used to extend the performance of the original requirement for...

38 CFR 8.25 - Options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 8.25 Section 8.25 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS NATIONAL SERVICE LIFE INSURANCE Optional Settlements § 8.25 Options. Insurance will be paid in a lump sum only when selected by...

Bounds for Asian basket options

NASA Astrophysics Data System (ADS)

Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

2008-09-01

In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

OPTION(5) versus OPTION(12) instruments to appreciate the extent to which healthcare providers involve patients in decision-making.

PubMed

Stubenrouch, Fabienne E; Pieterse, Arwen H; Falkenberg, Rijan; Santema, T Katrien B; Stiggelbout, Anne M; van der Weijden, Trudy; Aarts, J Annemijn W M; Ubbink, Dirk T

2016-06-01

The 12-item "observing patient involvement" (OPTION(12))-instrument is commonly used to assess the extent to which healthcare providers involve patients in health-related decision-making. The five-item version (OPTION(5)) claims to be a more efficient measure. In this study we compared the Dutch versions of the OPTION-instruments in terms of inter-rater agreement and correlation in outpatient doctor-patient consultations in various settings, to learn if we can safely switch to the shorter OPTION(5)-instrument. Two raters coded 60 audiotaped vascular surgery and oncology patient consultations using OPTION(12) and OPTION(5). Unweighted Cohen's kappa was used to compute inter-rater agreement on item-level. The association between the total scores of the two OPTION-instruments was investigated using Pearson's correlation coefficient (r) and a Bland & Altman plot. After fine-tuning the OPTION-manuals, inter-rater agreement for OPTION(12) and OPTION(5) was good to excellent (kappa range 0.69-0.85 and 0.63-0.72, respectively). Mean total scores were 23.7 (OPTION(12); SD=7.8) and 39.3 (OPTION(5); SD=12.7). Correlation between the total scores was high (r=0.71; p=0.01). OPTION(5) scored systematically higher with a wider range than OPTION(12). Both OPTION-instruments had a good inter-rater agreement and correlated well. OPTION(5) seems to differentiate better between various levels of patient involvement. The OPTION(5)-instrument is recommended for clinical application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

24 CFR 206.19 - Payment options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Payment options. 206.19 Section 206... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgages § 206.19 Payment options. (a) Term payment option. Under the term payment option, equal monthly payments are made by the mortgagee to the...

Potable water scarcity: options and issues in the coastal areas of Bangladesh.

PubMed

Islam, Atikul; Sakakibara, Hiroyuki; Karim, Rezaul; Sekine, Masahiko

2013-09-01

In the coastal areas of Bangladesh, scarcity of drinking water is acute as freshwater aquifers are not available at suitable depths and surface water is highly saline. Households are mainly dependent on rainwater harvesting, pond sand filters and pond water for drinking purposes. Thus, individuals in these areas often suffer from waterborne diseases. In this paper, water consumption behaviour in two southwestern coastal districts of Bangladesh has been investigated. The data for this study were collected through a survey conducted on 750 rural households in 39 villages of the study area. The sample was selected using a random sampling technique. Households' choice of water source is complex and seasonally dependent. Water sourcing patterns, households' preference of water sourcing options and economic feasibility of options suggest that a combination of household and community-based options could be suitable for year-round water supply. Distance and time required for water collection were found to be difficult for water collection from community-based options. Both household and community-based options need regular maintenance. In addition to installation of water supply facilities, it is necessary to make the residents aware of proper operation and maintenance of the facilities.

Current progress on aptamer-targeted oligonucleotide therapeutics

PubMed Central

Dassie, Justin P; Giangrande, Paloma H

2014-01-01

Exploiting the power of the RNAi pathway through the use of therapeutic siRNA drugs has remarkable potential for treating a vast array of human disease conditions. However, difficulties in delivery of these and similar nucleic acid-based pharmacological agents to appropriate organs or tissues, remains a major impediment to their broad clinical application. Synthetic nucleic acid ligands (aptamers) have emerged as effective delivery vehicles for therapeutic oligonucleotides, including siRNAs. In this review, we summarize recent attractive developments in creatively employing cell-internalizing aptamers to deliver therapeutic oligonucleotides (e.g., siRNAs, miRNAs, anti-miRs and antisense oligos) to target cells. We also discuss advancements in aptamer-siRNA chimera technology, as well as, aptamer-functionalized nanoparticles for siRNA delivery. In addition, the challenges and future prospects of aptamer-targeted oligonucleotide drugs for clinical translation are further highlighted. PMID:24304250

24 CFR 35.120 - Options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Options. 35.120 Section 35.120... and Definitions for All Programs. § 35.120 Options. (a) Standard treatments. Where interim controls are required by this part, the designated party has the option to presume that lead-based paint or...

Toughening reinforced epoxy composites with brominated polymeric additives

NASA Technical Reports Server (NTRS)

Nir, Z. (Inventor); Gilwee, W. J., Jr. (Inventor)

1985-01-01

Cured polyfunctional epoxy resins including tris(hydroxyphenyl)methane triglycidyl ether are toughened by addition of polybrominated polymeric additives having an EE below 1500 to the pre-cure composition. Carboxy-terminated butadiene-acrylonitrile rubber is optionally present in the pre-cure mixture as such or as a pre-formed copolymer with other reactants. Reinforced composites, particularly carbon-reinforced composites, of these resins are disclosed and shown to have improved toughness.

Toughening reinforced epoxy composites with brominated polymeric additives

NASA Technical Reports Server (NTRS)

Nir, Z.; Gilwee, W. J., Jr. (Inventor)

1985-01-01

Cured polyfunctional epoxy resins including tris (hydroxyphenyl) methane triglycidyl ether are toughened by addition of polybrominated polymeric additives having an EE below 1500 to the pre-cure composition. Carboxy terminated butadiene acrylonitrile rubber is optionally present in the precure mixture as such or as a pre-formed copolymer with other reactants. Reinforced composites, particularly carbon reinforced composites, of these resins are disclosed and shown to have improved toughness.

CRISPR therapeutic tools for complex genetic disorders and cancer (Review)

PubMed Central

Baliou, Stella; Adamaki, Maria; Kyriakopoulos, Anthony M.; Spandidos, Demetrios A.; Panayiotidis, Mihalis; Christodoulou, Ioannis; Zoumpourlis, Vassilis

2018-01-01

One of the fundamental discoveries in the field of biology is the ability to modulate the genome and to monitor the functional outputs derived from genomic alterations. In order to unravel new therapeutic options, scientists had initially focused on inducing genetic alterations in primary cells, in established cancer cell lines and mouse models using either RNA interference or cDNA overexpression or various programmable nucleases [zinc finger nucleases (ZNF), transcription activator-like effector nucleases (TALEN)]. Even though a huge volume of data was produced, its use was neither cheap nor accurate. Therefore, the clustered regularly interspaced short palindromic repeats (CRISPR) system was evidenced to be the next step in genome engineering tools. CRISPR-associated protein 9 (Cas9)-mediated genetic perturbation is simple, precise and highly efficient, empowering researchers to apply this method to immortalized cancerous cell lines, primary cells derived from mouse and human origins, xenografts, induced pluripotent stem cells, organoid cultures, as well as the generation of genetically engineered animal models. In this review, we assess the development of the CRISPR system and its therapeutic applications to a wide range of complex diseases (particularly distinct tumors), aiming at personalized therapy. Special emphasis is given to organoids and CRISPR screens in the design of innovative therapeutic approaches. Overall, the CRISPR system is regarded as an eminent genome engineering tool in therapeutics. We envision a new era in cancer biology during which the CRISPR-based genome engineering toolbox will serve as the fundamental conduit between the bench and the bedside; nonetheless, certain obstacles need to be addressed, such as the eradication of side-effects, maximization of efficiency, the assurance of delivery and the elimination of immunogenicity. PMID:29901119

Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients.

PubMed

Pérez-Matute, Patricia; Pérez-Martínez, Laura; Aguilera-Lizarraga, Javier; Blanco, José R; Oteo, José A

2015-08-01

The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the development of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity. Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut. Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales. MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics.

PubMed

Shah, Dhaval K

2015-10-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized.

Pharmacokinetic and pharmacodynamic considerations for the next generation protein therapeutics

PubMed Central

Shah, Dhaval K.

2015-01-01

Increasingly sophisticated protein engineering efforts have been undertaken lately to generate protein therapeutics with desired properties. This has resulted in the discovery of the next generation of protein therapeutics, which include: engineered antibodies, immunoconjugates, bi/multi-specific proteins, antibody mimetic novel scaffolds, and engineered ligands/receptors. These novel protein therapeutics possess unique physicochemical properties and act via a unique mechanism-of-action, which collectively makes their pharmacokinetics (PK) and pharmacodynamics (PD) different than other established biological molecules. Consequently, in order to support the discovery and development of these next generation molecules, it becomes important to understand the determinants controlling their PK/PD. This review discusses the determinants that a PK/PD scientist should consider during the design and development of next generation protein therapeutics. In addition, the role of systems PK/PD models in enabling rational development of the next generation protein therapeutics is emphasized. PMID:26373957

Mediterranean diet and non-alcoholic fatty liver disease: New therapeutic option around the corner?

PubMed Central

Sofi, Francesco; Casini, Alessandro

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease in Western countries, being considered as the hepatic manifestation of metabolic syndrome. NAFLD has a common pathogenic background to that of metabolic syndrome, and shares many risk factors such as obesity, hypertension, insulin resistance and dyslipidemia. Although there is no currently available evidence-based established treatment for NAFLD, all the recommendations from the medical associations indicate that the most effective treatment is to reduce weight through lifestyle modifications. Diet, indeed, plays a key role in the management of NAFLD patients, as both the quantity and quality of the diet have been reported to have a beneficial role in the onset and severity of the liver disease. Among all the diets that have been proposed, a Mediterranean diet was the most effective dietary option for inducing weight loss together with beneficial effects on all the risk factors associated with metabolic syndrome and NAFLD. Over the last few years, research has demonstrated a beneficial effect of a Mediterranean diet in NAFLD. In this review, we will examine all the available data on the association between diet, nutrients and the Mediterranean diet in association with onset and severity of NAFLD. PMID:24966604

Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

PubMed

Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

2015-01-01

Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

PubMed Central

Johnston, Atholl

2013-01-01

The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay of immunosuppression in solid organ transplantation. Generic formulations of these drugs are now available. With increasing pressure on healthcare budgets and the consequent need to match health expectations to available resources, substitution with a generic product appears an attractive option to reduce costs. Approval of generic products differs from innovator drugs, and narrow therapeutic index drugs (NTIs; including CNIs) bring their own particular considerations. With NTIs, small variations in drug exposure could result in reduced immunosuppression or drug toxicity with potentially adverse effects on patient outcomes. NTIs are subject to stricter regulatory approval versus many other generic drugs. However, different generic formulations may still not necessarily be therapeutically equivalent in individuals, raising the possibility of significant differences in exposure between products. Although regional recommendations vary, many guidelines emphasise the need for NTI drug substitution to be initiated by the transplant physician, thus ensuring careful therapeutic monitoring and reduced negative patient impact. The need for therapeutic monitoring during generic substitution has important implications for the overall costs of generic treatment as these costs have to be factored in to the potential savings made from using generic formulations. The reduced acquisition costs of generic products may not necessarily translate into lower overall healthcare costs. This article examines the issue of equivalence and interchangeability of NTI drugs used in organ transplantation, the implications of the approval process for generic drugs on treatment efficacy and safety, and the effective management of substitutions between products. PMID:24089632

Patients' experiences with technology during inpatient rehabilitation: opportunities to support independence and therapeutic engagement.

PubMed

Fager, Susan Koch; Burnfield, Judith M

2014-03-01

To understand individuals' perceptions of technology use during inpatient rehabilitation. A qualitative phenomenological study using semi-structured interviews of 10 individuals with diverse underlying diagnoses and/or a close family member who participated in inpatient rehabilitation. Core themes focused on assistive technology usage (equipment set-up, reliability and fragility of equipment, expertise required to use assistive technology and use of mainstream technologies) and opportunities for using technology to increase therapeutic engagement (opportunities for practice outside of therapy, goals for therapeutic exercises and technology for therapeutic exercises: motivation and social interaction). Interviews revealed the need for durable, reliable and intuitive technology without requiring a high level of expertise to install and implement. A strong desire for the continued use of mainstream devices (e.g. cell phones, tablet computers) reinforces the need for a wider range of access options for those with limited physical function. Finally, opportunities to engage in therapeutically meaningful activities beyond the traditional treatment hours were identified as valuable for patients to not only improve function but to also promote social interaction. Assistive technology increases functional independence of severely disabled individuals. End-users (patients and families) identified a need for designs that are durable, reliable, intuitive, easy to consistently install and use. Technology use (adaptive or commercially available) provides a mechanism to extend therapeutic practice beyond the traditional therapy day. Adapting skeletal tracking technology used in gaming software could automate exercise tracking, documentation and feedback for patient motivation and clinical treatment planning and interventions.

17 CFR 32.3 - Trade options.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 17 Commodity and Securities Exchanges 1 2014-04-01 2014-04-01 false Trade options. 32.3 Section 32... OPTION TRANSACTIONS § 32.3 Trade options. (a) Subject to paragraphs (b), (c), and (d) of this section... period preceding the date on which the trade option is entered into, (iv) In connection with any non...

17 CFR 32.3 - Trade options.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Trade options. 32.3 Section 32... OPTION TRANSACTIONS § 32.3 Trade options. (a) Subject to paragraphs (b), (c), and (d) of this section... period preceding the date on which the trade option is entered into, (iv) In connection with any non...

The option value of innovative treatments in the context of chronic myeloid leukemia.

PubMed

Sanchez, Yuri; Penrod, John R; Qiu, Xiaoli Lily; Romley, John; Thornton Snider, Julia; Philipson, Tomas

2012-11-01

To quantify in the context of chronic myeloid leukemia (CML) the additional value patients receive when innovative treatments enable them to survive until the advent of even more effective future treatments (ie, the "option value"). Observational study using data from the Surveillance, Epidemiology and End Results (SEER) cancer registry comprising all US patients with CML diagnosed between 2000 and 2008 (N = 9,760). We quantified the option value of recent breakthroughs in CML treatment by first conducting retrospective survival analyses on SEER data to assess the effectiveness of TKI treatments, and then forecasting survival from CML and other causes to measure expected future medical progress. We then developed an analytical framework to calculate option value of innovative CML therapies, and used an economic model to value these gains. We calculated the option value created both by future innovations in CML treatment and by medical progress in reducing background mortality. For a recently diagnosed CML patient, the option value of innovative therapies from future medical innovation amounts to 0.76 life-years. This option value is worth $63,000, equivalent to 9% of the average survival gains from existing treatments. Future innovations in CML treatment jointly account for 96% of this benefit. The option value of innovative treatments has significance in the context of CML and, more broadly, in disease areas with rapid innovation. Incorporating option value into traditional valuations of medical innovations is both a feasible and a necessary practice in health technology assessment.

Discovery and design of carbohydrate-based therapeutics.

PubMed

Cipolla, Laura; Araújo, Ana C; Bini, Davide; Gabrielli, Luca; Russo, Laura; Shaikh, Nasrin

2010-08-01

Till now, the importance of carbohydrates has been underscored, if compared with the two other major classes of biopolymers such as oligonucleotides and proteins. Recent advances in glycobiology and glycochemistry have imparted a strong interest in the study of this enormous family of biomolecules. Carbohydrates have been shown to be implicated in recognition processes, such as cell-cell adhesion, cell-extracellular matrix adhesion and cell-intruder recognition phenomena. In addition, carbohydrates are recognized as differentiation markers and as antigenic determinants. Due to their relevant biological role, carbohydrates are promising candidates for drug design and disease treatment. However, the growing number of human disorders known as congenital disorders of glycosylation that are being identified as resulting from abnormalities in glycan structures and protein glycosylation strongly indicates that a fast development of glycobiology, glycochemistry and glycomedicine is highly desirable. The topics give an overview of different approaches that have been used to date for the design of carbohydrate-based therapeutics; this includes the use of native synthetic carbohydrates, the use of carbohydrate mimics designed on the basis of their native counterpart, the use of carbohydrates as scaffolds and finally the design of glyco-fused therapeutics, one of the most recent approaches. The review covers mainly literature that has appeared since 2000, except for a few papers cited for historical reasons. The reader will gain an overview of the current strategies applied to the design of carbohydrate-based therapeutics; in particular, the advantages/disadvantages of different approaches are highlighted. The topic is presented in a general, basic manner and will hopefully be a useful resource for all readers who are not familiar with it. In addition, in order to stress the potentialities of carbohydrates, several examples of carbohydrate-based marketed therapeutics are given

26 CFR 1.544-4 - Options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Options. 1.544-4 Section 1.544-4 Internal Revenue... (CONTINUED) Personal Holding Companies § 1.544-4 Options. The shares of stock which may be acquired by reason of an option shall be considered to be constructively owned by the individual having the option to...

Imaging of athletic pubalgia and core muscle injuries: clinical and therapeutic correlations.

PubMed

Palisch, Andrew; Zoga, Adam C; Meyers, William C

2013-07-01

Athletes frequently injure their hips and core muscles. Accurate diagnosis and proper treatment of groin pain in the athlete can be tricky, frequently posing vexing problem for trainers and physicians. Clinical presentations of the various hip problems overlap with respect to history and physical examination. This article reviews clinical presentations and magnetic resonance imaging findings specific to the various causes of groin pain in the athlete. The focus is on the core muscle injuries (athletic pubalgia or "sports hernia"). The goal is to raise awareness about the variety of injuries that occur and therapeutic options. Copyright © 2013 Elsevier Inc. All rights reserved.

Hypertension in pregnancy: natural history and treatment options.

PubMed

Foo, L; Tay, J; Lees, C C; McEniery, C M; Wilkinson, I B

2015-05-01

Hypertensive disorders of pregnancy affect approximately 5-10% of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

Current and future treatment options for polycythemia vera.

PubMed

Griesshammer, Martin; Gisslinger, Heinz; Mesa, Ruben

2015-06-01

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

Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

PubMed

Malan, Tina; Moodley, Keymanthri

2016-02-01

Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic

PubMed Central

Bird, Gregory H.; Madani, Navid; Perry, Alisa F.; Princiotto, Amy M.; Supko, Jeffrey G.; He, Xiaoying; Gavathiotis, Evripidis; Sodroski, Joseph G.; Walensky, Loren D.

2010-01-01

The pharmacologic utility of lengthy peptides can be hindered by loss of bioactive structure and rapid proteolysis, which limits bioavailability. For example, enfuvirtide (Fuzeon, T20, DP178), a 36-amino acid peptide that inhibits human immunodeficiency virus type 1 (HIV-1) infection by effectively targeting the viral fusion apparatus, has been relegated to a salvage treatment option mostly due to poor in vivo stability and lack of oral bioavailability. To overcome the proteolytic shortcomings of long peptides as therapeutics, we examined the biophysical, biological, and pharmacologic impact of inserting all-hydrocarbon staples into an HIV-1 fusion inhibitor. We find that peptide double-stapling confers striking protease resistance that translates into markedly improved pharmacokinetic properties, including oral absorption. We determined that the hydrocarbon staples create a proteolytic shield by combining reinforcement of overall α-helical structure, which slows the kinetics of proteolysis, with complete blockade of peptide cleavage at constrained sites in the immediate vicinity of the staple. Importantly, double-stapling also optimizes the antiviral activity of HIV-1 fusion peptides and the antiproteolytic feature extends to other therapeutic peptide templates, such as the diabetes drug exenatide (Byetta). Thus, hydrocarbon double-stapling may unlock the therapeutic potential of natural bioactive polypeptides by transforming them into structurally fortified agents with enhanced bioavailability. PMID:20660316

45 CFR 1306.34 - Combination program option.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Combination program option. 1306.34 Section 1306... START PROGRAM HEAD START STAFFING REQUIREMENTS AND PROGRAM OPTIONS Head Start Program Options § 1306.34 Combination program option. (a) Combination program option requirements: (1) Grantees implementing a...

ANMCO/ISS/AMD/ANCE/ARCA/FADOI/GICR-IACPR/SICI-GISE/SIBioC/SIC/SICOA/SID/SIF/SIMEU/SIMG/SIMI/SISA Joint Consensus Document on cholesterol and cardiovascular risk: diagnostic–therapeutic pathway in Italy

PubMed Central

Colivicchi, Furio; Ricciardi, Gualtiero; Giampaoli, Simona; Maggioni, Aldo Pietro; Averna, Maurizio; Graziani, Maria Stella; Ceriotti, Ferruccio; Mugelli, Alessandro; Rossi, Francesco; Medea, Gerardo; Parretti, Damiano; Abrignani, Maurizio Giuseppe; Arca, Marcello; Perrone Filardi, Pasquale; Perticone, Francesco; Catapano, Alberico; Griffo, Raffaele; Nardi, Federico; Riccio, Carmine; Di Lenarda, Andrea; Scherillo, Marino; Musacchio, Nicoletta; Panno, Antonio Vittorio; Zito, Giovanni Battista; Campanini, Mauro; Bolognese, Leonardo; Faggiano, Pompilio Massimo; Musumeci, Giuseppe; Pusineri, Enrico; Ciaccio, Marcello; Bonora, Enzo; Cantelli Forti, Giorgio; Ruggieri, Maria Pia; Cricelli, Claudio; Romeo, Francesco; Ferrari, Roberto; Maseri, Attilio

2017-01-01

Abstract Atherosclerotic cardiovascular disease still represents the leading cause of death in Western countries. A wealth of scientific evidence demonstrates that increased blood cholesterol levels have a major impact on the outbreak and progression of atherosclerotic plaques. Moreover, several cholesterol-lowering pharmacological agents, including statins and ezetimibe, have proved effective in improving clinical outcomes. This document focuses on the clinical management of hypercholesterolaemia and has been conceived by 16 Italian medical associations with the support of the Italian National Institute of Health. The authors discuss in detail the role of hypercholesterolaemia in the genesis of atherosclerotic cardiovascular disease. In addition, the implications for high cholesterol levels in the definition of the individual cardiovascular risk profile have been carefully analysed, while all available therapeutic options for blood cholesterol reduction and cardiovascular risk mitigation have been explored. Finally, this document outlines the diagnostic and therapeutic pathways for the clinical management of patients with hypercholesterolaemia. PMID:28751833

Therapeutic interventions for hypertension in metabolic syndrome: a comprehensive approach.

PubMed

Ganne, Sudha; Arora, Surender; Karam, Jocelyne; McFarlane, Samy I

2007-03-01

Hypertension is a major component of the metabolic syndrome and a major cardiovascular risk factor. Both disorders are rapidly increasing in frequency, with hypertension affecting nearly 60 million Americans and over 1 billion people worldwide, and metabolic syndrome affecting 44% of the US population above the age of 60 years. Sedentary lifestyle, together with obesity and aging of the population, are the major contributing factors for this growing epidemic. Hypertension in metabolic syndrome possesses unique pathophysiological aspects that have considerable implications on therapy of this disease. In this article, we review the pathophysiology and provide a rationale for the current therapeutic options in light of the most recent clinical trials in the field.

Cardiovascular pleiotropic actions of DPP-4 inhibitors: a step at the cutting edge in understanding their additional therapeutic potentials.

PubMed

Balakumar, Pitchai; Dhanaraj, Sokkalingam A

2013-09-01

Dipeptidyl peptidase 4 (DPP-4) is a serine protease enzyme expressed widely in many tissues, including the cardiovascular system. The incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from the small intestine into the vasculature during a meal, and these incretins have a potential to release insulin from pancreatic beta cells of islets of Langerhans, affording a glucose-lowering action. However, both incretins are hurriedly degraded by the DPP-4. Inhibitors of DPP-4, therefore, enhance the bioavailability of GLP-1 and GIP, and thus have been approved for better glycemic management in patients afflicted with type 2 diabetes mellitus (T2DM). Five different DPP-4 inhibitors, often called as 'gliptins', namely sitagliptin, vildagliptin, saxagliptin, linagliptin and alogliptin have been approved hitherto for clinical use. These drugs are used along with diet and exercise to lower blood sugar in diabetic subjects. T2DM is intricately related with an increased risk of cardiovascular disease. Growing body of evidence suggests that gliptins, in addition to their persuasive anti-diabetic action, have a beneficial pleiotropic action on the heart and vessels. In view of the fact of cardiovascular disease susceptibility of patients afflicted with T2DM, gliptins might offer additional therapeutic benefits in treating diabetic cardiovascular complications. Exploring further the cardiovascular pleiotropic potentials of gliptins might open a panorama in impeccably employing these agents for the dual management of T2DM and T2DM-associated perilous cardiovascular complications. This review will shed lights on the newly identified beneficial pleiotropic actions of gliptins on the cardiovascular system. Copyright © 2013 Elsevier Inc. All rights reserved.

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

PubMed

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-11-01

Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea

PubMed Central

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-01-01

Abstract Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP. This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA. Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively. The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA. These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP. PMID:27861349

Do follow-on therapeutic substitutes induce price competition between hospital medicines? Evidence from the Danish hospital sector.

PubMed

Hostenkamp, Gisela

2013-06-01

The pricing of follow-on drugs, that offer only limited health benefits over existing therapeutic alternatives, is a recurring health policy debate. This study investigates whether follow-on therapeutic substitutes create price competition between branded hospital medicines. New follow-on drugs and their incumbent therapeutic competitors were identified from Danish sales and product registration data on hospital pharmaceuticals using medically relevant criteria. We examined whether follow-on drugs adopt lower prices than their incumbent competitors, and whether incumbent competitors react to entry of follow-ons through price adjustments using a random intercept panel model. We found no evidence that follow-on drugs adopt lower prices than their incumbent competitors. Furthermore, potentially due to low sample size, we found no evidence that prices for incumbent pioneer products were significantly reduced as a reaction to competition from follow-on drugs. Competition between patented therapeutic substitutes did not seem to increase price competition and containment of pharmaceutical expenditures in the Danish hospital market. Strengthening hospitals' incentives to consider the price of alternative treatment options paired with a more active formulary management may increase price competition between therapeutic substitutes in the Danish hospital sector in the future. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Delay, doubt, and decision: how delaying a choice reduces the appeal of (descriptively) normative options.

PubMed

van de Ven, Niels; Gilovich, Thomas; Zeelenberg, Marcel

2010-04-01

To help explain a regularity in democratic elections, we examined whether choosing to delay making a choice between a focal option and an alternative tends to make people subsequently less likely to choose what they would otherwise have chosen. The results of two experiments demonstrated that participants who were induced to delay making a decision were indeed less likely to choose the descriptively normative option. An additional experiment that primed a sense of doubt in participants provided support for a self-perception account of this result. Electing to delay making a choice is interpreted as an indication of doubt--doubt that tends to be attributed to the most prominent option. Delay-induced doubt about the normative option makes it less likely to be selected.

24 CFR 982.625 - Homeownership option: General.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Homeownership option: General. 982... Types Homeownership Option § 982.625 Homeownership option: General. (a) The homeownership option is used... family assisted under the homeownership option may be a newly admitted or existing participant in the...

48 CFR 517.207 - Exercise of options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Exercise of options. 517... METHODS AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 517.207 Exercise of options. Before exercising an option, you must: (a) Synopsize it unless you meet of the following conditions: (1) The option...

New therapeutic options for IBS: the role of the first in class mixed µ- opioid receptor agonist and δ-opioid receptor antagonist (mudelta) eluxadoline.

PubMed

Corsetti, Maura; Whorwell, Peter

2017-04-01

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to healthcare services. IBS-D patients represent about one-third of the IBS population and are currently treated with antispasmodics, loperamide, bile acid sequestrants and antidepressants. Alosetron and rifaximin are also available in USA, ramosetron in Japan, Korea and Thailand and ondansetron as an off-label treatment. Areas covered: This article focuses on eluxadoline, a novel pharmacological agent that has recently been approved by both the FDA and EMA for treatment of patients with IBS-D. Expert commentary: The efficacy and safety of eluxadoline in treating bowel habit alterations and pain, both in the short and long-term, make the drug a welcome addition to our therapeutic alternatives in IBS-D. Its positioning in any IBS algorithm will depend on the 'real world' prevalence of the small risk of sphincter of Oddi spasm and mild pancreatitis.

Somatic mutations in salivary duct carcinoma and potential therapeutic targets

PubMed Central

Smith, Joel A.; Clarke, Angus J.; Luk, Peter P.; Selinger, Christina I.; Mahon, Kate L.; Kraitsek, Spiridoula; Palme, Carsten; Boyer, Michael J.; Dinger, Marcel E.; Cowley, Mark J.; O’Toole, Sandra A.

2017-01-01

Background Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. Results 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p.H1047R: Everolimus), ERBB2 (p.V842I: Lapatinib), HRAS (p.Q61R: Selumetinib) and KIT (p.T670I: Sorafenib). Furthermore, alterations in PTEN, PIK3CA and HRAS that alter response to androgen deprivation therapy and HER2 inhibition were also seen. Materials and Methods Somatic mutation analysis was performed on DNA extracted from 15 archival cases of SDCa using the targeted Illumina TruSeq Amplicon Cancer Panel. Potential targetable genetic alterations were identified using extensive literature and international somatic mutation database (COSMIC, KEGG) search. Immunohistochemistry for androgen receptor and immunohistochemistry and fluorescent in situ hybridization for HER2 were also performed. Conclusions SDCa show multiple somatic mutations, some that are amenable to pharmacologic manipulation and others that confer resistance to treatments currently under investigation. These findings emphasize the need to develop testing and treatment strategies for SDCa. PMID:29100278

Reducing the Deficit: Spending and Revenue Options

DTIC Science & Technology

2011-03-01

the Conservation Reserve Program 25AgricultureOption 6 Reduce the Premium Subsidy in the Crop Insurance Program 26Option 7 Reduce by 20 Percentage...Graduate Students 31Option 11 Change the Interest Rate Structure for Student Loans 32HealthOption 12 Add a “Public Plan” to the Health Insurance Exchanges...Health Episodes Covered by Medicare 48Option 21 Reduce Medicare Costs by Changing the Cost-Sharing Structures for Medicare and Medigap Insurance 49Option

Therapeutic Uses of Triphala in Ayurvedic Medicine

PubMed Central

Denniston, Kate; Chopra, Deepak

2017-01-01

Abstract Aim: The aim of this article is to review the current literature on the therapeutic uses and efficacy of Triphala. Herbal remedies are among the most ancient medicines used in traditional systems of healthcare such as Ayurveda. Triphala, a well-recognized and highly efficacious polyherbal Ayurvedic medicine consisting of fruits of the plant species Emblica officinalis (Amalaki), Terminalia bellerica (Bibhitaki), and Terminalia chebula (Haritaki), is a cornerstone of gastrointestinal and rejuvenative treatment. Methods: A search of the PubMed database was conducted. Results: In addition, numerous additional therapeutic uses described both in the Ayurvedic medical literature and anecdotally are being validated scientifically. In addition to laxative action, Triphala research has found the formula to be potentially effective for several clinical uses such as appetite stimulation, reduction of hyperacidity, antioxidant, anti-inflammatory, immunomodulating, antibacterial, antimutagenic, adaptogenic, hypoglycemic, antineoplastic, chemoprotective, and radioprotective effects, and prevention of dental caries. Polyphenols in Triphala modulate the human gut microbiome and thereby promote the growth of beneficial Bifidobacteria and Lactobacillus while inhibiting the growth of undesirable gut microbes. The bioactivity of Triphala is elicited by gut microbiota to generate a variety of anti-inflammatory compounds. Conclusions: This review summarizes recent data on pharmacological properties and clinical effects of Triphala while highlighting areas in need of additional investigation and clinical development. PMID:28696777

42 CFR 413.355 - Additional payment: QIO photocopy and mailing costs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Prospective Payment for Skilled Nursing Facilities § 413.355 Additional payment: QIO photocopy and mailing costs. An additional payment is made to a skilled nursing facility in accordance with § 476.78 of this...

42 CFR 413.355 - Additional payment: QIO photocopy and mailing costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RENAL DISEASE SERVICES; OPTIONAL PROSPECTIVELY DETERMINED PAYMENT RATES FOR SKILLED NURSING FACILITIES Prospective Payment for Skilled Nursing Facilities § 413.355 Additional payment: QIO photocopy and mailing costs. An additional payment is made to a skilled nursing facility in accordance with § 476.78 of this...

Valuing options in shot noise market

NASA Astrophysics Data System (ADS)

Laskin, Nick

2018-07-01

A new exactly solvable option pricing model has been introduced and elaborated. It is assumed that a stock price follows a Geometric shot noise process. An arbitrage-free integro-differential option pricing equation has been obtained and solved. The new Greeks have been analytically calculated. It has been shown that in diffusion approximation the developed option pricing model incorporates the well-known Black-Scholes equation and its solution. The stochastic dynamic origin of the Black-Scholes volatility has been uncovered. To model the observed market stock price patterns consisting of high frequency small magnitude and low frequency large magnitude jumps, the superposition of two Geometric shot noises has been implemented. A new generalized option pricing equation has been obtained and its exact solution was found. Merton's jump-diffusion formula for option price was recovered in diffusion approximation. Despite the non-Gaussian nature of probability distributions involved, the new option pricing model has the same degree of analytical tractability as the Black-Scholes model and the Merton jump-diffusion model. This attractive feature allows one to derive exact formulas to value options and option related instruments in the market with jump-like price patterns.

SEATSAT programs option analysis

NASA Technical Reports Server (NTRS)

Luckl, L.

1976-01-01

A preliminary analysis of the costs of SEASAT follow-on options is presented. All the options assume the existence of SEASAT-A as currently defined in the SEASAT Economic Assessment. It is assumed that each option will continue through the year 2000 and approach operational system status in the 1983-1986 period, depending upon the sensor package selected. The launch vehicle assumed through 1983 is the Atlas Agena. After 1983, it is assumed SEASAT-A will switch to the use of the Space Shuttle. All cost estimates are 1976 dollars for fiscal year cost accounting, with no inflation rate included.

Pleiotropic effects of statins: new therapeutic targets in drug design.