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.

Clostridium difficile infection: New insights into therapeutic options.

PubMed

Kachrimanidou, Melina; Sarmourli, Theopisti; Skoura, Lemonia; Metallidis, Symeon; Malisiovas, Nikolaos

2016-09-01

Clostridium difficile infection (CDI) is an important cause of mortality and morbidity in healthcare settings and represents a major social and economic burden. The major virulence determinants are large clostridial toxins, toxin A (TcdA) and toxin B (TcdB), encoded within the pathogenicity locus. Traditional therapies, such as metronidazole and vancomycin, frequently lead to a vicious circle of recurrences due to their action against normal human microbiome. New disease management strategies together with the development of novel therapeutic and containment approaches are needed in order to better control outbreaks and treat patients. This article provides an overview of currently available CDI treatment options and discusses the most promising therapies under development.

Endometriosis: Survey of Current Diagnostic and Therapeutic Options and Latest Research Work

PubMed Central

Juhasz-Böss, I.; Laschke, M. W.; Müller, F.; Rosenbaum, P.; Baum, S.; Solomayer, E. F.; Ulrich, U.

2014-01-01

Endometriosis is one of the most frequent benign diseases in women of child-bearing age. The main symptoms are chronic upper abdominal pain and infertility. However, the aetiology and pathogenesis of endometriosis are as yet insufficiently clarified. Thus, therapy is mainly symptomatic with laparoscopic surgery being the gold standard. The aim of drug therapy is to achieve a hypo-oestrogenic condition. In cases of severe endometriosis and a desire to have children there is often an indication for assisted reproduction. The present article illustrates almost all current aspects on the diagnosis of and therapy of endometriosis. From the clinical viewpoint, emphasis is placed on the rare cases of deeply infiltrating endometriosis that are, however, accompanied with a high morbidity. Current therapeutic options in cases of infertility are also presented in more detail. Furthermore, special attention is paid to the latest research results from both clinical and basic research fields in order to demonstrate our current knowledge on the pathogenesis and, where possible, potentially related therapeutic options. PMID:25221341

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

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

PubMed

Gimeno-Ballester, Vicente; Mar, Javier; O'Leary, Aisling; Adams, Róisín; San Miguel, Ramón

2017-01-01

This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

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

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

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.

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.

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

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.

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

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

[Venous and arteriovenous malformations in the head and neck region. Therapeutic options and challenges].

PubMed

Eivazi, B; Werner, J A

2014-01-01

Venous malformations are the prototype low-flow malformations in the head and neck region. Arteriovenous malformations (AVM) represent the main high-flow malformations. In recent years it has been possible to significantly optimize the therapeutic options for venous malformations. In addition to conventional surgery, laser treatment and sclerotherapy have become established techniques and the importance of embolization with new alcohol-based materials is increasing. AVM are progressive and destructive diseases. Therapy of choice is usually a combined treatment comprising embolization and surgical removal of the arteriovenous nidus. This curative approach is usually possible if diagnosis is made at an early stage. Incomplete embolization or sole ligation of the arterial supply causes progression. There is a clear need for improved therapeutic methods and pharmacotherapeutic approaches.

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.

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.

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 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.

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

[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.

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.

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.

[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.

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

The effect of including an opt-out option in discrete choice experiments.

PubMed

Veldwijk, Jorien; Lambooij, Mattijs S; de Bekker-Grob, Esther W; Smit, Henriëtte A; de Wit, G Ardine

2014-01-01

to determine to what extent the inclusion of an opt-out option in a DCE may have an effect on choice behaviour and therefore might influence the attribute level estimates, the relative importance of the attributes and calculated trade-offs. 781 Dutch Type 2 Diabetes Mellitus patients completed a questionnaire containing nine choice tasks with an opt-out option and nice forced choice tasks. Mixed-logit models were used to estimate the relative importance of the five lifestyle program related attributes that were included. Willingness to pay (WTP) values were calculated and it was tested whether results differed between respondents who answered the choice tasks with an opt-out option in the first or second part of the questionnaire. 21.4% of the respondents always opted out. Respondents who were given the opt-out option in the first part of the questionnaire as well as lower educated respondents significantly more often opted out. For both the forced and unforced choice model, different attributes showed significant estimates, the relative importance of the attributes was equal. However, due to differences in relative importance weights, the WTP values for the PA schedule differed significantly between both datasets. Results show differences in opting out based on the location of the opt-out option and respondents' educational level; this resulted in small differences between the forced and unforced choice model. Since respondents seem to learn from answering forced choice tasks, a dual response design might result in higher data quality compared to offering a direct opt-out option. Future research should empirically explore how choice sets should be presented to make them as easy and less complex as possible in order to reduce the proportion of respondents that opts-out due to choice task complexity. Moreover, future research should debrief respondents to examine the reasons for choosing the opt-out alternative.

[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.

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

The Effect of Including an Opt-Out Option in Discrete Choice Experiments

PubMed Central

Veldwijk, Jorien; Lambooij, Mattijs S.; de Bekker-Grob, Esther W.; Smit, Henriëtte A.; de Wit, G. Ardine

2014-01-01

Objective to determine to what extent the inclusion of an opt-out option in a DCE may have an effect on choice behaviour and therefore might influence the attribute level estimates, the relative importance of the attributes and calculated trade-offs. Methods 781 Dutch Type 2 Diabetes Mellitus patients completed a questionnaire containing nine choice tasks with an opt-out option and nice forced choice tasks. Mixed-logit models were used to estimate the relative importance of the five lifestyle program related attributes that were included. Willingness to pay (WTP) values were calculated and it was tested whether results differed between respondents who answered the choice tasks with an opt-out option in the first or second part of the questionnaire. Results 21.4% of the respondents always opted out. Respondents who were given the opt-out option in the first part of the questionnaire as well as lower educated respondents significantly more often opted out. For both the forced and unforced choice model, different attributes showed significant estimates, the relative importance of the attributes was equal. However, due to differences in relative importance weights, the WTP values for the PA schedule differed significantly between both datasets. Conclusions Results show differences in opting out based on the location of the opt-out option and respondents' educational level; this resulted in small differences between the forced and unforced choice model. Since respondents seem to learn from answering forced choice tasks, a dual response design might result in higher data quality compared to offering a direct opt-out option. Future research should empirically explore how choice sets should be presented to make them as easy and less complex as possible in order to reduce the proportion of respondents that opts-out due to choice task complexity. Moreover, future research should debrief respondents to examine the reasons for choosing the opt-out alternative. PMID:25365169

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.

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.

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.

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

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.

Patient and Clinician Openness to Including a Broader Range of Healing Options in Primary Care

PubMed Central

Hsu, Clarissa; Cherkin, Daniel C.; Hoffmeyer, Sylvia; Sherman, Karen J.; Phillips, William R.

2011-01-01

PURPOSE We studied the openness of patients and clinicians to introducing a broader range of healing options into primary care. METHODS Focus groups were conducted with primary care patients (4 groups) and clinicians (3 groups) from an integrated medical care system in 2008. Transcripts of discussions were analyzed using an immersion/crystallization approach. RESULTS Both patients (n = 44) and clinicians (n = 32) were open to including a wider variety of healing options in primary care. Patients desired some evidence of effectiveness, although there was wide variation in the type of evidence required. Many patients believed that the clinician’s personal and practice experience was an important form of evidence. Patients wanted to share in the decision to refer and the choice of options. Clinicians were most concerned with safety of specific treatments, including some of the herbs and dietary supplements. They also believed they lacked adequate information about the nature, benefits, and risks of many alternatives, and they were not aware of local practitioners and resources to whom they could confidently refer their patients. Both patients and clinicians were concerned that services recommended be covered by insurance or be affordable to patients. CONCLUSIONS Integrating additional healing options into primary care may be feasible and desirable, as well as help meet the needs of patients with conditions that have not been responsive to standard medical treatments. PMID:21911764

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.

21 CFR 1.233 - What optional items are included in the registration form?

Code of Federal Regulations, 2010 CFR

2010-04-01

... extracts) and 11b (e.g., grain products, amino acids); (i) Type of storage, if the facility is primarily a... 21 Food and Drugs 1 2010-04-01 2010-04-01 false What optional items are included in the registration form? 1.233 Section 1.233 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

21 CFR 1.233 - What optional items are included in the registration form?

Code of Federal Regulations, 2011 CFR

2011-04-01

... extracts) and 11b (e.g., grain products, amino acids); (i) Type of storage, if the facility is primarily a... 21 Food and Drugs 1 2011-04-01 2011-04-01 false What optional items are included in the registration form? 1.233 Section 1.233 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

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

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.

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.

[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.

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.

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

Assessing CO2 Mitigation Options Utilizing Detailed Electricity Characteristics and Including Renewable Generation

NASA Astrophysics Data System (ADS)

Bensaida, K.; Alie, Colin; Elkamel, A.; Almansoori, A.

2017-08-01

This paper presents a novel techno-economic optimization model for assessing the effectiveness of CO2 mitigation options for the electricity generation sub-sector that includes renewable energy generation. The optimization problem was formulated as a MINLP model using the GAMS modeling system. The model seeks the minimization of the power generation costs under CO2 emission constraints by dispatching power from low CO2 emission-intensity units. The model considers the detailed operation of the electricity system to effectively assess the performance of GHG mitigation strategies and integrates load balancing, carbon capture and carbon taxes as methods for reducing CO2 emissions. Two case studies are discussed to analyze the benefits and challenges of the CO2 reduction methods in the electricity system. The proposed mitigations options would not only benefit the environment, but they will as well improve the marginal cost of producing energy which represents an advantage for stakeholders.

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.

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.

[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.

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.

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.

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

25 CFR 162.541 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false What must the lease include if it contains an option to renew? 162.541 Section 162.541 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Wind and Solar Resource Leases Wsr Leases § 162.541 What must the lease include...

25 CFR 162.541 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false What must the lease include if it contains an option to renew? 162.541 Section 162.541 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER LEASES AND PERMITS Wind and Solar Resource Leases Wsr Leases § 162.541 What must the lease include...

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

25 CFR 162.312 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2013 CFR

2013-04-01

... WATER LEASES AND PERMITS Residential Leases Lease Requirements § 162.312 What must the lease include if... any, that will be due upon the exercise of the option to renew or the start of the renewal term; and...

25 CFR 162.312 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2014 CFR

2014-04-01

... WATER LEASES AND PERMITS Residential Leases Lease Requirements § 162.312 What must the lease include if... any, that will be due upon the exercise of the option to renew or the start of the renewal term; and...

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...

25 CFR 162.412 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2014 CFR

2014-04-01

... WATER LEASES AND PERMITS Business Leases Lease Requirements § 162.412 What must the lease include if it..., if any, that will be due upon the exercise of the option to renew or the start of the renewal term...

25 CFR 162.412 - What must the lease include if it contains an option to renew?

Code of Federal Regulations, 2013 CFR

2013-04-01

... WATER LEASES AND PERMITS Business Leases Lease Requirements § 162.412 What must the lease include if it..., if any, that will be due upon the exercise of the option to renew or the start of the renewal term...

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.

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.

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.

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

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.

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.

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.

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

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.

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

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.

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.

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

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.

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.

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

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.

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

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.

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

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

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.

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.

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.

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.

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.

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

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

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.

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.

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.

42 CFR 417.155 - How the HMO option must be included in the health benefits plan.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HMO or of transfer from HMO to non-HMO coverage, or exclusions, or limitations based on health status... this selection, lose their eligibility for free-standing dental, optical, or prescription drug benefits... option.) - (ii) The non-HMO option provides free-standing coverage for optical services (such as...

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.

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.

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.

42 CFR 417.155 - How the HMO option must be included in the health benefits plan.

Code of Federal Regulations, 2012 CFR

2012-10-01

... enrollment in the HMO or of transfer from HMO to non-HMO coverage, or exclusions, or limitations based on..., because of this selection, lose their eligibility for free-standing dental, optical, or prescription drug... option.) - (ii) The non-HMO option provides free-standing coverage for optical services (such as...

42 CFR 417.155 - How the HMO option must be included in the health benefits plan.

Code of Federal Regulations, 2013 CFR

2013-10-01

... enrollment in the HMO or of transfer from HMO to non-HMO coverage, or exclusions, or limitations based on..., because of this selection, lose their eligibility for free-standing dental, optical, or prescription drug... option.) - (ii) The non-HMO option provides free-standing coverage for optical services (such as...

42 CFR 417.155 - How the HMO option must be included in the health benefits plan.

Code of Federal Regulations, 2014 CFR

2014-10-01

... enrollment in the HMO or of transfer from HMO to non-HMO coverage, or exclusions, or limitations based on..., because of this selection, lose their eligibility for free-standing dental, optical, or prescription drug... option.) - (ii) The non-HMO option provides free-standing coverage for optical services (such as...

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

[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.

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.

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.

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.

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.

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

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.

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.

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

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.

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.

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

43 CFR 3137.50 - What optional terms may I include in a unit agreement?

Code of Federal Regulations, 2012 CFR

2012-10-01

... following optional terms for a unit agreement if they promote additional development or enhanced production... modification; or (d) Other terms that BLM determines will promote the greatest economic recovery of oil and gas...

43 CFR 3137.50 - What optional terms may I include in a unit agreement?

Code of Federal Regulations, 2013 CFR

2013-10-01

... following optional terms for a unit agreement if they promote additional development or enhanced production... modification; or (d) Other terms that BLM determines will promote the greatest economic recovery of oil and gas...

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

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...

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

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

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.

Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF

PubMed Central

Phan, Kevin; Malham, Greg; Seex, Kevin; Rao, Prashanth J.

2015-01-01

Degenerative disc and facet joint disease of the lumbar spine is common in the ageing population, and is one of the most frequent causes of disability. Lumbar spondylosis may result in mechanical back pain, radicular and claudicant symptoms, reduced mobility and poor quality of life. Surgical interbody fusion of degenerative levels is an effective treatment option to stabilize the painful motion segment, and may provide indirect decompression of the neural elements, restore lordosis and correct deformity. The surgical options for interbody fusion of the lumbar spine include: posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), minimally invasive transforaminal lumbar interbody fusion (MI-TLIF), oblique lumbar interbody fusion/anterior to psoas (OLIF/ATP), lateral lumbar interbody fusion (LLIF) and anterior lumbar interbody fusion (ALIF). The indications may include: discogenic/facetogenic low back pain, neurogenic claudication, radiculopathy due to foraminal stenosis, lumbar degenerative spinal deformity including symptomatic spondylolisthesis and degenerative scoliosis. In general, traditional posterior approaches are frequently used with acceptable fusion rates and low complication rates, however they are limited by thecal sac and nerve root retraction, along with iatrogenic injury to the paraspinal musculature and disruption of the posterior tension band. Minimally invasive (MIS) posterior approaches have evolved in an attempt to reduce approach related complications. Anterior approaches avoid the spinal canal, cauda equina and nerve roots, however have issues with approach related abdominal and vascular complications. In addition, lateral and OLIF techniques have potential risks to the lumbar plexus and psoas muscle. The present study aims firstly to comprehensively review the available literature and evidence for different lumbar interbody fusion (LIF) techniques. Secondly, we propose a set of recommendations and guidelines

Problem Patrons: Reviewing Your Options.

ERIC Educational Resources Information Center

Shuman, Bruce A.

2002-01-01

Considers possible options for public librarians dealing with problem patrons. Highlights include considering the safety of the patrons and staff; general considerations of library security, including security guards, legal responsibility for patrons and staff safety; and working through possible options ahead of time to be more prepared. (LRW)

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.

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 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

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.

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

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

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 siRNAs for dominant genetic skin diseases including pachyonychia congenita

PubMed Central

Leachman, Sancy A.; Hickerson, Robyn P.; Hull, Peter R.; Smith, Frances J. D.; Milstone, Leonard M.; Lane, E. Birgitte; Bale, Sherri J.; Roop, Dennis R.; McLean, W. H. Irwin; Kaspar, Roger L.

2008-01-01

The field of science and medicine has experienced a flood of data and technology associated with the human genome project. Over 10,000 human diseases have been genetically defined, but little progress has been made with respect to the clinical application of this knowledge. A notable exception to this exists for pachyonychia congenita (PC), a rare, dominant negative keratin disorder. The establishment of a non-profit organization, PC Project, has led to an unprecedented coalescence of patients, scientists, and physicians with a unified vision of developing novel therapeutics for PC. Utilizing the technological by-products of the human genome project, such as RNA interference (RNAi) and quantitative RT-PCR (qRT-PCR), physicians and scientists have collaborated to create a candidate siRNA therapeutic that selectively inhibits a mutant allele of KRT6A, the most commonly affected PC keratin. In vitro investigation of this siRNA demonstrates potent inhibition of the mutant allele and reversal of the cellular aggregation phenotype. In parallel, an allele-specific quantitative real time RT-PCR assay has been developed and validated on patient callus samples in preparation for clinical trials. If clinical efficacy is ultimately demonstrated, this “first-in-skin” siRNA may herald a paradigm shift in the treatment of dominant negative genetic disorders. PMID:18495438

Therapeutic siRNAs for dominant genetic skin disorders including pachyonychia congenita.

PubMed

Leachman, Sancy A; Hickerson, Robyn P; Hull, Peter R; Smith, Frances J D; Milstone, Leonard M; Lane, E Birgitte; Bale, Sherri J; Roop, Dennis R; McLean, W H Irwin; Kaspar, Roger L

2008-09-01

The field of science and medicine has experienced a flood of data and technology associated with the human genome project. Over 10,000 human diseases have been genetically defined, but little progress has been made with respect to the clinical application of this knowledge. A notable exception to this exists for pachyonychia congenita (PC), a rare, dominant-negative keratin disorder. The establishment of a non-profit organization, PC Project, has led to an unprecedented coalescence of patients, scientists, and physicians with a unified vision of developing novel therapeutics for PC. Utilizing the technological by-products of the human genome project, such as RNA interference (RNAi) and quantitative RT-PCR (qRT-PCR), physicians and scientists have collaborated to create a candidate siRNA therapeutic that selectively inhibits a mutant allele of KRT6A, the most commonly affected PC keratin. In vitro investigation of this siRNA demonstrates potent inhibition of the mutant allele and reversal of the cellular aggregation phenotype. In parallel, an allele-specific quantitative real-time RT-PCR assay has been developed and validated on patient callus samples in preparation for clinical trials. If clinical efficacy is ultimately demonstrated, this "first-in-skin" siRNA may herald a paradigm shift in the treatment of dominant-negative genetic disorders.

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.

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.

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.

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.

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.

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

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

[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.

Should a colon cancer screening decision aid include the option of no testing? A comparative trial of two decision aids

PubMed Central

Griffith, Jennifer M; Fichter, Marlie; Fowler, Floyd J; Lewis, Carmen; Pignone, Michael P

2008-01-01

Background An important question in the development of decision aids about colon cancer (CRC) screening is whether to include an explicit discussion of the option of not being screened. We examined the effect of including or not including an explicit discussion of the option of deciding not to be screened in a CRC screening decision aid on subjective measures of decision aid content; interest in screening; and knowledge. Methods Adults ages 50–85 were assigned to view one of two versions of the decision aid. The two versions differed only in the inclusion of video segments of two men, one of whom decided against being screened. Participants completed questionnaires before and after viewing the decision aid to compare subjective measures of content, screening interest and intent, and knowledge between groups. Likert response categories (5-point) were used for subjective measures of content (eg. clarity, balance in favor/against screening, and overall rating), and screening interest. Knowledge was measured with a three item index and individual questions. Higher scores indicated favorable responses for subjective measures, greater interest, and better knowledge. For the subjective balance, lower numbers were associated with the impression of the decision aid favoring CRC screening. Results 57 viewed the "with" version which included the two segments and 49 viewed the "without" version. After viewing, participants found the "without" version to have better subjective clarity about benefits of screening ("with" 3.4, "without" 4.1, p < 0.01), and to have greater clarity about downsides of screening ("with" 3.2, "without" 3.6, p = 0.03). The "with" version was considered to be less strongly balanced in favor of screening. ("with" 1.8, "without" 1.6, p = 0.05); but the "without" version received a better overall rating ("with" 3.5, "without" 3.8, p = 0.03). Groups did not differ in screening interest after viewing a decision aid or knowledge. Conclusion A decision aid

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.

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

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.

48 CFR 17.202 - Use of options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Use of options. 17.202... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 17.202 Use of options. (a) Subject to the..., the contracting officer may include options in contracts when it is in the Government's interest. When...

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

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.

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

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

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.

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.

New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

PubMed

Matera, Robert; Saif, Muhammad Wasif

2017-09-01

Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

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.

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

Space station data system analysis/architecture study. Task 2: Options development, DR-5. Volume 2: Design options

NASA Technical Reports Server (NTRS)

1985-01-01

The primary objective of Task 2 is the development of an information base that will support the conduct of trade studies and provide sufficient data to make key design/programmatic decisions. This includes: (1) the establishment of option categories that are most likely to influence Space Station Data System (SSDS) definition; (2) the identification of preferred options in each category; and (3) the characterization of these options with respect to performance attributes, constraints, cost and risk. This volume contains the options development for the design category. This category comprises alternative structures, configurations and techniques that can be used to develop designs that are responsive to the SSDS requirements. The specific areas discussed are software, including data base management and distributed operating systems; system architecture, including fault tolerance and system growth/automation/autonomy and system interfaces; time management; and system security/privacy. Also discussed are space communications and local area networking.

Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of Sacroiliac Joint Interventions.

PubMed

Simopoulos, Thomas T; Manchikanti, Laxmaiah; Gupta, Sanjeeva; Aydin, Steve M; Kim, Chong Hwan; Solanki, Daneshvari; Nampiaparampil, Devi E; Singh, Vijay; Staats, Peter S; Hirsch, Joshua A

2015-01-01

The sacroiliac joint is well known as a cause of low back and lower extremity pain. Prevalence estimates are 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis based on multiple diagnostic studies and systematic reviews. However, at present there are no definitive management options for treating sacroiliac joint pain. To evaluate the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. A systematic review of the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. The available literature on diagnostic and therapeutic sacroiliac joint interventions was reviewed. The quality assessment criteria utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for diagnostic accuracy studies, Cochrane review criteria to assess sources of risk of bias, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) criteria for randomized therapeutic trials and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational therapeutic assessments. The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources. For the diagnostic accuracy assessment, and for the therapeutic modalities, the primary outcome measure of pain relief and improvement in functional status were utilized. A total of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at least 70% pain relief as the criterion

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.

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.

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.

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.

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.

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.

[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.

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.

Mesenchymal Stem Cells: A Multimodality Option for Wound Healing.

PubMed

Hanson, Summer E

2012-08-01

Although significant resources are invested in wound care and healing annually, chronic wounds remain a major medical problem as they often present a more difficult challenge than the underlying disease. Current treatment options include a multitude of dressing materials, topical agents including antibiotics, enzymatic debriders, and growth factors, mechanical debridement, and optimization of medical comorbidities. Even under optimal circumstances, the healing process leads to some form of fibrosis and scarring. Studies suggest that mesenchymal stem/stromal cells (MSCs) isolated from these diverse tissues possess similar biological characteristics, differentiation potential, and immunological properties. Enthusiasm about MSCs for use in reconstruction and regenerative medicine has been fueled by evidence that these cells possess the ability to participate in the tissue repair process through a variety of paracrine mechanisms affecting tissue regeneration and inflammation. Recent advances in stem cell immunobiology have led to increased interest in MSCs as a new therapeutic modality to address chronic wounds and other inflammatory pathology. A thorough understanding of the immunobiology of MSCs is necessary to realize the complement of pathological processes that could be affected by MSC-based therapy. The novel methods reviewed here are highly promising, with the collective goal of identifying new therapeutic approaches to wound healing that are broadly applicable to many chronic diseases, and can safely accelerate the transition of basic research findings into clinical advances in many areas of regenerative medicine and reconstructive surgery.

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

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

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

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.

47 CFR 32.5002 - Optional extended area revenue.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Optional extended area revenue. 32.5002 Section... Optional extended area revenue. This account shall include total revenue derived from the provision of optional extended area service. ...

47 CFR 32.5002 - Optional extended area revenue.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Optional extended area revenue. 32.5002 Section... Optional extended area revenue. This account shall include total revenue derived from the provision of optional extended area service. ...

47 CFR 32.5002 - Optional extended area revenue.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Optional extended area revenue. 32.5002 Section... Optional extended area revenue. This account shall include total revenue derived from the provision of optional extended area service. ...

47 CFR 32.5002 - Optional extended area revenue.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Optional extended area revenue. 32.5002 Section... Optional extended area revenue. This account shall include total revenue derived from the provision of optional extended area service. ...

Retirement Options to Offer College Faculty.

ERIC Educational Resources Information Center

Felicetti, Daniel A.

1982-01-01

Retirement options available to institutions are outlined, including early retirement incentives, phased retirement, facilitating consulting opportunities, travel and outplacement services, maintaining community involvement, annuities, and pensions. Suggestions are made for increasing cost-effectiveness and fitting the options to local…

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.

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.

New and Emerging Treatment Options for Irritable Bowel Syndrome

PubMed Central

Lacy, Brian E.; Chey, William D.; Lembo, Anthony J.

2015-01-01

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with abdominal pain, diarrhea, constipation, or a mix of symptoms. The pathophysiology of IBS is not completely understood but appears to involve genetics, the gut microbiome, immune activation, altered intestinal permeability, and brain-gut interactions. There is no gold standard for diagnosis. Several sets of symptom-based guidelines exist. Treatment strategies for IBS may include both nonpharmacologic and pharmacologic approaches. Lifestyle modifications that aim to improve exercise, sleep, diet, and stress may be warranted. Recent data suggest that a gluten-free diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) may benefit some patients. For patients with diarrhea-predominant IBS, treatment options include the synthetic peripheral μ-opioid receptor agonist loperamide, antispasmodic agents, antidepressants, serotonin 5-HT3 antagonists, and the gut-specific antibiotic rifaximin. Ongoing research is evaluating the use of probiotics. For patients with constipation-predominant IBS, therapeutic strategies may include dietary fiber, laxatives, and the prosecretory agents lubiprostone and linaclotide. Research is continuing to optimize the use of available agents and evaluating new approaches to further improve the care of patients with IBS. PMID:26491416

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.

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

Small Satellite Propulsion Options

NASA Technical Reports Server (NTRS)

Myers, Roger M.; Oleson, Steven R.; Curran, Francis M.; Schneider, Steven J.

1994-01-01

Advanced chemical and low power electric propulsion offer attractive options for small satellite propulsion. Applications include orbit raising, orbit maintenance, attitude control, repositioning, and deorbit of both Earth-space and planetary spacecraft. Potential propulsion technologies for these functions include high pressure Ir/Re bipropellant engines, very low power arcjets, Hall thrusters, and pulsed plasma thrusters, all of which have been shown to operate in manners consistent with currently planned small satellites. Mission analyses show that insertion of advanced propulsion technologies enables and/or greatly enhances many planned small satellite missions. Examples of commercial, DoD, and NASA missions are provided to illustrate the potential benefits of using advanced propulsion options on small satellites.

Shungnak Energy Configuration Options.

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

Rosewater, David Martin; Eddy, John P.

Power systems in rural Alaska villages face a unique combination of challenges that can increase the cost of energy and lowers energy supply reliability. In the case of the remote village of Shungnak, diesel and heating fuel is either shipped in by barge or flown in by aircraft. This report presents a technical analysis of several energy infrastructure upgrade and modification options to reduce the amount of fuel consumed by the community of Shungnak. Reducing fuel usage saves money and makes the village more resilient to disruptions in fuel supply. The analysis considers demand side options, such as energy efficiency,more » alongside the installation of wind and solar power generation options. Some novel approaches are also considered including battery energy storage and the use of electrical home heating stoves powered by renewable generation that would otherwise be spilled and wasted. This report concludes with specific recommendations for Shungnak based on economic factors, and fuel price sensitivity. General conclusions are also included to support future work analyzing similar energy challenges in remote arctic regions.« less

[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.

42 CFR 436.229 - Optional targeted low-income children.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 4 2011-10-01 2011-10-01 false Optional targeted low-income children. 436.229... Options for Coverage as Categorically Needy Options for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women § 436.229 Optional targeted low-income children...

42 CFR 436.229 - Optional targeted low-income children.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Optional targeted low-income children. 436.229... Options for Coverage as Categorically Needy Options for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women § 436.229 Optional targeted low-income children...

42 CFR 436.229 - Optional targeted low-income children.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 4 2013-10-01 2013-10-01 false Optional targeted low-income children. 436.229... Options for Coverage as Categorically Needy Options for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women § 436.229 Optional targeted low-income children...

42 CFR 436.229 - Optional targeted low-income children.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 4 2012-10-01 2012-10-01 false Optional targeted low-income children. 436.229... Options for Coverage as Categorically Needy Options for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women § 436.229 Optional targeted low-income children...

42 CFR 436.229 - Optional targeted low-income children.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 4 2014-10-01 2014-10-01 false Optional targeted low-income children. 436.229... Options for Coverage as Categorically Needy Options for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women § 436.229 Optional targeted low-income children...

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.

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.

Document Delivery: Evaluating the Options.

ERIC Educational Resources Information Center

Ward, Suzanne M.

1997-01-01

Discusses options available to libraries for document delivery. Topics include users' needs; cost; copyright compliance; traditional interlibrary loan; types of suppliers; selection criteria, including customer service; new developments in interlibrary loan, including outsourcing arrangements; and the need to evaluate suppliers. (LRW)

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

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.

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

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.

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

PubMed Central

Park, Young Gun; Roh, Young-Jung

2016-01-01

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results. PMID:26881240

20 CFR 416.2035 - Optional supplementation: Additional State options.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Optional supplementation: Additional State options. 416.2035 Section 416.2035 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL... § 416.2035 Optional supplementation: Additional State options. (a) Residency requirement. A State or...

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.

Flexibility and Project Value: Interactions and Multiple Real Options

NASA Astrophysics Data System (ADS)

Čulík, Miroslav

2010-06-01

This paper is focused on a project valuation with embedded portfolio of real options including their interactions. Valuation is based on the criterion of Net Present Value on the simulation basis. Portfolio includes selected types of European-type real options: option to expand, contract, abandon and temporarily shut down and restart a project. Due to the fact, that in reality most of the managerial flexibility takes the form of portfolio of real options, selected types of options are valued not only individually, but also in combination. The paper is structured as follows: first, diffusion models for forecasting of output prices and variable costs are derived. Second, project value is estimated on the assumption, that no real options are present. Next, project value is calculated with the presence of selected European-type options; these options and their impact on project value are valued first in isolation and consequently in different combinations. Moreover, intrinsic value evolution of given real options with respect to the time of exercising is analysed. In the end, results are presented graphically; selected statistics and risk measures (Value at Risk, Expected Shortfall) of the NPV's distributions are calculated and commented.

ARSENIC TREATMENT OPTIONS

EPA Science Inventory

The PPT presentation will provide information on the drinking water treatment options for small utilities to remove arsenic from ground water. The discussion will include information on the EPA BAT listed processes and on some of the newer technologies, such as the iron based ad...

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.

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

Mind-mapping for lung cancer: Towards a personalized therapeutics approach

PubMed Central

Mollberg, N; Surati, M; Demchuk, C; Fathi, R; Salama, AK; Husain, AN; Hensing, T; Salgia, R

2011-01-01

There will be over 220,000 people diagnosed with lung cancer and over 160,000 dying of lung cancer this year alone in the United States. In order to arrive at better control, prevention, diagnosis, and therapeutics for lung cancer, we must be able to personalize the approach towards lung cancer. Mind-mapping has existed for centuries for physicians to properly think about various “flows” of personalized medicine. We include here the epidemiology, diagnosis, histology, and treatment of lung cancer—specifically, non-small cell lung cancer. As we have new molecular signatures for lung cancer, this is further detailed. This review is not meant to be a comprehensive review, but rather its purpose is to highlight important aspects of lung cancer diagnosis, management, and personalized treatment options. PMID:21337123

Space station data system analysis/architecture study. Task 2: Options development, DR-5. Volume 3: Programmatic options

NASA Technical Reports Server (NTRS)

1985-01-01

Task 2 in the Space Station Data System (SSDS) Analysis/Architecture Study is the development of an information base that will support the conduct of trade studies and provide sufficient data to make design/programmatic decisions. This volume identifies the preferred options in the programmatic category and characterizes these options with respect to performance attributes, constraints, costs, and risks. The programmatic category includes methods used to administrate/manage the development, operation and maintenance of the SSDS. The specific areas discussed include standardization/commonality; systems management; and systems development, including hardware procurement, software development and system integration, test and verification.

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.

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.

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

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.

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.

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.

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.

The relationship between patients' knowledge of diabetes therapeutic goals and self-management behaviour, including adherence.

PubMed

Waheedi, Mohammad; Awad, Abdelmoneim; Hatoum, Hind T; Enlund, Hannes

2017-02-01

Background The Middle East region has one the highest prevalence rates of diabetes in the world. Little is known about the determinants of adherence and the role of knowledge in diabetes self-management within these populations. Objective To investigate the relationship between patients knowledge of diabetes therapeutic targets with adherence to self-care measures in a sample of patients with type 2 diabetes in Kuwait. Setting Primary care chronic care clinics within the Ministry of Health of Kuwait. Methods A cross sectional survey was carried out with 238 patients from six clinics. A multistage stratified clustered sampling method was used to first randomly select the clinics and the patients. Self-reported adherence to three behaviours: medication taking, diet and physical activity. Results Respondents were able to correctly report a mean (SD) of 1.6 (1.3) out of 5 of the pre-specified treatment targets. Optimal adherence to physical activity, diet and medications was reported in 25, 33 and 47 % of the study cohort, respectively. A structural equation model analysis showed better knowledge of therapeutic goals and own current levels translated into better adherence to medications, diet and physical activity. Conclusion Knowledge of therapeutic goals and own recent levels is associated with adherence to medications, diet, or physical activity in this Kuwaiti cohort of patients with diabetes. Low adherence to self-care management and poor overall knowledge of diabetes is a big challenge to successful diabetes care in Kuwait.

Our Energy Options.

ERIC Educational Resources Information Center

Meyers, Paul A.; Witt, Frank C.

Presented is an analysis of alternatives available to the United States in dealing with energy problems. Options explained and evaluated include coal, solar, hydroelectric, nuclear, geothermal, wind, biomass, and energy conservation. The booklet is part of Project APEC (America's Possible Energy Choices), a nationally validated Title IVc project…

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.

Function, therapeutic potential and cell biology of BACE proteases: current status and future prospects.

PubMed

Vassar, Robert; Kuhn, Peer-Hendrik; Haass, Christian; Kennedy, Matthew E; Rajendran, Lawrence; Wong, Philip C; Lichtenthaler, Stefan F

2014-07-01

The β-site APP cleaving enzymes 1 and 2 (BACE1 and BACE2) were initially identified as transmembrane aspartyl proteases cleaving the amyloid precursor protein (APP). BACE1 is a major drug target for Alzheimer's disease because BACE1-mediated cleavage of APP is the first step in the generation of the pathogenic amyloid-β peptides. BACE1, which is highly expressed in the nervous system, is also required for myelination by cleaving neuregulin 1. Several recent proteomic and in vivo studies using BACE1- and BACE2-deficient mice demonstrate a much wider range of physiological substrates and functions for both proteases within and outside of the nervous system. For BACE1 this includes axon guidance, neurogenesis, muscle spindle formation, and neuronal network functions, whereas BACE2 was shown to be involved in pigmentation and pancreatic β-cell function. This review highlights the recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer's disease. The protease BACE1 is a major drug target in Alzheimer disease. Together with its homolog BACE2, both proteases have an increasing number of functions within and outside of the nervous system. This review highlights recent progress in understanding cell biology, substrates, and functions of BACE proteases and discusses the therapeutic options and potential mechanism-based liabilities, in particular for BACE inhibitors in Alzheimer disease. © 2014 International Society for Neurochemistry.

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.

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.

48 CFR 52.217-3 - Evaluation Exclusive of Options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Options. 52.217-3 Section 52.217-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION....217-3 Evaluation Exclusive of Options. As prescribed in 17.208(a), insert a provision substantially the same as the following in solicitations when the solicitation includes an option clause and does...

Writing about Clients: Ethical Considerations and Options

ERIC Educational Resources Information Center

Sperry, Len; Pies, Ronald

2010-01-01

Today, the decision to prepare clinical case material for publication is a decision that cannot be taken lightly. The decision involves reviewing ethical considerations and choosing among various options to safeguard client privacy. Such options include seeking the client's permission, disguising case material, and developing composite case…

[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.

Nail Psoriasis: A Review of Treatment Options.

PubMed

Pasch, Marcel C

2016-04-01

Nail involvement affects 80-90 % of patients with plaque psoriasis, and is even more prevalent in patients with psoriatic arthritis. This review is the result of a systemic approach to the literature and covers topical, intralesional, conventional systemic, and biologic systemic treatments, as well as non-pharmacological treatment options for nail psoriasis. The available evidence suggests that all anti-tumor necrosis factor-α, anti-interleukin (IL)-17, and anti-IL-12/23 antibodies which are available for plaque psoriasis and psoriatic arthritis are highly effective treatments for nail psoriasis. Conventional systemic treatments, including methotrexate, cyclosporine, acitretin, and apremilast, as well as intralesional corticosteroids, can also be effective treatments for nail psoriasis. Topical treatments, including corticosteroids, calcipotriol, tacrolimus, and tazarotene, have also been shown to have a position in the treatment of nail psoriasis, particularly in mild cases. Finally, non-pharmacological treatment options, including phototherapy, photodynamic therapy, laser therapy, and several radiotherapeutic options, are also reviewed but cannot be advised as first-line treatment options. Another conclusion of this review is that the lack of a reliable core set of outcomes measures for trials in nail psoriasis hinders the interpretation of results, and is urgently needed.

Advances in Virus-Directed Therapeutics against Epstein-Barr Virus-Associated Malignancies

PubMed Central

Ghosh, Sajal K.; Perrine, Susan P.; Faller, Douglas V.

2012-01-01

Epstein-Barr virus (EBV) is the causal agent in the etiology of Burkitt's lymphoma and nasopharyngeal carcinoma and is also associated with multiple human malignancies, including Hodgkin's and non-Hodgkin's lymphoma, and posttransplantation lymphoproliferative disease, as well as sporadic cancers of other tissues. A causal relationship of EBV to these latter malignancies remains controversial, although the episomic EBV genome in most of these cancers is clonal, suggesting infection very early in the development of the tumor and a possible role for EBV in the genesis of these diseases. Furthermore, the prognosis of these tumors is invariably poor when EBV is present, compared to their EBV-negative counterparts. The physical presence of EBV in these tumors represents a potential “tumor-specific” target for therapeutic approaches. While treatment options for other types of herpesvirus infections have evolved and improved over the last two decades, however, therapies directed at EBV have lagged. A major constraint to pharmacological intervention is the shift from lytic infection to a latent pattern of gene expression, which persists in those tumors associated with the virus. In this paper we provide a brief account of new virus-targeted therapeutic approaches against EBV-associated malignancies. PMID:22500168

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

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.

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.

Ozone-augmented percutaneous discectomy: a novel treatment option for refractory discogenic sciatica.

PubMed

Crockett, M T; Moynagh, M; Long, N; Kilcoyne, A; Dicker, P; Synnott, K; Eustace, S J

2014-12-01

To assess the short and medium-term efficacy and safety of a novel, minimally invasive therapeutic option combining automated percutaneous lumbar discectomy, intradiscal ozone injection, and caudal epidural: ozone-augmented percutaneous discectomy (OPLD). One hundred and forty-seven patients with a clinical and radiological diagnosis of discogenic sciatica who were refractory to initial therapy were included. Fifty patients underwent OPLD whilst 97 underwent a further caudal epidural. Outcomes were evaluated using McNab's score, improvement in visual analogue score (VAS) pain score, and requirement for further intervention. Follow-up occurred at 1 and 6 months, and comparison was made between groups. OPLD achieved successful outcomes in almost three-quarters of patients in the short and medium term. OPLD achieved superior outcomes at 1 and 6 months compared to caudal epidural. There was a reduced requirement for further intervention in the OPLD group. No significant complications occurred in either group. OPLD is a safe and effective treatment for patients with refractory discogenic sciatica in the short and medium term. OPLD has the potential to offer an alternative second-line minimally invasive treatment option that could reduce the requirement for surgery in this patient cohort. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Fibromyalgia Pathogenesis and Treatment Options Update.

PubMed

Chinn, Steven; Caldwell, William; Gritsenko, Karina

2016-04-01

This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

An industry update: the latest news in therapeutic delivery.

PubMed

Harris, Elaine

2017-11-01

The present industry update covers the period 1-31 July 2017. Information was sourced primarily from company press releases, regulatory and patent agencies, scientific literature and various news websites. There was positive approval news this month for GlaxoSmithKline for its new self-injecting treatment for systemic lupus erythematosus but less positive news for Ocular Therapeutix, a new drug application for its treatment for postoperative ocular pain, DEXTENZA™ was rejected for a second time. Endo Pharmaceuticals agreed to withdraw its opioid formulation Opana ® Er due to abuse concerns. Collaborations for novel therapeutic delivery research were announced this month by Takeda and BioSurfaces, Catelent and Rutgers University, Lilly and Purdue University and Titan Pharmaceuticals with Walter Reed and the Southwest Research Institute. A number of companies announced significant financing deals to allow for the clinical development of products with enhanced delivery options including Sebacia and Diasome.

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.

Nonsurgical and surgical treatment of periodontitis: how many options for one disease?

PubMed

Graziani, Filippo; Karapetsa, Dimitra; Alonso, Bettina; Herrera, David

2017-10-01

Treatment of periodontitis aims at preventing further disease progression with the intentions to reduce the risk of tooth loss, minimize symptoms and perception of the disease, possibly restore lost periodontal tissue and provide information on maintaining a healthy periodontium. Therapeutic intervention includes introduction of techniques to change behavior, such as: individually tailored oral-hygiene instructions; a smoking-cessation program; dietary adjustment; subgingival instrumentation to remove plaque and calculus; local and systemic pharmacotherapy; and various types of surgery. No single treatment option has shown superiority, and virtually all types of mechanical periodontal treatment benefit from adjunctive antimicrobial chemotherapy. Periodontal treatment, because of the chronic nature of periodontitis, is a lifelong commitment to intricate oral-hygiene techniques, which, when properly implemented, will minimize the risk of disease initiation and progression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[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.

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

Greenhouse Gas Mitigation Options Database(GMOD)and Tool

EPA Science Inventory

Greenhouse Gas Mitigation Options Database (GMOD) is a decision support database and tool that provides cost and performance information for GHG mitigation options for the power, cement, refinery, landfill and pulp and paper sectors. The GMOD includes approximately 450 studies fo...

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.

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.

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

Osteitis pubis in elite athletes: Diagnostic and therapeutic approach

PubMed Central

Angoules, Antonios G

2015-01-01

Osteitis pubis (OP) is a debilitating overuse syndrome characterizing by pelvic pain and local tenderness over the pubic symphysis commonly encountered in athletes often involved in kicking, twisting and cutting activities in sports such as soccer and rugby and to a lesser degree distance running. It is a common source of groin pain in elite athletes attributable to pubis sympysis instability as the result of microtrauma caused by repetitive muscle strains on pubic bones. Diagnosis is based mainly on detailed sports history and a meticulous clinical examination, although occasionally is difficult to distinguish this nosological entity from other pathologies affecting the involved area which may occur concomitantly in the same patient. Radiologic examinations such as plain radiographs, magnetic resonance imaging and 3 phase bone isotope scanning may be helpful to differentiate from other clinical entities with similar clinical presentation. Most cases respond well to conservative treatment which includes several physical modalities and especially a progressive rehabilitation programmed individualized to each one of patients diagnosed with OP. Local injection therapies have been also been proposed as a non-operative therapeutic option for the efficient management of these patients. In refractory cases, surgical therapeutic strategies are warranted. These include several open or minimally invasive surgical interventions such as arthroscopic or open symphysis curettage, wedge or total resection of pubic sympysis, polypropylene mesh placement and pubic fusion. In this review a critical analysis of OP in elite athletes is performed with special focus on current concepts of diagnosis and management of this source of athletic groin pain. PMID:26495244

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.

Benefits and work-schedule options in hospital pharmacy practice.

PubMed

Gaither, C A; Mason, N A; Diokno, D A; Hoffman, E J

1994-03-15

Hospital pharmacy directors were surveyed to determine whether their departments offered specific family-related benefits and work-schedule options and how their attitudes about these options compared with those of female hospital pharmacists. Questionnaires were mailed to 300 randomly selected hospital pharmacy directors to collect the following information: vacancy rates and male:female ratios in hospital pharmacy positions, which of 13 selected benefits and work-schedule options were offered, barriers that prevented the other options from being offered, and attitudes about the listed options. The options included in the survey were selected because they represent ways of balancing home and work (e.g., maternity leave, job sharing, day care). The pharmacy directors' responses were compared with those from a similar survey of female hospital pharmacists. The usable response rate was 50.3%. Position vacancy rates ranged from 5.5% for directors to 35.8% for clinical supervisors. All full-time positions had an even distribution of men and women except for director and assistant or associate director positions. Of 13 options, only maternity leave, part-time schedules, and flexible schedules were offered by more than half of the hospitals. These three were also the only listed options that the respondents considered important in recruiting and retaining pharmacists. Barriers to offering other options included the perception that current benefits and work-schedule options were adequate, lack of staff coverage, lack of funds, and the perception that some positions are not compatible with alternative schedules. Respondents' ratings of the importance of the listed benefits and work-schedule options were significantly lower than ratings given by female hospital pharmacists in a separate survey.(ABSTRACT TRUNCATED AT 250 WORDS)

[Patient-centred prescription model to improve adequate prescription and therapeutic adherence in patients with multiple disorders].

PubMed

Espaulella-Panicot, Joan; Molist-Brunet, Núria; Sevilla-Sánchez, Daniel; González-Bueno, Javier; Amblàs-Novellas, Jordi; Solà-Bonada, Núria; Codina-Jané, Carles

Patients with multiple disorders and on multiple medication are often associated with clinical complexity, defined as a situation of uncertainty conditioned by difficulties in establishing a situational diagnosis and decision-making. The patient-centred care approach in this population group seems to be one of the best therapeutic options. In this context, the preparation of an individualised therapeutic plan is the most relevant practical element, where the pharmacological plan maintains an important role. There has recently been a significant increase in knowledge in the area of adequacy of prescription and adherence. In this context, we must find a model must be found that incorporates this knowledge into clinical practice by the professionals. Person-centred prescription is a medication review model that includes different strategies in a single intervention. It is performed by a multidisciplinary team, and allows them to adapt the pharmacological plan of patients with clinical complexity. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Mitochondrial encephalopathy, lactic acidosis, and strokelike episodes: basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome.

PubMed

Sproule, Douglas M; Kaufmann, Petra

2008-10-01

Since the initial description almost 25 years ago, the syndrome of mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS) has been a useful model to study the complex interplay of factors that define mitochondrial disease. This syndrome, most commonly caused by an A-to-G transition mutation at position 3243 of the mitochondrial genome, is typified by characteristic neurological manifestations including seizures, encephalopathy, and strokelike episodes, as well as other frequent secondary manifestations including short stature, cognitive impairment, migraines, depression, cardiomyopathy, cardiac conduction defects, and diabetes mellitus. In this review, we discuss the history, pathogenesis, clinical features, and diagnostic and management strategies of mitochondrial disease in general and of MELAS in particular. We explore features of mitochondrial genetics, including the concepts of heteroplasmy, mitotic segregation, and threshold effect, as a basis for understanding the variability and complicated inheritance patterns seen with this group of diseases. We also describe systemic manifestations of MELAS-associated mutations, including cardiac, renal, endocrine, gastrointestinal, and endothelial abnormalities and pathology, as well as the hypothetical role of derangements to COX enzymatic function in driving the unique pathology and clinical manifestations of MELAS. Although therapeutic options for MELAS and other mitochondrial diseases remain limited, and recent trials have been disappointing, we also consider current and potential therapeutic modalities.

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

Locally advanced and metastatic basal cell carcinoma: molecular pathways, treatment options and new targeted therapies.

PubMed

Ruiz Salas, Veronica; Alegre, Marta; Garcés, Joan Ramón; Puig, Lluis

2014-06-01

The hedgehog (Hh) signaling pathway has been identified as important to normal embryonic development in living organisms and it is implicated in processes including cell proliferation, differentiation and tissue patterning. Aberrant Hh pathway has been involved in the pathogenesis and chemotherapy resistance of different solid and hematologic malignancies. Basal cell carcinoma (BCC) and medulloblastoma are two well-recognized cancers with mutations in components of the Hh pathway. Vismodegib has recently approved as the first inhibitor of one of the components of the Hh pathway (smoothened). This review attempts to provide current data on the molecular pathways involved in the development of BCC and the therapeutic options available for the treatment of locally advanced and metastatic BCC, and the new targeted therapies in development.

Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

PubMed Central

Lev, Rachel

2018-01-01

Muscular diseases such as muscular dystrophies and muscle injuries constitute a large group of ailments that manifest as muscle weakness, atrophy or fibrosis. Although cell therapy is a promising treatment option, the delivery and retention of cells in the muscle is difficult and prevents sustained regeneration needed for adequate functional improvements. Various types of biomaterials with different physical and chemical properties have been developed to improve the delivery of cells and/or growth factors for treating muscle injuries. Hydrogels are a family of materials with distinct advantages for use as cell delivery systems in muscle injuries and ailments, including their mild processing conditions, their similarities to natural tissue extracellular matrix, and their ability to be delivered with less invasive approaches. Moreover, hydrogels can be made to completely degrade in the body, leaving behind their biological payload in a process that can enhance the therapeutic process. For these reasons, hydrogels have shown great potential as cell delivery matrices. This paper reviews a few of the hydrogel systems currently being applied together with cell therapy and/or growth factor delivery to promote the therapeutic repair of muscle injuries and muscle wasting diseases such as muscular dystrophies. PMID:29343633

[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.

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.

DISPOSITION PATHS FOR ROCKY FLATS GLOVEBOXES: EVALUATING OPTIONS

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

Lobdell, D.; Geimer, R.; Larsen, P.

2003-02-27

The Kaiser-Hill Company, LLC has the responsibility for closure activities at the Rocky Flats Environmental Technology Site (RFETS). One of the challenges faced for closure is the disposition of radiologically contaminated gloveboxes. Evaluation of the disposition options for gloveboxes included a detailed analysis of available treatment capabilities, disposal facilities, and lifecycle costs. The Kaiser-Hill Company, LLC followed several processes in determining how the gloveboxes would be managed for disposition. Currently, multiple disposition paths have been chosen to accommodate the needs of the varying styles and conditions of the gloveboxes, meet the needs of the decommissioning team, and to best managemore » lifecycle costs. Several challenges associated with developing a disposition path that addresses both the radiological and RCRA concerns as well as offering the most cost-effective solution were encountered. These challenges included meeting the radiological waste acceptance criteria of available disposal facilities, making a RCRA determination, evaluating treatment options and costs, addressing void requirements associated with disposal, and identifying packaging and transportation options. The varying disposal facility requirements affected disposition choices. Facility conditions that impacted decisions included radiological and chemical waste acceptance criteria, physical requirements, and measurement for payment options. The facility requirements also impacted onsite activities including management strategies, decontamination activities, and life-cycle cost.« less

Treatment Options for Plasma Cell Neoplasms (Including Multiple Myeloma)

MedlinePlus

... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

Treatment Option Overview (Plasma Cell Neoplasms Including Multiple Myeloma)

MedlinePlus

... Health Professional Plasma Cell Neoplasms Treatment Research Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)–Patient Version General Information About Plasma Cell Neoplasms Go to Health Professional Version Key Points ...

Treatment options for Primary CNS Lymphoma.

PubMed

Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad

2018-03-01

Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

Therapeutic approach to malnutrition and sarcopenia.

PubMed

Burgos Peláez, Rosa

2012-01-01

Sarcopenia is a syndrome characterized by the progressive loss of muscle mass and strength with a risk of undesirable effects such as physical disability, poor quality of life and death, and it is a major contributing factor of disability and loss of independence in the elderly. Its etiopathogenics include different mechanisms that are both intrinsic to the muscle itself and related to changes in the central nervous system, as well as hormonal and lifestyle factors. Several hormones and cytokines affect muscle function and mass. The reduction in testosterone and estrogens associated with ageing speeds up the loss of muscle mass. Growth hormone is also involved in the loss of lean body mass. Although sarcopenia does not completely revert with exercise, the absence of physical activity accelerates muscle mass loss. Diagnosing sarcopenia is hindered by a lack of reliable methods for measuring muscle mass. Different strategies have been tested for its treatment: testosterone replacement therapy/other anabolic androgens, estrogens in women, growth hormone, nutritional treatment and exercise. Of all the therapeutic options available, only resistance training with or without nutritional supplementation has shown its efficacy in increasing skeletal muscle mass. Copyright © 2012 S. Karger AG, Basel.

42 CFR 436.201 - Individuals included in optional groups.

Code of Federal Regulations, 2012 CFR

2012-10-01

... individual who is determined to be dependent) as specified in § 436.510; (6) Pregnant women; and (7... for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women ...

42 CFR 436.201 - Individuals included in optional groups.

Code of Federal Regulations, 2014 CFR

2014-10-01

... individual who is determined to be dependent) as specified in § 436.510; (6) Pregnant women; and (7... for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women ...

42 CFR 436.201 - Individuals included in optional groups.

Code of Federal Regulations, 2011 CFR

2011-10-01

... individual who is determined to be dependent) as specified in § 436.510; (6) Pregnant women; and (7... for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women ...

42 CFR 436.201 - Individuals included in optional groups.

Code of Federal Regulations, 2013 CFR

2013-10-01

... individual who is determined to be dependent) as specified in § 436.510; (6) Pregnant women; and (7... for Coverage of Families and Children and Aged, Blind, and Disabled Individuals, Including Pregnant Women ...

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.

DELIVERY OF THERAPEUTIC PROTEINS

PubMed Central

Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

2009-01-01

The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

Constipation: Pathophysiology and Current Therapeutic Approaches.

PubMed

Sharma, Amol; Rao, Satish

2017-01-01

Chronic constipation is a common, persistent condition affecting many patients worldwide, presenting significant economic burden and resulting in substantial healthcare utilization. In addition to infrequent bowel movements, the definition of constipation includes excessive straining, a sense of incomplete evacuation, failed or lengthy attempts to defecate, use of digital manoeuvres for evacuation of stool, abdominal bloating, and hard consistency of stools. After excluding secondary causes of constipation, chronic idiopathic or primary constipation can be classified as functional defecation disorder, slow-transit constipation (STC), and constipation-predominant irritable bowel syndrome (IBS-C). These classifications are not mutually exclusive and significant overlap exists. Initial therapeutic approach to primary constipation, regardless of aetiology, consists of diet and lifestyle changes such as encouraging adequate fluid and fibre intake, regular exercise, and dietary modification. Laxatives are the mainstay of pharmacologic treatment for potential long-term therapy in patients who do not respond to lifestyle or dietary modification. After a failed empiric trial of laxatives, diagnostic testing is necessary to understand underlying anorectal and/or colonic pathophysiology. No single test provides a comprehensive assessment for primary constipation; therefore, multiple tests are used to provide complementary information to one another. Dyssynergic defecation, a functional defecation disorder, is an acquired behavioural disorder of defecation present in two-thirds of adult patients, where an inability to coordinate the abdominal, recto-anal, and pelvic floor muscles during attempted defecation exists. Biofeedback therapy is the mainstay treatment for dyssynergic defecation aimed at improving coordination of abdominal and anorectal muscles. A large percentage of patients with dyssynergic defecation also exhibit rectal hyposensitivity and may benefit from the

Space station data system analysis/architecture study. Task 2: Options development DR-5. Volume 1: Technology options

NASA Technical Reports Server (NTRS)

1985-01-01

The second task in the Space Station Data System (SSDS) Analysis/Architecture Study is the development of an information base that will support the conduct of trade studies and provide sufficient data to make key design/programmatic decisions. This volume identifies the preferred options in the technology category and characterizes these options with respect to performance attributes, constraints, cost, and risk. The technology category includes advanced materials, processes, and techniques that can be used to enhance the implementation of SSDS design structures. The specific areas discussed are mass storage, including space and round on-line storage and off-line storage; man/machine interface; data processing hardware, including flight computers and advanced/fault tolerant computer architectures; and software, including data compression algorithms, on-board high level languages, and software tools. Also discussed are artificial intelligence applications and hard-wire communications.

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

Sexuality issues in gynaecological oncology patients: post treatment symptoms and therapeutic options.

PubMed

Iavazzo, C; Johnson, K; Savage, H; Gallagher, S; Datta, M; Winter-Roach, B A

2015-03-01

According to recent studies up to 80% of patients would like to receive more information about how cancer treatments can affect their sexual functioning. Moreover, 75 % of them would not feel comfortable being the first to bring up the subject. Our Gynaecological Advice Clinic was established in 2006 at the Christie Hospital and offers support to cancer patients who face sexuality issues. A previous evaluation established that the service sees approximately, 200 patients per year. The aims of this study are to evaluate the service by collecting data relating to levels of attendance, type and amount of clinical activity and to explore further patients' experiences and management. This is a retrospective study which was carried out in 2012-2013. Different models are used to evaluate our patients including history taking integrated therapy model, consultations to understand the normal anatomy and physiology with the use of diagrams and photographs, psycho-education and the international classification "Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition" (DSMV). The treatment options advised include medications such as hormone replacement treatment, testosterone, antidepressant, local oestrogen, tibolone, aqueous cream, lubrication to introitus, diprobase, dermal cream and advice for massage to areas of discomfort. Moreover, the use of vaginal dilators, the role of pelvic floor exercises, vulval care and self examination are explained. The team works closely with the psycho-oncology department. The most frequently discussed topics that were covered during the consultation are analysed. 41 outpatient clinics were held between 2012 and 2013. 194 patients attended those clinics during the study period. Single and not group therapy was offered to all the participants. 216 patients were offered appointments while 194 patients actually attended (90%). Patients' age ranged from 24 to 91 years with a mean age of 59 years. 45% had endometrial and 32% cervical

Modeling of Solid Waste Processing Options in BIO-Plex

NASA Technical Reports Server (NTRS)

Rodriguez, Luis F.; Finn, Cory; Kang, Sukwon; Hogan, John; Luna, Bernadette (Technical Monitor)

2000-01-01

BIO-Plex is a ground-based test bed currently under development by NASA for testing technologies and practices that may be utilized in future long-term life support missions. All aspects of such an Advanced Life Support (ALS) System must be considered to confidently construct a reliable system, which will not only allow the crew to survive in harsh environments, but allow the crew time to perform meaningful research. Effective handling of solid wastes is a critical aspect of the system, especially when recovery of resources contained in the waste is required. This is particularly important for ALS Systems configurations that include a Biomass Production Chamber. In these cases, significant amounts of inedible biomass waste may be produced, which can ultimately serve as a repository of necessary resources for sustaining life, notably carbon, water, and plant nutrients. Numerous biological and physicochemical solid waste processing options have been considered. Biological options include composting, aerobic digestion, and anaerobic digestion. Physicochemical options include pyrolysis, SCWO (supercritical water oxidation), various incineration configurations, microwave incineration, magnetically assisted gasification, and low temperature plasma reaction. Modeling of these options is a necessary step to assist in the design process. A previously developed top-level model of BIO-Plex implemented in MATLAB Simulink (r) for the use of systems analysis and design has been adopted for this analysis. Presently, this model only considered incineration for solid waste processing. Present work, reported here, includes the expansion of this model to include a wider array of solid waste processing options selected from the above options, bearing in mind potential, near term solid waste treatment systems. Furthermore, a trade study has also been performed among these solid waste processing technologies in an effort to determine the ideal technology for long-term life support

Healthy Option Preferences of Rural Restaurant Customers

PubMed Central

Nothwehr, Faryle; Snetselaar, Linda; Dawson, Jeffrey D.; Hradek, Christine; Sepulveda, Marisol

2009-01-01

In preparation for an intervention study in three rural Iowa restaurants, 250 customers were surveyed regarding their interest in dietary change, perceptions of the restaurant, and interest in healthy options. Customers were ages 18 to 88, with a mean age of 52, and 53% were women. Most agreed that the restaurant offers healthy meals. Options customers stated they were most likely to order if available included meat that is baked or broiled, whole-wheat bread, fresh fruit or steamed vegetables, and regular salad dressing on the side. They were least interested in low-fat sour cream, low-fat salad dressing, low-fat milk, low-calorie dessert, and holding high-fat ingredients. Women were more likely to indicate interest in healthy options than were men. Interest in several options was also positively associated with age. Increasing the healthy options in restaurants may be especially effective in changing the dietary intake of women and older adults. PMID:19515859

New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

PubMed Central

Szoka, Piotr; Kolodziejczyk, Patrycjusz; Kramkowski, Karol; Wojewodzka-Zelezniakowicz, Marzena; Chabielska, Ewa

2016-01-01

The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT1 receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT1 axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders. PMID:27439538

Options for Heart Valve Replacement

MedlinePlus

... which may include human or animal donor tissue) Ross Procedure — “Borrowing” your healthy valve and moving it ... Considerations for Surgery Medications Valve Repair Valve Replacement - Ross Procedure - Newer Surgery Options - What is TAVR? - Types ...

Multifractal analysis of implied volatility in index options

NASA Astrophysics Data System (ADS)

Oh, GabJin

2014-06-01

In this paper, we analyze the statistical and the non-linear properties of the log-variations in implied volatility for the CAC40, DAX and S& P500 daily index options. The price of an index option is generally represented by its implied volatility surface, including its smile and skew properties. We utilize a Lévy process model as the underlying asset to deepen our understanding of the intrinsic property of the implied volatility in the index options and estimate the implied volatility surface. We find that the options pricing models with the exponential Lévy model can reproduce the smile or sneer features of the implied volatility that are observed in real options markets. We study the variation in the implied volatility for at-the-money index call and put options, and we find that the distribution function follows a power-law distribution with an exponent of 3.5 ≤ γ ≤ 4.5. Especially, the variation in the implied volatility exhibits multifractal spectral characteristics, and the global financial crisis has influenced the complexity of the option markets.

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.

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.

Health financing options for Fiji's health system.

PubMed

Pande, Madhukar

2003-09-01

Fiji is currently implementing health care reforms with the first phase of reforms focusing on decentralization of the health system. Part of this effort focuses on looking at financing options. Some options for financing health care include private health insurance, social insurance, community financing, user-pays system (out-of-pocket), health savings accounts, government taxation and subsidies, and overseas loans and aid funding. This paper addresses all these options in detail and provides an analysis into each of these options relevance to Fiji and in some instances to other nations in the South Pacific region. Given the relative small populations of Fiji and its neighbouring nations, a regional approach to financing could prove more viable in the longer-term, however political, social, economic, legal and cultural issues will need to seriously explored.

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.

Combination therapeutics in complex diseases.

PubMed

He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

2016-12-01

The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

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.

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.

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

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

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

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.

Idiopathic recurrent pericarditis as an immune-mediated disease: current insights into pathogenesis and emerging treatment options.

PubMed

Imazio, Massimo

2014-11-01

Idiopathic recurrent pericarditis affects 30-50% of patients with a previous attack of pericarditis. The etiopathogenesis is incompletely understood and most cases remain idiopathic with a presumed immune-mediated pathogenesis. The mainstay of therapy is aspirin or a nonsteroidal anti-inflammatory drug plus colchicine and the possible adjunct of a low-to-moderate dose of a corticosteroid in more difficult cases. Colchicine as an adjunct to anti-inflammatory therapy reduces by 50% the subsequent recurrent rate. For true refractory cases with failure of standard combination therapies, new and emerging options especially include human intravenous immunoglobulins and biological agents (i.e., anakinra). The outcome of idiopathic recurrent pericarditis is good with a negligible risk of developing constrictive pericarditis. Thus, it is important to reassure patients on their prognosis, explaining the nature of the disease and the likely course. Moreover, therapeutic choices should include less toxic agents and favor cheaper drugs whenever possible.

Evaluating technology service options.

PubMed

Blumberg, D F

1997-05-01

Four service and support options are available to healthcare organizations for maintaining their growth arsenals of medical and information technology. These options include maintaining and servicing all equipment using a facility-based biomedical engineering and MIS service department; using a combination of facility-based service and subcontracted service; expanding facility-based biomedical and MIS service departments to provide service to other healthcare organizations to achieve economies of scale; and outsourcing all maintenance, repair, and technical support services. Independent service companies and original equipment manufacturers (OEMs) are offering healthcare organizations a wider array of service and support capabilities than ever before. However, some health systems have successfully developed their own independent service organizations to take care of their own--and other healthcare organizations'--service and support needs.

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

Community Options for Elders.

ERIC Educational Resources Information Center

Poulsen, Joyce G.

This paper describes the Winnebago County (Wisconsin) Community Options Program, begun in January, 1982, which provides for a comprehensive assessment of all elderly persons within the target area who are at risk of becoming institutionalized. The paper focuses on the planning activities for the first year of the pilot program including community…

Options Counseling for the Pregnant Adolescent Patient.

PubMed

Hornberger, Laurie L

2017-09-01

Each year, more than 500 000 girls and young women younger than 20 years become pregnant. It is important for pediatricians to have the ability and the resources in their offices to make a timely pregnancy diagnosis in their adolescent patients and provide them with nonjudgmental pregnancy options counseling. Counseling includes an unbiased discussion of the adolescent's legal options to either continue or terminate her pregnancy, supporting the adolescent in the decision-making process, and referring the adolescent to appropriate resources and services. Pediatricians who choose not to provide such discussions should promptly refer pregnant adolescent patients to a health care professional who will offer developmentally appropriate pregnancy options counseling. This approach to pregnancy options counseling has not changed since the original 1989 American Academy of Pediatrics statement on this issue. Copyright © 2017 by the American Academy of Pediatrics.

Evaluating State Options for Reducing Medicaid Churning

PubMed Central

Swartz, Katherine; Short, Pamela Farley; Graefe, Deborah R.; Uberoi, Namrata

2015-01-01

Medicaid churning - the constant exit and re-entry of beneficiaries as their eligibility changes - has long been a problem for both Medicaid administrators and recipients. Churning will continue under the Affordable Care Act, because despite new federal rules, Medicaid eligibility will continue to be based on current monthly income. We developed a longitudinal simulation model to evaluate four policy options for modifying or extending Medicaid eligibility to reduce churning. The simulations suggest that two options, extending Medicaid eligibility either to the end of a calendar year or for twelve months after enrollment, would be far more effective in reducing churning than the other options of a three-month extension or eligibility based on projected annual income. States should consider implementation of the option that best balances costs, including both administration and services, with improved health of Medicaid enrollees. PMID:26153313

Risky business: rhesus monkeys exhibit persistent preferences for risky options.

PubMed

Xu, Eric R; Kralik, Jerald D

2014-01-01

Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates.

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.

Helping Working Parents: Child Care Options for Business.

ERIC Educational Resources Information Center

North Carolina State Dept. of Administration, Raleigh.

Seven models representing the existing range of options of employer involvement in day care are described in this paper. The range of options are grouped into two categories: (1) company owned, operated, or subsidized child day care; and (2) employee assistance services, benefits, and policies. The models included in the first category are the…

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.

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.

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.

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 ...

ExpandED Options: Learning beyond High School Walls

ERIC Educational Resources Information Center

ExpandED Schools, 2014

2014-01-01

Through ExpandED Options by TASC, New York City high school students get academic credit for learning career-related skills that lead to paid summer jobs. Too many high school students--including those most likely to drop out--are bored or see classroom learning as irrelevant. ExpandED Options students live the connection between mastering new…

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...

[Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015].

PubMed

Vanacker, Hélène; Bally, Olivia; Kassem, Loay; Tredan, Olivier; Heudel, Pierre; Bachelot, Thomas

2015-06-01

Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients. Copyright © 2015 Société Françise du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.

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

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.

Therapeutic touch for anxiety disorders.

PubMed

Robinson, J; Biley, F C; Dolk, H

2007-07-18

Anxiety disorders are a common occurrence in today's society. There is interest from the community in the use of complementary therapies for anxiety disorders. This review examined the currently available evidence supporting the use of therapeutic touch in treating anxiety disorders. To examine the efficacy and adverse effects of therapeutic touch for anxiety disorders. We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (CCDANCTR-Studies and CCDANCTR-References) (search date 13/01/06), the Controlled Trials website and Dissertation Abstracts International. Searches of reference lists of retrieved papers were also carried out and experts in the field were contacted. Inclusion criteria included all published and unpublished randomised and quasi-randomised controlled trials comparing therapeutic touch with sham (mimic) TT, pharmacological therapy, psychological treatment, other treatment or no treatment /waiting list. The participants included adults with an anxiety disorder defined by the Diagnostic and Statistical Manual (DSM-IV),the International Classification of Diseases (ICD-10), validated diagnostic instruments, or other validated clinician or self-report instruments. Two review authors independently applied inclusion criteria. Further information was sought from trialists where papers contained insufficient information to make a decision about eligibility. No randomised or quasi-randomised controlled trials of therapeutic touch for anxiety disorders were identified. Given the high prevalence of anxiety disorders and the current paucity of evidence on therapeutic touch in this population, there is a need for well conducted randomised controlled trials to examine the effectiveness of therapeutic touch for anxiety disorders.

Evidence mapping based on systematic reviews of therapeutic interventions for gastrointestinal stromal tumors (GIST).

PubMed

Ballesteros, Mónica; Montero, Nadia; López-Pousa, Antonio; Urrútia, Gerard; Solà, Ivan; Rada, Gabriel; Pardo-Hernandez, Hector; Bonfill, Xavier

2017-09-07

Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach. We followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot. A total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm. The most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.

Diagnostic and therapeutic management of hepatocellular carcinoma

PubMed Central

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

2015-01-01

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

Polymer therapeutics: concepts and applications.

PubMed

Haag, Rainer; Kratz, Felix

2006-02-13

Polymer therapeutics encompass polymer-protein conjugates, drug-polymer conjugates, and supramolecular drug-delivery systems. Numerous polymer-protein conjugates with improved stability and pharmacokinetic properties have been developed, for example, by anchoring enzymes or biologically relevant proteins to polyethylene glycol components (PEGylation). Several polymer-protein conjugates have received market approval, for example the PEGylated form of adenosine deaminase. Coupling low-molecular-weight anticancer drugs to high-molecular-weight polymers through a cleavable linker is an effective method for improving the therapeutic index of clinically established agents, and the first candidates have been evaluated in clinical trials, including, N-(2-hydroxypropyl)methacrylamide conjugates of doxorubicin, camptothecin, paclitaxel, and platinum(II) complexes. Another class of polymer therapeutics are drug-delivery systems based on well-defined multivalent and dendritic polymers. These include polyanionic polymers for the inhibition of virus attachment, polycationic complexes with DNA or RNA (polyplexes), and dendritic core-shell architectures for the encapsulation of drugs. In this Review an overview of polymer therapeutics is presented with a focus on concepts and examples that characterize the salient features of the drug-delivery systems.

Therapeutic cancer vaccines

PubMed Central

Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

2015-01-01

The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

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.

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.

Gait analysis of patients with knee osteoarthritis highlights a pathological mechanical pathway and provides a basis for therapeutic interventions

PubMed Central

Favre, Julien; Jolles, Brigitte M.

2016-01-01

Knee osteoarthritis (OA) is a painful and incapacitating disease affecting a large portion of the elderly population, for which no cure exists. There is a critical need to enhance our understanding of OA pathogenesis, as a means to improve therapeutic options. Knee OA is a complex disease influenced by many factors, including the loading environment. Analysing knee biomechanics during walking - the primary cyclic load-bearing activity - is therefore particularly relevant. There is evidence of meaningful differences in the knee adduction moment, flexion moment and flexion angle during walking between non-OA individuals and patients with medial knee OA. Furthermore, these kinetic and kinematic gait variables have been associated with OA progression. Gait analysis provides the critical information needed to understand the role of ambulatory biomechanics in OA development, and to design therapeutic interventions. Multidisciplinary research is necessary to relate the biomechanical alterations to the structural and biological components of OA. Cite this article: Favre J, Jolles BM. Analysis of gait, knee biomechanics and the physiopathology of knee osteoarthritis in the development of therapeutic interventions. EFORT Open Rev 2016;1:368-374. DOI: 10.1302/2058-5241.1.000051. PMID:28461915

75 FR 40005 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Order Granting...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... including, but not limited to, stock index futures contracts, options on futures, options on securities and... holding and/ or managing portfolios or baskets of securities, commodity futures contracts, options on commodity futures contracts, swaps, forward contracts and/or options on physical commodities and/or non-U.S...

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.

Cluster headache: clinical features and therapeutic options.

PubMed

Gaul, Charly; Diener, Hans-Christoph; Müller, Oliver M

2011-08-01

Cluster headache is the most common type of trigemino-autonomic headache, affecting ca. 120 000 persons in Germany alone. The attacks of pain are in the periorbital area on one side, last 90 minutes on average, and are accompanied by trigemino-autonomic manifestations and restlessness. Most patients have episodic cluster headache; about 15% have chronic cluster headache, with greater impairment of their quality of life. The attacks often possess a circadian and seasonal rhythm. Selective literature review Oxygen inhalation and triptans are effective acute treatment for cluster attacks. First-line drugs for attack prophylaxis include verapamil and cortisone; alternatively, lithium and topiramate can be given. Short-term relief can be obtained by the subcutaneous infiltration of local anesthetics and steroids along the course of the greater occipital nerve, although most of the evidence in favor of this is not derived from randomized clinical trials. Patients whose pain is inadequately relieved by drug treatment can be offered newer, invasive treatments, such as deep brain stimulation in the hypothalamus (DBS) and bilateral occipital nerve stimulation (ONS). Pharmacotherapy for the treatment of acute attacks and for attack prophylaxis is effective in most patients. For the minority who do not gain adequate relief, newer invasive techniques are available in some referral centers. Definitive conclusions as to their value cannot yet be drawn from the available data.

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.

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.

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.

[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

Diagnosis and therapeutic options for peripheral vasculitic neuropathy

PubMed Central

2015-01-01

Vasculitis can affect the peripheral nervous system alone (nonsystemic vasculitic neuropathy) or can be a part of primary or secondary systemic vasculitis. In cases of pre-existing systemic vasculitis, the diagnosis can easily be made, whereas suspected vasculitic neuropathy as initial or only manifestation of vasculitis requires careful clinical, neurophysiological, laboratory and histopathological workout. The typical clinical syndrome is mononeuropathia multiplex or asymmetric neuropathy, but distal-symmetric neuropathy can frequently be seen. Standard treatments include steroids, azathioprine, methotrexate and cyclophosphamide. More recently the B-cell antibody rituximab and intravenous immunoglobulins have shown to be effective in some vasculitic neuropathy types. PMID:25829955

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

PubMed

Patterson, Amy S

2016-10-01

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

Assessment for advanced fuel cycle options in CANDU

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

Morreale, A.C.; Luxat, J.C.; Friedlander, Y.

2013-07-01

The possible options for advanced fuel cycles in CANDU reactors including actinide burning options and thorium cycles were explored and are feasible options to increase the efficiency of uranium utilization and help close the fuel cycle. The actinide burning TRUMOX approach uses a mixed oxide fuel of reprocessed transuranic actinides from PWR spent fuel blended with natural uranium in the CANDU-900 reactor. This system reduced actinide content by 35% and decreased natural uranium consumption by 24% over a PWR once through cycle. The thorium cycles evaluated used two CANDU-900 units, a generator and a burner unit along with a drivermore » fuel feedstock. The driver fuels included plutonium reprocessed from PWR, from CANDU and low enriched uranium (LEU). All three cycles were effective options and reduced natural uranium consumption over a PWR once through cycle. The LEU driven system saw the largest reduction with a 94% savings while the plutonium driven cycles achieved 75% savings for PWR and 87% for CANDU. The high neutron economy, online fuelling and flexible compact fuel make the CANDU system an ideal reactor platform for many advanced fuel cycles.« less

[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.

A capital idea. Bonds and nontraditional financing options.

PubMed

Wareham, Therese L

2004-05-01

Not-for-profit healthcare organizations have four basic sources of capital: internal sources, philanthropy, asset sales, and external sources. External sources, in particular, offer a wealth of options that are important for such organizations--especially those facing significant capital shortfalls--to consider. External sources include bond offerings and nontraditional offerings, such as receivables financing, off-balance-sheet options, real estate investment trusts, and subordinated securities.

Therapeutic modulation of gut microbiota: current clinical applications and future perspectives.

PubMed

Ianiro, Gianluca; Bibbò, Stefano; Gasbarrini, Antonio; Cammarota, Giovanni

2014-01-01

Human beings and gut microbiota are in a symbiotic relationship, and the hypothesis of a "super organism" composed of the human organism and microbes has been recently proposed. The gut microbiota fulfills important metabolic and immunological tasks, and the impairment of its composition might alter homeostasis and lead to the development of microbiota-related diseases. The most common illnesses associated with alterations of the gut microbiota include inflammatory bowel disease, gastroenteric infections, irritable bowel syndrome and other gastrointestinal functional diseases, colorectal cancer, metabolic syndrome and obesity, liver diseases, allergic diseases, and neurological diseases such as autism. In theory, every disease associated with the impairment of intestinal microflora might benefit from the therapeutic modulation of the gut microbiota. A number of attempts to manipulate the microbiota have not produced identical results for every disease. Although antibiotics and probiotics have been available for a long time, the so-called fecal microbiota transplantation, which is a very old remedy, was only recently re-evaluated as a promising therapeutic approach for microbiota impairment. A comprehensive understanding of the gut microbiota composition, in states of both health and various diseases, is needed for the development of future approaches for microbiota modulation and for developing targeted therapies. In this review, we describe the role of the microbiota in several diseases and the related treatment options that are currently available.

Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine

PubMed Central

Murphy, Matthew B; Moncivais, Kathryn; Caplan, Arnold I

2013-01-01

Mesenchymal stem cells (MSCs) are partially defined by their ability to differentiate into tissues including bone, cartilage and adipose in vitro, but it is their trophic, paracrine and immunomodulatory functions that may have the greatest therapeutic impact in vivo. Unlike pharmaceutical treatments that deliver a single agent at a specific dose, MSCs are site regulated and secrete bioactive factors and signals at variable concentrations in response to local microenvironmental cues. Significant progress has been made in understanding the biochemical and metabolic mechanisms and feedback associated with MSC response. The anti-inflammatory and immunomodulatory capacity of MSC may be paramount in the restoration of localized or systemic conditions for normal healing and tissue regeneration. Allogeneic MSC treatments, categorized as a drug by regulatory agencies, have been widely pursued, but new studies demonstrate the efficacy of autologous MSC therapies, even for individuals affected by a disease state. Safety and regulatory concerns surrounding allogeneic cell preparations make autologous and minimally manipulated cell therapies an attractive option for many regenerative, anti-inflammatory and autoimmune applications. PMID:24232253

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

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...

Stable coronary syndromes: pathophysiology, diagnostic advances and therapeutic need

PubMed Central

Corcoran, David

2018-01-01

The diagnostic management of patients with angina pectoris typically centres on the detection of obstructive epicardial CAD, which aligns with evidence-based treatment options that include medical therapy and myocardial revascularisation. This clinical paradigm fails to account for the considerable proportion (approximately one-third) of patients with angina in whom obstructive CAD is excluded. This common scenario presents a diagnostic conundrum whereby angina occurs but there is no obstructive CAD (ischaemia and no obstructive coronary artery disease—INOCA). We review new insights into the pathophysiology of angina whereby myocardial ischaemia results from a deficient supply of oxygenated blood to the myocardium, due to various combinations of focal or diffuse epicardial disease (macrovascular), microvascular dysfunction or both. Macrovascular disease may be due to the presence of obstructive CAD secondary to atherosclerosis, or may be dynamic due to a functional disorder (eg, coronary artery spasm, myocardial bridging). Pathophysiology of coronary microvascular disease may involve anatomical abnormalities resulting in increased coronary resistance, or functional abnormalities resulting in abnormal vasomotor tone. We consider novel clinical diagnostic techniques enabling new insights into the causes of angina and appraise the need for improved therapeutic options for patients with INOCA. We conclude that the taxonomy of stable CAD could improve to better reflect the heterogeneous pathophysiology of the coronary circulation. We propose the term ‘stable coronary syndromes’ (SCS), which aligns with the well-established terminology for ‘acute coronary syndromes’. SCS subtends a clinically relevant classification that more fully encompasses the different diseases of the epicardial and microvascular coronary circulation. PMID:29030424

TECHNOLOGICAL OPTIONS FOR ACID RAIN CONTROL

EPA Science Inventory

Discussed are acid rain control options available to the electric utility industry. They include coal switching, flue gas desulfurization, and such emerging lower cost technologies as Limestone Injection Multistage Burners (LIMB) and Advanced Silicate (ADVACATE), both developed ...

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.

The Therapeutic Relationship: Enhancing Referrals.

PubMed

Coyle, Mary Kathleen

2018-05-19

This article focuses on the ways rehabilitation nurses use the therapeutic relationship to lessen barriers some veterans experience when a referral to mental health treatment is recommended. Veterans presenting with posttraumatic stress symptoms are discussed, and possible interventions within the therapeutic relationship are proposed. Veterans' perception of mental health stigma, building a collaborative therapeutic relationship, recommending a referral and assessments of stress responses, posttraumatic stress symptoms, suicide risk, and intervention strategies are proposed. When changes in functioning and suicidality occur in veterans with posttraumatic stress disorder symptoms, it is important to screen and engage veterans at risk. When veterans in the rehabilitation process present with a need for mental health referral, barriers to treatment may include the stigma of mental health treatment. Rehabilitation nurses using the therapeutic relationship act as change agents to assist veterans in overcoming these barriers to treatment. The therapeutic relationship provides nurses with a foundation to provide opportunities for veterans to be supported and to seek treatment.

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.

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...

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

Therapeutic Nanodevices

NASA Astrophysics Data System (ADS)

Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

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.

RESIDUALS, QUANTITIES, CHARACTERISTICS AND DISPOSAL OPTIONS

EPA Science Inventory

Presentation will describe the characteristics and quantitites of residuals generated by the various arsenic removal technologies including adsorptive media, coagulation filtration and iron removal. Information is also presented on the disposal options for the various types of re...

Option generation in decision making: ideation beyond memory retrieval

PubMed Central

Del Missier, Fabio; Visentini, Mimì; Mäntylä, Timo

2015-01-01

According to prescriptive decision theories, the generation of options for choice is a central aspect of decision making. A too narrow representation of the problem may indeed limit the opportunity to evaluate promising options. However, despite the theoretical and applied significance of this topic, the cognitive processes underlying option generation are still unclear. In particular, while a cued recall account of option generation emphasizes the role of memory and executive control, other theoretical proposals stress the importance of ideation processes based on various search and thinking processes. Unfortunately, relevant behavioral evidence on the cognitive processes underlying option generation is scattered and inconclusive. In order to reach a better understanding, we carried out an individual-differences study employing a wide array of cognitive predictors, including measures of episodic memory, semantic memory, cognitive control, and ideation fluency. The criterion tasks consisted of three different poorly-structured decision-making scenarios, and the participants were asked to generate options to solve these problems. The main criterion variable of the study was the number of valid options generated, but also the diversity and the quality of generated options were examined. The results showed that option generation fluency and diversity in the context of ill-structured decision making are supported by ideation ability even after taking into account the effects of individual differences in several other aspects of cognitive functioning. Thus, ideation processes, possibly supported by search and thinking processes, seem to contribute to option generation beyond basic associative memory retrieval. The findings of the study also indicate that generating more options may have multifaceted consequences for choice, increasing the quality of the best option generated but decreasing the mean quality of the options in the generated set. PMID:25657628

Option generation in decision making: ideation beyond memory retrieval.

PubMed

Del Missier, Fabio; Visentini, Mimì; Mäntylä, Timo

2014-01-01

According to prescriptive decision theories, the generation of options for choice is a central aspect of decision making. A too narrow representation of the problem may indeed limit the opportunity to evaluate promising options. However, despite the theoretical and applied significance of this topic, the cognitive processes underlying option generation are still unclear. In particular, while a cued recall account of option generation emphasizes the role of memory and executive control, other theoretical proposals stress the importance of ideation processes based on various search and thinking processes. Unfortunately, relevant behavioral evidence on the cognitive processes underlying option generation is scattered and inconclusive. In order to reach a better understanding, we carried out an individual-differences study employing a wide array of cognitive predictors, including measures of episodic memory, semantic memory, cognitive control, and ideation fluency. The criterion tasks consisted of three different poorly-structured decision-making scenarios, and the participants were asked to generate options to solve these problems. The main criterion variable of the study was the number of valid options generated, but also the diversity and the quality of generated options were examined. The results showed that option generation fluency and diversity in the context of ill-structured decision making are supported by ideation ability even after taking into account the effects of individual differences in several other aspects of cognitive functioning. Thus, ideation processes, possibly supported by search and thinking processes, seem to contribute to option generation beyond basic associative memory retrieval. The findings of the study also indicate that generating more options may have multifaceted consequences for choice, increasing the quality of the best option generated but decreasing the mean quality of the options in the generated set.

Progress in the pharmacological treatment of human cystic and alveolar echinococcosis: Compounds and therapeutic targets

PubMed Central

Siles-Lucas, Mar; Casulli, Adriano; Cirilli, Roberto

2018-01-01

Human cystic and alveolar echinococcosis are helmintic zoonotic diseases caused by infections with the larval stages of the cestode parasites Echinococcus granulosus and E. multilocularis, respectively. Both diseases are progressive and chronic, and often fatal if left unattended for E. multilocularis. As a treatment approach, chemotherapy against these orphan and neglected diseases has been available for more than 40 years. However, drug options were limited to the benzimidazoles albendazole and mebendazole, the only chemical compounds currently licensed for treatment in humans. To compensate this therapeutic shortfall, new treatment alternatives are urgently needed, including the identification, development, and assessment of novel compound classes and drug targets. Here is presented a thorough overview of the range of compounds that have been tested against E. granulosus and E. multilocularis in recent years, including in vitro and in vivo data on their mode of action, dosage, administration regimen, therapeutic outcomes, and associated clinical symptoms. Drugs covered included albendazole, mebendazole, and other members of the benzimidazole family and their derivatives, including improved formulations and combined therapies with other biocidal agents. Chemically synthetized molecules previously known to be effective against other infectious and non-infectious conditions such as anti-virals, antibiotics, anti-parasites, anti-mycotics, and anti-neoplastics are addressed. In view of their increasing relevance, natural occurring compounds derived from plant and fungal extracts are also discussed. Special attention has been paid to the recent application of genomic science on drug discovery and clinical medicine, particularly through the identification of small inhibitor molecules tackling key metabolic enzymes or signalling pathways. PMID:29677189

Calcific tendinitis of the rotator cuff: management options.

PubMed

Suzuki, Kentaro; Potts, Aaron; Anakwenze, Oke; Singh, Anshu

2014-11-01

Calcific tendinitis of the rotator cuff tendons is a common cause of shoulder pain in adults and typically presents as activity-related shoulder pain. It is thought to be an active, cell-mediated process, although the exact pathophysiology remains unclear. Nonsurgical management continues to be the mainstay of treatment; most patients improve with modalities such as oral anti-inflammatory medication, physical therapy, and corticosteroid injections. Several options are available for patients who fail nonsurgical treatment, including extracorporeal shock wave therapy, ultrasound-guided needle lavage, and surgical débridement. These modalities alleviate pain by eliminating the calcific deposit, and several recent studies have demonstrated success with the use of these treatment options. Surgical management options include arthroscopic procedures to remove calcific deposits and subacromial decompression; however, the role of subacromial decompression and repair of rotator cuff defects created by removing these deposits remains controversial. Copyright 2014 by the American Academy of Orthopaedic Surgeons.

Options for change in the NHS consultant contract.

PubMed

Clarke, R W; Gray, C

The lead negotiators for the management and consultant sides in an NHS trust in northern England responded to debate in their trust about consultant contracts by offering to research the attitudes of their peers towards a variety of contract options. The options tested included the current contract; models already examined in the trust and elsewhere, such as time sensitive and mild performance related contracts; and some more radical and speculative possibilities, including consultants franchising their services to the trust. Beyond the predictable conclusion that consultants would prefer no change while managers desired it, a time sensitive contract emerged as having potential for successful negotiation. On the other hand, neither consultants nor managers favoured a strict performance related contract or a fee for service contract. There was a strong similarity of opinion between the two groups on the relative salary values of the options, though the consultants consistently priced these higher than the managers.

Options for change in the NHS consultant contract.

PubMed Central

Clarke, R. W.; Gray, C.

1994-01-01

The lead negotiators for the management and consultant sides in an NHS trust in northern England responded to debate in their trust about consultant contracts by offering to research the attitudes of their peers towards a variety of contract options. The options tested included the current contract; models already examined in the trust and elsewhere, such as time sensitive and mild performance related contracts; and some more radical and speculative possibilities, including consultants franchising their services to the trust. Beyond the predictable conclusion that consultants would prefer no change while managers desired it, a time sensitive contract emerged as having potential for successful negotiation. On the other hand, neither consultants nor managers favoured a strict performance related contract or a fee for service contract. There was a strong similarity of opinion between the two groups on the relative salary values of the options, though the consultants consistently priced these higher than the managers. PMID:8086915

A systematic review of model-based economic evaluations of diagnostic and therapeutic strategies for lower extremity artery disease.

PubMed

Vaidya, Anil; Joore, Manuela A; ten Cate-Hoek, Arina J; Kleinegris, Marie-Claire; ten Cate, Hugo; Severens, Johan L

2014-01-01

Lower extremity artery disease (LEAD) is a sign of wide spread atherosclerosis also affecting coronary, cerebral and renal arteries and is associated with increased risk of cardiovascular events. Many economic evaluations have been published for LEAD due to its clinical, social and economic importance. The aim of this systematic review was to assess modelling methods used in published economic evaluations in the field of LEAD. Our review appraised and compared the general characteristics, model structure and methodological quality of published models. Electronic databases MEDLINE and EMBASE were searched until February 2013 via OVID interface. Cochrane database of systematic reviews, Health Technology Assessment database hosted by National Institute for Health research and National Health Services Economic Evaluation Database (NHSEED) were also searched. The methodological quality of the included studies was assessed by using the Philips' checklist. Sixteen model-based economic evaluations were identified and included. Eleven models compared therapeutic health technologies; three models compared diagnostic tests and two models compared a combination of diagnostic and therapeutic options for LEAD. Results of this systematic review revealed an acceptable to low methodological quality of the included studies. Methodological diversity and insufficient information posed a challenge for valid comparison of the included studies. In conclusion, there is a need for transparent, methodologically comparable and scientifically credible model-based economic evaluations in the field of LEAD. Future modelling studies should include clinically and economically important cardiovascular outcomes to reflect the wider impact of LEAD on individual patients and on the society.

Emerging therapeutics in sleep.

PubMed

Saper, Clifford B; Scammell, Thomas E

2013-09-01

The development of new therapeutics for sleep disorders is increasingly dependent upon understanding the basic brain circuitry that underlies sleep-wake regulation, and how it may be pharmacologically manipulated. In this review, we consider the pathophysiological basis of major sleep disorders that often are seen by neurologists, including excessive daytime sleepiness, insomnia, narcolepsy, rapid eye movement sleep behavior disorder, and restless legs syndrome, as well as circadian disorders, and we review the current and potential future therapeutic approaches. Copyright © 2013 American Neurological Association.

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

Addressing the stimulant treatment gap: A call to investigate the therapeutic benefits potential of cannabinoids for crack-cocaine use.

PubMed

Fischer, Benedikt; Kuganesan, Sharan; Gallassi, Andrea; Malcher-Lopes, Renato; van den Brink, Wim; Wood, Evan

2015-12-01

Crack-cocaine use is prevalent in numerous countries, yet concentrated primarily - largely within urban contexts - in the Northern and Southern regions of the Americas. It is associated with a variety of behavioral, physical and mental health and social problems which gravely affect users and their environments. Few evidence-based treatments for crack-cocaine use exist and are available to users in the reality of street drug use. Numerous pharmacological treatments have been investigated but with largely disappointing results. An important therapeutic potential for crack-cocaine use may rest in cannabinoids, which have recently seen a general resurgence for varied possible therapeutic usages for different neurological diseases. Distinct potential therapeutic benefits for crack-cocaine use and common related adverse symptoms may come specifically from cannabidiol (CBD) - one of the numerous cannabinoid components found in cannabis - with its demonstrated anxiolytic, anti-psychotic, anti-convulsant effects and potential benefits for sleep and appetite problems. The possible therapeutic prospects of cannabinoids are corroborated by observational studies from different contexts documenting crack-cocaine users' 'self-medication' efforts towards coping with crack-cocaine-related problems, including withdrawal and craving, impulsivity and paranoia. Cannabinoid therapeutics offer further benefits of being available in multiple formulations, are low in adverse risk potential, and may easily be offered in community-based settings which may add to their feasibility as interventions for - predominantly marginalized - crack-cocaine user populations. Supported by the dearth of current therapeutic options for crack-cocaine use, we are advocating for the implementation of a rigorous research program investigating the potential therapeutic benefits of cannabinoids for crack-cocaine use. Given the high prevalence of this grave substance use problem in the Americas, opportunities for

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Therapeutic vaginal douche apparatus. 884.5900... Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche apparatus is a device that is a bag or bottle with tubing and a nozzle. The apparatus does not include...

21 CFR 884.5900 - Therapeutic vaginal douche apparatus.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Therapeutic vaginal douche apparatus. 884.5900... Devices § 884.5900 Therapeutic vaginal douche apparatus. (a) Identification. A therapeutic vaginal douche apparatus is a device that is a bag or bottle with tubing and a nozzle. The apparatus does not include...

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

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

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.

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.

Solar pumped laser technology options for space power transmission

NASA Technical Reports Server (NTRS)

Conway, E. J.

1986-01-01

An overview of long-range options for in-space laser power transmission is presented. The focus is on the new technology and research status of solar-pumped lasers and their solar concentration needs. The laser options include gas photodissociation lasers, optically-pumped solid-state lasers, and blackbody-pumped transfer lasers. The paper concludes with a summary of current research thrusts.

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

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.

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.

In Vitro Activity of the New Fluoroketolide Solithromycin (CEM-101) against a Large Collection of Clinical Neisseria gonorrhoeae Isolates and International Reference Strains, Including Those with High-Level Antimicrobial Resistance: Potential Treatment Option for Gonorrhea?

PubMed Central

Golparian, Daniel; Fernandes, Prabhavathi; Ohnishi, Makoto; Jensen, Jörgen S.

2012-01-01

Gonorrhea may become untreatable, and new treatment options are essential. We investigated the in vitro activity of the first fluoroketolide, solithromycin. Clinical Neisseria gonorrhoeae isolates and reference strains (n = 246), including the two extensively drug-resistant strains H041 and F89 and additional isolates with clinical cephalosporin resistance and multidrug resistance, were examined. The activity of solithromycin was mainly superior to that of other antimicrobials (n = 10) currently or previously recommended for gonorrhea treatment. Solithromycin might be an effective treatment option for gonorrhea. PMID:22354296

Surgical options in benign parotid tumors: a proposal for classification.

PubMed

Quer, Miquel; Vander Poorten, Vincent; Takes, Robert P; Silver, Carl E; Boedeker, Carsten C; de Bree, Remco; Rinaldo, Alessandra; Sanabria, Alvaro; Shaha, Ashok R; Pujol, Albert; Zbären, Peter; Ferlito, Alfio

2017-11-01

Different surgical options are currently available for treating benign tumors of the parotid gland, and the discussion on optimal treatment continues despite several meta-analyses. These options include more limited resections (extracapsular dissection, partial lateral parotidectomy) versus more extensive and traditional options (lateral parotid lobectomy, total parotidectomy). Different schools favor one option or another based on their experience, skills and tradition. This review provides a critical analysis of the literature regarding these options. The main limitation of all the studies is the bias of selection for different surgical approaches. For this reason, we propose a staging system that could facilitate clinical decision making and the comparison of results. We propose four categories based on the size of the tumor and its location within the parotid gland. Category I includes tumors up to 3 cm, which are mobile, close to the outer surface and close to the parotid borders. Category II includes deeper tumors up to 3 cm. Category III comprises tumors greater than 3 cm involving two levels of the parotid gland, and category IV tumors are greater than 3 cm and involve more than 2 levels. For each category and for the various pathologic types, a guideline of surgical extent is proposed. The objective of this classification is to facilitate prospective multicentric studies on surgical techniques in the treatment of benign parotid tumors and to enable the comparison of results of different clinical studies.

[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.

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.

Therapeutic antibodies against cancer

PubMed Central

Adler, Mark J.; Dimitrov, Dimiter S.

2012-01-01

Antibody-based therapeutics against cancer are highly successful in clinic and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States (one, mylotarg, was withdrawn from market in 2010). Three of the mAbs (bevacizumab, rituximab, trastuzumab) are in the top six selling protein therapeutics with sales in 2010 of more than $5 bln each. Hundreds of mAbs including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs and mAbs with optimized pharmacokinetics are in clinical trials. However, challenges remain and it appears that deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems and individual variations. PMID:22520975

Scope Complexity Options Risks Excursions (SCORE) Factor Mathematical Description.

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

Gearhart, Jared Lee; Samberson, Jonell Nicole; Shettigar, Subhasini

The purpose of the Scope, Complexity, Options, Risks, Excursions (SCORE) model is to estimate the relative complexity of design variants of future warhead options, resulting in scores. SCORE factors extend this capability by providing estimates of complexity relative to a base system (i.e., all design options are normalized to one weapon system). First, a clearly defined set of scope elements for a warhead option is established. The complexity of each scope element is estimated by Subject Matter Experts (SMEs), including a level of uncertainty, relative to a specific reference system. When determining factors, complexity estimates for a scope element canmore » be directly tied to the base system or chained together via comparable scope elements in a string of reference systems that ends with the base system. The SCORE analysis process is a growing multi-organizational Nuclear Security Enterprise (NSE) effort, under the management of the NA-12 led Enterprise Modeling and Analysis Consortium (EMAC). Historically, it has provided the data elicitation, integration, and computation needed to support the out-year Life Extension Program (LEP) cost estimates included in the Stockpile Stewardship Management Plan (SSMP).« less

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.

Evaluation of Options for Interpreting Environmental ...

EPA Pesticide Factsheets

Report Secondary data from the BioResponse Operational Testing and Evaluation project were used to study six options for interpreting culture-based/microbial count data sets that include left censored data, or measurements that are less than established quantification limits and/or detection limits.

Non-coding RNAs: Therapeutic Strategies and Delivery Systems.

PubMed

Ling, Hui

The vast majority of the human genome is transcribed into RNA molecules that do not code for proteins, which could be small ones approximately 20 nucleotide in length, known as microRNAs, or transcripts longer than 200 bp, defined as long noncoding RNAs. The prevalent deregulation of microRNAs in human cancers prompted immediate interest on the therapeutic value of microRNAs as drugs and drug targets. Many features of microRNAs such as well-defined mechanisms, and straightforward oligonucleotide design further make them attractive candidates for therapeutic development. The intensive efforts of exploring microRNA therapeutics are reflected by the large body of preclinical studies using oligonucleotide-based mimicking and blocking, culminated by the recent entry of microRNA therapeutics in clinical trial for several human diseases including cancer. Meanwhile, microRNA therapeutics faces the challenge of effective and safe delivery of nucleic acid therapeutics into the target site. Various chemical modifications of nucleic acids and delivery systems have been developed to increase targeting specificity and efficacy, and reduce the associated side effects including activation of immune response. Recently, long noncoding RNAs become attractive targets for therapeutic intervention because of their association with complex and delicate phenotypes, and their unconventional pharmaceutical activities such as capacity of increasing output of proteins. Here I discuss the general therapeutic strategies targeting noncoding RNAs, review delivery systems developed to maximize noncoding RNA therapeutic efficacy, and offer perspectives on the future development of noncoding RNA targeting agents for colorectal cancer.

Emerging Options for Emergency Contraception

PubMed Central

Koyama, Atsuko; Hagopian, Laura; Linden, Judith

2013-01-01

Emergency post-coital contraception (EC) is an effective method of preventing pregnancy when used appropriately. EC has been available since the 1970s, and its availability and use have become widespread. Options for EC are broad and include the copper intrauterine device (IUD) and emergency contraceptive pills such as levonorgestrel, ulipristal acetate, combined oral contraceptive pills (Yuzpe method), and less commonly, mifepristone. Some options are available over-the-counter, while others require provider prescription or placement. There are no absolute contraindications to the use of emergency contraceptive pills, with the exception of ulipristal acetate and mifepristone. This article reviews the mechanisms of action, efficacy, safety, side effects, clinical considerations, and patient preferences with respect to EC usage. The decision of which regimen to use is influenced by local availability, cost, and patient preference. PMID:24453516

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

Options for accounting carbon sequestration in German forests.

PubMed

Krug, Joachim; Koehl, Michael; Riedel, Thomas; Bormann, Kristin; Rueter, Sebastian; Elsasser, Peter

2009-08-03

The Accra climate change talks held from 21-27 August 2008 in Accra, Ghana, were part of an ongoing series of meetings leading up to the Copenhagen meeting in December 2009. During the meeting a set of options for accounting carbon sequestration in forestry on a post-2012 framework was presented. The options include gross-net and net-net accounting and approaches for establishing baselines. This article demonstrates the embedded consequences of Accra Accounting Options for the case study of German national GHG accounting. It presents the most current assessment of sequestration rates by forest management for the period 1990 - 2007, provides an outlook of future emissions and removals (up to the year 2042) as related to three different management scenarios, and shows that implementation of some Accra options may reverse sources to sinks, or sinks to sources. The results of the study highlight the importance of elaborating an accounting system that would prioritize the climate convention goals, not national preferences.

Management options of varicoceles

PubMed Central

Chan, Peter

2011-01-01

Varicocele is one of the most common causes of male infertility. Treatment options for varicoceles includes open varicocelectomy performed at various anatomical levels. Laparoscopic varicocelectomy has been established to be a safe and effective treatment for varicoceles. Robotic surgery has been introduced recently as an alternative surgical option for varicocelectomy. Microsurgical varicocelectomy has gained increasing popularity among experts in male reproductive medicine as the treatment of choice for varicocele because of its superior surgical outcomes. There is a growing volume of literature in the recent years on minimal invasive varicocele treatment with percutaneous retrograde and anterograde venous embolization/sclerotherapy. In this review, we will discuss the advantages and limitations associated with each treatment modality for varicoceles. Employment of these advanced techniques of varicocelectomy can provide a safe and effective approach aiming to eliminate varicocele, preserve testicular function and, in a substantial number of men, increase semen quality and the likelihood of pregnancy. PMID:21716892

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.

[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.

Breaking the Mold: A Review of Mucormycosis and Current Pharmacological Treatment Options.

PubMed

Riley, Treavor T; Muzny, Christina A; Swiatlo, Edwin; Legendre, Davey P

2016-09-01

To review the current literature for the pathogenesis of mucormycosis, discuss diagnostic strategies, and evaluate the efficacy of polyenes, triazoles, and echinocandins as pharmacological treatment options. An electronic literature search was conducted in PubMed using the MESH terms Rhizopus, zygomycetes, zygomycosis, Mucorales and mucormycosis, with search terms amphotericin B, micafungin, anidulafungin, caspofungin, extended infusion amphotericin B, liposomal amphotericin B, combination therapy, triazole, posaconazole, isavuconazole, diagnosis, and clinical manifestations. Studies written in the English language from January 1960 to March 2016 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by the authors independently. Mucormycosis is a rare invasive fungal infection with an exceedingly high mortality and few therapeutic options. It has a distinct predilection for invasion of endothelial cells in the vascular system, which is likely important in dissemination of disease from a primary focus of infection. Six distinct clinical syndromes can occur in susceptible hosts, including rhino-orbital-cerebral, pulmonary, gastrointestinal, cutaneous, widely disseminated, and miscellaneous infection. Diagnosis of mucormycosis is typically difficult to make based on imaging studies, sputum culture, bronchoalveolar lavage culture, or needle aspirate. Surgical debridement prior to dissemination of infection improves clinical outcomes. Surgery combined with early, high-dose systemic antifungal therapy yields greater than a 1.5-fold increase in survival rates. The Mucorales are inherently resistant to most widely used antifungal agents. Amphotericin B is appropriate for empirical therapy, whereas posaconazole and isavuconazole are best reserved for de-escalation, refractory cases, or patients intolerant to amphotericin B. © The Author(s) 2016.

[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.

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.

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

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.

Internet Connections: Understanding Your Access Options.

ERIC Educational Resources Information Center

Notess, Greg R.

1994-01-01

Describes levels of Internet connectivity, physical connections, and connection speeds. Compares options for connecting to the Internet, including terminal accounts, dial-up terminal accounts, direct connections through a local area network, and direct connections using SLIP (Serial Line Internet Protocol) or PPP (Point-to-Point Protocol). (eight…

Therapeutic writing and chronic pain: experiences of therapeutic writing in a cognitive behavioural programme for people with chronic pain.

PubMed

Furnes, Bodil; Dysvik, Elin

2012-12-01

To examine the experiences of therapeutic writing from the perspectives of patients attending a chronic pain management programme. Pain is a multifaceted experience. Increased awareness, understanding and gaining new insights are essential aspects of dealing with chronic pain. It is crucial to find powerful ways to cope with chronic pain. Several studies point to writing as a tool for managing such demanding life experiences. Therapeutic writing in a cognitive behavioural approach may be used to facilitate the rehabilitation process. A qualitative study with a descriptive and explorative design including a phenomenological perspective was used. A consecutive sample of 34 outpatients with chronic pain was recruited to an eight-week group-based pain management programme. A therapeutic writing tool was developed and included as part of the homework tasks. Guidelines were used to initiate and guide the therapeutic writing activity. Written reports were collected after completion. Three thematic findings emerged from the analysis: 'increased understanding of chronic pain as a multifaceted experience', 'new insights into managing the chronic pain situation' and 'different performances lead to different experiences with therapeutic writing'. Increased awareness, understanding and new insights are essential to dealing with chronic pain. People with chronic pain need tools and skills for optimal adaptation. Our findings suggest therapeutic writing may strengthen cognitive behavioural therapy by facilitating cognitive restructuring processes. Therapeutic writing may be used as a tool to express individual experiences and to improve adaptation to chronic pain. © 2012 Blackwell Publishing Ltd.

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.

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…

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.

Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

PubMed

Kelly, Cynthia W

2008-04-01

To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

Engineering Options Assessment Report. Nitrate Salt Waste Stream Processing

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

Anast, Kurt Roy

2015-11-13

This report examines and assesses the available systems and facilities considered for carrying out remediation activities on remediated nitrate salt (RNS) and unremediated nitrate salt (UNS) waste containers at Los Alamos National Laboratory (LANL). The assessment includes a review of the waste streams consisting of 60 RNS, 29 above-ground UNS, and 79 candidate below-ground UNS containers that may need remediation. The waste stream characteristics were examined along with the proposed treatment options identified in the Options Assessment Report . Two primary approaches were identified in the five candidate treatment options discussed in the Options Assessment Report: zeolite blending and cementation.more » Systems that could be used at LANL were examined for housing processing operations to remediate the RNS and UNS containers and for their viability to provide repackaging support for remaining LANL legacy waste.« less

Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing

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

Anast, Kurt Roy

2015-11-18

This report examines and assesses the available systems and facilities considered for carrying out remediation activities on remediated nitrate salt (RNS) and unremediated nitrate salt (UNS) waste containers at Los Alamos National Laboratory (LANL). The assessment includes a review of the waste streams consisting of 60 RNS, 29 aboveground UNS, and 79 candidate belowground UNS containers that may need remediation. The waste stream characteristics were examined along with the proposed treatment options identified in the Options Assessment Report . Two primary approaches were identified in the five candidate treatment options discussed in the Options Assessment Report: zeolite blending and cementation.more » Systems that could be used at LANL were examined for housing processing operations to remediate the RNS and UNS containers and for their viability to provide repackaging support for remaining LANL legacy waste.« less

Initial Business Case Analysis of Two Integrated Heat Pump HVAC Systems for Near-Zero-Energy Homes -- Update to Include Analyses of an Economizer Option and Alternative Winter Water Heating Control Option

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

Baxter, Van D

2006-12-01

The long range strategic goal of the Department of Energy's Building Technologies (DOE/BT) Program is to create, by 2020, technologies and design approaches that enable the construction of net-zero energy homes at low incremental cost (DOE/BT 2005). A net zero energy home (NZEH) is a residential building with greatly reduced needs for energy through efficiency gains, with the balance of energy needs supplied by renewable technologies. While initially focused on new construction, these technologies and design approaches are intended to have application to buildings constructed before 2020 as well resulting in substantial reduction in energy use for all building typesmore » and ages. DOE/BT's Emerging Technologies (ET) team is working to support this strategic goal by identifying and developing advanced heating, ventilating, air-conditioning, and water heating (HVAC/WH) technology options applicable to NZEHs. Although the energy efficiency of heating, ventilating, and air-conditioning (HVAC) equipment has increased substantially in recent years, new approaches are needed to continue this trend. Dramatic efficiency improvements are necessary to enable progress toward the NZEH goals, and will require a radical rethinking of opportunities to improve system performance. The large reductions in HVAC energy consumption necessary to support the NZEH goals require a systems-oriented analysis approach that characterizes each element of energy consumption, identifies alternatives, and determines the most cost-effective combination of options. In particular, HVAC equipment must be developed that addresses the range of special needs of NZEH applications in the areas of reduced HVAC and water heating energy use, humidity control, ventilation, uniform comfort, and ease of zoning. In FY05 ORNL conducted an initial Stage 1 (Applied Research) scoping assessment of HVAC/WH systems options for future NZEHs to help DOE/BT identify and prioritize alternative approaches for further

Advanced policy options to regulate sugar-sweetened beverages to support public health.

PubMed

Pomeranz, Jennifer L

2012-02-01

Consumption of sugar-sweetened beverages (SSBs) has increased worldwide. As public health studies expose the detrimental impact of SSBs, consumer protection and public health advocates have called for increased government control. A major focus has been on restricting marketing of SSBs to children, but many innovative policy options--legally defensible ways to regulate SSBs and support public health--are largely unexplored. We describe the public health, economic, and retail marketing research related to SSBs (including energy drinks). We review policy options available to governments, including mandatory factual disclosures, earmarked taxation, and regulating sales, including placement within retail and food service establishments, and schools. Our review describes recent international initiatives and classifies options available in the United States by jurisdiction (federal, state, and local) based on legal viability.

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

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.

Therapeutic nucleic acids: current clinical status

PubMed Central

Sridharan, Kannan

2016-01-01

Abstract Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are simple linear polymers that have been the subject of considerable research in the last two decades and have now moved into the realm of being stand‐alone therapeutic agents. Much of this has stemmed from the appreciation that they carry out myriad functions that go beyond mere storage of genetic information and protein synthesis. Therapy with nucleic acids either uses unmodified DNA or RNA or closely related compounds. From both a development and regulatory perspective, they fall somewhere between small molecules and biologics. Several of these compounds are in clinical development and many have received regulatory approval for human use. This review addresses therapeutic uses of DNA based on antisense oligonucleotides, DNA aptamers and gene therapy; and therapeutic uses of RNA including micro RNAs, short interfering RNAs, ribozymes, RNA decoys and circular RNAs. With their specificity, functional diversity and limited toxicity, therapeutic nucleic acids hold enormous promise. However, challenges that need to be addressed include targeted delivery, mass production at low cost, sustaining efficacy and minimizing off‐target toxicity. Technological developments will hold the key to this and help accelerate drug approvals in the years to come. PMID:27111518

Ethical Perspectives on RNA Interference Therapeutics

PubMed Central

Ebbesen, Mette; Jensen, Thomas G.; Andersen, Svend; Pedersen, Finn Skou

2008-01-01

RNA interference is a mechanism for controlling normal gene expression which has recently begun to be employed as a potential therapeutic agent for a wide range of disorders, including cancer, infectious diseases and metabolic disorders. Clinical trials with RNA interference have begun. However, challenges such as off-target effects, toxicity and safe delivery methods have to be overcome before RNA interference can be considered as a conventional drug. So, if RNA interference is to be used therapeutically, we should perform a risk-benefit analysis. It is ethically relevant to perform a risk-benefit analysis since ethical obligations about not inflicting harm and promoting good are generally accepted. But the ethical issues in RNA interference therapeutics not only include a risk-benefit analysis, but also considerations about respecting the autonomy of the patient and considerations about justice with regard to the inclusion criteria for participation in clinical trials and health care allocation. RNA interference is considered a new and promising therapeutic approach, but the ethical issues of this method have not been greatly discussed, so this article analyses these issues using the bioethical theory of principles of the American bioethicists, Tom L. Beauchamp and James F. Childress. PMID:18612370

Initial Business Case Analysis of Two Integrated Heat Pump HVAC Systems for Near-Zero-Energy Homes - Update to Include Evaluation of Impact of Including a Humidifier Option

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

Baxter, Van D

2007-02-01

The long range strategic goal of the Department of Energy's Building Technologies (DOE/BT) Program is to create, by 2020, technologies and design approaches that enable the construction of net-zero energy homes at low incremental cost (DOE/BT 2005). A net zero energy home (NZEH) is a residential building with greatly reduced needs for energy through efficiency gains, with the balance of energy needs supplied by renewable technologies. While initially focused on new construction, these technologies and design approaches are intended to have application to buildings constructed before 2020 as well resulting in substantial reduction in energy use for all building typesmore » and ages. DOE/BT's Emerging Technologies (ET) team is working to support this strategic goal by identifying and developing advanced heating, ventilating, air-conditioning, and water heating (HVAC/WH) technology options applicable to NZEHs. In FY05 ORNL conducted an initial Stage 1 (Applied Research) scoping assessment of HVAC/WH systems options for future NZEHs to help DOE/BT identify and prioritize alternative approaches for further development. Eleven system concepts with central air distribution ducting and nine multi-zone systems were selected and their annual and peak demand performance estimated for five locations: Atlanta (mixed-humid), Houston (hot-humid), Phoenix (hot-dry), San Francisco (marine), and Chicago (cold). Performance was estimated by simulating the systems using the TRNSYS simulation engine (Solar Energy Laboratory et al. 2006) in two 1800-ft{sup 2} houses--a Building America (BA) benchmark house and a prototype NZEH taken from BEopt results at the take-off (or crossover) point (i.e., a house incorporating those design features such that further progress towards ZEH is through the addition of photovoltaic power sources, as determined by current BEopt analyses conducted by NREL). Results were summarized in a project report, HVAC Equipment Design options for Near

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.

Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

PubMed

Laffey, John G; Matthay, Michael A

2017-08-01

On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

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

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.

Functional dyspepsia pathogenesis and therapeutic options--implications for management.

PubMed

Smith, M Lancaster

2005-08-01

Functional dyspepsia is far more common than dyspepsia due to organic disease, both in the community and general practice. Proposed aetiopathogenic factors include gastric acid, Helicobacter pylori infection, delayed emptying, hypersensitivity or impaired accommodation of the stomach, dysfunction of the duodenum or brain-gut axis, psychosocial morbidity and post-infective mucosal damage. More effective therapy will depend on the development of drugs targeted at these putative pathophysiological mechanisms. On current evidence tricyclic antidepressants appear to be more effective than either acid suppressants or H. pylori eradication.

78 FR 77185 - Self-Regulatory Organizations; BOX Options Exchange LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-20

... options, including NDX. Rule 6090 permits the Exchange to list up to seven expiration months at any one...) specifically references options on NDX as one of the European-style index options approved for trading on BOX...

Potential Therapeutic Targets of Epithelial-Mesenchymal Transition in Melanoma

PubMed Central

Pearlman, Ross L.; de Oca, Mary Katherine Montes; Pal, Harish Chandra; Afaq, Farrukh

2017-01-01

Melanoma is a cutaneous neoplastic growth of melanocytes with great potential to invade and metastasize, especially when not treated early and effectively. Epithelial-mesenchymal transition (EMT) is the process by which melanocytes lose their epithelial characteristics and acquire mesenchymal phenotypes. Mesenchymal protein expression increases the motility, invasiveness, and metastatic potential of melanoma. Many pathways play a role in promotion of mesenchymal protein expression including RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, Wnt/β-catenin, and several others. Downstream effectors of these pathways induce expression of EMT transcription factors including Snail, Slug, Twist, and Zeb that promote repression of epithelial and induction of mesenchymal character. Emerging research has demonstrated that a variety of small molecule inhibitors as well as phytochemicals can influence the progression of EMT and may even reverse the process, inducing re-expression of epithelial markers. Phytochemicals are of particular interest as supplementary treatment options because of their relatively low toxicities and anti-EMT properties. Modulation of EMT signaling pathways using synthetic small molecules and phytochemicals is a potential therapeutic strategy for reducing the aggressive progression of metastatic melanoma. In this review, we discuss the emerging pathways and transcription factor targets that regulate EMT and evaluate potential synthetic small molecules and naturally occurring compounds that may reduce metastatic melanoma progression. PMID:28131904

Therapeutic Efficacy of a Combination Therapy of Topical 17α-Estradiol and Topical Minoxidil on Female Pattern Hair Loss: A Noncomparative, Retrospective Evaluation.

PubMed

Choe, Sung Jay; Lee, Solam; Choi, Jaewoong; Lee, Won-Soo

2017-06-01

A variety of agents have been used to treat female pattern hair loss (FPHL), including topical minoxidil, topical 17α-estradiol, oral anti-androgen agents, and mineral supplements. Compared with these single agent regimens, combination therapies could be a better therapeutic option in expectation of superior treatment outcome. This study was designed to determine the efficacy of a combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil in Korean patients with FPHL. Therapeutic efficacy was evaluated in 34 women who applied topical 0.025% 17α-estradiol and 3% minoxidil once daily for more than 6 months. Phototrichogram analysis was performed before and after therapy. The efficacy was evaluated with respect to total hair count, hair caliber (as assessed by phototrichogram analysis), and photographic assessment. Total hair count and hair caliber both increased from baseline to 6 months in patients treated with the combination therapy of topical 0.025% 17α-estradiol and 3% minoxidil ( p <0.001). Photographic assessment also revealed significant disease improvement, thus supporting the therapeutic efficacy. A combination therapy consisting of topical 0.025% 17α-estradiol and 3% minoxidil can be tried as an effective treatment for FPHL.

Reconstruction Options for Pancreaticoduodenectomy in Patients with Prior Roux-en-Y Gastric Bypass.

PubMed

Shah, Mihir M; Martin, Benjamin M; Stetler, Jamil L; Patel, Ankit D; Davis, S Scott; Sarmiento, Juan M; Lin, Edward

2017-11-01

Patients with prior Roux-en-Y gastric bypass (RYGB) operations for weight loss present reconstruction challenges during a pancreaticoduodenectomy (PD). With over 60,000 RYGB performed annually, the increasing odds of encountering such patients during a PD make it imperative to understand the RYGB anatomy and anticipate reconstruction options. This article describes the possible reconstruction options and their rationale. We reviewed our PD reconstruction options, compared them to what have been described in the literature, and derived a consensus from internal conferences comprising bariatric and hepatopancreatobiliary surgeons to describe known reconstruction options. In general, reconstruction options can include one of three options: (1) remnant gastrectomy, (2) preservation of gastric remnant, or (3) reversal of gastric bypass. This article describes individualized reconstruction options for RYGB patients undergoing PD. The reconstruction options can be tailored to the needs of the patient.

[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.

Ethics Audit of a Therapeutic Recreation Course

ERIC Educational Resources Information Center

Nisbett, Nancy; Hinton, Jennifer

2008-01-01

The purpose of this study was to enhance awareness of the presence of ethics education within the allied health discipline of therapeutic recreation. To achieve this end, a curriculum audit was conducted in a therapeutic recreation course to determine the existence of ethics education within the course. Included topics, methods of delivery, and…

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

Controlling Legionella and Pseudomonas aeruginosa re-growth in therapeutic spas: implementation of physical disinfection treatments, including UV/ultrafiltration, in a respiratory hydrotherapy system.

PubMed

Leoni, E; Sanna, T; Zanetti, F; Dallolio, L

2015-12-01

The study aimed to assess the efficacy of an integrated water safety plan (WSP) in controlling Legionella re-growth in a respiratory hydrotherapy system located in a spa centre, supplied with sulphurous water, which was initially colonized by Legionella pneumophila. Heterotrophic plate counts, Pseudomonas aeruginosa, Legionella spp. were detected in water samples taken 6-monthly from the hydrotherapy equipment (main circuit, entry to benches, final outlets). On the basis of the results obtained by the continuous monitoring and the changes in conditions, the original WSP, including physical treatments of water and waterlines, environmental surveillance and microbiological monitoring, was integrated introducing a UV/ultrafiltration system. The integrated treatment applied to the sulphurous water (microfiltration/UV irradiation/ultrafiltration), waterlines (superheated stream) and distal outlets (descaling/disinfection of nebulizers and nasal irrigators), ensured the removal of Legionella spp. and P. aeruginosa and a satisfactory microbiological quality over time. The environmental surveillance was successful in evaluating the hazard and identifying the most suitable preventive strategies to avoid Legionella re-growth. Ultrafiltration is a technology to take into account in the control of microbial contamination of therapeutic spas, since it does not modify the chemical composition of the water, thus allowing it to retain its therapeutic properties.

Options for accounting carbon sequestration in German forests

PubMed Central

Krug, Joachim; Koehl, Michael; Riedel, Thomas; Bormann, Kristin; Rueter, Sebastian; Elsasser, Peter

2009-01-01

Background The Accra climate change talks held from 21–27 August 2008 in Accra, Ghana, were part of an ongoing series of meetings leading up to the Copenhagen meeting in December 2009. During the meeting a set of options for accounting carbon sequestration in forestry on a post-2012 framework was presented. The options include gross-net and net-net accounting and approaches for establishing baselines. Results This article demonstrates the embedded consequences of Accra Accounting Options for the case study of German national GHG accounting. It presents the most current assessment of sequestration rates by forest management for the period 1990 – 2007, provides an outlook of future emissions and removals (up to the year 2042) as related to three different management scenarios, and shows that implementation of some Accra options may reverse sources to sinks, or sinks to sources. Conclusion The results of the study highlight the importance of elaborating an accounting system that would prioritize the climate convention goals, not national preferences. PMID:19650896

Development of Antibody Therapeutics against Flaviviruses

PubMed Central

Sun, Haiyan; Chen, Qiang; Lai, Huafang

2017-01-01

Recent outbreaks of Zika virus (ZIKV) highlight the urgent need to develop efficacious interventions against flaviviruses, many of which cause devastating epidemics around the world. Monoclonal antibodies (mAb) have been at the forefront of treatment for cancer and a wide array of other diseases due to their specificity and potency. While mammalian cell-produced mAbs have shown promise as therapeutic candidates against several flaviviruses, their eventual approval for human application still faces several challenges including their potential risk of predisposing treated patients to more severe secondary infection by a heterologous flavivirus through antibody-dependent enhancement (ADE). The high cost associated with mAb production in mammalian cell cultures also poses a challenge for the feasible application of these drugs to the developing world where the majority of flavivirus infection occurs. Here, we review the current therapeutic mAb candidates against various flaviviruses including West Nile (WNV), Dengue virus (DENV), and ZIKV. The progress of using plants for developing safer and more economical mAb therapeutics against flaviviruses is discussed within the context of their expression, characterization, downstream processing, neutralization, and in vivo efficacy. The progress of using plant glycoengineering to address ADE, the major impediment of flavivirus therapeutic development, is highlighted. These advancements suggest that plant-based systems are excellent alternatives for addressing the remaining challenges of mAb therapeutic development against flavivirus and may facilitate the eventual commercialization of these drug candidates. PMID:29295568

[Predictors of the therapeutic discharge in patients with dual pathology admitted to a therapeutic community with a psychiatric unit].

PubMed

Madoz-Gúrpide, Agustín; García Vicent, Vicente; Luque Fuentes, Encarnación; Ochoa Mangado, Enriqueta

2013-01-01

This study aims to analyze the variables on which depends therapeutic discharge, in patients with a severe dual diagnosis admitted to a professional therapeutic community where their pathology is treated. 325 patients admitted between June 2000 and June 2009 to the therapeutic community. This is a retrospective, cross-sectional study with no control group, based on the detailed analysis of the information collected in a model of semi-structured clinical interview designed in the therapeutic community. The 29.5% of the individuals included in the sample were therapeutically discharged. Of all the variables introduced in this analysis the most significant ones were gender, age at the beginning of treatment, education level, opiate dependence, polidrug abuse, and the presence of psychotic disorders and borderline personality disorder. In our study, gender determines the type of discharge, being therapeutic discharge more frequent among women. A higher educational also increases a better prognosis with a higher rate of therapeutic discharge among individuals with higher education level. A later age at the beginning of the treatment reduces the likelihood of therapeutic discharge. Likewise, polidrug abuse, diagnosis of psychotic disorders and borderline personality disorder are associated to a lower rate of therapeutic discharge. Recognizing these characteristics will allow the early identification of those patients more at risk of dropping treatment hastily, while trying to prevent it by increasing the therapeutic intensity.

Guaranteed Student Loans: Potential Default and Cost Reduction Options. Briefing Report to Congressional Requesters.

ERIC Educational Resources Information Center

General Accounting Office, Washington, DC. Div. of Human Resources.

Thirty options for reducing guaranteed student loan defaults and related federal costs are provided by the General Accounting Office (GAO). The options are presented by groups of program participants: students, schools, lenders, guaranty agencies, and the Department of Education. These options include: adopt GAO's past recommendation to increase…

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...

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.

[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.

Mixed waste management options

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

Owens, C.B.; Kirner, N.P.

1991-12-31

Disposal fees for mixed waste at proposed commercial disposal sites have been estimated to be $15,000 to $40,000 per cubit foot. If such high disposal fees are imposed, generators may be willing to apply extraordinary treatment or regulatory approaches to properly dispose of their mixed waste. This paper explores the feasibility of several waste management scenarios and attempts to answer the question: Can mixed waste be managed out of existence? Existing data on commercially generated mixed waste streams are used to identify the realm of mixed waste known to be generated. Each waste stream is evaluated from both a regulatorymore » and technical perspective in order to convert the waste into a strictly low-level radioactive or a hazardous waste. Alternative regulatory approaches evaluated in this paper include a delisting petition, no migration petition, and a treatability variance. For each waste stream, potentially available treatment options are identified that could lead to these variances. Waste minimization methodology and storage for decay are also considered. Economic feasibility of each option is discussed broadly.« less

Greenhouse Gas Mitigation Options Database and Tool - Data ...

EPA Pesticide Factsheets

Industry and electricity production facilities generate over 50 percent of greenhouse gas (GHG) emissions in the United States. There is a growing consensus among scientists that the primary cause of climate change is anthropogenic greenhouse gas (GHG) emissions. Reducing GHG emissions from these sources is a key part of the United States’ strategy to reduce the impacts of these global-warming emissions. As a result of the recent focus on GHG emissions, the U.S. Environmental Protection Agency (EPA) and state agencies are implementing policies and programs to quantify and regulate GHG emissions from key emitting sources in the United States. These policies and programs have generated a need for a reliable source of information regarding GHG mitigation options for both industry and regulators. In response to this need, EPA developed a comprehensive GHG mitigation options database (GMOD) that was compiled based on information from industry, government research agencies, and academia. The GMOD and Tool (GMODT) is a comprehensive data repository and analytical tool being developed by EPA to evaluate alternative GHG mitigation options for several high-emitting industry sectors, including electric power plants, cement plants, refineries, landfills and other industrial sources of GHGs. The data is collected from credible sources including peer-reviewed journals, reports, and others government and academia data sources which include performance, applicability, develop

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.…

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.

Targeting Glutamatergic Signaling for the Development of Novel Therapeutics for Mood Disorders

PubMed Central

Machado-Vieira, R.; Salvadore, G.; Ibrahim, L.; DiazGranados, N.; Zarate, C.A.

2009-01-01

There have been no recent advances in drug development for mood disorders in terms of identifying drug targets that are mechanistically distinct from existing ones. As a result, existing antidepressants are based on decades-old notions of which targets are relevant to the mechanisms of antidepressant action. Low rates of remission, a delay of onset of therapeutic effects, continual residual depressive symptoms, relapses, and poor quality of life are unfortunately common in patients with mood disorders. Offering alternative options is requisite in order to reduce the individual and societal burden of these diseases. The glutamatergic system is a promising area of research in mood disorders, and likely to offer new possibilities in therapeutics. There is increasing evidence that mood disorders are associated with impairments in neuroplasticity and cellular resilience, and alterations of the glutamatergic system are known to play a major role in cellular plasticity and resilience. Existing antidepressants and mood stabilizers have prominent effects on the glutamate system, and modulating glutamatergic ionotropic or metabotropic receptors results in antidepressant-like properties in animal models. Several glutamatergic modulators targeting various glutamate components are currently being studied in the treatment of mood disorders, including release inhibitors of glutamate, N-methyl-D-aspartate (NMDA) antagonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) throughput enhancers, and glutamate transporter enhancers. This paper reviews the currently available knowledge regarding the role of the glutamatergic system in the etiopathogenesis of mood disorders and putative glutamate modulators. PMID:19442176

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.

What Women Want from Their Health Care Providers about Pregnancy Options Counseling: A Qualitative Study.

PubMed

French, Valerie A; Steinauer, Jody E; Kimport, Katrina

Unintended pregnancy is common in the United States, yet scant research has evaluated women's preferences on pregnancy options counseling. This study explores pregnant women's preferences for pregnancy options counseling from health care providers. We conducted semistructured interviews with pregnant women at a prenatal clinic and an abortion clinic. We asked women about recent discussions-or lack thereof-about pregnancy options (parenting, adoption, and abortion) with a clinician, and what they would want their provider to discuss about pregnancy options. We analyzed transcripts using modified grounded theory. We interviewed 10 women in prenatal care and 18 women seeking abortion. In both settings, most said clinicians should discuss pregnancy options with pregnant women and 1) respect patient autonomy, 2) avoid assumptions about a woman's desired pregnancy outcome, and 3) consider the patient-including her health and fertility intentions-beyond her pregnancy. Participants wanted their doctors to assess a pregnancy's individual circumstances to determine the appropriateness of options counseling. A few participants, including women who did and did not receive options counseling, reported they personally preferred not to receive such counseling. Explaining this preference, they cited preservation of privacy, having already made a decision for the pregnancy, or just not wanting to discuss abortion. Regarding best practices for providing options counseling, participants said it should be done in a routine manner, with discretion, and early in pregnancy. Pregnant women seeking both prenatal and abortion care broadly support options counseling. Discussion of pregnancy options, including abortion, provides patient-centered care and supports women's preferences. Copyright © 2017 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

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.

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

Valuing the Student Loan Consolidation Option. Congressional Budget Office Background Paper

ERIC Educational Resources Information Center

Weinberg, Steven

2006-01-01

Federal student loans include a complex consolidation option that gives borrowers the opportunity to combine several loans into a single loan with a longer term to maturity and, for loans originated before July 2006, to convert from a variable- to a fixed-rate loan. The consolidation option adds substantial costs to the federal student loan…

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.

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

Scope Complexity Options Risks Excursions (SCORE) Version 3.0 Mathematical Description.

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

Gearhart, Jared Lee; Samberson, Jonell Nicole; Shettigar, Subhasini

The purpose of the Scope, Complexity, Options, Risks, Excursions (SCORE) model is to estimate the relative complexity of design variants of future warhead options. The results of this model allow those considering these options to understand the complexity tradeoffs between proposed warhead options. The core idea of SCORE is to divide a warhead option into a well- defined set of scope elements and then estimate the complexity of each scope element against a well understood reference system. The uncertainty associated with estimates can also be captured. A weighted summation of the relative complexity of each scope element is used tomore » determine the total complexity of the proposed warhead option or portions of the warhead option (i.e., a National Work Breakdown Structure code). The SCORE analysis process is a growing multi-organizational Nuclear Security Enterprise (NSE) effort, under the management of the NA- 12 led Enterprise Modeling and Analysis Consortium (EMAC), that has provided the data elicitation, integration and computation needed to support the out-year Life Extension Program (LEP) cost estimates included in the Stockpile Stewardship Management Plan (SSMP).« less

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.

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

Fractional CO2 laser is an effective therapeutic modality for xanthelasma palpebrarum: a randomized clinical trial.

PubMed

Esmat, Samia M; Elramly, Amany Z; Abdel Halim, Dalia M; Gawdat, Heba I; Taha, Hanaa I

2014-12-01

Xanthelasma palpebrarum (XP) is a common cosmetic concern. Although there is a wide range of therapeutic modalities for XP, there is no general consensus on the optimal treatment for such condition. Compare the efficacy and safety of super pulsed (SP) and fractional CO2 lasers in the treatment of XP. This prospective randomized comparative clinical study included 20 adult patients with bilateral and symmetrical XP lesions. Xanthelasma palpebrarum lesions were randomly assigned to treatment by either single session of ablative SP CO2 laser or 3 to 5 sessions of ablative fractional CO2 laser with monthly intervals. All patients were assessed using digital photography and optical coherence tomography images. Xanthelasma palpebrarum lesions on both sides were successfully removed with significant improvement in size, color, and thickness. Although lesions treated by SP CO2 laser showed significantly better improvement regarding color and thickness of the lesions, downtime and patient satisfaction were significantly better for lesions treated with fractional CO2 laser. Scarring and recurrence were significantly higher in lesions treated by SP CO2 laser. Ablative fractional CO2 laser is an effective and safe therapeutic option for XP with significantly shorter downtime and higher patient satisfaction compared with SP CO2 laser.

Exploring Therapeutic Potential Of Nanocarrier Systems Against Breast Cancer.

PubMed