Plateau Iris - Therapeutic options and functional results after treatment.

PubMed

Feraru, Crenguța; Bâlha, Andrei; Aursulesei, Victor; Filip, Andrei; Pantalon, Anca

2017-01-01

We present the therapeutic options and functional results in patients with plateau iris (syndrome or configuration) in consecutive case series. Material and method: Our study included newly diagnosed patients with acute angle closure by "plateau iris" (configuration or syndrome), between June 2016 and April 2017. Series of 8 consecutive patients met the inclusion criteria, all being females. All the patients underwent an individualized treatment according to the underlying mechanism and evolution. Functional results (visual acuity, IOP, topical medication) were reported in the current paper. Results: For 10 months, we diagnosed 14 eyes, from 9 patients with acute angle closure by Plateau Iris, distributed as it follows: 6 eyes with closed angle glaucoma (optic disk and visual field changes), 8 eyes with plateau iris syndrome and 2 eyes with plateau iris configuration. 7/ 8 patients were misdiagnosed with primary open angle glaucoma, whereas only one patient had the correct diagnosis of closed angle glaucoma and underwent peripheral laser iridotomy. As treatment options in our study, we recommended and performed argon laser peripheral iridoplasty + iridotomy in 10/ 14 eyes, cataract lens was extracted in 4 eyes and then replaced with PC-IOL, whereas 2 eyes required a filtering anti-glaucoma surgery (trabeculectomy + PI). 2 eyes from the same patient could not be treated as intended as the patient refused the treatment. In this unique case, Pilocarpine (4%) was temporarily indicated. Conclusion: Plateau iris represents a diagnostic trap, but based on a thorough gonioscopic examination and a good patient history, the right diagnosis can be made, all along with a correct therapeutic approach.

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

Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools

ERIC Educational Resources Information Center

Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

2011-01-01

Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

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

Options of sustainable groundwater supply from safe aquifers in areas with elevated arsenic - a case study from Bangladesh

NASA Astrophysics Data System (ADS)

Jakariya, M.; Bhattacharya, P.; Bromssen, M. V.

2008-05-01

Access to safe drinking water is a basic human right. Several millions of people, mainly in developing countries are affected by arsenic in drinking water and the global impact now makes it a top priority water quality issue. A wide gap between the number of exposed people and the pace of mitigation programmes in rural areas of developing countries is the main problem in providing safe drinking water. The main challenge is to develop a sustainable mitigation option that rural and disadvantaged people can adopt and implement themselves to overcome possible public heath hazards. During the recent years, new approaches have emerged in Bangladesh, primarily emerging out of people's own initiative. The local drillers target presumed safe aquifers on the basis of colour and texture of the sediments. A recent study by our research group revealed a distinct correlation between the colour characteristics of the sediments and the groundwater redox conditions. The coupling between the colour of sediments and the redox characteristics of groundwater may thus be used as a tool to assess the risk for As mobilization from the aquifers. The study showed that it is possible to assess the relative risk of high concentrations of As in aquifers if the colour characteristics of the sediments are known and thus, local drillers may target safe aquifers. For validating the sustainability of this mitigation option geological, hydrogeological and microbiological investigations are needed. The sustainability of the aquifers needs to be assessed by combining results from various field and laboratory investigations and by running predictive models. There is also a need to raise the awareness and thereby create a platform for motivating the local drillers to be educated in installing safe tubewells. Awareness raising and community mobilisation are two top priorities for implementing a sustainable safe water project in rural village areas. Significant preparation, attention, and focus must be

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.

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

Stress urinary incontinence in women: Current and emerging therapeutic options

PubMed Central

Shamout, Samer; Campeau, Lysanne

2017-01-01

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

Inner ear symptoms and disease: Pathophysiological understanding and therapeutic options

PubMed Central

Ciuman, Raphael R.

2013-01-01

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

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

PubMed

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

2014-08-01

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

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

PubMed

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

2009-06-01

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

Dysregulated GPCR Signaling and Therapeutic Options in Uveal Melanoma

PubMed Central

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

2017-01-01

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

Achalasia: current therapeutic options

PubMed Central

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

2017-01-01

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

"Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.

PubMed

Kemp, Jessica A; Shim, Min Suk; Heo, Chan Yeong; Kwon, Young Jik

2016-03-01

The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

Lessons Learned from Safe Kids/Safe Streets. Juvenile Justice Bulletin

ERIC Educational Resources Information Center

Cronin, Roberta; Gragg, Frances; Schultz, Dana; Eisen, Karla

2006-01-01

This bulletin reports results from an evaluation of six sites of the Safe Kids/Safe Streets (SK/SS) program, which applies a comprehensive, collaborative approach to the child maltreatment field. The bulletin provides insights into collaboration building, systems reform, service options, and other strategies. Among the findings were that the SK/SS…

[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.

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

PubMed

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

2014-08-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-04-01

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

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

PubMed

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

2016-02-01

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

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.

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.

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.

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.

[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.

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

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

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.

[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.

Strategies for Countering Terrorist Safe Havens

DTIC Science & Technology

2014-02-20

within safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to...leadership targeting within safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case ...surrogate forces and pseudo operations—provide viable potential options for USSOF to counter the complex problem of safe havens. Overall, the case

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

Recurrent pericarditis: new and emerging therapeutic options.

PubMed

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

2016-02-01

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

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

PubMed Central

Castagnari, Aldo

2008-01-01

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

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

PubMed

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

2006-05-05

Recovery of therapeutic protein from high cell density yeast fermentations at commercial scale is a challenging task. In this study, we investigate and compare three different harvest approaches, namely centrifugation followed by depth filtration, centrifugation followed by filter-aid enhanced depth filtration, and microfiltration. This is achieved by presenting a case study involving recovery of a therapeutic protein from Pichia pastoris fermentation broth. The focus of this study is on performance of the depth filtration and the microfiltration steps. The experimental data has been fitted to the conventional models for cake filtration to evaluate specific cake resistance and cake compressibility. In the case of microfiltration, the experimental data agrees well with flux predicted by shear induced diffusion model. It is shown that, under optimal conditions, all three options can deliver the desired product recovery ( >80%), harvest time ( <15 h including sequential concentration/diafiltration step), and clarification ( <6 NTU). However, the three options differ in terms of process development time required, capital cost, consumable cost, ease of scale-ability and process robustness. It is recommended that these be kept under consideration when making a final decision on a harvesting approach.

Generation of safe and therapeutically effective human induced pluripotent stem cell‐derived hepatocyte‐like cells for regenerative medicine

PubMed Central

Takayama, Kazuo; Akita, Naoki; Mimura, Natsumi; Akahira, Rina; Taniguchi, Yukimasa; Ikeda, Makoto; Sakurai, Fuminori; Ohara, Osamu; Morio, Tomohiro

2017-01-01

Hepatocyte‐like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells are expected to be applied for regenerative medicine. In this study, we attempted to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. First, human iPS‐HLCs were generated from a human leukocyte antigen‐homozygous donor on the assumption that the allogenic transplantation might be carried out. Highly efficient hepatocyte differentiation was performed under a feeder‐free condition using human recombinant laminin 111, laminin 511, and type IV collagen. The percentage of asialoglycoprotein receptor 1‐positive cells was greater than 80%, while the percentage of residual undifferentiated cells was approximately 0.003%. In addition, no teratoma formation was observed even at 16 weeks after human iPS‐HLC transplantation. Furthermore, harmful genetic somatic single‐nucleotide substitutions were not observed during the hepatocyte differentiation process. We also developed a cryopreservation protocol for hepatoblast‐like cells without negatively affecting their hepatocyte differentiation potential by programming the freezing temperature. To evaluate the therapeutic potential of human iPS‐HLCs, these cells (1 × 106 cells/mouse) were intrasplenically transplanted into acute liver injury mice treated with 3 mL/kg CCl4 only once and chronic liver injury mice treated with 0.6 mL/kg CCl4 twice weekly for 8 weeks. By human iPS‐HLC transplantation, the survival rate of the acute liver injury mice was significantly increased and the liver fibrosis level of chronic liver injury mice was significantly decreased. Conclusion: We were able to generate safe and therapeutically effective human iPS‐HLCs for hepatocyte transplantation. (Hepatology Communications 2017;1:1058–1069) PMID:29404442

Free-flap harvesting from paralytic limbs of poliomyelitis patients--a safe and feasible option.

PubMed

Chan, R C L; Liu, H L; Chan, Y W

2012-06-01

Many patients who had childhood poliomyelitis are still suffering from the late sequalae of the condition. Free-flap harvesting from the paralytic limbs from these patients is a logical approach for functional preservation. However, concerns have been raised regarding its safety due to its hypoplastic vascular system and potential donor site healing problems. A 53-year-old man with known childhood poliomyelitis presented with left facial sarcoma. After wide excision, the defect was reconstructed with a dual-island fasciocutaneous-free anterolateral thigh flap harvested from his paralytic limb. The pedicle and perforators were found to be no different from those in normal limbs. His recovery was smooth without complications. On the basis of our experience and current evidence in the literature, we believe that free-flap harvesting from the paralytic lower limb in poliomyelitis patients is a safe option that incurs no additional risk and allows maximal function preservation. Copyright © 2011. Published by Elsevier Ltd.

SAFE DRINKING WATER FROM SMALL SYSTEMS: TREATMENT OPTIONS

EPA Science Inventory

Bringing small water systems into compliance with the ever-increasing number of regulations will require flexibility in terms of technology application and institional procedures. his article looks at the means by which small systems can provide safe drinking water, focusing on t...

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

PubMed

Kendrick, Jessica; Chonchol, Michel

2015-01-01

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

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

PubMed Central

Kendrick, Jessica; Chonchol, Michel

2015-01-01

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

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

2017-01-01

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

Attention deficit and hyperactivity disorder: a therapeutic option

PubMed Central

Topczewski, Abram

2014-01-01

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

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

PubMed

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

2018-02-10

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

Strategies for Countering Terrorist Safe Havens

DTIC Science & Technology

2013-12-01

tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to examine these strategies...safe havens, tactical containment, pseudo operations, and surrogate security forces. The thesis draws from four historical case studies to examine...pseudo operations—provide viable potential options for USSOF to counter the complex problem of safe havens. Overall, the case studies will demonstrate

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.

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

PubMed

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

2010-10-01

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

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

PubMed Central

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

2017-01-01

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

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.

[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.

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

Disease modeling and cell based therapy with iPSC: future therapeutic option with fast and safe application.

PubMed

Kim, Changsung

2014-03-01

Induced pluripotent stem cell (iPSC) technology has shown us great hope to treat various human diseases which have been known as untreatable and further endows personalized medicine for future therapy without ethical issues and immunological rejection which embryonic stem cell (hES) treatment has faced. It has been agreed that iPSCs knowledge can be harnessed from disease modeling which mimics human pathological development rather than trials utilizing conventional rodent and cell lines. Now, we can routinely generate iPSC from patient specific cell sources, such as skin fibroblast, hair follicle cells, patient blood samples and even urine containing small amount of epithelial cells. iPSC has both similarity and dissimilarity to hES. iPSC is similar enough to regenerate tissue and even full organism as ES does, however what we want for therapeutic advantage is limited to regenerated tissue and lineage specific differentiation. Depending on the lineage and type of cells, both tissue memory containing (DNA rearrangement/epigenetics) and non-containing iPSC can be generated. This makes iPSC even better choice to perform disease modeling as well as cell based therapy. Tissue memory containing iPSC from mature leukocytes would be beneficial for curing cancer and infectious disease. In this review, the benefit of iPSC for translational approaches will be presented.

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.

Therapeutic Phlebotomy is Safe in Children with Sickle Cell Anaemia and can be Effective Treatment for Transfusional Iron Overload

PubMed Central

Aygun, Banu; Mortier, Nicole A.; Kesler, Karen; Lockhart, Alexandre; Schultz, William H.; Cohen, Alan R.; Alvarez, Ofelia; Rogers, Zora R.; Kwiatkowski, Janet L.; Miller, Scott T.; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A.; Ware, Russell E.

2015-01-01

SUMMARY Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (−8.7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment. PMID:25612463

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

PubMed

Haque, Azizul; Hober, Didier; Blondiaux, Joel

2015-10-01

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

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

PubMed Central

Hober, Didier; Blondiaux, Joel

2015-01-01

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

Current Therapeutic Approach to Hypertrophic Scars

PubMed Central

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

2017-01-01

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

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

Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be effective treatment for transfusional iron overload.

PubMed

Aygun, Banu; Mortier, Nicole A; Kesler, Karen; Lockhart, Alexandre; Schultz, William H; Cohen, Alan R; Alvarez, Ofelia; Rogers, Zora R; Kwiatkowski, Janet L; Miller, Scott T; Sylvestre, Pamela; Iyer, Rathi; Lane, Peter A; Ware, Russell E

2015-04-01

Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (-8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment. © 2015 John Wiley & Sons Ltd.

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

PubMed

Ashby, Emma Louise; Kehoe, Patrick G

2013-10-01

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

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

PubMed

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

2004-07-01

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

A safe treatment option for esophageal bezoars

PubMed Central

Yaqub, Sheraz; Shafique, Muhammad; Kjæstad, Erik; Thorsen, Yngve; Lie, Erik S.; Dahl, Vegard; Bakka, Njål; Røkke, Ola

2012-01-01

INTRODUCTION Bezoar in the esophagus is a rare condition and associated with structural or functional abnormalities of the esophagus. Endoscopy is the main tool for diagnosis and treatment for bezoar in the esophagus. PRESENTATION OF CASE Here we present a case where an endoscopic evacuation of an esophageal bezoar was unsuccessful. We treated the bezoar through a nasogastric tube using a cocktail composed of pancreatic enzymes dissolved in Coca-Cola. DISCUSSION Endoscopy is regarded as the mainstay for the diagnosis and treatment of esophageal bezoars. However, when this approach fails, other treatment options include dissolution therapy, and surgical exploration and removal of the bezoar. Surgical removal of an esophageal bezoar is associated with a high risk of morbidity and mortality. We advocate that dissolving therapy should be the first choice of treatment when endoscopic evacuation is not possible. CONCLUSION This is the first report describing a successful treatment of an esophageal bezoar with a cocktail of Coca-Cola and pancreatic enzymes. It is an effective, inexpensive, and worldwide available treatment and should be considered when endoscopic evacuation fails. PMID:22609703

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.

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.

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.

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.

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.

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 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.

[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.

Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

PubMed Central

Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

2016-01-01

ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease. PMID:27063030

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.

The diet game. Weighing the options.

PubMed Central

Lemaire, D.

1993-01-01

As a major source of nutrition information for the public, physicians have a responsibility to assist their patients to make safe choices about weight loss programs. While most diet programs result in weight loss, the "quick fix" potentially is harmful. This article describes weight control options and their strengths and weaknesses. PMID:8471909

Assembled nanomedicines as efficient and safe therapeutics for articular inflammation.

PubMed

Che, Ling; Zhou, Jianzhi; Li, Shuhui; He, Hongmei; Zhu, Yuxuan; Zhou, Xing; Jia, Yi; Liu, Yao; Zhang, Jianxiang; Li, Xiaohui

2012-12-15

Highly efficient nanomedicines were successfully fabricated by the indomethacin (IND) directed self-assembly of β-cyclodextrin (β-CD)-conjugated polyethyleneimine (PEI-CD), taking advantage of the multiple interactions between drug and polymer. These nanoscaled assemblies exhibited spherical shape and positively charged surface. Compared with the commercial tablet, the relative oral bioavailability of IND-nanomedicines was significantly enhanced. Evaluation based on either carrageenan-induced paw edema or complete Freund's adjuvant (CFA)-induced arthritis suggested the newly developed nanomedicines were more effective than raw IND or IND tablet in terms of prophylactic effect and therapeutic activity. Even the low dose of nanomedicines offered the comparable results to those of control groups at the high dosage in most cases. Moreover, the nanoformulation exhibited ameliorated gastrointestinal stimulation. All these positive results indicated that this type of nanomedicines might serve as a highly efficient and effective delivery nanoplatform for the oral delivery of water-insoluble therapeutics. Copyright © 2012 Elsevier B.V. All rights reserved.

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.

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.

OPTION(5) versus OPTION(12) instruments to appreciate the extent to which healthcare providers involve patients in decision-making.

PubMed

Stubenrouch, Fabienne E; Pieterse, Arwen H; Falkenberg, Rijan; Santema, T Katrien B; Stiggelbout, Anne M; van der Weijden, Trudy; Aarts, J Annemijn W M; Ubbink, Dirk T

2016-06-01

The 12-item "observing patient involvement" (OPTION(12))-instrument is commonly used to assess the extent to which healthcare providers involve patients in health-related decision-making. The five-item version (OPTION(5)) claims to be a more efficient measure. In this study we compared the Dutch versions of the OPTION-instruments in terms of inter-rater agreement and correlation in outpatient doctor-patient consultations in various settings, to learn if we can safely switch to the shorter OPTION(5)-instrument. Two raters coded 60 audiotaped vascular surgery and oncology patient consultations using OPTION(12) and OPTION(5). Unweighted Cohen's kappa was used to compute inter-rater agreement on item-level. The association between the total scores of the two OPTION-instruments was investigated using Pearson's correlation coefficient (r) and a Bland & Altman plot. After fine-tuning the OPTION-manuals, inter-rater agreement for OPTION(12) and OPTION(5) was good to excellent (kappa range 0.69-0.85 and 0.63-0.72, respectively). Mean total scores were 23.7 (OPTION(12); SD=7.8) and 39.3 (OPTION(5); SD=12.7). Correlation between the total scores was high (r=0.71; p=0.01). OPTION(5) scored systematically higher with a wider range than OPTION(12). Both OPTION-instruments had a good inter-rater agreement and correlated well. OPTION(5) seems to differentiate better between various levels of patient involvement. The OPTION(5)-instrument is recommended for clinical application. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

32 CFR 105.12 - SAFE Kit collection and preservation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... response, to include mental healthcare. The SAFE of a sexual assault victim should be conducted by a healthcare provider who has specialized education and clinical experience in the collection of forensic... under this reporting option. The healthcare provider shall encourage the victim to obtain referrals for...

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.

14 CFR 1214.203 - Optional reflight guarantee.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Optional reflight guarantee. 1214.203 Section 1214.203 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION SPACE FLIGHT... guarantee only applies if the payload is in a safe retrievable condition as determined by NASA. (b) Reflight...

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

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.

CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

PubMed

Manet, R; Schmidt, E A; Vassal, F; Charier, D; Gergelé, L

2016-01-01

External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

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.

Safe accommodation of bicyclists on high-speed roadways in Maryland : research report.

DOT National Transportation Integrated Search

2016-12-01

This study investigated bicycle infrastructure design options and treatments to facilitate safe accommodation of bicyclists : on high-speed roadways. The bicycle safety research literature, design guidelines from federal, state, and international : h...

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

PubMed

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

2018-01-01

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

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

PubMed

Lacy, B E

2016-01-01

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

Safe and Affordable Drinking Water for Developing Countries

NASA Astrophysics Data System (ADS)

Gadgil, Ashok

2008-09-01

Safe drinking water remains inaccessible for about 1.2 billion people in the world, and the hourly toll from biological contamination of drinking water is 200 deaths mostly among children under five years of age. This chapter summarizes the need for safe drinking water, the scale of the global problem, and various methods tried to address it. Then it gives the history and current status of an innovation ("UV Waterworks™") developed to address this major public health challenge. It reviews water disinfection technologies applicable to achieve the desired quality of drinking water in developing countries, and specifically, the limitations overcome by one particular invention: UV Waterworks. It then briefly describes the business model and financing option than is accelerating its implementation for affordable access to safe drinking water to the unserved populations in these countries. Thus this chapter describes not only the innovation in design of a UV water disinfection system, but also innovation in the delivery model for safe drinking water, with potential for long term growth and sustainability.

Treatment for anal fissure: Is there a safe option?

PubMed

Brady, Justin T; Althans, Alison R; Neupane, Ruel; Dosokey, Eslam M G; Jabir, Murad A; Reynolds, Harry L; Steele, Scott R; Stein, Sharon L

2017-10-01

Surgeons often approach anal fissure with chemical denervation (Botulinum toxin, BT) instead of initial lateral internal sphincterotomy (LIS) due to concerns for long-term incontinence. We evaluated the characteristics and outcomes of patients who received BT or LIS. We performed a retrospective chart review of patients undergoing LIS and BT for anal fissure between 2009 and 2015. In 2015, a telephone survey was performed to evaluate durability, long-term incontinence and patient satisfaction. Ninety-four patients met criteria: 73 LIS and 21 BT. Age (BT 49 vs. LIS 52) was similar between groups (p = 1.0). Cleveland Clinic Fecal Incontinence (CCFI) score pre-intervention was higher in BT than LIS patients (2.1 vs. 0.4, p = 0.007) with fewer BT patients with perfect continence (50% vs. 88%). Telephone survey response was 61%. Fissure recurrence was significantly higher for BT than LIS patients (36% vs. 9%, p = 0.03). Patients undergoing LIS were less likely to recur. Both LIS and BT patients had some durable changes in continence raising the question of whether there is a safe technique. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Engineered Option Treatment of Remediated Nitrate Salts: Surrogate Batch-Blending Testing

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

Anast, Kurt Roy

2016-03-11

This report provides results from batch-blending test work for remediated nitrate salt (RNS) treatment. Batch blending was identified as a preferred option for blending RNS and unremediated nitrate salt (UNS) material with zeolite to effectively safe the salt/Swheat material identified as ignitable (U.S. Environmental Protection Agency code D001). Blending with zeolite was the preferred remediation option identified in the Options Assessment Report and was originally proposed as the best option for remediation by Clark and Funk in their report, Chemical Reactivity and Recommended Remediation Strategy for Los Alamos Remediated Nitrate Salt (RNS) Wastes, and also found to be a preferredmore » option in the Engineering Options Assessment Report: Nitrate Salt Waste Stream Processing. This test work evaluated equipment and recipe alternatives to achieve effective blending of surrogate waste with zeolite.« less

Options for Affordable Fission Surface Power Systems

NASA Technical Reports Server (NTRS)

Houts, Mike; Gaddis, Steve; Porter, Ron; VanDyke, Melissa; Martin Jim; Godfroy, Tom; Bragg-Sitton, Shannon; Garber, Anne; Pearson, Boise

2006-01-01

Fission surface power systems could provide abundant power anywhere on free surface of the moon or Mars. Locations could include permanently shaded regions on the moon and high latitudes on Mars. To be fully utilized; however, fission surface power systems must be safe, have adequate performance, and be affordable. This paper discusses options for the design and development of such systems.

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

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.

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.

Therapeutics for Equine Endocrine Disorders.

PubMed

Durham, Andy E

2017-04-01

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

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

PubMed

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

2018-05-04

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

Novel therapeutic options for relapsed hairy cell leukemia.

PubMed

Jain, Preetesh; Polliack, Aaron; Ravandi, Farhad

2015-01-01

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

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

PubMed

Carr, Warner W

2013-01-01

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

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

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.

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

PubMed

Wirth, Rainer; Lueg, Gero; Dziewas, Rainer

2018-02-01

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

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

PubMed Central

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

2017-01-01

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

The effects of therapeutic touch on pain.

PubMed

Monroe, Carolyn Magdalen

2009-06-01

To better understand how Therapeutic Touch can be used in today's health care arena, this integrative literature review will examine current research that will help answer the question, Does Therapeutic Touch reduce pain? An extensive search was conducted of the online databases MEDLINE, CINAHL, Cochrane Library, EMBASE, PsychLIT, and PubMed to retrieve research articles published from 1997 to 2007. Seven studies that were conducted between 1997 and 2004 were found and only five of the seven were included as pertinent evidence to answer the question. All of the research that was reviewed to answer whether Therapeutic Touch could significantly reduce pain revealed a majority of statistically significant positive results for implementing this intervention. Because there are no identified risks to Therapeutic Touch as a pain relief measure, it is safe to recommend despite the limitations of current research. Therapeutic Touch should be considered among the many possible nursing interventions for the treatment of pain.

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.

Implementation Options for the PROPEL Electrodynamic Tether Demonstration Mission

NASA Technical Reports Server (NTRS)

Bilen, Sven G.; Johnson, Les; Gilchrist, Brian E.; Hoyt, Robert P.; Elder, Craig H.; Fuhrhop, Keith P.; Scadera, Michael P.; Stone, Nobie H.

2014-01-01

The PROPEL flight mission concept will demonstrate the safe use of an electrodynamic tether for generating thrust. PROPEL is being designed to be a versatile electrodynamic-tether system for multiple end users and to be flexible with respect to platform. As such, several implementation options are being explored, including a comprehensive mission design for PROPEL with a mission duration of six months; a space demonstration mission concept design with configuration of a pair of tethered satellites, one of which is the Japanese H-II Transfer Vehicle; and an ESPA-based system. We report here on these possible implementation options for PROPEL. electrodynamic tether; PROPEL demonstration mission; propellantless propulsion

Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways

PubMed Central

Rahmani, Arshad H.; Alzohairy, Mohammad A.; Khan, Masood A.; Aly, Salah M.

2014-01-01

The cancer is probably the most dreaded disease in both men and women and also major health problem worldwide. Despite its high prevalence, the exact molecular mechanisms of the development and progression are not fully understood. The current chemotherapy/radiotherapy regime used to treat cancer shows adverse side effect and may alter gene functions. Natural products are generally safe, effective, and less expensive substitutes of anticancer chemotherapeutics. Based on previous studies of their potential therapeutic uses, Nigella sativa and its constituents may be proved as good therapeutic options in the prevention of cancer. Black seeds are used as staple food in the Middle Eastern Countries for thousands of years and also in the treatment of diseases. Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ) have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways. PMID:24959190

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.

Therapeutic Gene Editing Safety and Specificity.

PubMed

Lux, Christopher T; Scharenberg, Andrew M

2017-10-01

Therapeutic gene editing is significant for medical advancement. Safety is intricately linked to the specificity of the editing tools used to cut at precise genomic targets. Improvements can be achieved by thoughtful design of nucleases and repair templates, analysis of off-target editing, and careful utilization of viral vectors. Advancements in DNA repair mechanisms and development of new generations of tools improve targeting of specific sequences while minimizing risks. It is important to plot a safe course for future clinical trials. This article reviews safety and specificity for therapeutic gene editing to spur dialogue and advancement. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Viral Oncolytic Therapeutics for Neoplastic Meningitis

DTIC Science & Technology

2012-07-01

will in due course approach DOD for approval of the animal protocol. 15. SUBJECT TERMS Viral oncolysis, neoplastic meningitis , cell lines, HSV-1...proposed study is to develop novel, safe and efficient therapy for neoplastic meningitis – that of HSV-1 oncolysis. The viral genome is genetically...1 AD_________________ Award Number: W81XWH-11-1-0388 TITLE: Viral Oncolytic Therapeutics for Neoplastic

Approaches for Sustainable Mitigation of Arsenic Calamity in Bangladesh: Search for Safe Drinking Water

NASA Astrophysics Data System (ADS)

Alauddin, M.; Bhattacharjee, M.; Zakaria, A. B.; Rahman, M. M.; Seraji, M. S.

2008-05-01

Arsenic contamination of groundwater in Gangetic plain of Bihar, West Bengal in India and Bengal delta plain Bangladesh is shaping up as the greatest environmental health disaster in the current century. About 450 million combined population in these regions are at risk of developing adverse health effects due to arsenic contamination in groundwater. For an effective and sustainable mitigation, it is essential that we improve our understanding of fundamental processes of arsenic mobilization in sediments, biogeochemistry of arsenic in aquifer sediments and weigh a wide range of options for arsenic safe water for the vast population. In this paper, aspects of arsenic removal technology from groundwater in affected areas, sustainable development of household water filtration systems, deep aquifer water as potential arsenic safe water will be presented. In addition, sustainable development of water purification systems such as pond sand filtration (PSF), river sand filtration (RSF), rain water harvesting (RWH), dug well and their acceptability by the community will be discussed. A recent development of indigenous technology by local masons involves searching safe water through bore hole sediment color. The viability of this option in certain areas of Bangladesh will be discussed. Also, one of the household filtration systems approved by the government and locally known as SONO filter was recognized recently by the National Academy of Engineering -Grainger Challenge Prize for sustainability. Over 30, 000 of this unit were deployed in arsenic affected areas of Bangladesh. The affordability, ease of maintenance, social acceptability and environmental friendliness of all options will be addressed in the presentation.

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

The transobturator suburethral sling: a safe and effective option for all degrees of post prostatectomy urinary incontinence.

PubMed

Sullivan, John F; Stassen, Paul N; Moran, Diarmuid; Bolton, Eva M; Smyth, Lisa G; Browne, Cliodhna M; Forde, James C; Tal, Raanan; Lynch, Thomas H

2018-04-01

Male stress urinary incontinence (SUI) after radical prostatectomy (RP) is common. The surgical standard of care traditionally has been placement of an artificial urinary sphincter (AUS) but since its introduction the transobturator male sling has been shown to have particular unique advantages. Our aim was to assess outcomes of a consecutive series of suburethral sling insertions in men presenting with all degrees of post RP SUI. A consecutive cohort of men undergoing AdVance sling insertion following RP were studied. Parameters assessed included pre and postoperative urinary function, 24 hour pad use, quality of life (QoL) outcomes, complications and further treatments. Degree of incontinence was categorized as mild (1-2), moderate (3-5) or severe (≥ 6) depending on daily pad use. Patients were reviewed at 1, 4 and 6 months. The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used to assess symptom severity and QoL outcomes. Seventy-seven patients were included, mean age 68 and mean time to sling post RP 34 (8-113) months. Preoperative degree of incontinence: mild 22%, moderate 58%, severe 20%. Fourteen percent had undergone post RP radiation therapy (RT). In total 73% experienced complete resolution of symptoms post sling, 12% significant improvement, 15% no reduction in pad use. Sixty percent with severe incontinence were classified as cured (no pad or 1 dry pad for security reasons). When patients with preoperative RT were excluded, cure rate rose to 82%. On follow up survey at 30 months (mean), the ICIQ-SF score decreased from baseline 17.7 (9-21.0) to 8.0 (0-20) (p < 0.0001), CI 95% (8-12). Suburethral slings are effective and safe for all degrees of post RP incontinence, are associated with improved QoL parameters and with appropriate selection and counseling are a viable option for more severe degrees of post RP SUI.

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.

Safe Haven Configurations for Deep Space Transit Habitats

NASA Technical Reports Server (NTRS)

Smitherman, David; Polsgrove, Tara; Rowe, Justin; Simon, Matthew

2017-01-01

Throughout the human space flight program there have been instances where smoke, fire, and pressure loss have occurred onboard space vehicles, putting crews at risk for loss of mission and loss of life. In every instance the mission has been in Low-Earth-Orbit (LEO) with access to multiple volumes that could be used to quickly seal off the damaged module or escape vehicles for a quick return to Earth. For long duration space missions beyond LEO, including Mars transit missions of about 1000 days, the mass penalty for multiple volumes has been a concern as has operating in an environment where a quick return will not be possible. In 2016 a study was done to investigate a variety of dual pressure vessel configurations for habitats that could protect the crew from these hazards. It was found that for a modest increase in total mass it should be possible to provide significant protection for the crew. Several configurations were developed that either had a small safe haven to provide 30-days to recover, or a full duration safe haven using two equal size pressure vessel volumes. The 30-day safe haven was found to be the simplest, yielding the least total mass impact but still with some risk if recovery is not possible during that timeframe. The full duration safe haven was the most massive option but provided the most robust solution. This paper provides information on the various layouts considered in the study and provides a discussion of the findings for implementing a safe haven in future habitat designs.

Safe sex

MedlinePlus

... sex; Sexually transmitted - safe sex; GC - safe sex; Gonorrhea - safe sex; Herpes - safe sex; HIV - safe sex; ... contact. STIs include: Chlamydia Genital herpes Genital warts Gonorrhea Hepatitis HIV HPV Syphilis STIs are also called ...

Therapeutic cloning and tissue engineering.

PubMed

Koh, Chester J; Atala, Anthony

2004-01-01

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

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

PubMed

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

2016-01-01

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

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.

Cell-based therapeutics: the next pillar of medicine.

PubMed

Fischbach, Michael A; Bluestone, Jeffrey A; Lim, Wendell A

2013-04-03

Two decades ago, the pharmaceutical industry-long dominated by small-molecule drugs-was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this "third pillar" of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors.

Contraceptive options for women living with HIV.

PubMed

Phillips, Sharon; Steyn, Petrus; Temmerman, Marleen

2014-08-01

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

Hemorrhoidectomy - making sense of the surgical options

PubMed Central

Yeo, Danson; Tan, Kok-Yang

2014-01-01

While debate continues as to which is the best surgical method for the treatment of hemorrhoids, none of the currently available surgical methods approach the ideal surgical option, which is one that is effective while being safe and painless. In reality, the less painful the procedure, the more likely it is to be associated with recurrence post-op. Where hemorrhoids surgery is concerned, there isn’t a “one size fits all” option. Most of the randomized controlled trials performed to date include hemorrhoids of various grades and with a focus on only comparing surgical methods while failing to stratify the outcomes according to the grade of hemorrhoid. We believe that surgery needs to be tailored not only to the grade of the hemorrhoids, but also to the size, circumferential nature of the disease, and prevailing symptomatology. PMID:25493010

Hemorrhoidectomy - making sense of the surgical options.

PubMed

Yeo, Danson; Tan, Kok-Yang

2014-12-07

While debate continues as to which is the best surgical method for the treatment of hemorrhoids, none of the currently available surgical methods approach the ideal surgical option, which is one that is effective while being safe and painless. In reality, the less painful the procedure, the more likely it is to be associated with recurrence post-op. Where hemorrhoids surgery is concerned, there isn't a "one size fits all" option. Most of the randomized controlled trials performed to date include hemorrhoids of various grades and with a focus on only comparing surgical methods while failing to stratify the outcomes according to the grade of hemorrhoid. We believe that surgery needs to be tailored not only to the grade of the hemorrhoids, but also to the size, circumferential nature of the disease, and prevailing symptomatology.

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

PubMed

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

2012-06-01

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

Clinical research and the development of medical therapeutics.

PubMed

Antman, Elliott M

2014-01-01

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

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.

Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain-Barré Syndrome.

PubMed

Cortellini, Alessio; Parisi, Alessandro; Fargnoli, Maria Concetta; Cannita, Katia; Irelli, Azzurra; Porzio, Giampiero; Martinazzo, Claudio; Ficorella, Corrado

2018-01-01

Patients with autoimmune diseases were not evaluated in clinical trials with immune checkpoint inhibitors (ICIs), since a history of immune disorders, such as Guillain-Barré syndrome (GBS) and psoriasis, is one of the major risk factors for the development of immune-related adverse events (irAEs). This risk cannot be defined; therefore, physicians are called to manage these patients in clinical practice. We report the case of a 62-year-old male patient affected by metastatic melanoma, with a history of GBS and psoriasis, and treated with sequential ipilimumab, pembrolizumab, and nivolumab, without significant toxicities. This case report supports that although a history of immune disorders is one of the major risk factors for development of irAEs, in some patients, it could be possible to safely administer sequential treatments with ICIs. A proper decision should be made, considering therapeutic options, disease-related risks, and those related to a recurrence of preexisting autoimmune disorders.

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.

Combined in vivo and in vitro approach for the characterization of penicillin-specific polyclonal lymphocyte reactivity: tolerance tests with safe penicillins instead of challenge with culprit drugs.

PubMed

Sachs, B; Al Masaoudi, T; Merk, H F; Erdmann, S

2004-10-01

Amino-penicillins are a major cause of delayed-type reactions to penicillins. The aim of this study was to establish a diagnostic approach for the characterization of the individual penicillin-specific polyclonal lymphocyte reactivity in order to detect side chain-specific sensitization to amino-penicillins. Patients can then be advised to undergo a tolerance test with safe penicillins instead of provocation with culprit penicillins for confirmation of penicillin allergy. We investigated penicillin-specific polyclonal lymphocyte reactivity in nine patients with delayed-type reactions to amino-penicillins by a combined in vivo (patch, prick and intracutaneous tests with delayed readings) and in vitro (lymphocyte transformation test, LTT) approach. A combination of LTT and skin tests improved the sensitivity for the characterization of penicillin-specific polyclonal lymphocyte reactivity and allowed the detection of three different patterns of lymphocyte reactivity. Four patients showed a side chain-specific sensitization to amino-penicillins in vivo and in vitro and were advised to undergo tolerance tests with safe penicillins. Two patients agreed and were exposed to parenteral benzyl-penicillin and oral phenoxymethyl-penicillin which they tolerated without complications. These data suggest that a combined in vivo and in vitro approach is helpful for the detection of side chain-specific sensitization to amino-penicillins. Patients with such sensitization are very likely to tolerate safe penicillins, thereby expanding their therapeutic options when antibiotic treatment is required.

Safe Haven Configurations for Deep Space Transit Habitats

NASA Technical Reports Server (NTRS)

Smitherman, David; Polsgrove, Tara; Rowe, Justin; Simon, Matthew

2017-01-01

Throughout the human space flight program there have been instances where systems failures resulting in smoke, fire, and pressure loss have occurred onboard space vehicles, putting crews at risk for loss of mission and loss of life. In most instances the missions have been in Low-Earth-Orbit (LEO) or Earth-Moon vicinity, with access to multiple volumes that could be used to quickly seal off the damaged module or access escape vehicles for return to Earth. For long duration missions beyond LEO, including Mars transit missions of about 1100 days, the mass penalty for multiple volumes and operating in an environment where a quick return will not be possible have been concerns. In 2016, a study was done to investigate a variety of dual pressure vessel configurations for habitats that could protect the crew from these hazards. It was found that with a modest increase in total mass it should be possible to provide significant protection for the crew. Several configurations were considered that either had a small safe haven to provide 30-days to recover, or a full duration safe haven using two equal size pressure vessel volumes. The 30-day safe haven was found to be the simplest, yielding the least total mass impact but still with some risk if recovery is not possible during that timeframe. The full duration safe haven was the most massive option but provided the most robust solution. This paper provides information on the various layouts developed during the study and provides a discussion of the findings for implementing a safe haven in future habitat designs.

Cell-Based Therapeutics: The Next Pillar of Medicine

PubMed Central

Fischbach, Michael A.; Bluestone, Jeffrey A.; Lim, Wendell A.

2013-01-01

Two decades ago, the pharmaceutical industry—long dominated by small-molecule drugs—was revolutionized by the the advent of biologics. Today, biomedicine sits on the cusp of a new revolution: the use of microbial and human cells as versatile therapeutic engines. Here, we discuss the promise of this “third pillar” of therapeutics in the context of current scientific, regulatory, economic, and perceptual challenges. History suggests that the advent of cellular medicines will require the development of a foundational cellular engineering science that provides a systematic framework for safely and predictably altering and regulating cellular behaviors. PMID:23552369

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

Emerging treatment options for refractory angina pectoris: ranolazine, shock wave treatment, and cell-based therapies.

PubMed

Gennari, Marco; Gambini, Elisa; Bassetti, Beatrice; Capogrossi, Maurizio; Pompilio, Giulio

2014-01-01

A challenge of modern cardiovascular medicine is to find new, effective treatments for patients with refractory angina pectoris, a clinical condition characterized by severe angina despite optimal medical therapy. These patients are not candidates for surgical or percutaneous revascularization. Herein we review the most up-to-date information regarding the modern approach to the patient with refractory angina pectoris, from conventional medical management to new medications and shock wave therapy, focusing on the use of endothelial precursor cells (EPCs) in the treatment of this condition. Clinical limitations of the efficiency of conventional approaches justify the search for new therapeutic options. Regenerative medicine is considered the next step in the evolution of organ replacement therapy. It is driven largely by the same health needs as transplantation and replacement therapies, but it aims further than traditional approaches, such as cell-based therapy. Increasing knowledge of the role of circulating cells derived from bone marrow (EPCs) on cardiovascular homeostasis in physiologic and pathologic conditions has prompted the clinical use of these cells to relieve ischemia. The current state of therapeutic angiogenesis still leaves many questions unanswered. It is of paramount importance that the treatment is delivered safely. Direct intramyocardial and intracoronary administration has demonstrated acceptable safety profiles in early trials, and may represent a major advance over surgical thoracotomy. The combined efforts of bench and clinical researchers will ultimately answer the question of whether cell therapy is a suitable strategy for treatment of patients with refractory angina.

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

A safe lithium mimetic for bipolar disorder

PubMed Central

Singh, Nisha; Halliday, Amy C.; Thomas, Justyn M.; Kuznetsova, Olga; Baldwin, Rhiannon; Woon, Esther C. Y.; Aley, Parvinder K.; Antoniadou, Ivi; Sharp, Trevor; Vasudevan, Sridhar R.; Churchill, Grant C.

2012-01-01

Lithium is the most effective mood stabilizer for the treatment of bipolar disorder, but it is toxic at only twice the therapeutic dosage and has many undesirable side effects. It is likely that a small molecule could be found with lithium-like efficacy but without toxicity through target-based drug discovery; however, lithium’s therapeutic target remains equivocal. Inositol monophosphatase is a possible target but no bioavailable inhibitors exist. Here we report that the antioxidant ebselen inhibits inositol monophosphatase and induces lithium-like effects on mouse behaviour, which are reversed with inositol, consistent with a mechanism involving inhibition of inositol recycling. Ebselen is part of the National Institutes of Health Clinical Collection, a chemical library of bioavailable drugs considered clinically safe but without proven use. Therefore, ebselen represents a lithium mimetic with the potential both to validate inositol monophosphatase inhibition as a treatment for bipolar disorder and to serve as a treatment itself. PMID:23299882

What Safe Zone? The Vast Majority of Dislocated THAs Are Within the Lewinnek Safe Zone for Acetabular Component Position.

PubMed

Abdel, Matthew P; von Roth, Philipp; Jennings, Matthew T; Hanssen, Arlen D; Pagnano, Mark W

2016-02-01

< 0.0001). The historical target values for cup inclination and anteversion may be useful but should not be considered a safe zone given that the majority of these contemporary THAs that dislocated were within those target values. Stability is likely multifactorial; the ideal cup position for some patients may lie outside the Lewinnek safe zone and more advanced analysis is required to identify the right target in that subgroup. Level III, therapeutic study.

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

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

Salmonella and cancer: from pathogens to therapeutics.

PubMed

Chorobik, Paulina; Czaplicki, Dominik; Ossysek, Karolina; Bereta, Joanna

2013-01-01

Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.

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.

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

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

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

PubMed

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

2016-03-01

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

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.

41 CFR 102-80.115 - Is there more than one option for establishing that an equivalent level of safety exists?

Code of Federal Regulations, 2010 CFR

2010-07-01

... equivalent level of safety. (c) As a third option, other technical analysis procedures, as approved by the... Equivalent Level of Safety Analysis § 102-80.115 Is there more than one option for establishing that an... areas of safety. Available safe egress times would be developed based on analysis of a number of assumed...

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

Subscale Validation of the Subsurface Active Filtration of Exhaust (SAFE) Approach to the NTP Ground Testing

NASA Technical Reports Server (NTRS)

Marshall, William M.; Borowski, Stanley K.; Bulman, Mel; Joyner, Russell; Martin, Charles R.

2015-01-01

Nuclear thermal propulsion (NTP) has been recognized as an enabling technology for missions to Mars and beyond. However, one of the key challenges of developing a nuclear thermal rocket is conducting verification and development tests on the ground. A number of ground test options are presented, with the Sub-surface Active Filtration of Exhaust (SAFE) method identified as a preferred path forward for the NTP program. The SAFE concept utilizes the natural soil characteristics present at the Nevada National Security Site to provide a natural filter for nuclear rocket exhaust during ground testing. A validation method of the SAFE concept is presented, utilizing a non-nuclear sub-scale hydrogen/oxygen rocket seeded with detectible radioisotopes. Additionally, some alternative ground test concepts, based upon the SAFE concept, are presented. Finally, an overview of the ongoing discussions of developing a ground test campaign are presented.

New era of biologic therapeutics in atopic dermatitis.

PubMed

Guttman-Yassky, Emma; Dhingra, Nikhil; Leung, Donald Y M

2013-04-01

Atopic dermatitis (AD) is a common inflammatory skin disease regulated by genetic and environmental factors. Both skin barrier defects and aberrant immune responses are believed to drive cutaneous inflammation in AD. Existing therapies rely largely on allergen avoidance, emollients and topical and systemic immune-suppressants, some with significant toxicity and transient efficacy; no specific targeted therapies are in clinical use today. As our specific understanding of the immune and molecular pathways that cause different subsets of AD increases, a variety of experimental agents, particularly biologic agents that target pathogenic molecules bring the promise of safe and effective therapeutics for long-term use. This paper discusses the molecular pathways characterizing AD, the contributions of barrier and immune abnormalities to its pathogenesis, and development of new treatments that target key molecules in these pathways. In this review, we will discuss a variety of biologic therapies that are in development or in clinical trials for AD, perhaps revolutionizing treatment of this disease. Biologic agents in moderate to severe AD offer promise for controlling a disease that currently lacks good and safe therapeutics posing a large unmet need. Unfortunately, existing treatments for AD aim to decrease cutaneous inflammation, but are not specific for the pathways driving this disease. An increasing understanding of the immune mechanisms underlying AD brings the promise of narrow targeted therapies as has occurred for psoriasis, another inflammatory skin disease, for which specific biologic agents have been demonstrated to both control the disease and prevent occurrence of new skin lesions. Although no biologic is yet approved for AD, these are exciting times for active therapeutic development in AD that might lead to revolutionary therapeutics for this disease.

[Therapeutic excimer laser treatment of the cornea].

PubMed

Linke, S J; Steinberg, J; Katz, T

2013-06-01

Concomitant with new innovations in the field of refractive surgery, therapeutic excimer laser applications like phototherapeutic keratectomy (PTK) and topography-guided customised ablation treatment are gaining high importance and undergoing rapid evolution. Nowadays, PTK is an effective treatment modality for superficial corneal pathologies. Primary indications are decreased epithelial adherence, superficial opacifications and an irregular corneal surface. For the right indication and successful treatment of corneal pathologies with PTK, a knowledge of the size, depth and nature of the pathology, as well as the refractive status of both eyes is important. Next to slit-lamp examination, objective measuring systems like the topography, confocal microscopy and the anterior segment OCT facilitate presurgical planning. Regarding the treatment procedure the surgeon can choose between a variety of methods. PTK can be combined with manual epithelial debridement or done by only using the excimer laser. In the case of an irregular corneal surface, depending on the pathology, masking fluids or topography-guided custom ablation protocols can increase the visual outcome. To avoid recurrence of the underlying pathology (e.g., corneal dystrophy, haze), the topical application of 0.02% mitomycin C for 20-60 seconds has proved to be a safe and effective procedure. If the surgeon considers all the patient-related factors carefully and manages to combine the available treatment options correctly, PTK embodies an effective and minimally invasive alternative to lamellar or penetrating keratoplasty. Georg Thieme Verlag KG Stuttgart · New York.

Flywheel Rotor Safe-Life Technology

NASA Technical Reports Server (NTRS)

Ratner, J. K. H.; Chang, J. B.; Christopher, D. A.; McLallin, Kerry L. (Technical Monitor)

2002-01-01

Since the 1960s, research has been conducted into the use of flywheels as energy storage systems. The-proposed applications include energy storage for hybrid and electric automobiles, attitude control and energy storage for satellites, and uninterruptible power supplies for hospitals and computer centers. For many years, however, the use of flywheels for space applications was restricted by the total weight of a system employing a metal rotor. With recent technological advances in the manufacturing of composite materials, however, lightweight composite rotors have begun to be proposed for such applications. Flywheels with composite rotors provide much higher power and energy storage capabilities than conventional chemical batteries. However, the failure of a high speed flywheel rotor could be a catastrophic event. For this reason, flywheel rotors are classified by the NASA Fracture Control Requirements Standard as fracture critical parts. Currently, there is no industry standard to certify a composite rotor for safe and reliable operation forth( required lifetime of the flywheel. Technical problems hindering the development of this standard include composite manufacturing inconsistencies, insufficient nondestructive evaluation (NDE) techniques for detecting defects and/or impact damage, lack of standard material test methods for characterizing composite rotor design allowables, and no unified proof (over-spin) test for flight rotors. As part of a flywheel rotor safe-life certification pro-ram funded b the government, a review of the state of the art in composite rotors is in progress. The goal of the review is to provide a clear picture of composite flywheel rotor technologies. The literature review has concentrated on the following topics concerning composites and composite rotors: durability (fatigue) and damage tolerance (safe-life) analysis/test methods, in-service NDE and health monitoring techniques, spin test methods/ procedures, and containment options

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

Affinity-tuning leukocyte integrin for development of safe therapeutics

NASA Astrophysics Data System (ADS)

Park, Spencer

Much attention has been given to the molecular and cellular pathways linking inflammation with cancer and the local tumor environment to identify new target molecules that could lead to improved diagnosis and treatment. Among the many molecular players involved in the complex response, central to the induction of inflammation is intercellular adhesion molecule (ICAM)-1, which is of particular interest for its highly sensitive and localized expression in response to inflammatory signals. ICAM-1, which has been implicated to play a critical role in tumor progression in various types of cancer, has also been linked to cancer metastases, where ICAM-1 facilitates the spread of metastatic cancer cells to secondary sites. This unique expression profile of ICAM-1 throughout solid tumor microenvironment makes ICAM-1 an intriguing molecular target, which holds great potential as an important diagnostic and therapeutic tool. Herein, we have engineered the ligand binding domain, or the inserted (I) domain of a leukocyte integrin, to exhibit a wide range of monovalent affinities to the natural ligand, ICAM-1. Using the resulting I domain variants, we have created drug and gene delivery nanoparticles, as well as targeted immunotherapeutics that have the ability to bind and migrate to inflammatory sites prevalent in tumors and the associated microenvironment. Through the delivery of diagnostic agents, chemotherapeutics, and immunotherapeutics, the following chapters demonstrate that the affinity enhancements achieved by directed evolution bring the affinity of I domains into the range optimal for numerous applications.

Effective and Safe Use of Glucocorticosteroids for Rescue of Late ARDS

PubMed Central

Diana, Paolo; Money, Dustin T.; Gelvin, Michael G.

2017-01-01

We describe a case of severe refractory hypoxemia requiring prolonged extra corporeal membrane oxygenation (ECMO) support in a case of postpartum acute respiratory distress syndrome (ARDS). The clinical course was marked by persistently poor lung compliance and several complications of ECMO, that is, significant hemolysis, hemothorax, and intracranial bleeding. We report marked improvement of lung mechanics and respiratory function, leading to accelerated separation from ECMO, following rescue administration of low dose methylprednisolone 24 days after the onset of ARDS. Corticosteroid treatment was safe and well tolerated. In contrast with the conclusions of the 2006 ARDS Network trial, our report establishes a case in support of the use of low dose methylprednisolone as a safe and effective rescue treatment option in selected subsets of patients with nonresolving ARDS. PMID:28337348

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

PubMed

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

2018-06-15

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

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

PubMed

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

2018-05-15

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

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

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.

Is electroconvulsive therapy during pregnancy safe?

PubMed

Jiménez-Cornejo, Magdalena; Zamorano-Levi, Natalia; Jeria, Álvaro

2016-12-07

Therapeutic options for psychiatric conditions are limited during pregnancy because many drugs are restricted or contraindicated. Electroconvulsive therapy constitutes an alternative, however there is controversy over its safety. Using the Epistemonikos database, which is maintained by searching multiple databases, we found five systematic reviews, including 81 studies overall describing case series or individual cases. Data were extracted from the identified reviews and summary tables of the results were prepared using the GRADE method. We concluded it is not clear what are the risks associated with electroconvulsive therapy during pregnancy because the certainty of the existing evidence is very low. Likewise, existing systematic reviews and international clinical guidelines differ in their conclusions and recommendations.

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

PubMed

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

2016-04-14

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

Therapeutic cloning applications for organ transplantation.

PubMed

Koh, Chester J; Atala, Anthony

2004-04-01

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

Safe practices and financial considerations in using oral chemotherapeutic agents.

PubMed

Bartel, Sylvia B

2007-05-01

Safe handling practices and financial concerns associated with oral chemotherapy in non-traditional settings are discussed. Oral chemotherapy may pose a risk to patients because of a narrow therapeutic index, complex dosing regimen, dispensing by community pharmacists without prescription order review by an oncology pharmacist or nurse, or self-administration in the home or another nontraditional setting, where patient monitoring is infrequent. Errors in prescribing, dispensing, and administration and patient or caregiver misunderstandings are potential problems with the use of oral chemotherapy that need to be addressed when developing safe practices. Changes in Medicare pharmaceutical reimbursement rates and rules need to be monitored because they have the potential to affect patient care and outcomes. Patient assistance programs and advocacy groups can help alleviate financial concerns associated with oral chemotherapy. Consensus guidelines specific to safe handling of oral chemotherapy in the home or other nontraditional setting need to be developed. Also, healthcare providers must understand reimbursement and provide direction to patients when patient assistance programs or advocacy groups can assist with the financial challenges of oral chemotherapy.

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.

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.

(131)I-MIBG radionuclide therapy is safe and cost-effective in the control of symptoms of the carcinoid syndrome.

PubMed

Pathirana, A A; Vinjamuri, S; Byrne, C; Ghaneh, P; Vora, J; Poston, G J

2001-06-01

The standard treatment used to control the symptoms of carcinoid syndrome (CS) involves subcutaneous injections of the somatostatin analogue octreotide. This is expensive (US $8000--16,000 per year), and treatment may be for many years. The aim of this study was to evaluate the efficacy and cost-effectiveness of our experience over the last 5 years with 1-131-labelled metaiodobenzylguanidine (MIBG) radionuclide therapy in the palliation of patients with CS. A consecutive series of 20 symptomatic patients (referred between 1994 and 1999) with CS were evaluated. Fifteen of them underwent(123)I-MIBG scanning. Of the 13 patients with significant tracer uptake in metastatic deposits compared to background, 12 underwent a course of therapeutic(131)I-MIBG (one patient refused). Symptoms, biochemical markers, CT scans, follow-up(123)I-MIBG scans, and the requirement for octreotide were used to assess outcome of treatment. Costs of(131)I-MIBG and octreotide treatments were compared. MIBG treatment was well tolerated in all with only transient side-effects. Ten patients showed a measurable clinical improvement. Seven had a complete clinical response. The mean duration of response was 15.4 months. Octreotide was not required or was reduced in eight patients. Treatment with(131)I-MIBG resulted in a saving of US $1000 per patient, with effective symptom control, when compared to octreotide. 1-131 MIBG therapy is a safe and cost-effective therapeutic option to successfully control symptoms in patients with carcinoid syndrome. Copyright Harcourt Publishers Limited.

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.

New treatment options in the management of hypertension: appraising the potential role of azilsartan medoxomil

PubMed Central

Volpe, Massimo; Savoia, Carmine

2012-01-01

Renin–angiotensin–system (RAS) activation plays a key role in the development of hypertension and cardiovascular disease. Drugs that antagonize the RAS (angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]) have proven clinical efficacy in reducing blood pressure values and cardiovascular morbidity and mortality. ACE inhibitors partially inhibit plasma ACE, and angiotensin II generation. Thus, ARBs, which block selectively type 1 angiotensin II receptor (AT1R), have been developed and used in the clinical management of hypertension and cardiovascular disease. Experimental and clinical trials with ARBs indicate that this class of drug represents an effective, safe and well tolerated therapeutic option for the prevention and care of hypertension, even though there is no proven superiority as compared to ACE inhibitors except for the better tolerability. Most ARBs may not completely inhibit the AT1R at the approved clinical doses. Azilsartan medoxomil is a newly approved ARB for the management of hypertension. This ARB induces a potent and long-lasting antihypertensive effect and may have cardioprotective properties. This article reviews the current evidence on the clinical effectiveness of azilsartan in hypertension. PMID:22457601

Therapeutic Vaccination for HPV Induced Cervical Cancers

PubMed Central

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

2007-01-01

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

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

PubMed

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

2017-03-01

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

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.

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.

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...

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

Current and Novel Therapeutic Options for Irritable Bowel Syndrome Management

PubMed Central

Camilleri, Michael; Andresen, Viola

2009-01-01

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

Therapeutic interventions in sepsis: current and anticipated pharmacological agents

PubMed Central

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

2014-01-01

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

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.

Effect of Safe Water on Arsenicosis: A Follow-up Study.

PubMed

Majumdar, Kunal K; Ghose, Aloke; Ghose, Nilima; Biswas, Anirban; Mazumder, D N Guha

2014-04-01

Arsenic pollution in groundwater, used for drinking purposes, has been envisaged as a problem of global concern. Treatment options for the management symptoms of chronic arsenicosis are limited. Mitigation option available for dealing with the health problem of ground water arsenic contamination rests mainly on supply of arsenic safe water in arsenic-endemic region of Indo-Bangladesh subcontinent. Limited information is available regarding the long-term effect of chronic arsenic toxicity after stoppage of consumption of arsenic-containing water. The current study was, therefore, done to assess, objectively, the effect of drinking arsenic safe water (<50 μg/L) on disease manifestation of arsenicosis. Manifestations of various skin lesions and systemic diseases associated with chronic arsenic exposure were ascertained initially by carrying on baseline study on 208 participants in Nadia (Cohort-I, with skin lesion and Cohort-II, without skin lesion) using a scoring system, as developed by us, and compared objectively at the end of each year for 3 year follow-up period. All the participants who had arsenic contaminated drinking water source in their houses were supplied with arsenic removal filters for getting arsenic-free water during the follow-up period. In participants belonging to Cohort-I, the skin score was found to improve significantly at the end of each year, and it was found to be reduced significantly from 2.17 ± 1.09 to 1.23 ± 1.17; P < 0.001 at the end of 3 year's intervention study indicating beneficial effect of safe water on skin lesions. The systemic disease symptom score was also found to improve, but less significantly, at the end of 3 years in both the cohorts. Most important observation during the follow-up study was persistence of severe symptoms of chronic lung disease and severe skin lesion including Bowen's disease in spite of taking arsenic-safe water. Further, death could not be prevented to occur because of lung cancer and severe lung

Continuous infusion of calcium gluconate in 5% albumin is safe and prevents most hypocalcemic reactions during therapeutic plasma exchange.

PubMed

Kankirawatana, Suthida; Huang, Shu T; Marques, Marisa B

2007-01-01

While therapeutic plasma exchanges (TPEs) performed with 5% albumin are considered safe, concerns regarding venous access and hypocalcemic toxicity remain. We reviewed the frequency of complications during TPEs performed with 5% albumin supplemented with calcium gluconate and potassium chloride for a 5 year period in our institution. Eighty-four adult patients (46 males and 38 females) underwent 581 plasma exchanges during the study period. The most common indications were myasthenia gravis (37%), acute inflammatory demyelinating polyradiculoneuropathy (31%), and chronic inflammatory demyelinating polyneuropathy (13%). All procedures used 2.2% ACD-A delivered at a calculated average rate of 0.26 mg/kg/min, which led to a mean dose of citrate per TPE of 2.18 +/- 0.48 g or 27.8 +/- 5.24 mg/kg of body weight. Venous access difficulties occurred in 85 procedures (14.6%), but most TPEs were completed successfully. Hypotension and citrate toxicity were seen in <5% of the TPEs and were mostly reversible. Only 17 exchanges (3%) had to be aborted because of the loss of venous access (n = 9), hypocalcemic toxicity (n = 3), hypotension (n = 2), panic attacks (n = 2), and one atypical reaction due to the interaction with an angiotensin converting enzyme inhibitor. Comparison between pre- and post-TPE potassium levels showed a statistically significant mean decrease of 7%, from 4.1 mequiv/l to 3.8 mequiv/l (P < 0.0001). We attribute the low rate of hypocalcemia to our practice of adding calcium and potassium to the replacement fluid and suggest that this method could become standard of care. Copyright 2007 Wiley-Liss, Inc.

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.

Cool and Safe: Multiplicity in Safe Innovation at Unilever

ERIC Educational Resources Information Center

Penders, Bart

2011-01-01

This article presents the making of a safe innovation: the application of ice structuring protein (ISP) in edible ices. It argues that safety is not the absence of risk but is an active accomplishment; innovations are not "made safe afterward" but "safe innovations are made". Furthermore, there are multiple safeties to be accomplished in the…

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.

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

PubMed

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

2018-01-15

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

Next-Generation Therapeutics for Inflammatory Bowel Disease.

PubMed

Dulai, Parambir S; Sandborn, William J

2016-09-01

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

Next generation therapeutics for inflammatory bowel disease

PubMed Central

Dulai, Parambir S.; Sandborn, William J.

2018-01-01

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

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.

Options For Development of Space Fission Propulsion Systems

NASA Technical Reports Server (NTRS)

Houta, Mike; VanDyke, Melissa; Godfroy, Tom; Pedersen, Kevin; Martin, James; Dickens, Ricky; Salvail, Pat; Hrbud, Ivana; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. Potential fission-based transportation options include high specific power continuous impulse propulsion systems and bimodal nuclear thermal rockets. Despite their tremendous potential for enhancing or enabling deep space and planetary missions, to date space fission system have only been used in Earth orbit. The first step towards utilizing advanced fission propulsion systems is development of a safe, near-term, affordable fission system that can enhance or enable near-term missions of interest. An evolutionary approach for developing space fission propulsion systems is proposed.

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

Health care provider communication: an empirical model of therapeutic effectiveness.

PubMed

Chochinov, Harvey M; McClement, Susan E; Hack, Thomas F; McKeen, Nancy A; Rach, Amanda M; Gagnon, Pierre; Sinclair, Shane; Taylor-Brown, Jill

2013-05-01

Patients who are facing life-threatening and life-limiting cancer almost invariably experience psychological distress. Responding effectively requires therapeutic sensitivity and skill. In this study, we examined therapeutic effectiveness within the setting of cancer-related distress with the objective of understanding its constituent parts. Seventy-eight experienced psychosocial oncology clinicians from 24 health care centers across Canada were invited to participate in 3 focus groups each. In total, 29 focus groups were held over 2 years, during which clinicians articulated the therapeutic factors deemed most helpful in mitigating patient psychosocial distress. The content of each focus group was summarized into major themes and was reviewed with participants to confirm their accuracy. Upon completion of the focus groups, workshops were held in various centers, eliciting participant feedback on an empirical model of therapeutic effectiveness based on the qualitative analysis of focus group data. Three primary, interrelated therapeutic domains emerged from the data, forming a model of optimal therapeutic effectiveness: 1) personal growth and self-care (domain A), 2) therapeutic approaches (domain B), and 3) creation of a safe space (domain C). Areas of domain overlap were identified and labeled accordingly: domain AB, therapeutic humility; domain BC, therapeutic pacing; and domain AC, therapeutic presence. This empirical model provides detailed insights regarding the elements and pedagogy of effective communication and psychosocial care for patients who are experiencing cancer-related distress. Copyright © 2012 American Cancer Society.

[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.

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.

[Safe school].

PubMed

Liberal, Edson Ferreira; Aires, Roberto Tschoepke; Aires, Mariana Tschoepke; Osório, Ana Carla de Albuquerque

2005-11-01

To review the strategies to make school a safe environment. The paper first addresses the social context of accidents and violence in the school environment, and makes recommendations, based on the literature data, for the implementation of safe schools. Articles published between 1993 and 2005 in the MEDLINE database. Brazilian epidemiological and literature data have also been searched. There is growing evidence that intervention has multiple components, focusing on health education practices, with the participation of the whole community. The aim of those interventions is to help students and community members to adopt healthy and safe behaviors. Schools are taking on an increasing role in health promotion, disease prevention, and injury prevention. In the context of prevention of external causes of morbidity and mortality, it is important to recognize a risky environment, places, and risk behaviors as favorable to injury and violence, as well as the concept of accident as something one can avoid. Implementation of safe schools represents a promising new direction for school-based preventive work. It is important to note that a safe school should intervene not only in its physical structure, but it should also make it as safe as possible by gathering the school community through health education, and mainly encouraging healthy behavior.

Angiogenic inhibitors delivered by the type III secretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice.

PubMed

Shi, Lei; Yu, Bin; Cai, Chun-Hui; Huang, Jian-Dong

2016-12-01

Despite of a growing number of bacterial species that apparently exhibit intrinsic tumor-targeting properties, no bacterium is able to inhibit tumor growth completely in the immunocompetent hosts, due to its poor dissemination inside the tumors. Oxygen and inflammatory reaction form two barriers and restrain the spread of the bacteria inside the tumors. Here, we engineered a Salmonella typhimurium strain named ST8 which is safe and has limited ability to spread beyond the anaerobic regions of tumors. When injected systemically to tumor-bearing immunocompetent mice, ST8 accumulated in tumors at levels at least 100-fold greater than parental obligate anaerobic strain ST4. ST8/pSEndo harboring therapeutic plasmids encoding Endostatin fused with a secreted protein SopA could target vasculature at the tumor periphery, can stably maintain and safely deliver a therapeutic vector, release angiogenic inhibitors through a type III secretion system (T3SS) to interfere with the pro-angiogenic action of growth factors in tumors. Mice with murine CT26 colon cancer that had been injected with ST8/pSEndo showed efficient tumor suppression by inducing more severe necrosis and inhibiting blooding vessel density within tumors. Our findings provide a therapeutic platform for indirectly acting therapeutic strategies such as anti-angiogenesis and immune therapy.

CE: Can Your Older Patients Drive Safely?

PubMed

Staplin, Loren; Lococo, Kathy H; Mastromatto, Tia; Sifrit, Kathy J; Trazzera, Kathleen M

2017-09-01

: In many areas of the world, driving is an essential part of life and for reasons of comfort, convenience, and security remains the primary mode of transportation among older adults. Both normal aging and diseases that are more prevalent in advanced age can substantially reduce older drivers' functional abilities, elevating their risk of involvement in motor vehicle accidents and serious injury or death. Identifying and intervening with older drivers at increased crash risk is an important aspect of preventive medicine. The authors discuss the specific driving risks adults face as they age and how nurses can raise older patients' awareness of these risks. They also discuss the importance of connecting older adults to community resources that may help them continue driving safely for a longer period or find alternative transportation options.

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.

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

PubMed Central

Peppas, Nicholas A.; Carr, Daniel A

2009-01-01

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

Therapeutic Options for Controlling Fluids in the Visual System

NASA Technical Reports Server (NTRS)

Curry, Kristina M.; Wotring, Virginia E.

2014-01-01

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

ROCK as a therapeutic target for ischemic stroke.

PubMed

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

2017-12-01

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

Investigation of safe-life fail-safe criteria for the space shuttle

NASA Technical Reports Server (NTRS)

1972-01-01

An investigation was made to determine the effects of a safe-life design approach and a fail-safe design approach on the space shuttle booster vehicle structure, and to recommend any changes to the structural design criteria. Two configurations of the booster vehicle were considered, one incorporating a delta wing (B-9U configuration) and the other a swept wing (B-16B configuration). Several major structural components of the booster were studied to determine the fatigue life, safe-life, and fail-safe capabilities of the baseline design. Each component was investigated to determine the practicability of applying a safe-life or fail-safe design philosophy, the changes such design approaches might require, and the impact of these changes on weight, cost, development plans, and performance.

Therapeutic management of perforated gastro-duodenal ulcer: literature review.

PubMed

Mouly, C; Chati, R; Scotté, M; Regimbeau, J-M

2013-11-01

Management of perforated gastro-duodenal ulcer (GDU) is not consensual, from no operative treatment to surgery by simple closure, gastrectomy and vagotomy. The purpose of this study is to report results of the literature concerning management of perforated GDU. Two authors, identified in the databases Pubmed and Embase studies, related to the therapeutic management of perforated GDU. The data were extracted from articles published between 1940 and 2012. Non-operative treatment is feasible for patients in good general condition and in good local circumstances without evolved peritonitis with a success rate more than 50%. Simple closure is the standard method. Laparoscopy is a safe and feasible method for patient with delay of treatment less than 24 hours and without associated complications with a success (meaning non conversion) of 80% and a mortality less than 1%. Rate of conversion is 7.9%, and increases in case of ulcer size >6 mm, frail ulcer edges, bleeding associated, unusual location and septic shock. Helicobacter pylori eradication is essential. Gastric tube, abdominal irrigation and drainage are still debated. Two-stage treatment for perforated gastric carcinoma, which represents 10 to 16% of gastric perforation, is a good option for frail patients with resectable tumors. Management of perforated GDU is still a subject of debate without guidelines but with several possibilities of treatment depending of local circumstances of peritonitis and size of defect >20 mm, general conditions, surgeon patterns and experience. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Therapeutic genome engineering via CRISPR-Cas systems.

PubMed

Moreno, Ana M; Mali, Prashant

2017-07-01

Differences in genomes underlie most organismal diversity, and aberrations in genomes underlie many disease states. With the growing knowledge of the genetic and pathogenic basis of human disease, development of safe and efficient platforms for genome and epigenome engineering will transform our ability to therapeutically target human diseases and also potentially engineer disease resistance. In this regard, the recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) RNA-guided nuclease systems have transformed our ability to target nucleic acids. Here we review therapeutic genome engineering applications with a specific focus on the CRISPR-Cas toolsets. We summarize past and current work, and also outline key challenges and future directions. WIREs Syst Biol Med 2017, 9:e1380. doi: 10.1002/wsbm.1380 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Technologies for safe births.

PubMed

1984-01-01

The basic elements of a safe birth are proper prenatal care, adequate preparation of the mother, health worker, and site, awareness of the progress of labor and safe delivery, recognition of danger signs, and appropriate follow-up care. Technologies are differentiated by determining 1) the needs of rural birth attendants, 2) the nature of delivery kits, 3) proper cleanliness of the hands and equipment, and appropriate use of 5) disinfecting equipment, 6) drugs and medications, 7) the vertical position, 8) specialized instruments, and 9) records and support materials. Alternatives for measuring time are indicated. Customized kits available from UNICEF are described; some of the problems with these kits are reported. The logistics, referral procedures, and training and supervision needed for appropriate program managements are discussed. Adapting technologies to the local environment requires assessing the practices of traditional birth attendants (TBAs), the provision of kits (cost, ease of use and maintenance, replacement, durability, availability), the training required for proper use of equipment, the logistics of kit use, side effects of technologies, community attitudes, and evaluation. The advantages and disadvantages of including or not including particular supplies in the kit are discussed, i.e., the container for boiling water would either be a local pot or the aluminum carrying case. In lieu of a fingernail brush, a twig may be used for nail cleaning. Hand washing where water shortages exist might entail using a tin with a hole plugged with a stick to let water trickle as needed. Antiseptic solutions such a Dettol or Savlon can be used where a severe shortage exists. Basic equipment includes: soap and water, a container for boiling, other sterile containers, a protective cover of delivery area, towels, swabs, an optional apron, cord ties, a cutting instrument, gauze, a receiving blanket, records, and a carrying case.

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.

Safe use of vaccines and vaccine compliance with food safety requirements.

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels.

Safe Zones: Creating LGBT Safe Space Ally Programs

ERIC Educational Resources Information Center

Poynter, Kerry John; Tubbs, Nancy Jean

2008-01-01

This article discusses model LGBT Safe Space Ally programs. These programs, often called "Safe Zones," include self selected students, faculty, and employees who publicly show support by displaying stickers, signs, and other identifiable items. Issues covered in the article include history, development, training, membership, assessment, and…

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.

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

When the Safe Alternative Is Not That Safe: Tramadol Prescribing in Children.

PubMed

Rodieux, Frédérique; Vutskits, Laszlo; Posfay-Barbe, Klara M; Habre, Walid; Piguet, Valérie; Desmeules, Jules A; Samer, Caroline F

2018-01-01

Children represent a vulnerable population in which management of nociceptive pain is complex. Drug responses in children differ from adults due to age-related differences. Moreover, therapeutic choices are limited by the lack of indication for a number of analgesic drugs due to the challenge of conducting clinical trials in children. Furthermore the assessment of efficacy as well as tolerance may be complicated by children's inability to communicate properly. According to the World Health Organization, weak opioids such as tramadol and codeine, may be used in addition to paracetamol and ibuprofen for moderate nociceptive pain in both children and adults. However, codeine prescription has been restricted for the last 5 years in children because of the risk of fatal overdoses linked to the variable activity of cytochrome P450 (CYP) 2D6 which bioactivates codeine. Even though tramadol has been considered a safe alternative to codeine, it is well established that tramadol pharmacodynamic opioid effects, efficacy and safety, are also largely influenced by CYP2D6 activity. For this reason, the US Food and Drug Administration recently released a boxed warning regarding the use of tramadol in children. To provide safe and effective tramadol prescription in children, a personalized approach, with dose adaptation according to CYP2D6 activity, would certainly be the safest method. We therefore recommend this approach in children requiring chronic or recurrent nociceptive pain treatment with tramadol. In case of acute inpatients nociceptive pain management, prescribing tramadol at the minimal effective dose, in a child appropriate dosage form and after clear instructions are given to the parents, remains reasonable based on current data. In all other situations, morphine should be preferred for moderate to severe nociceptive pain conditions.

Renal Sympathetic Denervation System via Intraluminal Ultrasonic Ablation: Therapeutic Intravascular Ultrasound Design and Preclinical Evaluation.

PubMed

Chernin, Gil; Szwarcfiter, Iris; Bausback, Yvonne; Jonas, Michael

2017-05-01

To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries. Copyright © 2017 SIR. Published

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.

Turmeric (Curcuma longa) and its major constituent (curcumin) as nontoxic and safe substances: Review.

PubMed

Soleimani, Vahid; Sahebkar, Amirhossein; Hosseinzadeh, Hossein

2018-06-01

Curcumin is the major constituent of turmeric (Curcuma longa). Turmeric has been widely used as a spice in foods and for therapeutic applications such as anti-inflammatory, antihyperlipidemic, and antimicrobial activities. Turmeric and curcumin are nonmutagenic and nongenotoxic. Oral use of turmeric and curcumin did not have reproductive toxicity in animals at certain doses. Studies on human did not show toxic effects, and curcumin was safe at the dose of 6 g/day orally for 4-7 weeks. However, some adverse effects such as gastrointestinal upsets may occur. Moreover, oral bioavailable formulations of curcumin were safe for human at the dose of 500 mg two times in a day for 30 days, but there are still few trials and more studies are needed specially on nanoformulations and it should be discussed in a separate article. In addition, curcumin is known as a generally recognized as safe substance. This review discusses the safety and toxicity of turmeric and curcumin in medicine. Turmeric and curcumin are nontoxic for human especially in oral administration. Turmeric and curcumin are also safe in animals. They are nonmutagenic and are safe in pregnancy in animals but more studies in human are needed. Copyright © 2018 John Wiley & Sons, Ltd.

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 bond judgments: Congruence and incongruence.

PubMed

Atzil-Slonim, Dana; Bar-Kalifa, Eran; Rafaeli, Eshkol; Lutz, Wolfgang; Rubel, Julian; Schiefele, Ann-Kathrin; Peri, Tuvia

2015-08-01

The present study had 2 aims: (a) to implement West and Kenny's (2011) Truth-and-Bias model to simultaneously assess the temporal congruence and directional discrepancy between clients' and therapists' ratings of the bond facet of the therapeutic alliance, as they cofluctuate from session to session; and (b) to examine whether symptom severity and a personality disorder (PD) diagnosis moderate congruence and/or discrepancy. Participants included 213 clients treated by 49 therapists. At pretreatment, clients were assessed for a PD diagnosis and completed symptom measures. Symptom severity was also assessed at the beginning of each session, using client self-reports. Both clients and therapists rated the therapeutic bond at the end of each session. Therapists and clients exhibited substantial temporal congruence in their session-by-session bond ratings, but therapists' ratings tended to be lower than their clients' across sessions. Additionally, therapeutic dyads whose session-by-session ratings were more congruent also tended to have a larger directional discrepancy (clients' ratings being higher). Pretreatment symptom severity and PD diagnosis did not moderate either temporal congruence or discrepancy at the dyad level; however, during sessions when clients were more symptomatic, therapist and client ratings were both farther apart and tracked each other less closely. Our findings are consistent with a "better safe than sorry" pattern, which suggests that therapists are motivated to take a vigilant approach that may lead both to underestimation and to attunement to fluctuations in the therapeutic bond. (c) 2015 APA, all rights reserved).

Structurally flexible triethanolamine-core poly(amidoamine) dendrimers as effective nanovectors to deliver RNAi-based therapeutics.

PubMed

Liu, Xiaoxuan; Liu, Cheng; Catapano, Carlo V; Peng, Ling; Zhou, Jiehua; Rocchi, Palma

2014-01-01

RNAi-based nucleic acid molecules have attracted considerable attention as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing nanocarriers for nucleic acid delivery thanks to their unique well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure. The present review offers a brief overview of the structurally flexible triethanolamine-core poly(amidoamine) (PAMAM) dendrimers developed in our group as nanovectors for the delivery of RNAi therapeutics. Their excellent activity for delivering different RNAi therapeutics in various disease models in vitro and in vivo will be highlighted here. © 2013.

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.

Options Assessment Report: Treatment of Nitrate Salt Waste at Los Alamos National Laboratory

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

Robinson, Bruce Alan; Stevens, Patrice Ann

2015-12-17

This report documents the methodology used to select a method of treatment for the remediated nitrate salt (RNS) and unremediated nitrate salt (UNS) waste containers at Los Alamos National Laboratory (LANL). The method selected should treat the containerized waste in a manner that renders the waste safe and suitable for transport and final disposal in the Waste Isolation Pilot Plant (WIPP) repository, under specifications listed in the WIPP Waste Acceptance Criteria (DOE/CBFO, 2013). LANL recognizes that the results must be thoroughly vetted with the New Mexico Environment Department (NMED) and that a modification to the LANL Hazardous Waste Facility Permitmore » is a necessary step before implementation of this or any treatment option. Likewise, facility readiness and safety basis approvals must be received from the Department of Energy (DOE). This report presents LANL’s preferred option, and the documentation of the process for reaching the recommended treatment option for RNS and UNS waste, and is presented for consideration by NMED and DOE.« less

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.

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

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.

Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

PubMed Central

Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander

2017-01-01

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted. PMID:27009803

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

Assessment of Options for the Treatment of Nitrate Salt Wastes at Los Alamos National Laboratory

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

Robinson, Bruce Alan; Funk, David John; Stevens, Patrice Ann

2016-03-17

This paper summarizes the methodology used to evaluate options for treatment of the remediated nitrate salt waste containers at Los Alamos National Laboratory. The method selected must enable treatment of the waste drums, which consist of a mixture of complex nitrate salts (oxidizer) improperly mixed with sWheat Scoop®1, an organic kitty litter and absorbent (fuel), in a manner that renders the waste safe, meets the specifications of waste acceptance criteria, and is suitable for transport and final disposal in the Waste Isolation Pilot Plant located in Carlsbad, New Mexico. A Core Remediation Team was responsible for comprehensively reviewing the options,more » ensuring a robust, defensible treatment recommendation. The evaluation process consisted of two steps. First, a prescreening process was conducted to cull the list on the basis for a decision of feasibility of certain potential options with respect to the criteria. Then, the remaining potential options were evaluated and ranked against each of the criteria in a consistent methodology. Numerical scores were established by consensus of the review team. Finally, recommendations were developed based on current information and understanding of the scientific, technical, and regulatory situation. A discussion of the preferred options and documentation of the process used to reach the recommended treatment options are presented.« less

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.

Separation, Aspiration, and Fat Equalization: SAFE Liposuction Concepts for Comprehensive Body Contouring.

PubMed

Wall, Simeon H; Lee, Michael R

2016-12-01

Separation, aspiration, and fatty equilibration (SAFE) liposuction uses a process approach to body contouring and minimizes injury to surrounding structures. The multistep process allows for (1) fat separation, (2) lipoaspiration, and (3) fat equalization. The purpose of this study was to review both outcomes and complications of primary SAFE liposuction. Retrospective chart review was completed of patients undergoing SAFE liposuction from January of 2006 to January of 2011. Patient selection was limited to those undergoing liposuction alone with no adjuvant excisional procedures. Data were collected regarding demographics, body mass index, operative details, and outcomes. Seven hundred thirty-four patients were identified as having undergone SAFE liposuction. One hundred twenty-nine patients were found to have been treated with liposuction alone. Patient age ranged from 18 to 42 years and body mass index ranged from 18 to 42 kg/m (mean, 26.3 kg/m). Seven patients (5.4 percent) underwent treatment of the face and neck, six patients (4.7 percent) underwent treatment of upper extremities, 13 patients (10.1 percent) underwent treatment of the chest, 20 patients (15.5 percent) underwent treatment of lower extremities, 32 patients (24.8 percent) underwent treatment of the circumferential trunk, and 51 patients (39.5 percent) underwent treatment of circumferential trunk and additional area(s). No major complications occurred. Five of the 129 patients (3.87 percent) developed the minor complication of seroma formation. SAFE liposuction is a multistep process approach to body contouring consisting of (1) fat separation, (2) lipoaspiration, and (3) fat equalization. The results of this study show such technique to be safe and effective. Therapeutic, IV.

Soap Suds Enemas Are Efficacious and Safe for Treating Fecal Impaction in Children With Abdominal Pain.

PubMed

Chumpitazi, Corrie E; Henkel, Erin B; Valdez, Karina L; Chumpitazi, Bruno P

2016-07-01

Constipation is a common cause of pediatric abdominal pain and emergency department (ED) presentation. Despite the high prevalence, there is a dearth of clinical information and wide practice variation in childhood constipation management in the ED. The objective of the study was to assess the efficacy and safety of soap suds enema (SSE) in the therapy for fecal impaction in children with abdominal pain within the pediatric ED setting. The primary outcome was stool output following SSE. Secondary outcomes were adverse events, admissions, and return visits within 72 hours. The present study is a retrospective cross-sectional study performed in the ED at a quaternary care children's hospital of patients seen during a 12-month period who received an SSE for fecal impaction. Five hundred twelve patients (53% girls, median age 7.8 years, range: 8 months-23 years) received SSE therapy during a 1-year period. Successful therapy (bowel movement) following SSE occurred in 419 (82%). Adverse events included abdominal pain in 24 (5%) and nausea/vomiting in 18 (4%). No SSE-related serious adverse events were identified. Following SSE, 405 (79%) were subsequently discharged, of which 15 (3.7%) returned to the ED for re-evaluation within 72 hours. SSE is an efficacious and safe therapeutic option for the acute treatment of childhood fecal impaction in the ED setting.

Soap Suds Enema are Efficacious and Safe for Treating Fecal Impaction in Children with Abdominal Pain

PubMed Central

Chumpitazi, Corrie E.; Henkel, Erin B.; Valdez, Karina L.; Chumpitazi, Bruno P.

2016-01-01

Importance Constipation is a common cause of pediatric abdominal pain and emergency department (ED) presentation. Despite the high prevalence, there is a dearth of clinical information and wide practice variation in childhood constipation management in the ED. Objective To assess the efficacy and safety of soap suds enema (SSE) in the treatment of fecal impaction in children with abdominal pain within the pediatric emergency department (ED) setting. The primary outcome was stool output following SSE. Secondary outcomes were adverse events, admissions, and return visits within 72 hours. Methods This is a retrospective cross-sectional study performed in the ED at a quaternary care children’s hospital of patients seen over a 12-month period who received a SSE for fecal impaction. Results Five hundred twelve patients (53% female, median age 7.8 years, range: 8 months-23 years) received SSE therapy over a 1-year period. Successful therapy (bowel movement) following SSE occurred in 419 (82%). Adverse events included abdominal pain in 24 (5%) and nausea/vomiting in 18 (4%). No SSE-related serious adverse events were identified. Following SSE, 405 (79%) were subsequently discharged, of which 15 (3.7%) returned to the ED for re-evaluation within 72 hours. Conclusions and Relevance SSE is an efficacious and safe therapeutic option for the acute treatment of childhood fecal impaction in the ED setting. PMID:26655947

Safe Schools, Safe Communities.

ERIC Educational Resources Information Center

Lewis, Julie E.; Pickett, Dean; Pulliam, Janet L.; Schwartz, Richard A.; St. Germaine, Anne-Marie; Underwood, Julie; Worona, Jay

Schools must work together with agencies, groups, and individuals to eliminate the forces leading children to violence. Chapter 1, "School Safety: Working Together to Keep Schools Safe," stresses the importance of community collaboration in violence prevention. Effective prevention requires sharing information about students, consistent…

Synergizing vaccinations with therapeutics for measles eradication.

PubMed

Plemper, Richard K; Hammond, Anthea L

2014-02-01

The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas. This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles. Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.

[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.

Using therapeutic cloning to fight human disease: a conundrum or reality?

PubMed

Hall, Vanessa J; Stojkovic, Petra; Stojkovic, Miodrag

2006-07-01

The development and transplantation of autologous cells derived from nuclear transfer embryonic stem cell (NT-ESC) lines to treat patients suffering from disease has been termed therapeutic cloning. Human NT is still a developing field, with further research required to improve somatic cell NT and human embryonic stem cell differentiation to deliver safe and effective cell replacement therapies. Furthermore, the implications of transferring mitochondrial heteroplasmic cells, which may harbor aberrant epigenetic gene expression profiles, are of concern. The production of human NT-ESC lines also remains plagued by ethical dilemmas, societal concerns, and controversies. Recently, a number of alternate therapeutic strategies have been proposed to circumvent the moral implications surrounding human nuclear transfer. It will be critical to overcome these biological, legislative, and moral restraints to maximize the potential of this therapeutic strategy and to alleviate human disease.

Femoral artery transposition is a safe and durable option for the treatment of popliteal artery aneurysms.

PubMed

Bounkong, Gaël; Davaine, Jean-Michel; Tresson, Philippe; Derycke, Lucie; Kagan, Nicolas; Couture, Thibault; Lawton, James; Kashi, Mahine; Gaudric, Julien; Chiche, Laurent; Koskas, Fabien

2018-03-29

stenoses, 11 thromboses, 1 infection, and 1 aneurysmal degeneration of the graft; 6 patients died of unrelated causes. The 1-, 3-, 5-, and 10-year primary and secondary patency rates were 93% and 96%, 85% and 90%, 78% and 87%, and 56% and 87%, respectively. These data suggest that SFAA use to treat PAA is a safe and durable option. A prospective and comparative work is necessary to confirm these results and to determine the interest of this technique as a first-line strategy. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

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.

Need for Better Diabetes Treatment: The Therapeutic Potential of NMDA Receptor Antagonists.

PubMed

Welters, A; Lammert, E; Mayatepek, E; Meissner, T

2017-01-01

Diabetes mellitus is the most common metabolic disorder in children and adolescents. Optimal control of blood glucose concentration is essential to prevent acute and diabetic long-term complications. The options to treat diabetes have clearly improved over the last decades, however, to date neither type 1 diabetes nor type 2 diabetes mellitus can be cured. Therefore, diabetes research aims at developing β-cell protective agents that prevent or even reverse diabetes onset. N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are widely expressed in the central nervous system (CNS) where they hold central roles in CNS function. NMDAR dysfunction is associated with several neurological and psychiatric disorders and therefore NMDAR modulators have several potential therapeutic indications. Only little is known about the role of pancreatic NMDA receptors. Our data provide evidence that inhibition of pancreatic NMDARs, either genetically or pharmacologically with the over-the-counter drug dextromethorphan, increases glucose-stimulated insulin secretion from mouse and human pancreatic islets, improves glucose tolerance in mice and individuals with diabetes and promotes islet cell survival under diabetogenic conditions. Thus, our data indicate for the first time that NMDAR antagonists could serve as adjunct treatment for diabetes mellitus. The development of a safe, blood glucose lowering and particularly β-cell protective medication would significantly enhance current diabetes treatment. © Georg Thieme Verlag KG Stuttgart · New York.

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.

A virtual therapeutic environment with user projective agents.

PubMed

Ookita, S Y; Tokuda, H

2001-02-01

Today, we see the Internet as more than just an information infrastructure, but a socializing place and a safe outlet of inner feelings. Many personalities develop aside from real world life due to its anonymous environment. Virtual world interactions are bringing about new psychological illnesses ranging from netaddiction to technostress, as well as online personality disorders and conflicts in multiple identities that exist in the virtual world. Presently, there are no standard therapy models for the virtual environment. There are very few therapeutic environments, or tools especially made for virtual therapeutic environments. The goal of our research is to provide the therapy model and middleware tools for psychologists to use in virtual therapeutic environments. We propose the Cyber Therapy Model, and Projective Agents, a tool used in the therapeutic environment. To evaluate the effectiveness of the tool, we created a prototype system, called the Virtual Group Counseling System, which is a therapeutic environment that allows the user to participate in group counseling through the eyes of their Projective Agent. Projective Agents inherit the user's personality traits. During the virtual group counseling, the user's Projective Agent interacts and collaborates to recover and increase their psychological growth. The prototype system provides a simulation environment where psychologists can adjust the parameters and customize their own simulation environment. The model and tool is a first attempt toward simulating online personalities that may exist only online, and provide data for observation.

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.

Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

PubMed

Roh, Kyung-Ho; Nerem, Robert M; Roy, Krishnendu

2016-06-07

Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules. This paradigm shift in modern medicine of using cells as novel therapeutics can be realized only if suitable manufacturing technologies for large-scale, cost-effective, reproducible production of high-quality cells can be developed. Here we review the state of the art in therapeutic cell manufacturing, including cell purification and isolation, activation and differentiation, genetic modification, expansion, packaging, and preservation. We identify current challenges and discuss opportunities to overcome them such that cell therapies become highly effective, safe, and predictively reproducible while at the same time becoming affordable and widely available.

[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.

A Zebrafish Heart Failure Model for Assessing Therapeutic Agents.

PubMed

Zhu, Xiao-Yu; Wu, Si-Qi; Guo, Sheng-Ya; Yang, Hua; Xia, Bo; Li, Ping; Li, Chun-Qi

2018-03-20

Heart failure is a leading cause of death and the development of effective and safe therapeutic agents for heart failure has been proven challenging. In this study, taking advantage of larval zebrafish, we developed a zebrafish heart failure model for drug screening and efficacy assessment. Zebrafish at 2 dpf (days postfertilization) were treated with verapamil at a concentration of 200 μM for 30 min, which were determined as optimum conditions for model development. Tested drugs were administered into zebrafish either by direct soaking or circulation microinjection. After treatment, zebrafish were randomly selected and subjected to either visual observation and image acquisition or record videos under a Zebralab Blood Flow System. The therapeutic effects of drugs on zebrafish heart failure were quantified by calculating the efficiency of heart dilatation, venous congestion, cardiac output, and blood flow dynamics. All 8 human heart failure therapeutic drugs (LCZ696, digoxin, irbesartan, metoprolol, qiliqiangxin capsule, enalapril, shenmai injection, and hydrochlorothiazide) showed significant preventive and therapeutic effects on zebrafish heart failure (p < 0.05, p < 0.01, and p < 0.001) in the zebrafish model. The larval zebrafish heart failure model developed and validated in this study could be used for in vivo heart failure studies and for rapid screening and efficacy assessment of preventive and therapeutic drugs.

Sodium Based Heat Pipe Modules for Space Reactor Concepts: Stainless Steel SAFE-100 Core

NASA Technical Reports Server (NTRS)

Martin, James J.; Reid, Robert S.

2004-01-01

A heat pipe cooled reactor is one of several candidate reactor cores being considered for advanced space power and propulsion systems to support future space exploration applications. Long life heat pipe modules, with designs verified through a combination of theoretical analysis and experimental lifetime evaluations, would be necessary to establish the viability of any of these candidates, including the heat pipe reactor option. A hardware-based program was initiated to establish the infrastructure necessary to build heat pipe modules. This effort, initiated by Los Alamos National Laboratory and referred to as the Safe Affordable Fission Engine (SAFE) project, set out to fabricate and perform non-nuclear testing on a modular heat pipe reactor prototype that can provide 100 kilowatt from the core to an energy conversion system at 700 C. Prototypic heat pipe hardware was designed, fabricated, filled, closed-out and acceptance tested.

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

PubMed Central

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-01-01

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path. PMID:28587212

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use.

PubMed

Gimona, Mario; Pachler, Karin; Laner-Plamberger, Sandra; Schallmoser, Katharina; Rohde, Eva

2017-06-03

Extracellular vesicles (EVs) derived from stem and progenitor cells may have therapeutic effects comparable to their parental cells and are considered promising agents for the treatment of a variety of diseases. To this end, strategies must be designed to successfully translate EV research and to develop safe and efficacious therapies, whilst taking into account the applicable regulations. Here, we discuss the requirements for manufacturing, safety, and efficacy testing of EVs along their path from the laboratory to the patient. Development of EV-therapeutics is influenced by the source cell types and the target diseases. In this article, we express our view based on our experience in manufacturing biological therapeutics for routine use or clinical testing, and focus on strategies for advancing mesenchymal stromal cell (MSC)-derived EV-based therapies. We also discuss the rationale for testing MSC-EVs in selected diseases with an unmet clinical need such as critical size bone defects, epidermolysis bullosa and spinal cord injury. While the scientific community, pharmaceutical companies and clinicians are at the point of entering into clinical trials for testing the therapeutic potential of various EV-based products, the identification of the mode of action underlying the suggested potency in each therapeutic approach remains a major challenge to the translational path.

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

A fully integrated new paradigm for lithium's mode of action - lithium utilizes latent cellular fail-safe mechanisms.

PubMed

van Woerkom, Arthur Ernst

2017-01-01

It is proposed that lithium's therapeutic effects occur indirectly by augmenting a cascade of protective "fail-safe" pathways pre-configured to activate in response to a dangerous low cell [Mg ++ ] situation, eg, posttraumatic brain injury, alongside relative cell adenosine triphosphate depletion. Lithium activates cell protection, as it neatly mimics a lowered intracellular [Mg ++ ] level.

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

PubMed

Mathalone, Nurit; Wolf, Alvit; Geyer, Orna

2015-06-01

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

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

PubMed

Huard, J; Mu, X; Lu, A

2016-08-01

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

Dry eye syndrome. Etiological and therapeutic aspects.

PubMed

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

2003-01-01

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

Medical therapeutics: from induction to scientific evolution.

PubMed

Nunes, José Pedro Lopes

2013-01-01

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

Novel unconventional therapeutic approaches to atopic eczema.

PubMed

Worm, M; Henz, B M

2000-01-01

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

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.

Therapeutic Plasma Exchange in Critically Ill Children Requiring Intensive Care.

PubMed

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

2018-02-01

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

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.

Safe sex self-efficacy and safe sex practice in a Southern United States College

PubMed Central

Addoh, Ovuokerie; Sng, Eveleen; Loprinzi, Paul D.

2017-01-01

Background: The purpose of this study was to assess the association between safe sex self-efficacy and safe-sex practice in a Southern college setting. Methods: Multivariable logistic regression models were used to examine the association between safe sex self-efficacy in four domains (mechanics, partner disapproval, assertiveness, intoxicants) and safe sex practice (outcome variable). Results: For every 1-unit increase in the composite condom use self-efficacy score, there was an 8% increase in the odds of being beyond the median safe-sex practice score (odds ration [OR]: 1.08, 95% CI: 1.02-1.15). Additionally, for every 1-unit increase in intoxicants self-efficacy score, there was a 31% increase in the odds of being beyond the median safe-sex practice score (OR: 1.31, 95% CI: 1.08-1.58). Conclusion: A greater degree of safe-sex self-efficacy is associated with increased odds of safe-sex practice. These findings are informative for the development of targeted approaches to foster safe-sex behavior in Southern US colleges. PMID:28326287

DroidSafe

DTIC Science & Technology

2016-12-01

branches of our work . 3.1 Understanding Sensitive API Call and API Information Usage Android applications are written in a type- safe language (Java...directly invoke resolved targets. Because DroidSafe works with a comprehensive model of the Android environment , it supports precise resolution of...STATEMENT. FOR THE CHIEF ENGINEER: / S / / S / MARK K. WILLIAMS WARREN H. DEBANY, JR. Work Unit Manager

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

PubMed Central

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

2017-01-01

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

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

PubMed

Bhatt, Kunal N; Butler, Javed

2018-06-01

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

A Safe Ride to School; A Safe Ride Home.

ERIC Educational Resources Information Center

Illinois State Board of Education, Springfield.

Text and illustrations are used to teach safe school bus riding practices. The guide begins with instructions to parents or guardians to set a good example of safe behavior, and to help children learn safety rules and be on time. Instructions to children concern obeying the bus driver, boarding the bus, riding the bus, crossing the road, and using…

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

PubMed

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

2013-05-22

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

Emerging Non-Cancer Applications of Therapeutic Ultrasound

PubMed Central

O’Reilly, Meaghan A.; Hynynen, Kullervo

2015-01-01

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

Treatment options for diabetic foot osteomyelitis.

PubMed

Senneville, Eric; Robineau, Olivier

2017-06-01

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

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.

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

Is long-term physical activity safe for older adults with knee pain?: a systematic review.

PubMed

Quicke, J G; Foster, N E; Thomas, M J; Holden, M A

2015-09-01

To determine whether long-term physical activity is safe for older adults with knee pain. A comprehensive systematic review and narrative synthesis of existing literature was conducted using multiple electronic databases from inception until May 2013. Two reviewers independently screened, checked data extraction and carried out quality assessment. Inclusion criteria for study designs were randomised controlled trials (RCTs), prospective cohort studies or case control studies, which included adults of mean age over 45 years old with knee pain or osteoarthritis (OA), undertaking physical activity over at least 3 months and which measured a safety related outcome (adverse events, pain, physical functioning, structural OA imaging progression or progression to total knee replacement (TKR)). Of the 8614 unique references identified, 49 studies were included in the review, comprising 48 RCTs and one case control study. RCTs varied in quality and included an array of low impact therapeutic exercise interventions of varying cardiovascular intensity. There was no evidence of serious adverse events, increases in pain, decreases in physical function, progression of structural OA on imaging or increased TKR at group level. The case control study concluded that increasing levels of regular physical activity was associated with lower risk of progression to TKR. Long-term therapeutic exercise lasting 3 to 30 months is safe for most older adults with knee pain. This evidence supports current clinical guideline recommendations. However, most studies investigated selected, consenting older adults carrying out low impact therapeutic exercise which may affect result generalizability. PROSPERO 2014:CRD42014006913. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety of pharmacotherapy options for bulimia nervosa and binge eating disorder.

PubMed

Bello, Nicholas T; Yeomans, Bryn L

2018-01-01

Eating disorders represent a set of psychiatric illnesses with lifelong complications and high relapse rates. Individuals with eating disorders are often stigmatized and clinicians have a limited set of treatments options. Pharmacotherapy has the potential to improve long term compliance and patient commitment to treatment for eating disorders. Areas covered: This review will examine the efficacy and safety profile of the FDA-approved medications for the treatment of bulimia nervosa (BN) and binge eating disorder (BED). This will include the evaluation of fluoxetine for BN, and lisdexamfetamine for BED. Safety information will be review from randomized control trials (RCT), open label trials, and case reports. Expert opinion: Fluoxetine for BN and lisdexamfetamine for BED are relatively safe and well-tolerated. Despite these properties, these two medications represent a limited arsenal for the pharmacological treatment of eating disorders. Thus, more research-based strategies are needed to develop safe, effective, and more targeted therapies for eating disorders.

An update on adjunctive treatment options for bipolar disorder.

PubMed

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

2018-03-01

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

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

PubMed Central

Castillo, Luis; Bugedo, Guillermo; Rovegno, Max

2015-01-01

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

Use Medicines Safely

MedlinePlus

... Medicines Safely Print This Topic En español Use Medicines Safely Browse Sections The Basics Overview Prescription Medicines ... Medicines 1 of 7 sections The Basics: Prescription Medicines There are different types of medicine. The 2 ...

Picture Me Safe

ERIC Educational Resources Information Center

Irvin, Daniel W.

1977-01-01

The validity of well-written articles can be destroyed by poor illustration, especially when the pictures show unsafe practices. The responsibility lies with the author to provide clear printable pictures showing safe working environments and safe practices. (Editor)

Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study.

PubMed

Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D

2013-06-01

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including establishing a safe therapeutic environment, reprocessing the trauma, constructing a new narrative, and managing emotional dysregulation. Therapeutic Assessment (TA) is a semistructured, brief intervention that uses psychological testing to promote positive change. The case study of Kelly, a middle-aged woman with a history of repeated interpersonal trauma, illustrates delivery of the TA model for CPTSD. Results of this single-case time-series experiment indicate statistically significant symptom improvement as a result of participating in TA. We discuss the implications of these findings for assessing and treating trauma-related concerns, such as CPTSD.

Therapeutic Assessment of Complex Trauma: A Single-Case Time-Series Study

PubMed Central

Tarocchi, Anna; Aschieri, Filippo; Fantini, Francesca; Smith, Justin D.

2013-01-01

The cumulative effect of repeated traumatic experiences in early childhood incrementally increases the risk of adjustment problems later in life. Surviving traumatic environments can lead to the development of an interrelated constellation of emotional and interpersonal symptoms termed complex posttraumatic stress disorder (CPTSD). Effective treatment of trauma begins with a multimethod psychological assessment and requires the use of several evidence-based therapeutic processes, including establishing a safe therapeutic environment, reprocessing the trauma, constructing a new narrative, and managing emotional dysregulation. Therapeutic Assessment (TA) is a semistructured, brief intervention that uses psychological testing to promote positive change. The case study of Kelly, a middle-aged woman with a history of repeated interpersonal trauma, illustrates delivery of the TA model for CPTSD. Results of this single-case time-series experiment indicate statistically significant symptom improvement as a result of participating in TA. We discuss the implications of these findings for assessing and treating trauma-related concerns, such as CPTSD. PMID:24159267

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2014-12-01

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

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

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

2017-05-01

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

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.

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.

Safe Schools/Safe Communities: A Directory of Resources for Pennsylvania.

ERIC Educational Resources Information Center

Pennsylvania State Dept. of Education, Harrisburg.

This document contains a directory of resources available in Pennsylvania to help achieve the goal of safe schools. Following a copy of the Safe Schools Act of 1993, nine sections list agencies that provide services and products under the headings of: conflict resolution/mediation, gangs, suicide, crisis response, family violence, diversity,…

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

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.

The inpatient psychiatric unit as both a safe and unsafe place: implications for absconding.

PubMed

Muir-Cochrane, Eimear; Oster, Candice; Grotto, Jessica; Gerace, Adam; Jones, Julia

2013-08-01

Absconding from acute psychiatric inpatient units is a significant issue with serious social, economic, and emotional costs. A qualitative study was undertaken to explore the experiences of people (n = 12) who had been held involuntarily under the local mental health act in an Australian inpatient psychiatric unit, and who had absconded (or attempted to abscond) during this time. The aim of the study was to explore why people abscond from psychiatric inpatient units, drawing on published work from health geography on the significance of the person-place encounter, and in particular the concept of 'therapeutic landscapes'. The findings show that the inpatient unit is perceived as a safe or unsafe place, dependent on the dialectical relationship between the physical, individual, social, and symbolic aspects of the unit. Consumers absconded when the unit was perceived as unsafe. Forming a therapeutic relationship with staff, familiarity with the unit, a comfortable environment, and positive experiences with other consumers all supported perceptions that the unit was safe, decreasing the likelihood of absconding. Findings extend existing work on the person-place encounter within psychiatric inpatient units, and bring new knowledge about the reasons why consumers abscond. Implications for practice are discussed. © 2012 The Authors; International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

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

76 FR 12719 - Safe Schools/Healthy Students Program; Office of Safe and Drug-Free Schools; Safe Schools/Healthy...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

... official version of this document is the document published in the Federal Register. Free Internet access... DEPARTMENT OF EDUCATION Safe Schools/Healthy Students Program; Office of Safe and Drug- Free... telecommunications device for the deaf (TDD), call the Federal Relay Service (FRS), toll free, at 1-800-877-8339...

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.

Functional Nanostructures for Effective Delivery of Small Interfering RNA Therapeutics

PubMed Central

Hong, Cheol Am; Nam, Yoon Sung

2014-01-01

Small interfering RNA (siRNA) has proved to be a powerful tool for target-specific gene silencing via RNA interference (RNAi). Its ability to control targeted gene expression gives new hope to gene therapy as a treatment for cancers and genetic diseases. However, siRNA shows poor pharmacological properties, such as low serum stability, off-targeting, and innate immune responses, which present a significant challenge for clinical applications. In addition, siRNA cannot cross the cell membrane for RNAi activity because of its anionic property and stiff structure. Therefore, the development of a safe, stable, and efficient system for the delivery of siRNA therapeutics into the cytoplasm of targeted cells is crucial. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major hurdles facing the therapeutic uses of siRNA. This review covers a broad spectrum of non-viral siRNA delivery systems developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and discusses their characteristics and opportunities for clinical applications of therapeutic siRNA. PMID:25285170

RNAi therapeutics and applications of microRNAs in cancer treatment.

PubMed

Uchino, Keita; Ochiya, Takahiro; Takeshita, Fumitaka

2013-06-01

RNA interference-based therapies are proving to be powerful tools for combating various diseases, including cancer. Scientists are researching the development of safe and efficient systems for the delivery of small RNA molecules, which are extremely fragile in serum, to target organs and cells in the human body. A dozen pre-clinical and clinical trials have been under way over the past few years involving biodegradable nanoparticles, lipids, chemical modification and conjugation. On the other hand, microRNAs, which control the balance of cellular biological processes, have been studied as attractive therapeutic targets in cancer treatment. In this review, we provide an overview of RNA interference-based therapeutics in clinical trials and discuss the latest technology for the systemic delivery of nucleic acid drugs. Furthermore, we focus on dysregulated microRNAs in human cancer, which have progressed in pre-clinical trials as therapeutic targets, and describe a wide range of strategies to control the expression levels of endogenous microRNAs. Further development of RNA interference technologies and progression of clinical trials will contribute to the achievement of practical applications of nucleic acid drugs.

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.

Safe syringe disposal is related to safe syringe access among HIV-positive injection drug users.

PubMed

Coffin, Phillip O; Latka, Mary H; Latkin, Carl; Wu, Yingfeng; Purcell, David W; Metsch, Lisa; Gomez, Cynthia; Gourevitch, Marc N

2007-09-01

We evaluated the effect of syringe acquisition on syringe disposal among HIV-positive injection drug users (IDUs) in Baltimore, New York City, and San Francisco (N = 680; mean age 42 years, 62% male, 59% African-American, 21% Hispanic, 12% White). Independent predictors of safe disposal were acquiring syringes through a safe source and ever visiting a syringe exchange program. Weaker predictors included living in San Francisco, living in the area longer, less frequent binge drinking, injecting with an HIV+ partner, peer norms supporting safe injection, and self-empowerment. Independent predictors of safe "handling"-both acquiring and disposing of syringes safely-also included being from New York and being older. HIV-positive IDUs who obtain syringes from a safe source are more likely to safely dispose; peer norms contribute to both acquisition and disposal. Interventions to improve disposal should include expanding sites of safe syringe acquisition while enhancing disposal messages, alternatives, and convenience.

Personalized gene silencing therapeutics for Huntington disease.

PubMed

Kay, C; Skotte, N H; Southwell, A L; Hayden, M R

2014-07-01

Gene silencing offers a novel therapeutic strategy for dominant genetic disorders. In specific diseases, selective silencing of only one copy of a gene may be advantageous over non-selective silencing of both copies. Huntington disease (HD) is an autosomal dominant disorder caused by an expanded CAG trinucleotide repeat in the Huntingtin gene (HTT). Silencing both expanded and normal copies of HTT may be therapeutically beneficial, but preservation of normal HTT expression is preferred. Allele-specific methods can selectively silence the mutant HTT transcript by targeting either the expanded CAG repeat or single nucleotide polymorphisms (SNPs) in linkage disequilibrium with the expansion. Both approaches require personalized treatment strategies based on patient genotypes. We compare the prospect of safe treatment of HD by CAG- and SNP-specific silencing approaches and review HD population genetics used to guide target identification in the patient population. Clinical implementation of allele-specific HTT silencing faces challenges common to personalized genetic medicine, requiring novel solutions from clinical scientists and regulatory authorities. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Maternal morbidity: Neglected dimension of safe motherhood in the developing world

PubMed Central

Hardee, Karen; Gay, Jill; Blanc, Ann K.

2012-01-01

In safe motherhood programming in the developing world, insufficient attention has been given to maternal morbidity, which can extend well beyond childbirth. For every woman who dies of pregnancy-related causes, an estimated 20 women experience acute or chronic morbidity. Maternal morbidity adversely affects families, communities and societies. Maternal morbidity has multiple causes, with duration ranging from acute to chronic, severity ranging from transient to permanent and with a range of diagnosis and treatment options. This article addresses six selected relatively neglected aspects of maternal morbidity to illustrate the range of acute and chronic morbidities that can affect women related to pregnancy and childbearing that are prevalent in developing countries: anaemia, maternal depression, infertility, fistula, uterine rupture and scarring and genital and uterine prolapse. Based on this review, recommendations to reduce maternal morbidity include: expand the focus of safe motherhood to explicitly include morbidity; improve data on incidence and prevalence of maternal morbidity; link mortality and morbidity outcomes and programming; increase access to facility- and community-based maternal health care and reproductive health care; and address the antecedents to poor maternal health through a lifecycle approach. PMID:22424546

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

PubMed Central

Griffiths, Cameron

2016-01-01

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

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

PubMed

Arze Aimaretti, L; Arze, S

2016-03-01

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

Current Status of Dengue Therapeutics Research and Development

PubMed Central

Ooi, Eng Eong; Vasudevan, Subhash G.

2017-01-01

Abstract Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. PMID:28403438

Xenograft model for therapeutic drug testing in recurrent respiratory papillomatosis.

PubMed

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

2015-02-01

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

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression

PubMed Central

2017-01-01

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

Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression.

PubMed

Lee, Gihyun; Bae, Hyunsu

2017-01-01

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

Rehabilitation Options

MedlinePlus

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

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

Anti-respiratory syncytial virus (RSV) G monoclonal antibodies reduce lung inflammation and viral lung titers when delivered therapeutically in a BALB/c mouse model.

PubMed

Caidi, Hayat; Miao, Congrong; Thornburg, Natalie J; Tripp, Ralph A; Anderson, Larry J; Haynes, Lia M

2018-06-01

RSV continues to be a high priority for vaccine and antiviral drug development. Unfortunately, no safe and effective RSV vaccine is available and treatment options are limited. Over the past decade, several studies have focused on the role of RSV G protein on viral entry, viral neutralization, and RSV-mediated pathology. Anti-G murine monoclonal antibody (mAb) 131-2G treatment has been previously shown to reduce weight loss, bronchoalveolar lavage (BAL) cell number, airway reactivity, and Th2-type cytokine production in RSV-infected mice more rapidly than a commercial humanized monoclonal antibody (mAb) against RSV F protein (Palivizumab). In this study, we have tested two human anti-RSV G mAbs, 2B11 and 3D3, by both prophylactic and therapeutic treatment for RSV in the BALB/c mouse model. Both anti-G mAbs reduced viral load, leukocyte infiltration and IFN-γ and IL-4 expression in cell-free BAL supernatants emphasizing the potential of anti-G mAbs as anti-inflammatory and antiviral strategies. Published by Elsevier B.V.

Beyond usual care: the economic consequences of expanding treatment options in early pregnancy loss.

PubMed

Dalton, Vanessa K; Liang, Angela; Hutton, David W; Zochowski, Melissa K; Fendrick, A Mark

2015-02-01

The objective of this study was to estimate the economic consequences of expanding options for early pregnancy loss (EPL) treatment beyond expectant management and operating room surgical evacuation (usual care). We constructed a decision model using a hypothetical cohort of women undergoing EPL management within a 30 day horizon. Treatment options under the usual care arm include expectant management and surgical uterine evacuation in an operating room (OR). Treatment options under the expanded care arm included all evidence-based safe and effective treatment options for EPL: expectant management, misoprostol treatment, surgical uterine evacuation in an office setting, and surgical uterine evacuation in an OR. Probabilities of entering various treatment pathways were based on previously published observational studies. The cost per case was US $241.29 lower for women undergoing treatment in the expanded care model as compared with the usual care model (US $1033.29 per case vs US $1274.58 per case, expanded care and usual care, respectively). The model was the most sensitive to the failure rate of the expectant management arm, the cost of the OR surgical procedure, the proportion of women undergoing an OR surgical procedure under usual care, and the additional cost per patient associated with implementing and using the expanded care model. This study demonstrates that expanding women's treatment options for EPL beyond what is typically available can result in lower direct medical expenditures. Copyright © 2015 Elsevier Inc. All rights reserved.

Therapeutic Touch(®) in a geriatric Palliative Care Unit - A retrospective review.

PubMed

Senderovich, Helen; Ip, Mary Lou; Berall, Anna; Karuza, Jurgis; Gordon, Michael; Binns, Malcolm; Wignarajah, Shaira; Grossman, Daphna; Dunal, Lynda

2016-08-01

Complementary therapies are increasingly used in palliative care as an adjunct to the standard management of symptoms to achieve an overall well-being for patients with malignant and non-malignant terminal illnesses. A Therapeutic Touch Program was introduced to a geriatric Palliative Care Unit (PCU) in October 2010 with two volunteer Therapeutic Touch Practitioners providing treatment. To conduct a retrospective review of Therapeutic Touch services provided to patients in an in-patient geriatric palliative care unit in order to understand their responses to Therapeutic Touch. A retrospective medical chart review was conducted on both patients who received Therapeutic Touch as well as a random selection of patients who did not receive Therapeutic Touch from October 2010-June 2013. Client characteristics and the Therapeutic Touch Practitioners' observations of the patients' response to treatment were collected and analyzed. Patients who did not receive Therapeutic Touch tended to have lower admitting Palliative Performance Scale scores, shorter length of stay and were older. Based on a sample of responses provided by patients and observed by the Therapeutic Touch practitioner, the majority of patients receiving treatment achieved a state of relaxation or sleep. This retrospective chart review suggests that implementation of a TT program for an inpatient geriatric Palliative Care Unit is feasible, and appears to be safe, and well-tolerated. Moreover, patient responses, as recorded in the Therapeutic Touch practitioners' session notes, suggest beneficial effects of Therapeutic Touch for a significant number of participants with no evidence of negative sequelae. Therefore, the use of TT in this difficult setting appears to have potential value as an adjunct or complementary therapy to help patients relax. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

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

Code of Federal Regulations, 2010 CFR

2010-01-01

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

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

PubMed

Vaccarezza, María Magdalena; Silva, Walter Horacio

2015-09-01

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

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

Backflow-free catheters for efficient and safe convection-enhanced delivery of therapeutics.

PubMed

Lueshen, Eric; Tangen, Kevin; Mehta, Ankit I; Linninger, Andreas

2017-07-01

Convection-enhanced delivery (CED) is an invasive drug delivery technique used to target specific regions of the brain for the treatment of cancer and neurodegenerative diseases while bypassing the blood-brain barrier. In order to prevent the possibility of backflow, low volumetric flow rates are applied which limit the achievable drug distribution volumes from CED. This can render CED treatment ineffective since a small convective flow produces narrow drug distribution inside the treatment region. Novel catheter designs and CED protocols are needed to improve the drug distribution inside the treatment region. This is especially important when administering toxic chemotherapeutics which could adversely affect other organs if backflow occurred and these drugs entered the circulating blood stream. In order to help elucidate the causes of backflow and to design backflow-free catheters, we have studied the impact that microfluid flow has on deformable brain phantom gels experimentally as well as numerically. We found that fluid injections into porous media have considerable effects on local transport properties such as porosity and hydraulic conductivity. These phenomena not only alter the bulk flow velocity distribution of the microfluid flow due to the changing porosity, but significantly modify flow direction and even volumetric flow distribution due to induced local hydraulic conductivity anisotropy. These studies led us to the development of novel backflow-free catheters with safe volumetric flow rates up to 10 µL/min. The catheter designs, numerical simulations and experimental results are described throughout this article. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

Process and product development in the manufacturing of molecular therapeutics.

PubMed

Atkinson, E M; Christensen, J R

1999-08-01

In the development of molecular therapies, a great deal of attention has focused on tissue targets, gene delivery vectors, and expression cassettes. In order to become an approved therapy, however, a molecular therapeutic has to pass down the same product registration pathway as any other biological product. Moving from research into industrial production requires careful attention to regulatory, manufacturing and quality concerns. Early work on developing and characterizing robust and scaleable manufacturing processes will ultimately be rewarded by ease of implementation as the product is successful in clinical trials. Regulatory agencies require solid process and product characterization studies to demonstrate control and understanding of the molecular therapeutic. As the gene therapy industry matures, standards will continue to rise, creating an industry that is capable of producing safe, high-quality and effective therapies for many of the world's most difficult disease targets.

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.

Leaving patients to their own devices? Smart technology, safety and therapeutic relationships.

PubMed

Ho, Anita; Quick, Oliver

2018-03-06

This debate article explores how smart technologies may create a double-edged sword for patient safety and effective therapeutic relationships. Increasing utilization of health monitoring devices by patients will likely become an important aspect of self-care and preventive medicine. It may also help to enhance accurate symptom reports, diagnoses, and prompt referral to specialist care where appropriate. However, the development, marketing, and use of such technology raise significant ethical implications for therapeutic relationships and patient safety. Drawing on lessons learned from other direct-to-consumer health products such as genetic testing, this article explores how smart technology can also pose regulatory challenges and encourage overutilization of healthcare services. In order for smart technology to promote safer care and effective therapeutic encounters, the technology and its utilization must be safe. This article argues for unified regulatory guidelines and better education for both healthcare providers and patients regarding the benefits and risks of these devices.

Safe Grid

NASA Technical Reports Server (NTRS)

Chow, Edward T.; Stewart, Helen; Korsmeyer, David (Technical Monitor)

2003-01-01

The biggest users of GRID technologies came from the science and technology communities. These consist of government, industry and academia (national and international). The NASA GRID is moving into a higher technology readiness level (TRL) today; and as a joint effort among these leaders within government, academia, and industry, the NASA GRID plans to extend availability to enable scientists and engineers across these geographical boundaries collaborate to solve important problems facing the world in the 21 st century. In order to enable NASA programs and missions to use IPG resources for program and mission design, the IPG capabilities needs to be accessible from inside the NASA center networks. However, because different NASA centers maintain different security domains, the GRID penetration across different firewalls is a concern for center security people. This is the reason why some IPG resources are been separated from the NASA center network. Also, because of the center network security and ITAR concerns, the NASA IPG resource owner may not have full control over who can access remotely from outside the NASA center. In order to obtain organizational approval for secured remote access, the IPG infrastructure needs to be adapted to work with the NASA business process. Improvements need to be made before the IPG can be used for NASA program and mission development. The Secured Advanced Federated Environment (SAFE) technology is designed to provide federated security across NASA center and NASA partner's security domains. Instead of one giant center firewall which can be difficult to modify for different GRID applications, the SAFE "micro security domain" provide large number of professionally managed "micro firewalls" that can allow NASA centers to accept remote IPG access without the worry of damaging other center resources. The SAFE policy-driven capability-based federated security mechanism can enable joint organizational and resource owner approved remote

Tools for translation: non-viral materials for therapeutic mRNA delivery

NASA Astrophysics Data System (ADS)

Hajj, Khalid A.; Whitehead, Kathryn A.

2017-10-01

In recent years, messenger RNA (mRNA) has come into the spotlight as a versatile therapeutic with the potential to prevent and treat a staggering range of diseases. Billions of dollars have been invested in the commercial development of mRNA drugs, with ongoing clinical trials focused on vaccines (for example, influenza and Zika viruses) and cancer immunotherapy (for example, myeloma, leukaemia and glioblastoma). Although significant progress has been made in the design of in vitro-transcribed mRNA that retains potency while minimizing unwanted immune responses, the widespread use of mRNA drugs requires the development of safe and effective drug delivery vehicles. In this Review, we provide an overview of the field of mRNA therapeutics and describe recent advances in the development of synthetic materials that encapsulate and deliver mRNA payloads.

Safe Manual Jettison

NASA Technical Reports Server (NTRS)

Barton, Jay

2008-01-01

In space, the controlled release of certain cargoes is no less useful than the maritime jettisons from which they take their name but is also much more dangerous. Experience has shown that jettisons can be performed safely, but the process is complicated with the path to performing a jettison taking months or even years. In the background, time is also required to write procedures, train the crew, configure the vehicle, and many other activities. This paper outlines the current process used by the National Aeronautics and Space Administration (NASA) for manual jettisons, detailing the methods used to assure that the jettisons and the jettisoned objects are as safe as achievable and that the crew is adequately trained to be able to affect the safe jettison. The goal of this paper is not only to capture what it takes to perform safe jettisons in the near Earth environment but to extrapolate this knowledge to future space exploration scenarios that will likely have Extravehicular Activity (EVA) and International Partner (IP) interfaces.

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.

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.

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 scrapbooking: a technique to promote positive coping and emotional strength in parents of pediatric oncology patients.

PubMed

McCarthy, Paula G; Sebaugh, Jill Genone

2011-01-01

Therapeutic scrapbooking is an intervention being used with parents and caregivers of children with cancer. The purpose of the group is to promote hopefulness, mobilize internal strengths, and thereby enhance the parents' and caregivers' coping abilities to benefit pediatric oncology patients. Facilitators, licensed in medical social work, provide a safe environment for participants to verbalize their stories and share their distress. Scrapbooking is a "normal" activity without the negative stigma that a "support group" may carry, minimizing the reluctance to attend this supportive group. Outcome measurements indicate this therapeutic intervention achieves positive results.

Adherence to national recommendations for safe methotrexate dispensing in community pharmacies.

PubMed

Koster, Ellen S; Walgers, Joelle C D; van Grinsven, Mariska C J; Winters, Nina A; Bouvy, Marcel L

2014-02-01

The number of patients using methotrexate (MTX) has increased during the last decade. Because of the narrow therapeutic range and potential risks of incorrect use, vigilance is required when dispensing MTX. In 2009, the Royal Dutch Pharmacists Society, in accordance with the Dutch Health Care Inspectorate, published safe MTX dispensing recommendations for community pharmacies. To examine adherence to recommendations aimed at safe 
MTX dispensing. This study was conducted within a convenience sample of 78 community pharmacies belonging to the Utrecht Pharmacy Practice Network for Education and Research (UPPER). Data were collected in May 2011. 95 pharmacists and 337 pharmacy technicians were interviewed to assess self-reported adherence with dispensing recommendations. In addition, medication records for patients using MTX were extracted in 52 pharmacies in order to objectively assess adoption of recommendations. More than 75% of the pharmacists and pharmacy technicians reported to be adherent to 6 of the 11 recommendations. There are variations in reported adherence between team members working in 1 pharmacy; higher adherence rates ( greater than 75%) for the pharmacy team as a whole were only shown for 2 recommendations (recording of day of intake on the label and moment of authorization by the pharmacist). The medication records showed that adherence with working procedures significantly increased: The number of dispensed records with notification of the day of intake on the medication label increased from 9.9% of the records per pharmacy in 2008 to 77.1% in 2010 (P  less than  0.001). Dutch community pharmacies seem to be adherent to most safe dispensing recommendations. However, inconsistencies exist between team members that emphasize the importance of addressing this issue and discussing recommendations within the team, as there is still room for improvement to ensure safe dispensing.

[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.

Access to safe abortion: building choices for women living with HIV and AIDS

PubMed Central

2011-01-01

In many areas of the world where HIV prevalence is high, rates of unintended pregnancy and unsafe abortion have also been shown to be high. Of all pregnancies worldwide in 2008, 41% were reported as unintended or unplanned, and approximately 50% of these ended in abortion. Of the estimated 21.6 million unsafe abortions occurring worldwide in 2008 (around one in 10 pregnancies), approximately 21.2 million occurred in developing countries, often due to restrictive abortion laws and leading to an estimated 47,000 maternal deaths and untold numbers of women who will suffer long-term health consequences. Despite this context, little research has focused on decisions about and experiences of women living with HIV with regard to terminating a pregnancy, although this should form part of comprehensive promotion of sexual and reproductive health rights. In this paper, we explore the existing evidence related to global and country-specific barriers to safe abortion for all women, with an emphasis on research gaps around the right of women living with HIV to choose safe abortion services as an option for dealing with unwanted pregnancies. The main focus is on the situation for women living with HIV in Brazil, Namibia and South Africa as examples of three countries with different conditions regarding women's access to safe legal abortions: a very restrictive setting, a setting with several indications for legal abortion but non-implementation of the law, and a rather liberal setting. Similarities and differences are discussed, and we further outline global and country-specific barriers to safe abortion for all women, ending with recommendations for policy makers and researchers. PMID:22078463

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

Safe paediatric intensive care. Part 1: Does more medical care lead to improved outcome?

PubMed

Frey, Bernhard; Argent, Andrew

2004-06-01

Neonatal and paediatric intensive care has improved the prognosis for seriously sick infants and children. This has happened because of a pragmatic approach focused on stabilisation of vital functions and immense technological advances in diagnostic and therapeutic procedures. However, the belief that more medical care must inevitably lead to improved health is increasingly being questioned. This issue is especially relevant in developing countries where the introduction of highly specialised paediatric intensive care may not lead to an overall fall in child mortality. Even in developed countries, the complexity and availability of therapeutics and invasive procedures may put seriously ill children at additional risk. In both developing and industrialised countries the use of safe and simple procedures for appropriate periods, particular attention to drug prescription patterns and selection of appropriate aims and modes of therapy, including non-invasive methods, may minimise the risks of paediatric intensive care.

Current Status of Dengue Therapeutics Research and Development.

PubMed

Low, Jenny G H; Ooi, Eng Eong; Vasudevan, Subhash G

2017-03-01

Dengue is a significant global health problem. Even though a vaccine against dengue is now available, which is a notable achievement, its long-term protective efficacy against each of the 4 dengue virus serotypes remains to be definitively determined. Consequently, drugs directed at the viral targets or critical host mechanisms that can be used safely as prophylaxis or treatment to effectively ameliorate disease or reduce disease severity and fatalities are still needed to reduce the burden of dengue. This review will provide a brief account of the status of therapeutics research and development for dengue. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

Treating ADHD With Suggestion: Neurofeedback and Placebo Therapeutics.

PubMed

Thibault, Robert T; Veissière, Samuel; Olson, Jay A; Raz, Amir

2018-06-01

We propose that clinicians can use suggestion to help treat conditions such as ADHD. We use EEG neurofeedback as a case study, alongside evidence from a recent pilot experiment utilizing a sham MRI scanner to highlight the therapeutic potential of suggestion-based treatments. The medical literature demonstrates that many practitioners already prescribe treatments that hardly outperform placebo comparators. Moreover, the sham MRI experiment showed that, even with full disclosure of the procedure, suggestion alone can reduce the symptomatology of ADHD. Non-deceptive suggestion-based treatments, especially those drawing on accessories from neuroscience, may offer a safe complement and potential alternative to current standard of care for individuals with ADHD.

Therapeutic effects of hydrogen on chronic graft-versus-host disease.

PubMed

Qian, Liren; Liu, Xiaopeng; Shen, Jianliang; Zhao, Defeng; Yin, Wenjie

2017-10-01

The incidence of chronic graft-versus-host disease (cGVHD) is rising recent years, which has been the leading cause of non-transplantation mortality post allogenetic hematopoietic stem cell transplantation (HSCT). Imbalance of inflammatory cytokines and fibrosis plays critical roles in the pathogenesis of cGVHD. Recent studies showed that molecular hydrogen has anti-inflammatory, antioxidant, anti-fibrosis effects. Therefore, we hypothesized that molecular hydrogen may have therapeutic effects on cGVHD. To determine whether hydrogen could protect mice from cGVHD in an MHC-incompatible murine bone marrow transplantation (BMT) model, survival rates of mice were calculated, and skin lesions were also evaluated after BMT. This article demonstrated that administration of hydrogen-rich saline increased survival rate of cGVHD mice. Administration of hydrogen-rich saline after transplantation also reduced skin lesions of cGVHD mice. Previously, we reported the therapeutic effects of hydrogen on acute GVHD. However, there was no report on the therapeutic effects of hydrogen on cGVHD mice. It is suggested that hydrogen has a potential as an effective and safe therapeutic agent on cGVHD. This study will provide new ideas on the treatment of cGVHD and has important theoretical values. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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...

Treatment Options for the Cardinal Symptoms of Disruptive Mood Dysregulation Disorder

PubMed Central

Tourian, Leon; LeBoeuf, Amélie; Breton, Jean-Jacques; Cohen, David; Gignac, Martin; Labelle, Réal; Guile, Jean-Marc; Renaud, Johanne

2015-01-01

Objective: DSM-5 has added a new developmentally appropriate child and adolescent mood disorder subtype called disruptive mood dysregulation disorder (DMDD). The core features of DMDD are temper outbursts (manifested by either verbal rages and/or physical aggression) and unrelenting irritability or anger. Currently, the literature is lacking a thorough review of the possible treatment options for the cardinal symptoms constituting DMDD. The objective of this article is to provide a thorough review of peer-reviewed studies on the subject of pharmacological treatment options for children and adolescents with the cardinal symptoms of DMDD. Methods: Relevant articles for this study were obtained through Pubmed, Medline, PsychINFO and PsychINDEXplus using the key words: “adolescents,” “children,” “paediatric,” “youth,” “irritability,” “temper outbursts,” “aggression,” “rage,” “disruptive behaviour,” “treatment,” “dysphoria,” “autism,” “mental retardation/intellectual disability,” “impulsivity,” “ADHD,” “oppositional defiant disorder,” and “conduct disorder.” A total of 823 studies were generated; only English studies focusing on pharmacological treatment were retained. Results: Currently there are no established guidelines or thorough reviews summarizing the treatment of DMDD. Pharmacotherapeutic treatment options of both aggression and chronic irritability include: antidepressants/selective norepinephrine reuptake inhibitors, mood stabilizers, psychostimulants, antipsychotics, and alpha-2 agonists. Conclusion: Treatment options of severe, persistent irritability in youth are numerous, and a consensual treatment algorithm has not yet emerged from the literature. Further studies and clinical trials are warranted to determine efficacious and safe treatment modalities. PMID:26336379

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.

Buying & Using Medicine Safely

MedlinePlus

... Generic Drugs - Patient Education Resources Patient and Prescriber materials: Videos, PSAs, factsheets and more. Spotlight Drugs@FDA Index to Drug-Specific Information Protecting Yourself Safe Disposal of Medicines Generic Medicines – safe, effective and ...

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...

Safe and efficient drug delivery system with liposomes for intrathecal application of an antivasospastic drug, fasudil.

PubMed

Ishida, Tatsuhiro; Takanashi, Yoshihiro; Kiwada, Hiroshi

2006-03-01

Pharmacological treatment for cerebral ischemia and cerebral vasospasm following subarachnoid hemorrhage (SAH) cannot attain sufficiently high concentrations of the drugs in the cerebrospinal fluid (CSF) without precipitating systemic side effects. We recently developed a liposomal drug delivery system for intrathecal application that can maintain effective concentrations of cerebral vasodilator, fasudil, in the CSF. A single intrathecal injection of liposomal fasudil could maintain a therapeutic drug concentration in the CSF over a period time due to their sustained-release property, significantly decreasing infarct size in a rat model of acute ischemia and reducing vasoconstriction of the rat and dog basilar artery in a model of SAH. In this review, we are introducing our new less-invasive intrathecal drug delivery system that provides an alternative and safe method to deliver therapeutic agents.

Biological and therapeutic properties of bee pollen: a review.

PubMed

Denisow, Bożena; Denisow-Pietrzyk, Marta

2016-10-01

Natural products, including bee products, are particularly appreciated by consumers and are used for therapeutic purposes as alternative drugs. However, it is not known whether treatments with bee products are safe and how to minimise the health risks of such products. Among others, bee pollen is a natural honeybee product promoted as a valuable source of nourishing substances and energy. The health-enhancing value of bee pollen is expected due to the wide range of secondary plant metabolites (tocopherol, niacin, thiamine, biotin and folic acid, polyphenols, carotenoid pigments, phytosterols), besides enzymes and co-enzymes, contained in bee pollen. The promising reports on the antioxidant, anti-inflammatory, anticariogenic antibacterial, antifungicidal, hepatoprotective, anti-atherosclerotic, immune enhancing potential require long-term and large cohort clinical studies. The main difficulty in the application of bee pollen in modern phytomedicine is related to the wide species-specific variation in its composition. Therefore, the variations may differently contribute to bee-pollen properties and biological activity and thus in therapeutic effects. In principle, we can unequivocally recommend bee pollen as a valuable dietary supplement. Although the bee-pollen components have potential bioactive and therapeutic properties, extensive research is required before bee pollen can be used in therapy. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Next-Gen Therapeutics for Skin Cancer: Nutraceuticals.

PubMed

Sreedhar, Annapoorna; Li, Jun; Zhao, Yunfeng

2018-05-15

Growing modernization and lifestyle changes with limited physical activity have impacted diet and health, leading to an increased cancer mortality rate worldwide. As a result, there is a greater need than before to develop safe and novel anticancer drugs. Current treatment options such as chemotherapy, radiotherapy and surgery, induce unintended side effects, compromising patient's quality of life, and physical well-being. Therefore, there has been an increased global interest in the use of dietary supplements and traditional herbal medicines for treatment of cancer. Recently, nutraceuticals or "natural" substances isolated from food have attracted considerable attention in the cancer field. Emerging research suggests that nutraceuticals may indeed prevent and protect against cancer. The intent of this article is to review some of the current spice-derived nutraceuticals in the treatment of melanoma and skin cancer.

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

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.

Cultivating the Art of Safe Space

ERIC Educational Resources Information Center

Hunter, Mary Ann

2008-01-01

Performance-making and peace-building are processes predicated on the production of safe space. But what is "safe space"? In performance-making, what is it that makes space safe without losing the creative potential of tension? What role is there for risk? And, once achieved, how does safe space become meaningful beyond its immediate…

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential into the Brain using MRI-Guided Focused Ultrasound

PubMed Central

Etame, Arnold B.; Diaz, Roberto J.; O’Reilly, Meaghan A.; Smith, Christian A.; Mainprize, Todd G.; Hynynen, Kullervo; Rutka, James T.

2014-01-01

The blood brain barrier (BBB) is a major impediment to the delivery of therapeutics into the central nervous system (CNS). Gold nanoparticles (AuNPs) have been successfully employed in multiple potential therapeutic and diagnostic applications outside the CNS. However, AuNPs have very limited biodistribution within the CNS following intravenous administration. Magnetic resonance imaging guided focused ultrasound (MRgFUS) is a novel technique that can transiently increase BBB permeability allowing delivery of therapeutics into the CNS. MRgFUS has not been previously employed for delivery of AuNPs into the CNS. This work represents the first demonstration of focal enhanced delivery of AuNPs into the CNS using MRgFUS in a rat model both safely and effectively. Histologic visualization and analytical quantification of AuNPs within the brain parenchyma suggest BBB transgression. These results suggest a role for MRgFUS in the delivery of AuNPs with therapeutic potential into the CNS for targeting neurological diseases. PMID:22349099

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

Safe Affordable Fission Engine-(SAFE-) 100a Heat Exchanger Thermal and Structural Analysis

NASA Technical Reports Server (NTRS)

Steeve, B. E.

2005-01-01

A potential fission power system for in-space missions is a heat pipe-cooled reactor coupled to a Brayton cycle. In this system, a heat exchanger (HX) transfers the heat of the reactor core to the Brayton gas. The Safe Affordable Fission Engine- (SAFE-) 100a is a test program designed to thermally and hydraulically simulate a 95 Btu/s prototypic heat pipe-cooled reactor using electrical resistance heaters on the ground. This Technical Memorandum documents the thermal and structural assessment of the HX used in the SAFE-100a program.

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

PubMed

Yoshihara, Hiroyuki

2014-07-01

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

Cachexia and pancreatic cancer: Are there treatment options?

PubMed Central

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

2014-01-01

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

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

PubMed

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

2017-08-17

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

Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization

PubMed Central

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

2010-01-01

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

Breastfeeding FAQs: Safely Storing Breast Milk

MedlinePlus

... Staying Safe Videos for Educators Search English Español Breastfeeding FAQs: Safely Storing Breast Milk KidsHealth / For Parents / Breastfeeding FAQs: Safely Storing Breast Milk What's in this ...

Maximizing value in opioid utilization: Is oxycodone immediate release a good option for pain management?

PubMed

Pergolizzi, Joseph V; Köknel Talu, Gül; Zmponga, Gianpetrio; Erdine, Serdar; Taylor, Robert; Ayan, Burak; Raffa, Robert B

2015-01-01

The modern approach to the management of pain involves optimizing all aspects of the process. This includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiology of the pain with the analgesic's mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfies all of the requirements for all patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are effective options for inflammatory pain and, as is acetaminophen, for mild pain. Specialized agents are helpful for particular pains, such as for migraine headache. Opioids remain the standard option for severe pain. Although they are generally a safe and effective option, opioids can produce dose-limiting adverse effects and have abuse potential. The goal of pain therapy is thus to achieve the maximum pain relief with the least amount of opioid exposure. Against this background of measured approach to the use of analgesics, an immediate release (IR) oral formulation of the established opioid oxycodone has been developed to provide rapid onset of action and rate of titration, both of which could maximize temporal matching of dose with pain level and reduce total exposure to drug. This article considers the option of an immediate release (IR) oral formulation for the management of pain.

Intrauterine transfusion and non-invasive treatment options for hemolytic disease of the fetus and newborn - review on current management and outcome.

PubMed

Zwiers, Carolien; van Kamp, Inge; Oepkes, Dick; Lopriore, Enrico

2017-04-01

Hemolytic disease of the fetus and newborn (HDFN) remains a serious pregnancy complication which can lead to severe fetal anemia, hydrops and perinatal death. Areas covered: This review focusses on the current prenatal management, treatment with intrauterine transfusion (IUT) and promising non-invasive treatment options for HDFN. Expert commentary: IUTs are the cornerstone in prenatal management of HDFN and have significantly improved perinatal outcome in the past decades. IUT is now a relatively safe procedure, however the risk of complications is still high when performed early in the second trimester. Non-invasive management using intravenous immunoglobulin may be a safe alternative and requires further investigation.

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.

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases.

PubMed

Rupaimoole, Rajesha; Slack, Frank J

2017-03-01

In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

Obstetric therapeutics-how pharmacogenetics may inform drug therapy for pregnant women in the future.

PubMed

Haas, David M

2013-09-01

Most pregnant women take prescription medications. There are many factors related to pregnancy that make finding the most effective and safe dose of a therapeutic drug difficult for providers. Genetic differences in drug-metabolizing enzymes, transporters, and receptors may also account for some of the differences in drug response. Single-nucleotide polymorphisms in drug-metabolizing enzymes, such as the cytochrome P450 families, have been studied in relation to drugs used in pregnancy. Combining clinical characteristics, physiologic parameters in pregnancy, and possibly pharmacogenetic models may allow for providers to individualize pharmacotherapy in pregnancy and get to the most effective and safe dose of medication more quickly than in the current practice model. This article discusses these issues along with helpful Web sites and references for providers.

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.

The safe home project.

PubMed

Arphorn, Sara; Jiraniratisai, Sopaphan; Rungtakul, Rungsri; Phutta, Nikom

2011-12-01

The Thai Health Promotion Foundation supported the Improvement of Quality of Life of Informal Workers project in Ban Luang District, Amphur Photaram, Ratchaburi Province. There were many informal workers in Ban Luang District. Sweet-crispy fish producers in Ban Luang were the largest group among the sweet-crispy fish producers in Thailand. This project was aimed at improving living and working conditions of informal workers, with a focus on the sweet-crispy fish group. Good practices of improved living and working conditions were used to help informal workers build safe, healthy and productive work environments. These informal workers often worked in substandard conditions and were exposed to various hazards in the working area. These hazards included risk of exposure to hot work environment, ergonomics-related injuries, chemical hazards, electrical hazards etc. Ergonomics problems were commonly in the sweet-crispy fish group. Unnatural postures such as prolonged sitting were performed dominantly. One hundred and fifty informal workers participated in this project. Occupational health volunteers were selected to encourage occupational health and safety in four groups of informal workers in 2009. The occupational health volunteers trained in 2008 were farmers, beauty salon workers and doll makers. The occupational health and safety knowledge is extended to a new informal worker group: sweet-crispy fish producer, in 2009. The occupational health and safety training for sweet-crispy fish group is conducted by occupational health volunteers. The occupational health volunteers increased their skills and knowledge assist in to make safe home and safe community through participatory oriented training. The improvement of living and working condition is conducted by using a modified WISH, Work Improvement for Safe Home, checklist. The plans of improvement were recorded. The informal workers showed improvement mostly on material handling and storage. The safe uses and safe

New therapeutic potentials of milk thistle (Silybum marianum).

PubMed

Milić, Natasa; Milosević, Natasa; Suvajdzić, Ljiljana; Zarkov, Marija; Abenavoli, Ludovico

2013-12-01

Silymarin is a bioflavonoid complex extract derived from dry seeds of Milk thistle [(Silybum marianum(L.) Gaemrnt. (Fam. Asteraceae/Compositaceae)] whose hepatoprotective effect has clinically been proved. Low toxicity, favorable pharmacokinetics, powerful antioxidant, detoxifying, preventive, protective and regenerative effects and side effects similar to placebo make silymarin extremely attractive and safe for therapeutic use. The medicinal properties of silymarin and its main component silibinin have been studied in the treatment of Alzheimer's disease, Parkinson's disease, sepsis, burns, osteoporosis, diabetes, cholestasis and hypercholesterolemia. Owing to its apoptotic effect, without cytotoxic effects, silymarin possesses potential applications in the treatment of various cancers. Silymarin is being examined as a neuro-, nephro- and cardio-protective in the damage of different etiologies due to its strong antioxidant potentials. Furthermore, it has fetoprotective (against the influence of alcohol) and prolactin effects and is safe to be used during pregnancy and lactation. Finally, the cosmetics industry is examining the antioxidant and UV-protective effects of silymarin. Further clinical studies and scientific evidence that silymarin and silibinin are effective in the therapy of various pathologies are indispensable in order to confirm their different flavonolignan pharmacological effects.

Application of Hazard Analysis Critical Control Point in the local manufacture of ready-to-use therapeutic foods (RUTFs).

PubMed

Henry, C Jeya K; Xin, Janice Lim Wen

2014-06-01

The local manufacture of ready-to-use therapeutic foods (RUTFs) is increasing, and there is a need to develop methods to ensure their safe production. We propose the application of Hazard Analysis Critical Control Point (HACCP) principles to achieve this goal. The basic principles of HACCP in the production of RUTFs are outlined. It is concluded that the implementation of an HACCP system in the manufacture of RUTFs is not only feasible but also attainable. The introduction of good manufacturing practices, coupled with an effective HACCP system, will ensure that RUTFs are produced in a cost-effective, safe, and hygienic manner.

Will Synergizing Vaccination with Therapeutics Boost Measles Virus Eradication?

PubMed Central

Plemper, Richard K; Hammond, Anthea L

2014-01-01

Introduction Measles virus is a major human pathogen responsible for approximately 150,000 measles deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence combined with public anxieties about vaccination safety has increased vaccine refusal especially in the European region, which has resulted in measles resurgence in some areas. Areas covered Here, we discuss whether synergizing effective measles therapeutics with vaccination could contribute to solving an endgame conundrum of measles elimination by accelerating the eradication effort. Based on an anticipated use for protection of high-risk contacts of confirmed measles cases through post-exposure prophylaxis, we identify key elements of the desirable drug profile, review current disease management strategies and the state of experimental inhibitor candidates, evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics for the management of persistent viral infection of the CNS. Assuming a post-measles world with waning measles immunity, we contemplate the possible impact of therapeutics on controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles virus. Expert opinion Efficacious therapeutics given for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent patient population dictates the drug profile; the article must be safe and efficacious, orally available, shelf-stable at ambient temperature, and amenable to cost-effective manufacture

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.

Safe genetic modification of cardiac stem cells using a site-specific integration technique.

PubMed

Lan, Feng; Liu, Junwei; Narsinh, Kazim H; Hu, Shijun; Han, Leng; Lee, Andrew S; Karow, Marisa; Nguyen, Patricia K; Nag, Divya; Calos, Michele P; Robbins, Robert C; Wu, Joseph C

2012-09-11

Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. We used the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells. Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared with unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging, and positron emission tomography. Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function 2 weeks after cell delivery, as assessed by echocardiography (P=0.002) and MRI (P=0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated human endothelial cells, which enhanced hind limb perfusion (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging. The phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types.

Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

PubMed Central

Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

2010-01-01

Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

Robot-assisted rectopexy is a safe and feasible option for treatment of rectal prolapse.

PubMed

Haahr, Camilla; Jakobsen, Henrik Loft; Gögenur, Ismail

2014-05-01

Rectal prolapse is seen in up to one in 100 elderly women and results in symptoms such as incontinence, mucus secretion and constipation. The aim of this study was to present short- and longterm outcomes after robot-assisted rectopexy in patients with rectal prolapse. All patients diagnosed with rectal prolapse at our institution underwent robot-assisted rectopexy. Data regarding the surgical procedure and post-operative morbidity were collected retrospectively. Patients were contacted to register long-term results regarding recurrence, incontinence and satisfaction. A total of 24 consecutive patients underwent robot-assisted rectopexy from October 2010 to July 2012. Data regarding their long-term outcome was available for 18 patients at follow-up (average ten months). 50% of the patients suffered from faecal incontinence before surgery (n = 9/18, 50%). The mean age at surgery was 72 years (28-93 years). The mean duration of surgery was 123 min. (70-245 min.). The median length of stay in hospital was 4.1 days (0-15 days). There was one procedure-related complication (small-bowel obstruction) resulting in reoperation. At the time of follow-up, two patients (11%) had a subjective recurrence of rectal prolapse, and three patients (17%) had faecal incontinence. 89% were satisfied with the operation, and 94% would recommend this operation to other patients with the same condition. Robot-assisted rectopexy is a safe procedure for patients with rectal prolapse and is associated with acceptable functional outcomes and recurrence rates. There is no evidence in the literature of advantages compared with the corresponding laparoscopic procedure. not relevant. not relevant.

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

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.

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.

Primary intestinal lymphangiectasia in children: is octreotide an effective and safe option in the treatment?

PubMed

Sari, Sinan; Baris, Zeren; Dalgic, Buket

2010-10-01

Octreotide has been suggested as a medical treatment option in refractory cases of primary intestinal lymphangiectasia (IL). There are few data about the long-term effect and safety of octreotide for IL in the literature. In the present article we analyzed pediatric cases of primary IL with long-term octreotide treatment and discussed its safety profile. Between 1999 and 2008, 13 children were diagnosed in our clinic as having IL. Six patients with primary IL were followed up, receiving octreotide therapy. The clinical data of the patients and duration of therapy, dose, and side effects of octreotide were evaluated. Octreotide, 15 to 20 μg per body weight 2 times daily subcutaneously, was given to all of the patients. Duration of the octreotide treatment changed between 3 and 37 months. Stool frequency decreased in all of the patients after starting octreotide treatment. Serum albumin could be maintained at normal levels in 3 patients. The requirement of albumin infusions decreased in all of the patients. Acute pancreatitis was observed as a side effect of octreotide in 1 patient. Octreotide may help to maintain serum albumin levels, improve clinical findings, and decrease the requirement of albumin infusions in refractory cases of primary IL.

[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.

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections.

PubMed

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

2017-06-01

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

[Psychological aspects of pruritus and therapy options].

PubMed

Stumpf, A; Schut, C; Schneider, G

2016-08-01

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

Pectus excavatum: history, hypotheses and treatment options

PubMed Central

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

2012-01-01

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

Efficient Trajectory Options Allocation for the Collaborative Trajectory Options Program

NASA Technical Reports Server (NTRS)

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

2017-01-01

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

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.

Failed Ventriculoperitoneal Shunt: Is Retrograde Ventriculosinus Shunt a Reliable Option?

PubMed

Oliveira, Matheus Fernandes de; Teixeira, Manoel Jacobsen; Reis, Rodolfo Casimiro; Petitto, Carlo Emanuel; Gomes Pinto, Fernando Campos

2016-08-01

Currently, the treatment of hydrocephalus is mainly carried out through a ventriculoperitoneal shunt (VPS) insertion. However, in some cases, there may be surgical revisions and requirement of an alternative distal site for shunting. There are several described distal sites, and secondary options after VPS include ventriculopleural and ventriculoatrial shunt, which have technical difficulties and harmful complications. In this preliminary report we describe our initial experience with retrograde ventriculosinus shunt (RVSS) after failed VPS. In 3 consecutive cases we applied RVSS to treat hydrocephalus in shunt-dependent patients who had previously undergone VPS revision and in which peritoneal space was full of adhesions and fibrosis. RVSS was performed as described by Shafei et al., with some modifications to each case. All 3 patients kept the same clinical profile after RVSS, with no perioperative or postoperative complications. However, revision surgery was performed in the first operative day in 1 out of 3 patients, in which the catheter was not positioned in the superior sagittal sinus. We propose that in cases where VPS is not feasible, RVSS may be a safe and applicable second option. Nevertheless, the long-term follow-up of patients and further learning curve must bring stronger evidence. Copyright © 2016 Elsevier Inc. All rights reserved.

Relapse of extinguished fear after exposure to a dangerous context is mitigated by testing in a safe context.

PubMed

Goode, Travis D; Kim, Janice J; Maren, Stephen

2015-03-01

Aversive events can trigger relapse of extinguished fear memories, presenting a major challenge to the long-term efficacy of therapeutic interventions. Here, we examined factors regulating the relapse of extinguished fear after exposure of rats to a dangerous context. Rats received unsignaled shock in a distinct context ("dangerous" context) 24 h prior to auditory fear conditioning in another context. Fear to the auditory conditioned stimulus (CS) was subsequently extinguished either in the conditioning context ("ambiguous" context) or in a third novel context ("safe" context). Exposure to the dangerous context 30 min before a CS retention test caused relapse to the CS in the ambiguous and safe test contexts relative to nonextinguished controls. When rats were tested 24 h later (with or without short-term testing), rats tested in the ambiguous context continued to exhibit relapse, whereas rats tested in the safe context did not. Additionally, exposure of rats to the conditioning context--in place of the unsignaled shock context--did not result in relapse of fear to the CS in the safe testing context. Our work highlights the vulnerabilities of extinction recall to interference, and demonstrates the importance of context associations in the relapse of fear after extinction. © 2015 Goode et al.; Published by Cold Spring Harbor Laboratory Press.

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.

Update on therapeutic interventions for the management of achalasia.

PubMed

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

2016-08-01

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

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

PubMed

Feldman, Eric J

2015-06-01

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

Therapeutic application of RNAi: is mRNA targeting finally ready for prime time?

PubMed Central

Grimm, Dirk; Kay, Mark A.

2007-01-01

With unprecedented speed, RNA interference (RNAi) has advanced from its basic discovery in lower organisms to becoming a powerful genetic tool and perhaps our single most promising biotherapeutic for a wide array of diseases. Numerous studies document RNAi efficacy in laboratory animals, and the first clinical trials are underway and thus far suggest that RNAi is safe to use in humans. Yet substantial hurdles have also surfaced and must be surmounted before therapeutic RNAi applications can become a standard therapy. Here we review the most critical roadblocks and concerns for clinical RNAi transition, delivery, and safety. We highlight emerging solutions and concurrently discuss novel therapeutic RNAi-based concepts. The current rapid advances create realistic optimism that the establishment of RNAi as a new and potent clinical modality in humans is near. PMID:18060021

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.

ESTIMATION OF EXPOSURE DOSES FOR THE SAFE MANAGEMENT OF NORM WASTE DISPOSAL.

PubMed

Jeong, Jongtae; Ko, Nak Yul; Cho, Dong-Keun; Baik, Min Hoon; Yoon, Ki-Hoon

2018-03-16

Naturally occurring radioactive materials (NORM) wastes with different radiological characteristics are generated in several industries. The appropriate options for NORM waste management including disposal options should be discussed and established based on the act and regulation guidelines. Several studies calculated the exposure dose and mass of NORM waste to be disposed in landfill site by considering the activity concentration level and exposure dose. In 2012, the Korean government promulgated an act on the safety control of NORM around living environments to protect human health and the environment. For the successful implementation of this act, we suggest a reference design for a landfill for the disposal of NORM waste. Based on this reference landfill, we estimate the maximum exposure doses and the relative impact of each pathway to exposure dose for three scenarios: a reference scenario, an ingestion pathway exclusion scenario, and a low leach rate scenario. Also, we estimate the possible quantity of NORM waste disposal into a landfill as a function of the activity concentration level of U series, Th series and 40K and two kinds of exposure dose levels, 1 and 0.3 mSv/y. The results of this study can be used to support the establishment of technical bases of the management strategy for the safe disposal of NORM waste.

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

ERIC Educational Resources Information Center

Lengyel, Dorothy L.; And Others

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

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

PubMed Central

Houston, Brian A; Mukherjee, Monica

2014-01-01

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

Clinical and therapeutic aspects of childhood kerosene poisoning in Djibouti.

PubMed

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

2009-10-01

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

How Safe Are Kid-Safe Search Engines?

ERIC Educational Resources Information Center

Masterson-Krum, Hope

2001-01-01

Examines search tools available to elementary and secondary school students, both human-compiled and crawler-based, to help direct them to age-appropriate Web sites; analyzes the procedures of search engines labeled family-friendly or kid safe that use filters; and tests the effectiveness of these services to students in school libraries. (LRW)

SOME PROBLEMS OF "SAFE DOSE" ESTIMATION

EPA Science Inventory

In environmental carcinogenic risk assessment, the usually defined "safe doses" appear subjective in some sense. n this paper a method of standardizing "safe doses" based on some objective parameters is introduced and a procedure of estimating safe doses under the competing risks...

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

PubMed

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

2015-07-01

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

Expensing options solves nothing.

PubMed

Sahlman, William A

2002-12-01

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

Distributed Energy Implementation Options

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

Shah, Chandralata N

2017-09-13

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

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

PubMed

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

2018-09-01

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

Liver cell-targeted delivery of therapeutic molecules.

PubMed

Kang, Jeong-Hun; Toita, Riki; Murata, Masaharu

2016-01-01

The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

Therapeutic lighting design for the elderly: a review.

PubMed

Shikder, Shariful; Mourshed, Monjur; Price, Andrew

2012-11-01

Research suggests that specialised lighting design is essential to cater for the elderly users of a building because of reduced visual performance with increased age. This review aims to document what is known of the physical and psychological aspects of lighting and their role in promoting a healthy and safe environment for the elderly. A methodical review was carried out of published literature on the physical and psychological impacts of light on the elderly. Design standards and guides from professional organizations were evaluated to identify synergies and gaps between the evidence base and current practice. Lighting has been identified as a significant environmental attribute responsible for promoting physical and mental health of the elderly. The evidence related to visual performance was found to be robust. However, guides and standards appeared to have focused mostly on illumination requirements for specific tasks and have lacked detailed guidelines on vertical lighting and luminance design. This review has identified a growing body of evidence on the therapeutic benefits of lighting and its use in treating psychological disorders among the elderly. The experiments using light as a therapy have improved our understanding of the underlying principles, but the integration of therapeutic aspects of lighting in design practice and guidelines is lacking. While design guidelines discuss the physical needs of lighting for the elderly fairly well, they lack incorporation of photobiological impacts. Despite positive outcomes from research, the implementation of therapeutic aspects of lighting in buildings is still debatable due to insufficient relevant investigations and robustness of their findings. Collaborations between designers and physicians can contribute in delivering customised lighting solutions by considering disease types and needs. Further investigation needs to be carried out for translating therapeutic benefits to photometric units to implement them

Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

PubMed

Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

2014-06-01

All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

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).

Using Opioids Safely After Surgery

MedlinePlus

... Adult , Geriatric Using Opioids Safely After Surgery Using Opioids Safely After Surgery Stick to the lowest dose ... need opioid pain medicine. If your doctor says opioids aren’t necessary. If your doctor thinks you ...

How Safe Is Safe Enough for Self-Driving Vehicles?

PubMed

Liu, Peng; Yang, Run; Xu, Zhigang

2018-05-21

Self-driving vehicles (SDVs) promise to considerably reduce traffic crashes. One pressing concern facing the public, automakers, and governments is "How safe is safe enough for SDVs?" To answer this question, a new expressed-preference approach was proposed for the first time to determine the socially acceptable risk of SDVs. In our between-subject survey (N = 499), we determined the respondents' risk-acceptance rate of scenarios with varying traffic-risk frequencies to examine the logarithmic relationships between the traffic-risk frequency and risk-acceptance rate. Logarithmic regression models of SDVs were compared to those of human-driven vehicles (HDVs); the results showed that SDVs were required to be safer than HDVs. Given the same traffic-risk-acceptance rates for SDVs and HDVs, their associated acceptable risk frequencies of SDVs and HDVs were predicted and compared. Two risk-acceptance criteria emerged: the tolerable risk criterion, which indicates that SDVs should be four to five times as safe as HDVs, and the broadly acceptable risk criterion, which suggests that half of the respondents hoped that the traffic risk of SDVs would be two orders of magnitude lower than the current estimated traffic risk. The approach and these results could provide insights for government regulatory authorities for establishing clear safety requirements for SDVs. © 2018 Society for Risk Analysis.

[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.

[Intratympanic injection therapy for therapy refractory acute hearing loss: A safe option for secondary treatment].

PubMed

Mühlmeier, G; Maier, S; Maier, M; Maier, H

2015-10-01

High-dose corticosteroids are currently recommended for idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. Intratympanic injections (ITI) are of growing importance, especially in cases of therapy resistance. The selection of patients for this procedure in SSNHL has not been adequately examined so far. A total of 77 patients with ISSNHL after ineffective systemic pretreatment underwent intratympanic administration of dexamethasone and hyaluronic acid. Improvement after treatment was determined by pure tone audiometry for both ears before and of the treated ear after ITI. In this study 34 female and 43 male patients with mean age of 57 years showed a pre-ITI hearing loss of 35 dB in the lower frequencies and 69 dB in the higher frequencies. The mean hearing gain was 10 dB and the response rate was 62%. Absolute hearing gain revealed significant improvements at 500 Hz, 1 kHz and 2 kHz. Under inclusion of contralateral thresholds there were hardly any differences up to 4 kHz. In a detailed analysis of responders moderate improvements could be observed even in higher frequencies. Overall, no relevant adverse events occurred. Treatment of ISSNHL resistant to systemic regimens by ITI of steroids provides an option that offers additional prospects of auditory improvement for affected patients. The presented results indicate that these modalities are also valid for patients with pancochlear ISSNHL.

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

How to Safely Give Acetaminophen

MedlinePlus

... Educators Search English Español How to Safely Give Acetaminophen KidsHealth / For Parents / How to Safely Give Acetaminophen ... without getting a doctor's OK first. What Is Acetaminophen Also Called? Acetaminophen is the generic name of ...

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

PubMed

Rommer, Paulus S; Zettl, Uwe K

2018-04-01

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

Therapeutic enhancement of newly derived bacteriocins against Giardia lamblia.

PubMed

Amer, Eglal I; Mossallam, Shereen F; Mahrous, Hoda

2014-11-01

Trials for identifying efficient anti-giardial agents are still ongoing. Nowadays, bacteriocins have attracted the attention as potential antimicrobial compounds. For the first time, the current study evaluated the therapeutic efficacy of bacteriocins derived from newly isolated Egyptian strains of probiotics Lactobacilli; L. acidophilus (P106) and L. plantarum (P164) against Giardia lamblia. Bacteriocins' efficacy was evaluated both in vitro; by growth inhibition and adherence assays, and in vivo; through estimation of parasite density, intestinal histopathological examination and ultrastructural analysis of Giardia trophozoites. In vivo bacteriocins' clinical safety was assessed. In vitro results proved that 50 µg of L. acidophilus bacteriocin induced reduction of the mean Giardia lamblia trophozoites by 58.3 ± 4.04%, while at lower concentrations of 10 and 20 µg of both L. acidophilus and L. plantarum, non significant reduction of the mean parasite density was achieved. In vitro trophozoites adherence was susceptible to the tested bacteriocins at all studied concentrations with variable degrees, while the highest adherence reduction was demonstrated using 50 µg of L acidophilus bacteriocin. In vivo, oral inoculation of 50 µg/mouse L. acidophilus bacteriocin for 5 successive days resulted in a noteworthy decline of the intestinal parasite density, along with amelioration of intestinal pathology of infected mice. Ultrastructural examination proved thatfive doses of L. acidophilus bacteriocin showed marked changes in cellular architecture of the trophozoites with evident disorganization of the cell membrane, adhesive disc and cytoplasmic components. This is the first reported study of the safe anti-giardial efficacy of L. acidophilus (P106) derived bacteriocin, hence highlighting its great promise as a potential therapeutic safe alternative to existing commercial drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

Ab Interno Trabeculectomy With the Trabectome as a Valuable Therapeutic Option for Failed Filtering Blebs.

PubMed

Wecker, Thomas; Neuburger, Matthias; Bryniok, Laura; Bruder, Kathrin; Luebke, Jan; Anton, Alexandra; Jordan, Jens F

2016-09-01

Uncontrolled intraocular pressure (IOP) after glaucoma filtration surgery is a challenging problem in the management of glaucoma patients. The Trabectome is a device for selective electroablation of the trabecular meshwork through a clear cornea incision without affecting the conjunctiva. Minimally invasive glaucoma surgery using the Trabectome is safe and effective as primary glaucoma surgery. Here we investigate the results of ab interno trabeculectomy with the Trabectome for IOP control in patients with a failed filtering bleb. A total of 60 eyes of 60 consecutive patients with primary open-angle glaucoma (POAG) or pseudoexfoliative glaucoma (PXG) were enrolled in this single center observational study. Trabectome surgery was performed alone or in combination with phacoemulsification by 2 experienced surgeons. IOP readings and number of IOP lowering medication as primary outcome parameters were taken by an independent examiner. Intraoperative and postoperative medication were recorded systematically. Mean IOP before surgery was 24.5±3.5 mm Hg and decreased to 15.7±3.4 (-36%) after mean follow-up of 415 days. The number of necessary IOP lowering medication dropped from 2.1±1.3 to 1.8±1.2 (14% reduction from baseline). A total of 25% (n=15) of cases reported here needed additional surgery after 517 days (range: 6 to 1563 d). No major complications were observed. After mean follow-up, we found a qualified success rate for PXG of 87% and 50% for POAG as revealed by the Kaplan-Meier analysis according to the definitions for success in advanced glaucoma cases according to the World Glaucoma Association (40% reduction from baseline IOP and maximum IOP of 15 mm Hg). Trabectome surgery for uncontrolled IOP after trabeculectomy is safe and effective especially in PXG patients. Given the demanding subgroup of patients studied here, it is not surprising that success rates are lower compared with previous studies investigating the Trabectome for primary glaucoma surgery

Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias.

PubMed

Lichter-Konecki, Uta; Nadkarni, Vinay; Moudgil, Asha; Cook, Noah; Poeschl, Johannes; Meyer, Michael T; Dimmock, David; Baumgart, Stephen

2013-08-01

Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely. Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5°C±1°C for 72h, they were then slowly rewarmed by 0.5°C every 3h over 18h. In addition data of age-matched historic controls were collected for comparison. Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension. Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was

Safe Genetic Modification of Cardiac Stem Cells Using a Site-Specific Integration Technique

PubMed Central

Lan, Feng; Liu, Junwei; Narsinh, Kazim H.; Hu, Shijun; Han, Leng; Lee, Andrew S.; Karow, Marisa; Nguyen, Patricia K.; Nag, Divya; Calos, Michele P.; Robbins, Robert C.; Wu, Joseph C.

2012-01-01

Background Human cardiac progenitor cells (hCPCs) are a promising cell source for regenerative repair after myocardial infarction. Exploitation of their full therapeutic potential may require stable genetic modification of the cells ex vivo. Safe genetic engineering of stem cells, using facile methods for site-specific integration of transgenes into known genomic contexts, would significantly enhance the overall safety and efficacy of cellular therapy in a variety of clinical contexts. Methods and Results We employed the phiC31 site-specific recombinase to achieve targeted integration of a triple fusion reporter gene into a known chromosomal context in hCPCs and human endothelial cells (hECs). Stable expression of the reporter gene from its unique chromosomal integration site resulted in no discernible genomic instability or adverse changes in cell phenotype. Namely, phiC31-modified hCPCs were unchanged in their differentiation propensity, cellular proliferative rate, and global gene expression profile when compared to unaltered control hCPCs. Expression of the triple fusion reporter gene enabled multimodal assessment of cell fate in vitro and in vivo using fluorescence microscopy, bioluminescence imaging (BLI), and positron emission tomography (PET). Intramyocardial transplantation of genetically modified hCPCs resulted in significant improvement in myocardial function two weeks after cell delivery, as assessed by echocardiography (P = 0.002) and magnetic resonance imaging (P = 0.001). We also demonstrated the feasibility and therapeutic efficacy of genetically modifying differentiated hECs, which enhanced hindlimb perfusion (P<0.05 at day 7 and 14 after transplantation) on laser Doppler imaging. Conclusions The phiC31 integrase genomic modification system is a safe, efficient tool to enable site-specific integration of reporter transgenes in progenitor and differentiated cell types. PMID:22965984

48 CFR 570.401 - Renewal options.

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

PubMed

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

2016-08-01

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

Nelson Syndrome: Update on Therapeutic Approaches.

PubMed

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

2015-06-01

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

Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.

PubMed

Liu, Jia; Shui, Sai-Lan

2016-12-28

The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing. Copyright © 2016 Elsevier B.V. All rights reserved.

Bioactive Antimicrobial Peptides as Therapeutics for Corneal Wounds and Infections

PubMed Central

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

2017-01-01

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

[Dendritic cell-based therapeutic cancer vaccines].

PubMed

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

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

Abort Options for Potential Mars Missions

NASA Technical Reports Server (NTRS)

Tartabini, P. V.; Striepe, S. A.; Powell, R. W.

1994-01-01

Mars trajectory design options were examined that would accommodate a premature termination of a nominal manned opposition class mission for opportunities between 2010 and 2025. A successful abort must provide a safe return to Earth in the shortest possible time consistent with mission constraints. In this study, aborts that provided a minimum increase in the initial vehicle mass in low Earth orbit (IMLEO) were identified by locating direct transfer nominal missions and nominal missions including an outbound or inbound Venus swing-by that minimized IMLEO. The ease with which these missions could be aborted while meeting propulsion and time constraints was investigated by examining free return (unpowered) and powered aborts. Further reductions in trip time were made to some aborts by the addition or removal of an inbound Venus swing-by. The results show that, although few free return aborts met the specified constraints, 85% of each nominal mission could be aborted as a powered abort without an increase in propellant. Also, in many cases, the addition or removal of a Venus swing-by increased the number of abort opportunities or decreased the total trip time during an abort.

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.…

Alternative Options for Safe Drinking Water in Arsenic and Salinity Affected Bornal-Iliasabad Union of Kalia Upazila, Narail District, Bangladesh

NASA Astrophysics Data System (ADS)

Rahman, M. M.; Hasan, M. A.; Ahmed, K. M.; Nawrin, N.

2016-12-01

The study area, Bornal-Ilisabad union, Kalia, Narail is one of the most vulnerable areas of Bangladesh in terms of access to safe drinking water. Shallow groundwater of this area is highly arsenic contaminated (mostly >500 μg/L) and deep groundwater is saline (EC ranges 1 to 8 mS/cm). Local communities rely on rainwater for drinking and cooking purposes during the monsoon and rest of the year they use surface water from pond which are mostly polluted. In areas where surface water is not available people are compelled to use arsenic contaminated groundwater and thus exposing themselves to serious health hazard. Principal objective of the research is to evaluate the effectiveness of managed aquifer recharge (MAR) and subsurface arsenic removal (SAR) technology in mitigating groundwater salinity and arsenic, to provide alternative sources of safe water. Surface water (pond water) and rainwater collected from roof top are used as source water to be recharged into the target aquifer for the MAR system. Source water is filtered through a sand filtration unit to remove turbidity and microorganisms before recharging through infiltration wells. For SAR system, on the other hand, a certain volume (2000L) of groundwater is abstracted from the target aquifer and then aerated for about half an hour to saturate with oxygen. The oxygenated water is injected into the aquifer and kept there for 6-8 hours and then abstracted for use. The MAR system constructed in the study area is found very effective in reducing groundwater salinity. The electrical conductivity (EC) of the groundwater of MAR system has been reduced 72-81% from the initial EC value of 3.4 mS/cm. A significant improvement in groundwater arsenic and iron concentration is also observed. The system is yielding groundwater with arsenic within permissible limit of Bangladesh drinking water standard (50 μg/L) which was 100 μg/L before introduction of MAR system. The SAR system is also found effective in reducing

Therapeutic monoclonal antibodies in human breast milk: a case study.

PubMed

Ross, Elle; Robinson, Steven E; Amato, Carol; McMillan, Colette; Westcott, Jay; Wolf, Tiffany; Robinson, William A

2014-04-01

Recently, therapeutic monoclonal antibodies have been introduced for the treatment of advanced melanoma and other diseases. It remains unclear whether these drugs can be safely administered to women who are breast feeding because of the potential hazardous side effects for nursing infants. One such therapy for metastatic melanoma is ipilimumab, a human monoclonal antibody that blocks cytotoxic T-lymphocyte-antigen-4, and is the preferred treatment for patients with metastatic melanoma when other molecular therapies are not viable. This study measured ipilimumab levels in the breast milk of a patient undergoing treatment that were enough to raise concerns for a nursing infant exposed to ipilimumab.

An Unusual Complication With the Administration of a Volatile Anesthetic Agent for Status Asthmaticus in the Pediatric Intensive Care Unit: Case Report and Review of the Literature.

PubMed

Shutes, Brittany; Frazier, W Joshua; Tobias, Joseph D

2017-07-01

In severe cases of status asthmaticus, when conventional therapies fail, volatile anesthetic agents remain a therapeutic option. When delivered outside of the operating room setting, specialized delivery techniques are needed to ensure the safe and effective use of volatile anesthetic agents. We present a 16-year-old adolescent with status asthmaticus who required the therapeutic administration of the volatile anesthetic agent, sevoflurane, in the pediatric intensive care unit (PICU). Although initially effective in reducing bronchospasm, progressive hypercarbia developed due to defective functioning of the carbon dioxide absorber of the anesthesia machine. This failure occurred as the soda lime compartment filled with water accumulated from circuit humidification and continuous albuterol therapy. The role of volatile anesthetic agents in the treatment of status asthmaticus in the PICU is discussed, options for delivery outside of the operating room presented, and potential problems with delivery reviewed.

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

InaSAFE applications in disaster preparedness

NASA Astrophysics Data System (ADS)

Pranantyo, Ignatius Ryan; Fadmastuti, Mahardika; Chandra, Fredy

2015-04-01

Disaster preparedness activities aim to reduce the impact of disasters by being better prepared to respond when a disaster occurs. In order to better anticipate requirements during a disaster, contingency planning activities can be undertaken prior to a disaster based on a realistic disaster scenario. InaSAFE is a tool that can inform this process. InaSAFE is a free and open source software that estimates the impact to people and infrastructure from potential hazard scenarios. By using InaSAFE, disaster managers can develop scenarios of disaster impacts (people and infrastructures affected) to inform their contingency plan and emergency response operation plan. While InaSAFE provides the software framework exposure data and hazard data are needed as inputs to run this software. Then InaSAFE can be used to forecast the impact of the hazard scenario to the exposure data. InaSAFE outputs include estimates of the number of people, buildings and roads are affected, list of minimum needs (rice and clean water), and response checklist. InaSAFE is developed by Indonesia's National Disaster Management Agency (BNPB) and the Australian Government, through the Australia-Indonesia Facility for Disaster Reduction (AIFDR), in partnership with the World Bank - Global Facility for Disaster Reduction and Recovery (GFDRR). This software has been used in many parts of Indonesia, including Padang, Maumere, Jakarta, and Slamet Mountain for emergency response and contingency planning.

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.

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.

Strategy escalation: an emerging paradigm for safe clinical development of T cell gene therapies.

PubMed

Junghans, Richard Paul

2010-06-10

Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs) for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

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

Treatment Options for Severe Obesity in the Pediatric Population: Current Limitations and Future Opportunities.

PubMed

Ryder, Justin R; Fox, Claudia K; Kelly, Aaron S

2018-06-01

Severe obesity is the only obesity classification increasing in prevalence among children and adolescents. Treatment options that produce meaningful and sustained weight loss and comorbidity resolution are urgently needed. The purpose of this review is to provide a brief overview of the current treatment options for pediatric severe obesity and offer suggestions regarding future opportunities for accelerating the development and evaluation of innovative treatment strategies. At present, there are three treatment options for youth with severe obesity: lifestyle modification therapy, pharmacotherapy, and bariatric surgery. Lifestyle modification therapy can be useful for improving many chronic disease risk factors and comorbid conditions but often fails to achieve clinically meaningful and sustainable weight loss. Pharmacotherapy holds promise as an effective adjunctive treatment but remains in the primordial stages of development in the pediatric population. Bariatric surgery provides robust weight loss and risk factor/comorbidity improvements but is accompanied by higher risks and lower uptake compared to lifestyle modification therapy and pharmacotherapy. New areas worth pursuing include combination pharmacotherapy, device therapy, identification of predictors of response aimed at precision treatment, and interventions in the postbariatric surgical setting to improve long-term outcomes. Treating pediatric severe obesity effectively and safely is extremely challenging. Some progress has been made, but substantially more effort and innovation are needed in the future to combat this serious and ongoing medical and public health issue. © 2018 The Obesity Society.

Amotosalen-inactivated plasma is as equally well tolerated as quarantine plasma in patients undergoing large volume therapeutic plasma exchange.

PubMed

Guignier, C; Benamara, A; Oriol, P; Coppo, P; Mariat, C; Garraud, O

2018-02-01

A retrospective - single center - survey compared tolerance of individual donor therapeutic plasma in a series of 88 patients principally presenting with thrombotic microangiopathy; all patients underwent therapeutic plasma exchange (TPE) performed with more than 90% of either of two types of plasma preparations. One plasma type used in TPE was prepared with pathogen reduction by amotosalen addition and UVA illumination, and the other one was non-manipulated (quarantine plasma). Both types of plasma were single donor. Occurrences of adverse reactions were equally low in either arm (amotosalen: 9 in 4689 bags of ∼200mL [0.019] versus quarantine: 2 in 828 bags [0.024]), confirming the safe use of amotosalen inactivated therapeutic plasma for TPE. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Therapeutic and prevention strategies against human enterovirus 71 infection

PubMed Central

Kok, Chee Choy

2015-01-01

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

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

Safe Schools, Safe Students. Proceedings of the National Education Goals Panel/National Alliance of Pupil Services Organizations Conference on "Safe Schools, Safe Students: A Collaborative Approach to Achieving Safe, Disciplined, and Drug-free Schools Conducive to Learning" (Washington, D.C., October 28-29, 1994).

ERIC Educational Resources Information Center

Talley, Ronda C., Ed.; Walz, Garry R., Ed.

The "Safe Schools, Safe Students" conference brought together leading researchers and practitioners in order to share knowledge about innovative safety strategies being used in America's schools. The papers here represent the thinking of scientific experts and school-based pupil service providers who are implementing programs to prevent…

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

Exploring Therapeutic Potential Of Nanocarrier Systems Against Breast Cancer.

PubMed

Kumar, Lalit; Baldi, Ashish; Verma, Shivani; Utreja, Puneet

2018-06-03

Breast cancer is most widely occurring non-cutaneous cancer in women. Treatment options available for breast cancer are limited and there are a number of toxicity concerns associated with them. Therefore, nanocarrier based approaches have been explored for breast cancer treatment. Nanocarriers implemented for breast cancer treatment are nanoliposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, dendrimers, and protein nanocages. Objective of this review was to explore the therapeutic efficacy of various nanocarrier systems against breast cancer. Existing literature regarding nanocarrier systems for breast cancer therapy was reviewed using Pubmed and Google Scholar. Nanocarriers may show prolonged circulation time of chemotherapeutic agent with efficient breast tumor targeting. Both active and passive targeting methodologies can be explored to target breast cancer cells using different nanocarriers. Targeted nanocarriers have the capability to reduce side effects caused by various conventional formulations used to treat breast cancer. Various nanocarriers listed above have shown their therapeutic potential in preclinical studies to treat breast cancer. Satisfactory clinical evaluation and scale up techniques can promote their entry into the pharmaceutical market in greater extent. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Steering teens safe: a randomized trial of a parent-based intervention to improve safe teen driving.

PubMed

Peek-Asa, Corinne; Cavanaugh, Joseph E; Yang, Jingzhen; Chande, Vidya; Young, Tracy; Ramirez, Marizen

2014-07-31

Crashes are the leading cause of death for teens, and parent-based interventions are a promising approach. We assess the effectiveness of Steering Teens Safe, a parent-focused program to increase safe teen driving. Steering Teens Safe aimed to improve parental communication with teens about safe driving using motivational interviewing techniques in conjunction with 19 safe driving lessons. A randomized controlled trial involved 145 parent-teen dyads (70 intervention and 75 control). Intervention parents received a 45-minute session to learn the program with four follow-up phone sessions, a DVD, and a workbook. Control parents received a standard brochure about safe driving. Scores were developed to measure teen-reported quantity and quality of parental communication about safe driving. The main outcome measure was a previously validated Risky Driving Score reported by teens. Because the Score was highly skewed, a generalized linear model based on a gamma distribution was used for analysis. Intervention teens ranked their parent's success in talking about driving safety higher than control teens (p = 0.035) and reported that their parents talked about more topics (non-significant difference). The Risky Driving Score was 21% lower in intervention compared to control teens (85% CI = 0.60, 1.00). Interaction between communication quantity and the intervention was examined. Intervention teens who reported more successful communication had a 42% lower Risky Driving Score (95% CI = 0.37, 0.94) than control parents with less successful communication. This program had a positive although not strong effect, and it may hold the most promise in partnership with other programs, such as Driver's Education or Graduated Driver's License policies. ClinicalTrials.gov NCT01014923. Registered Nov. 16, 2009.

Chemoembolic Hepatopulmonary Shunt Reduction to Allow Safe Yttrium-90 Radioembolization Lobectomy of Hepatocellular Carcinoma

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

Gaba, Ron C., E-mail: rgaba@uic.edu; VanMiddlesworth, Kyle A.

2012-12-15

Yttrium-90 ({sup 90}Y) radioembolization represents an emerging transcatheter treatment option for the management of hepatocellular carcinoma (HCC). Elevation of the hepatopulmonary shunt fraction risks nontarget radiation to the lungs and may limit the use of {sup 90}Y therapy in patients with locally advanced disease with vascular invasion, who often demonstrate increased shunting. We present two cases in which patients with HCC and portal vein invasion resulting in elevated hepatopulmonary shunt fractions underwent chemoembolic shunt closure to allow safe {sup 90}Y radioembolization. Both patients demonstrated excellent tumor response and patient survival. On this basis, we propose a role for chemoembolic reductionmore » of the lung shunt fraction before {sup 90}Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.« less

Consumer Satisfaction with Psychiatric Services: The Role of Shared Decision-Making and the Therapeutic Relationship

PubMed Central

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

2017-01-01

Objective Although dissatisfaction is a primary reason for disengagement from outpatient psychiatric care among consumers with serious mental illnesses, little is known about predictors of their satisfaction with medication management visits. The primary purpose of the present study was to explore how dimensions of consumer preferences for shared decision-making (i.e., preferences for obtaining knowledge about one’s mental illness, being offered and asked one’s opinion about treatment options, and involvement in treatment decisions) and the therapeutic relationship (i.e., positive collaboration and type of clinician input) were related to visit satisfaction. Methods Participants were 228 Veterans with serious mental illnesses who completed a 19-item self-report questionnaire assessing satisfaction with visits to prescribers (n=524 assessments) immediately after visits. In this correlational design, a 3-level mixed model with the restricted maximum likelihood estimation procedure was used to examine shared decision-making preferences and therapeutic alliance as predictors of visit satisfaction. Results Preferences for involvement in treatment decisions was the unique component of shared decision-making associated with satisfaction, such that the more consumers desired involvement, the less satisfied they were. Positive collaboration and prescriber input were associated with greater visit satisfaction. Conclusions and Implications for Practice When consumers with serious mental illnesses express preferences to be involved in shared decision-making, it may not be sufficient to only provide information and treatment options; prescribers should attend to consumers’ interest in involvement in actual treatment decisions. Assessment and tailoring of treatment approaches to consumer preferences for shared decision-making should occur within the context of a strong therapeutic relationship. PMID:25664755

48 CFR 17.107 - Options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Options. 17.107 Section 17... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multiyear Contracting 17.107 Options. Benefits may accrue by including options in a multiyear contract. In that event, contracting officers must follow the requirements...

Safe biodegradable fluorescent particles

DOEpatents

Martin, Sue I [Berkeley, CA; Fergenson, David P [Alamo, CA; Srivastava, Abneesh [Santa Clara, CA; Bogan, Michael J [Dublin, CA; Riot, Vincent J [Oakland, CA; Frank, Matthias [Oakland, CA

2010-08-24

A human-safe fluorescence particle that can be used for fluorescence detection instruments or act as a safe simulant for mimicking the fluorescence properties of microorganisms. The particle comprises a non-biological carrier and natural fluorophores encapsulated in the non-biological carrier. By doping biodegradable-polymer drug delivery microspheres with natural or synthetic fluorophores, the desired fluorescence can be attained or biological organisms can be simulated without the associated risks and logistical difficulties of live microorganisms.

48 CFR 2917.207 - Exercising options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Exercising options. 2917... AND CONTRACT TYPES SPECIAL CONTRACTING METHODS Options 2917.207 Exercising options. The contracting officer must use a standardized determination and finding before exercising an option in accordance with...

Safe Haven.

ERIC Educational Resources Information Center

Bush, Gail

2003-01-01

Discusses school libraries as safe havens for teenagers and considers elements that foster that atmosphere, including the physical environment, lack of judgments, familiarity, leisure, and a welcoming nature. Focuses on the importance of relationships, and taking the time to listen to teens and encourage them. (LRW)

New therapeutic approaches for treatment of tularaemia: a review.

PubMed

Boisset, Sandrine; Caspar, Yvan; Sutera, Vivien; Maurin, Max

2014-01-01

Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients' management and prognosis. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline), ketolides (telithromycin and cethromycin), and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin). The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors) on the course of F. tularensis infection was characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is

New therapeutic approaches for treatment of tularaemia: a review

PubMed Central

Boisset, Sandrine; Caspar, Yvan; Sutera, Vivien; Maurin, Max

2014-01-01

Antibiotic treatment of tularaemia is based on a few drugs, including the fluoroquinolones (e.g., ciprofloxacin), the tetracyclines (e.g., doxycycline), and the aminoglycosides (streptomycin and gentamicin). Because no effective and safe vaccine is currently available, tularaemia prophylaxis following proven exposure to F. tularensis also relies on administration of antibiotics. A number of reasons make it necessary to search for new therapeutic alternatives: the potential toxicity of first-line drugs, especially in children and pregnant women; a high rate of treatment relapses and failures, especially for severe and/or suppurated forms of the disease; and the possible use of antibiotic-resistant strains in the context of a biological threat. This review presents novel therapeutic approaches that have been explored in recent years to improve tularaemia patients' management and prognosis. These new strategies have been evaluated in vitro, in axenic media and cell culture systems and/or in animal models. First, the activities of newly available antibiotic compounds were evaluated against F. tularensis, including tigecycline (a glycylcycline), ketolides (telithromycin and cethromycin), and fluoroquinolones (moxifloxacin, gatifloxacin, trovafloxacin and grepafloxacin). The liposome delivery of some antibiotics was evaluated. The effect of antimicrobial peptides against F. tularensis was also considered. Other drugs were evaluated for their ability to suppress the intracellular multiplication of F. tularensis. The effects of the modulation of the innate immune response (especially via TLR receptors) on the course of F. tularensis infection was characterized. Another approach was the administration of specific antibodies to induce passive resistance to F. tularensis infection. All of these studies highlight the need to develop new therapeutic strategies to improve the management of patients with tularaemia. Many possibilities exist, some unexplored. Moreover, it is

Old and new challenges in Parkinson's disease therapeutics.

PubMed

Pires, Ana O; Teixeira, F G; Mendes-Pinheiro, B; Serra, Sofia C; Sousa, Nuno; Salgado, António J

2017-09-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons and/or loss od neuronal projections, in several dopaminergic networks. Current treatments for idiopathic PD rely mainly on the use of pharmacologic agents to improve motor symptomatology of PD patients. Nevertheless, so far PD remains an incurable disease. Therefore, it is of utmost importance to establish new therapeutic strategies for PD treatment. Over the last 20 years, several molecular, gene and cell/stem-cell therapeutic approaches have been developed with the aim of counteracting or retarding PD progression. The scope of this review is to provide an overview of PD related therapies and major breakthroughs achieved within this field. In order to do so, this review will start by focusing on PD characterization and current treatment options covering thereafter molecular, gene and cell/stem cell-based therapies that are currently being studied in animal models of PD or have recently been tested in clinical trials. Among stem cell-based therapies, those using MSCs as possible disease modifying agents for PD therapy and, specifically, the MSCs secretome contribution to meet the clinical challenge of counteracting or retarding PD progression, will be more deeply explored. Copyright © 2017 Elsevier Ltd. All rights reserved.

Therapeutic Use of Cannabis in Inflammatory Bowel Disease

PubMed Central

Katz, Seymour

2016-01-01

The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. Epidemiologic data and human therapy studies reveal a possible role for cannabinoids in the symptomatic treatment of IBD, although it has yet to be determined in human populations whether cannabinoids have therapeutic anti-inflammatory effects in IBD or are simply masking its many debilitating symptoms. Large, double-blind, randomized, placebo-controlled trials using serial inflammatory markers, biopsy findings, and endoscopic disease severity to demonstrate objective improvement in IBD are necessary before cannabis can be empirically accepted and recommended as an IBD treatment option. Questions concerning its safety profile and adverse effects prompt the need for further research, particularly in regard to dosing and route of administration to maximize benefits and limit potential harms. Cannabis use should be reserved for symptomatic control in patients with severe IBD refractory to the currently available standard-of-care and complementary and alternative medicines. PMID:28035196

Current issues of RNAi therapeutics delivery and development.

PubMed

Haussecker, D

2014-12-10

12 years following the discovery of the RNAi mechanism in Man, a number of RNAi therapeutics development candidates have emerged with profiles suggesting that they could become drugs of significant medical importance for diseases like TTR amyloidosis, HBV, solid cancers, and hemophilia. Despite this robust progress, the perception of RNAi therapeutics has been on a roller-coaster ride driven not only by science, but also regulatory trends, the stock markets, and Big Pharma business development decisions [1]. This presentation provides an update on the current state of RNAi therapeutics development with a particular focus on what RNAi delivery can achieve today and key challenges to be overcome to expand therapeutic opportunities. The delivery of RNAi triggers to disease-relevant cell types clearly represents the rate-limiting factor in broadly expanding the applicability of RNAi therapeutics. Today, with at least 3 delivery options (lipid nanoparticles/LNPs, GalNAc-siRNA conjugates, Dynamic PolyConjugates/DPCs) for which profound gene knockdowns have been demonstrated in non-human primates and in the clinic, RNAi therapeutics should in principle be able to address most diseases related to gene expression in the liver. Given the central importance of the liver in systemic physiology, this already represents a significant therapeutic and commercial opportunity rivaling that of e.g. monoclonal antibodies. Beyond the liver, there is a reason to believe that current RNAi therapeutics technologies can address a number of solid tumors (e.g. LNPs), diseases of the eye (e.g. self-delivering RNAi triggers) as well as diseases involving the respiratory epithelium (e.g. aerosolized LNPs), certain phagocytic cells (LNPs), hematopoietic stem cells and their progeny (lentiviral DNA-directed RNAi), vascular endothelial cells (cationic lipoplexes), and certain cell types in the kidney (self-delivering RNAi triggers, DPCs; Table 1). Despite this success, there has been a sense that

Efficacy and safety of electroconvulsive therapy in the first trimester of pregnancy: a case of severe manic catatonia.

PubMed

Pinna, Martina; Manchia, Mirko; Pillai, Gianluca; Salis, Piergiorgio; Minnai, Gian Paolo

2015-08-01

Electroconvulsive therapy (ECT) is an appropriate, albeit often neglected, option for managing severe or life-threatening psychiatric symptoms during pregnancy. We report on the rapid effectiveness and safety of ECT during the first trimester of pregnancy in a 28-year-old woman with severe catatonia. Catatonic symptoms were assessed using the Catatonia Rating Scale (CRS). The patient was treated with unilateral ECT using left anterior right temporal (LART) placement. Seizure quality and duration were monitored by a two-lead electroencephalograph (EEG) and by one-lead electromyography (EMG). During each ECT session, the fetal heart rate was monitored with electrocardiogram (ECG). After the second ECT treatment (day 13 of hospitalization), we observed remission of the catatonic symptoms, as shown by the drop in the CRS score from 22 to 0. No cognitive abnormalities were reported and no gynecological complications were detected (e.g. vaginal bleeding, abdominal pain, or uterine contraction). The patient delivered at term a healthy male neonate who presented normal growth as well as normal psychomotor development. This case highlights the effectiveness of ECT in treating severe catatonic mania during the first 3 months of pregnancy. In addition, ECT proved to be a safe therapeutic option, since neither mother nor infant experienced any adverse event. We suggest that ECT might be considered as a valid and safe option in the therapeutic decision-making process when catatonic symptoms manifest during pregnancy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

38 CFR 6.10 - Options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 6.10 Section 6.10 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS UNITED STATES GOVERNMENT LIFE INSURANCE Optional Settlement § 6.10 Options. Insurance will be payable in one sum only when...

Right and left partial iatrogenic injuries of the biliary tree. Therapeutic options.

PubMed

Mercado, Miguel Angel; Domínguez, Ismael; Arriola, Juan Carlos; Ramirez-Del Val, Fernando; Urencio, Miguel; Sánchez-Fernández, Norberto

2010-01-01

Bile duct injuries (BDI) have a wide array of presentation. Left partial injuries (Strasberg D) of the hepatic duct are the result of excessive traction, which dissects the hepatic hilum and provokes medial perforations without continuity loss. Right partial injuries (Strasberg A, B and C) are produced by direct damage to the hepatic duct or isolated injury to the right and accessory ducts. It is important to determine frequency, spectrum and treatment outcome of this BDI in the surgical scenario. Patients with BDI who underwent surgical treatment in our hospital were reviewed, right and left partial injuries were selected. Demographic, clinical and therapeutic data were analyzed. In a 16-year period, 405 patients underwent surgical treatment of BDI. 31 (8%) were classified as a left partial injury (Strasberg D): 23 injuries at the common hepatic duct treated with a Hepatojejunostomy (HJ); four at the confluence level which received a HJ with neoconfluence construction; two partial injuries in the left hepatic duct underwent a selective left HJ; and two complete occlusions of the left hepatic duct, one treated with a partial hepatectomy and the last case underwent a partial HJ. Right partial injuries (Strasberg A, B or C) were identified in 21 cases (5%), their treatment was tailored according to the type of BDI (conservative, selective HJ, or hepatectomy). In our series the frequency of left and right partial BDI injuries was 8% and 5%, respectively. The spectrum of analyzed injuries included four subtypes for the left partial and eight for the right partial lesions. Most BDI in the two analyzed groups presented concomitant devascularization of the extra-hepatic ducts, therefore receiving surgical treatment rather than endoscopic treatment was done.

Gentamicin-intercalated smectite as a new therapeutic option for Helicobacter pylori eradication.

PubMed

Jeong, Su Jin; Kim, Jie-Hyun; Jung, Da Hyun; Lee, Kyoung Hwa; Park, Soon Young; Song, Yungoo; Kang, Il-Mo; Song, Young Goo

2018-02-12

Novel antibacterial strategies against Helicobacter pylori are needed because H. pylori strains are acquiring resistance to antibiotics. We evaluated the efficacy of gentamicin-intercalated smectite hybrid (S-GEN)-based treatment regimens in a murine model of H. pylori infection. Two groups of 10 rats were administered either smectite or S-GEN to measure coverage of the gastric mucosa. To evaluate anti-H. pylori efficacy, mice were divided into eight groups of 10 mice each given different treatments, and H. pylori eradication was assessed by a Campylobacter-like organism (CLO) test and H. pylori PCR of the gastric mucosa, and H. pylori antigen and H. pylori PCR analysis of mouse faeces. The levels of proinflammatory cytokines were examined. S-GEN was retained in the gastric mucosal layer with a >60% distribution ratio for up to 1 h, and the S-GEN-based triple regimen decreased bacterial burden in vivo compared with that of untreated mice or mice treated with other regimens. The cure rates in the CLO test and H. pylori PCR from gastric mucosa were 70%, 60%, 80%, 50%, 60% and 60% in Groups III-VIII, respectively. Those for H. pylori PCR in the faeces of mice were 90% and 100% in Group III with standard therapy and Group V with triple therapy including S-GEN, respectively. S-GEN triple therapy also reduced the levels of proinflammatory cytokines. These results suggest that S-GEN is a promising and effective therapeutic agent for the treatment of H. pylori infection. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Therapeutic Symptomatic Strategies in the Parasomnias.

PubMed

Manni, Raffaele; Toscano, Gianpaolo; Terzaghi, Michele

2018-06-05

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

Derivation and validation of a novel risk score for safe discharge after acute lower gastrointestinal bleeding: a modelling study.

PubMed

Oakland, Kathryn; Jairath, Vipul; Uberoi, Raman; Guy, Richard; Ayaru, Lakshmana; Mortensen, Neil; Murphy, Mike F; Collins, Gary S

2017-09-01

Acute lower gastrointestinal bleeding is a common reason for emergency hospital admission, and identification of patients at low risk of harm, who are therefore suitable for outpatient investigation, is a clinical and research priority. We aimed to develop and externally validate a simple risk score to identify patients with lower gastrointestinal bleeding who could safely avoid hospital admission. We undertook model development with data from the National Comparative Audit of Lower Gastrointestinal Bleeding from 143 hospitals in the UK in 2015. Multivariable logistic regression modelling was used to identify predictors of safe discharge, defined as the absence of rebleeding, blood transfusion, therapeutic intervention, 28 day readmission, or death. The model was converted into a simplified risk scoring system and was externally validated in 288 patients admitted with lower gastrointestinal bleeding (184 safely discharged) from two UK hospitals (Charing Cross Hospital, London, and Hammersmith Hospital, London) that had not contributed data to the development cohort. We calculated C statistics for the new model and did a comparative assessment with six previously developed risk scores. Of 2336 prospectively identified admissions in the development cohort, 1599 (68%) were safely discharged. Age, sex, previous admission for lower gastrointestinal bleeding, rectal examination findings, heart rate, systolic blood pressure, and haemoglobin concentration strongly discriminated safe discharge in the development cohort (C statistic 0·84, 95% CI 0·82-0·86) and in the validation cohort (0·79, 0·73-0·84). Calibration plots showed the new risk score to have good calibration in the validation cohort. The score was better than the Rockall, Blatchford, Strate, BLEED, AIMS65, and NOBLADS scores in predicting safe discharge. A score of 8 or less predicts a 95% probability of safe discharge. We developed and validated a novel clinical prediction model with good discriminative

Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene.

PubMed

van Til, Niek P; de Boer, Helen; Mashamba, Nomusa; Wabik, Agnieszka; Huston, Marshall; Visser, Trudi P; Fontana, Elena; Poliani, Pietro Luigi; Cassani, Barbara; Zhang, Fang; Thrasher, Adrian J; Villa, Anna; Wagemaker, Gerard

2012-10-01

Recombination activating gene 2 (RAG2) deficiency results in severe combined immunodeficiency (SCID) with complete lack of T and B lymphocytes. Initial gammaretroviral gene therapy trials for other types of SCID proved effective, but also revealed the necessity of safe vector design. We report the development of lentiviral vectors with the spleen focus forming virus (SF) promoter driving codon-optimized human RAG2 (RAG2co), which improved phenotype amelioration compared to native RAG2 in Rag2(-/-) mice. With the RAG2co therapeutic transgene, T-cell receptor (TCR) and immunoglobulin repertoire, T-cell mitogen responses, plasma immunoglobulin levels and T-cell dependent and independent specific antibody responses were restored. However, the thymus double positive T-cell population remained subnormal, possibly due to the SF virus derived element being sensitive to methylation/silencing in the thymus, which was prevented by replacing the SF promoter by the previously reported silencing resistant element (ubiquitous chromatin opening element (UCOE)), and also improved B-cell reconstitution to eventually near normal levels. Weak cellular promoters were effective in T-cell reconstitution, but deficient in B-cell reconstitution. We conclude that immune functions are corrected in Rag2(-/-) mice by genetic modification of stem cells using the UCOE driven codon-optimized RAG2, providing a valid optional vector for clinical implementation.

48 CFR 317.107 - Options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Options. 317.107 Section... CONTRACT TYPES SPECIAL CONTRACTING METHODS Multi-year Contracting 317.107 Options. When used as part of a multi-year contract, options shall not be used to extend the performance of the original requirement for...

38 CFR 8.25 - Options.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Options. 8.25 Section 8.25 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS NATIONAL SERVICE LIFE INSURANCE Optional Settlements § 8.25 Options. Insurance will be paid in a lump sum only when selected by...

Bounds for Asian basket options

NASA Astrophysics Data System (ADS)

Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

2008-09-01

In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

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

PubMed

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

2017-05-19

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

More than a Safe Space