Cancer-associated fibroblasts as target and tool in cancer therapeutics and diagnostics.

PubMed

De Vlieghere, Elly; Verset, Laurine; Demetter, Pieter; Bracke, Marc; De Wever, Olivier

2015-10-01

Cancer-associated fibroblasts (CAFs) are drivers of tumour progression and are considered as a target and a tool in cancer diagnostic and therapeutic applications. An increased abundance of CAFs or CAF signatures are recognized as a bad prognostic marker in several cancer types. Tumour-environment biomimetics strongly improve our understanding of the communication between CAFs, cancer cells and other host cells. Several experimental drugs targeting CAFs are in clinical trials for multiple tumour entities; alternatively, CAFs can be exploited as a tool to characterize the functionality of circulating tumour cells or to capture them as a tool to prevent metastasis. The continuous interaction between tissue engineers, biomaterial experts and cancer researchers creates the possibility to biomimic the tumour-environment and provides new opportunities in cancer diagnostics and management.

Robotic Seals as Therapeutic Tools in an Aged Care Facility: A Qualitative Study

PubMed Central

Bodak, Marie; Barlas, Joanna; Harwood, June; Pether, Mary

2016-01-01

Robots, including robotic seals, have been used as an alternative to therapies such as animal assisted therapy in the promotion of health and social wellbeing of older people in aged care facilities. There is limited research available that evaluates the effectiveness of robot therapies in these settings. The aim of this study was to identify, explore, and describe the impact of the use of Paro robotic seals in an aged care facility in a regional Australian city. A qualitative, descriptive, exploratory design was employed. Data were gathered through interviews with the three recreational therapists employed at the facility who were also asked to maintain logs of their interactions with the Paro and residents. Data were transcribed and thematically analysed. Three major themes were identified from the analyses of these data: “a therapeutic tool that's not for everybody,” “every interaction is powerful,” and “keeping the momentum.” Findings support the use of Paro as a therapeutic tool, revealing improvement in emotional state, reduction of challenging behaviours, and improvement in social interactions of residents. The potential benefits justify the investment in Paro, with clear evidence that these tools can have a positive impact that warrants further exploration. PMID:27990301

Measurement Tools for Integrated Worker Health Protection and Promotion: Lessons Learned From the SafeWell Project.

PubMed

Pronk, Nicolaas P; McLellan, Deborah L; McGrail, Michael P; Olson, Shawn M; McKinney, Zeke J; Katz, Jeffrey N; Wagner, Gregory R; Sorensen, Glorian

2016-07-01

To describe (a) a conceptual approach, (b) measurement tools and data collection processes, (c) characteristics of an integrated feedback report and action plan, and (d) experiences of three companies with an integrated measurement approach to worker safety and health. Three companies implemented measurement tools designed to create an integrated view of health protection and promotion based on organizational- and individual-level assessments. Feedback and recommended actions were presented following assessments at baseline and 1-year follow-up. Measurement processes included group dialogue sessions, walk-through, online surveys, and focus groups. The approach and measurement tools generated actionable recommendations and documented changes in the physical (eg, safety hazards) and psychosocial (eg, health and safety culture) work environment between baseline and 1-year follow-up. The measurement tools studied were feasible, acceptable, and meaningful to companies in the SafeWell study.

Home Safe Home: Appliances, Tools, and Small Equipment. Proceed with Caution: Consumer Safety in the Home, III.

ERIC Educational Resources Information Center

Saskatchewan Consumer and Commercial Affairs, Regina.

Many accidents in the home are caused by faulty, defective or improperly designed tools, appliances, and equipment. Government, non-governmental organizations, and industries cooperate to develop and implement standards for the safe design and manufacture of consumer products. This booklet provides information to help consumers select products,…

Animal Toxins as Therapeutic Tools to Treat Neurodegenerative Diseases

PubMed Central

de Souza, Jessica M.; Goncalves, Bruno D. C.; Gomez, Marcus V.; Vieira, Luciene B.; Ribeiro, Fabiola M.

2018-01-01

Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death. Venoms are fruitful natural sources of new molecules, which have been relentlessly enhanced by evolution through natural selection. Several studies indicate that venom components can exhibit selectivity and affinity for a wide variety of targets in mammalian systems. For instance, an expressive number of natural peptides identified in venoms from animals, such as snakes, scorpions, bees, and spiders, were shown to lessen inflammation, regulate glutamate release, modify neurotransmitter levels, block ion channel activation, decrease the number of protein aggregates, and increase the levels of neuroprotective factors. Thus, these venom components hold potential as therapeutic tools to slow or even halt neurodegeneration. However, there are many technological issues to overcome, as venom peptides are hard to obtain and characterize and the amount obtained from natural sources is insufficient to perform all the necessary experiments and tests. Fortunately, technological improvements regarding heterologous protein expression, as well as peptide chemical synthesis will help to provide enough quantities and allow chemical and pharmacological enhancements of these natural occurring compounds. Thus, the main focus of this review is to highlight the most promising studies evaluating animal toxins as therapeutic tools to treat a wide variety of neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, brain

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.

Making and Executing Decisions for Safe and Independent Living (MED-SAIL): development and validation of a brief screening tool.

PubMed

Mills, Whitney L; Regev, Tziona; Kunik, Mark E; Wilson, Nancy L; Moye, Jennifer; McCullough, Laurence B; Naik, Aanand D

2014-03-01

Older adults prefer to remain in their own homes for as long as possible. The purpose of this article is to describe the development and preliminary validation of Making and Executing Decisions for Safe and Independent Living (MED-SAIL), a brief screening tool for capacity to live safely and independently in the community. Prospective preliminary validation study. Outpatient geriatrics clinic located in a community-based hospital. Forty-nine community-dwelling older adults referred to the clinic for a comprehensive capacity assessment. We examined internal consistency, criterion-based validity, concurrent validity, and accuracy of classification for MED-SAIL. The items included in MED-SAIL demonstrated internal consistency (5 items; α = 0.85). MED-SAIL was significantly correlated with the Independent Living Scales (r = 0.573, p ≤0.001) and instrumental activities of daily living (r = 0.440, p ≤0.01). The Mann-Whitney U test revealed significant differences between the no capacity and partial/full capacity classifications on MED-SAIL (U(48) = 60.5, Z = -0.38, p <0.0001). The area under the curve was 0.864 (95% confidence interval: 0.84-0.99). This study demonstrated the validity of MED-SAIL as a brief screening tool to identify older adults with impaired capacity for remaining safe and independent in their current living environment. MED-SAIL is useful tool for health and social service providers in the community for the purpose of referral for definitive capacity evaluation. Published by Elsevier Inc.

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

Enlight: A Comprehensive Quality and Therapeutic Potential Evaluation Tool for Mobile and Web-Based eHealth Interventions

PubMed Central

Faber, Keren; Mathur, Nandita; Kane, John M; Muench, Fred

2017-01-01

Background Studies of criteria-based assessment tools have demonstrated the feasibility of objectively evaluating eHealth interventions independent of empirical testing. However, current tools have not included some quality constructs associated with intervention outcome, such as persuasive design, behavior change, or therapeutic alliance. In addition, the generalizability of such tools has not been explicitly examined. Objective The aim is to introduce the development and further analysis of the Enlight suite of measures, developed to incorporate the aforementioned concepts and address generalizability aspects. Methods As a first step, a comprehensive systematic review was performed to identify relevant quality rating criteria in line with the PRISMA statement. These criteria were then categorized to create Enlight. The second step involved testing Enlight on 42 mobile apps and 42 Web-based programs (delivery mediums) targeting modifiable behaviors related to medical illness or mental health (clinical aims). Results A total of 476 criteria from 99 identified sources were used to build Enlight. The rating measures were divided into two sections: quality assessments and checklists. Quality assessments included usability, visual design, user engagement, content, therapeutic persuasiveness, therapeutic alliance, and general subjective evaluation. The checklists included credibility, privacy explanation, basic security, and evidence-based program ranking. The quality constructs exhibited excellent interrater reliability (intraclass correlations=.77-.98, median .91) and internal consistency (Cronbach alphas=.83-.90, median .88), with similar results when separated into delivery mediums or clinical aims. Conditional probability analysis revealed that 100% of the programs that received a score of fair or above (≥3.0) in therapeutic persuasiveness or therapeutic alliance received the same range of scores in user engagement and content—a pattern that did not appear in

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)

Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?

PubMed

Gopalakrishnan, Ranganath; Frolov, Andrey I; Knerr, Laurent; Drury, William J; Valeur, Eric

2016-11-10

Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.

Making and Executing Decisions for Safe and Independent Living (MED-SAIL): Development and Validation of a Brief Screening Tool

PubMed Central

Mills, Whitney L.; Regev, Tziona; Kunik, Mark E.; Wilson, Nancy L.; Moye, Jennifer; McCullough, Laurence B.; Naik, Aanand D.

2017-01-01

Objectives Older adults prefer to remain in their own homes for as long as possible. The purpose of this article is to describe the development and preliminary validation of Making and Executing Decisions for Safe and Independent Living (MED-SAIL), a brief screening tool for capacity to live safely and independently in the community. Design Prospective preliminary validation study. Setting Outpatient geriatrics clinic located in a community-based hospital. Participants Forty-nine community-dwelling older adults referred to the clinic for a comprehensive capacity assessment. Measurements We examined internal consistency, criterion-based validity, concurrent validity, and accuracy of classification for MED-SAIL. Results The items included in MED-SAIL demonstrated internal consistency (5 items; α = 0.85). MED-SAIL was significantly correlated with the Independent Living Scales (r = 0.573, p ≤ 0.001) and instrumental activities of daily living (r = 0.440, p ≤ 0.01). The Mann-Whitney U test revealed significant differences between the no capacity and partial/full capacity classifications on MED-SAIL (U(48) = 60.5, Z = −0.38, p <0.0001). The area under the curve was 0.864 (95% confidence interval: 0.84–0.99). Conclusions This study demonstrated the validity of MED-SAIL as a brief screening tool to identify older adults with impaired capacity for remaining safe and independent in their current living environment. MED-SAIL is useful tool for health and social service providers in the community for the purpose of referral for definitive capacity evaluation. PMID:23567420

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.

Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics

PubMed Central

Manning, M; Misicka, A; Olma, A; Bankowski, K; Stoev, S; Chini, B; Durroux, T; Mouillac, B; Corbani, M; Guillon, G

2012-01-01

We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V1a, V1b and V2 receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V1b receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V1a agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V2/V1a antagonist, conivaptan and the V2 antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V1a, V1b and V2 antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences. PMID:22375852

Enlight: A Comprehensive Quality and Therapeutic Potential Evaluation Tool for Mobile and Web-Based eHealth Interventions.

PubMed

Baumel, Amit; Faber, Keren; Mathur, Nandita; Kane, John M; Muench, Fred

2017-03-21

Studies of criteria-based assessment tools have demonstrated the feasibility of objectively evaluating eHealth interventions independent of empirical testing. However, current tools have not included some quality constructs associated with intervention outcome, such as persuasive design, behavior change, or therapeutic alliance. In addition, the generalizability of such tools has not been explicitly examined. The aim is to introduce the development and further analysis of the Enlight suite of measures, developed to incorporate the aforementioned concepts and address generalizability aspects. As a first step, a comprehensive systematic review was performed to identify relevant quality rating criteria in line with the PRISMA statement. These criteria were then categorized to create Enlight. The second step involved testing Enlight on 42 mobile apps and 42 Web-based programs (delivery mediums) targeting modifiable behaviors related to medical illness or mental health (clinical aims). A total of 476 criteria from 99 identified sources were used to build Enlight. The rating measures were divided into two sections: quality assessments and checklists. Quality assessments included usability, visual design, user engagement, content, therapeutic persuasiveness, therapeutic alliance, and general subjective evaluation. The checklists included credibility, privacy explanation, basic security, and evidence-based program ranking. The quality constructs exhibited excellent interrater reliability (intraclass correlations=.77-.98, median .91) and internal consistency (Cronbach alphas=.83-.90, median .88), with similar results when separated into delivery mediums or clinical aims. Conditional probability analysis revealed that 100% of the programs that received a score of fair or above (≥3.0) in therapeutic persuasiveness or therapeutic alliance received the same range of scores in user engagement and content-a pattern that did not appear in the opposite direction. Preliminary

Approaching Suspicious Substances Safely

NASA Technical Reports Server (NTRS)

2004-01-01

A mineral identification tool that was developed for NASA's Mars Rover Technology Development program is now serving as a powerful tool for U.S. law enforcement agencies and military personnel to identify suspicious liquid and solid substances. The tool can measure unknown substances through glass and plastic packaging materials with the RamanProbe(TradeMark) focused fiber-optic probe. The probe length can be extended up to 200 meters to enable users to analyze potentially dangerous substances at a safe distance. In many cases, the spectrometer and personnel are kept in a safe zone while the probe is positioned next to the sample being analyzed. Being able to identify chemicals in remote locations also saves users time and labor, since otherwise the samples would need to be collected, transported, and prepared prior to measurement in the laboratory.

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool.

PubMed

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo's time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo's time perspective offers both: 1) a potential diagnostic tool - the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD.

Laparohysteroscopy in female infertility: A diagnostic cum therapeutic tool in Indian setting.

PubMed

Puri, Suman; Jain, Dinesh; Puri, Sandeep; Kaushal, Sandeep; Deol, Satjeet Kaur

2015-01-01

To evaluate the role of laparohysteroscopy in female infertility andto study the effect of therapeutic procedures in achieving fertility. Patients with female infertility presenting to outpatient Department of Obstetrics and Gynecology were evaluated over a period of 18 months. Fifty consenting subjects excluding male factor infertility with normal hormonal profile and no contraindication to laparoscopy were subject to diagnostic laparoscopy and hysteroscopy. T-test. We studied 50 patients comprising of 24 (48%) cases of primary infertility and 26 (52%) patients of secondary infertility. The average age of active married life for 50 patients was between 8 and 9 years. In our study, the most commonly found pathologies were PCOD, endometroisis and tubal blockage. 11 (28.2) patients conceived after laparohysteroscopy followed by artificial reproductive techniques. This study demonstrates the benefit of laparohysteroscopy for diagnosis and as a therapeutic tool in patients with primary and secondary infertility. We were able to achieve a higher conception rate of 28.2%.

[Serious game as a therapeutic tool in psychiatry: A systematic review].

PubMed

Fovet, T; Micoulaud-Franchi, J-A; Vaiva, G; Thomas, P; Jardri, R; Amad, A

2016-10-01

The growing field of new technologies offers new ways to tackle psychiatric disorders (e.g. virtual reality therapy, neurofeedback, etc.). Serious games (SG) are computer applications combining serious aspects with the fun side of video games. This kind of new media could find applications to treat psychiatric disorders. This paper summarizes available data in the literature about therapeutic interventions using SG in psychiatry. A Medline search was conducted in May 2014 using the following Medical Subject Headings (MESH) terms: "video games", "mental disorders", and "psychotherapy". Only 10 relevant references were identified according to our inclusion criteria. These studies show that SG are very interesting tools to improve the management of psychiatric disorders. However, only low-level evidence is available to support treatment with SG in patients suffering from psychiatric disorders. Indeed, randomized controlled trials are rare in this field of research. SG provide promising therapeutic innovations for the management of psychiatric disorders. Moreover, they could easily be developed in accordance with current dimensional approaches. Finally, major issues to facilitate the implementation of future work on SG in psychiatry are discussed. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

ADHD and Present Hedonism: time perspective as a potential diagnostic and therapeutic tool

PubMed Central

Weissenberger, S; Klicperova-Baker, M; Zimbardo, P; Schonova, K; Akotia, D; Kostal, J; Goetz, M; Raboch, J; Ptacek, R

2016-01-01

The article draws primarily from the behavioral findings (mainly psychiatric and psychological observations) and points out the important relationships between attention-deficit/hyperactivity disorder (ADHD) symptoms and time orientation. Specifically, the authors argue that there is a significant overlap between the symptoms of ADHD and Present Hedonism. Present Hedonism is defined by Zimbardo’s time perspective theory and assessed by Zimbardo Time Perspective Inventory. Developmental data on Present Hedonism of males and females in the Czech population sample (N=2201) are also presented. The hypothesis of relationship between ADHD and Present Hedonism is mainly derived from the prevalence of addictive behavior (mainly excessive Internet use, alcohol abuse, craving for sweets, fatty foods, and fast foods), deficits in social learning, and increased aggressiveness both in ADHD and in the population scoring high on Present Hedonism in the Zimbardo Time Perspective Inventory. We conclude that Zimbardo’s time perspective offers both: 1) a potential diagnostic tool – the Zimbardo Time Perspective Inventory, particularly its Present Hedonism scale, and 2) a promising preventive and/or therapeutic approach by the Time Perspective Therapy. Time Perspective Therapy has so far been used mainly to treat past negative trauma (most notably, posttraumatic stress disorder); however, it also has value as a potential therapeutic tool for possible behavioral compensation of ADHD. PMID:27895485

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.

Pathogenesis of cerebral malaria: new diagnostic tools, biomarkers, and therapeutic approaches

PubMed Central

Sahu, Praveen K.; Satpathi, Sanghamitra; Behera, Prativa K.; Mishra, Saroj K.; Mohanty, Sanjib; Wassmer, Samuel Crocodile

2015-01-01

Cerebral malaria is a severe neuropathological complication of Plasmodium falciparum infection. It results in high mortality and post-recovery neuro-cognitive disorders in children, even after appropriate treatment with effective anti-parasitic drugs. While the complete landscape of the pathogenesis of cerebral malaria still remains to be elucidated, numerous innovative approaches have been developed in recent years in order to improve the early detection of this neurological syndrome and, subsequently, the clinical care of affected patients. In this review, we briefly summarize the current understanding of cerebral malaria pathogenesis, compile the array of new biomarkers and tools available for diagnosis and research, and describe the emerging therapeutic approaches to tackle this pathology effectively. PMID:26579500

Laparohysteroscopy in female infertility: A diagnostic cum therapeutic tool in Indian setting

PubMed Central

Puri, Suman; Jain, Dinesh; Puri, Sandeep; Kaushal, Sandeep; Deol, Satjeet Kaur

2015-01-01

Aims: To evaluate the role of laparohysteroscopy in female infertility andto study the effect of therapeutic procedures in achieving fertility. Settings and Design: Patients with female infertility presenting to outpatient Department of Obstetrics and Gynecology were evaluated over a period of 18 months. Materials and Methods: Fifty consenting subjects excluding male factor infertility with normal hormonal profile and no contraindication to laparoscopy were subject to diagnostic laparoscopy and hysteroscopy. Statistical Analysis Used: T-test. Results: We studied 50 patients comprising of 24 (48%) cases of primary infertility and 26 (52%) patients of secondary infertility. The average age of active married life for 50 patients was between 8 and 9 years. In our study, the most commonly found pathologies were PCOD, endometroisis and tubal blockage. 11 (28.2) patients conceived after laparohysteroscopy followed by artificial reproductive techniques. Conclusions: This study demonstrates the benefit of laparohysteroscopy for diagnosis and as a therapeutic tool in patients with primary and secondary infertility. We were able to achieve a higher conception rate of 28.2%. PMID:25664268

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

The Food-Safe Schools Action Guide

ERIC Educational Resources Information Center

Centers for Disease Control and Prevention, 2007

2007-01-01

"The Food-Safe School Needs Assessment and Planning Guide" is a tool that can help schools assess their food safety policies, procedures, and programs and develop plans for improvement. This tool includes a simple, straightforward questionnaire, score card, and planning guide that give administrators, school staff, families, and students a chance…

A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: An application to Ethiopia

USDA-ARS?s Scientific Manuscript database

Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed inter...

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.

Antisense-mediated exon skipping: A versatile tool with therapeutic and research applications

PubMed Central

Aartsma-Rus, Annemieke; van Ommen, Gert-Jan B.

2007-01-01

Antisense-mediated modulation of splicing is one of the few fields where antisense oligonucleotides (AONs) have been able to live up to their expectations. In this approach, AONs are implemented to restore cryptic splicing, to change levels of alternatively spliced genes, or, in case of Duchenne muscular dystrophy (DMD), to skip an exon in order to restore a disrupted reading frame. The latter allows the generation of internally deleted, but largely functional, dystrophin proteins and would convert a severe DMD into a milder Becker muscular dystrophy phenotype. In fact, exon skipping is currently one of the most promising therapeutic tools for DMD, and a successful first-in-man trial has recently been completed. In this review the applicability of exon skipping for DMD and other diseases is described. For DMD AONs have been designed for numerous exons, which has given us insight into their mode of action, splicing in general, and splicing of the DMD gene in particular. In addition, retrospective analysis resulted in guidelines for AON design for DMD and most likely other genes as well. This knowledge allows us to optimize therapeutic exon skipping, but also opens up a range of other applications for the exon skipping approach. PMID:17684229

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.

Aptamers: novel diagnostic and therapeutic tools for diabetes mellitus and metabolic diseases.

PubMed

Hu, Jingping; Ye, Mao; Zhou, Zhiguang

2017-03-01

Diabetes mellitus is one of the most common chronic diseases that threatens human health in worldwide populations. Despite enormous efforts invested in the study of diabetes mellitus, the development of precise diagnoses and treatments for this disease remains difficult due to the limitations of current techniques. Therefore, new methods are currently being developed. Aptamers are oligonucleotides that bind to specific target molecules and have been widely applied as diagnostic and therapeutic tools. In recent years, aptamers have been utilized in the study of diabetes mellitus and metabolic diseases. In this review, we highlight recent developments and new perspectives on aptamers in the field of diabetes mellitus and other metabolic diseases. Aptamers could potentially provide the means for efficient diagnoses and therapies against diabetes mellitus.

Assessing therapeutic relevance of biologically interesting, ampholytic substances based on their physicochemical and spectral characteristics with chemometric tools

NASA Astrophysics Data System (ADS)

Judycka, U.; Jagiello, K.; Bober, L.; Błażejowski, J.; Puzyn, T.

2018-06-01

Chemometric tools were applied to investigate the biological behaviour of ampholytic substances in relation to their physicochemical and spectral properties. Results of the Principal Component Analysis suggest that size of molecules and their electronic and spectral characteristics are the key properties required to predict therapeutic relevance of the compounds examined. These properties were used for developing the structure-activity classification model. The classification model allows assessing the therapeutic behaviour of ampholytic substances on the basis of solely values of descriptors that can be obtained computationally. Thus, the prediction is possible without necessity of carrying out time-consuming and expensive laboratory tests, which is its main advantage.

[Visual cues as a therapeutic tool in Parkinson's disease. A systematic review].

PubMed

Muñoz-Hellín, Elena; Cano-de-la-Cuerda, Roberto; Miangolarra-Page, Juan Carlos

2013-01-01

Sensory stimuli or sensory cues are being used as a therapeutic tool for improving gait disorders in Parkinson's disease patients, but most studies seem to focus on auditory stimuli. The aim of this study was to conduct a systematic review regarding the use of visual cues over gait disorders, dual tasks during gait, freezing and the incidence of falls in patients with Parkinson to obtain therapeutic implications. We conducted a systematic review in main databases such as Cochrane Database of Systematic Reviews, TripDataBase, PubMed, Ovid MEDLINE, Ovid EMBASE and Physiotherapy Evidence Database, during 2005 to 2012, according to the recommendations of the Consolidated Standards of Reporting Trials, evaluating the quality of the papers included with the Downs & Black Quality Index. 21 articles were finally included in this systematic review (with a total of 892 participants) with variable methodological quality, achieving an average of 17.27 points in the Downs and Black Quality Index (range: 11-21). Visual cues produce improvements over temporal-spatial parameters in gait, turning execution, reducing the appearance of freezing and falls in Parkinson's disease patients. Visual cues appear to benefit dual tasks during gait, reducing the interference of the second task. Further studies are needed to determine the preferred type of stimuli for each stage of the disease. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

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

PubMed

Furnes, Bodil; Dysvik, Elin

2012-12-01

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

Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines

PubMed Central

2011-01-01

Food-grade Lactic Acid Bacteria (LAB) have been safely consumed for centuries by humans in fermented foods. Thus, they are good candidates to develop novel oral vectors, constituting attractive alternatives to attenuated pathogens, for mucosal delivery strategies. Herein, this review summarizes our research, up until now, on the use of LAB as mucosal delivery vectors for therapeutic proteins and DNA vaccines. Most of our work has been based on the model LAB Lactococcus lactis, for which we have developed efficient genetic tools, including expression signals and host strains, for the heterologous expression of therapeutic proteins such as antigens, cytokines and enzymes. Resulting recombinant lactococci strains have been tested successfully for their prophylactic and therapeutic effects in different animal models: i) against human papillomavirus type 16 (HPV-16)-induced tumors in mice, ii) to partially prevent a bovine β-lactoglobulin (BLG)-allergic reaction in mice and iii) to regulate body weight and food consumption in obese mice. Strikingly, all of these tools have been successfully transposed to the Lactobacillus genus, in recent years, within our laboratory. Notably, anti-oxidative Lactobacillus casei strains were constructed and tested in two chemically-induced colitis models. In parallel, we also developed a strategy based on the use of L. lactis to deliver DNA at the mucosal level, and were able to show that L. lactis is able to modulate the host response through DNA delivery. Today, we consider that all of our consistent data, together with those obtained by other groups, demonstrate and reinforce the interest of using LAB, particularly lactococci and lactobacilli strains, to develop novel therapeutic protein mucosal delivery vectors which should be tested now in human clinical trials. PMID:21995317

Tool to assess causality of direct and indirect adverse events associated with therapeutic interventions.

PubMed

Zorzela, Liliane; Mior, Silvano; Boon, Heather; Gross, Anita; Yager, Jeromy; Carter, Rose; Vohra, Sunita

2018-03-01

To develop and test a tool to assess the causality of direct and indirect adverse events associated with therapeutic interventions. The intervention was one or more drugs and/or natural health products, a device, or practice (professional delivering the intervention). Through the assessment of causality of adverse events, we can learn about factors contributing to the harm and consider what modification may prevent its reoccurrence. Existing scales (WHO-UMC, Naranjo and Horn) were adapted to develop a tool (algorithm and table) to evaluate cases of serious harmful events reported through a national surveillance study. We also incorporated a novel approach that assesses indirect harm (caused by the delay in diagnosis/treatment) and the health provider delivering the intervention (practice). The tool was tested, revised and then implemented to assess all reported cases of serious events resulting from use of complementary therapies. The use of complementary therapies was the trigger to report the event. Each case was evaluated by two assessors, out of a panel of five, representing different health care professionals. The tool was used in assessment of eight serious adverse events. Each event was independently evaluated by two assessors. The algorithm facilitated assessment of a serious direct or indirect harm. Assessors agreed in the final score on seven of eight cases (weighted kappa coefficient of 0.75). A tool to support the assessment of causality of adverse events was developed and tested. We propose a novel method to assess direct and indirect harms related to product(s), device(s), practice or a combination of the previous. Further research will probably help evaluate this approach across different settings and interventions.

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.

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.

Connected: Recommendations and Techniques in Order to Employ Internet Tools for the Enhancement of Online Therapeutic Relationships. Experiences from Italy.

PubMed

Manfrida, Gianmarco; Albertini, Valentina; Eisenberg, Erica

2017-01-01

The article explores the different types of therapeutic relationship that can evolve both on- and offline, thanks to the use of tools, such as software and applications, which enable therapists and patients contact outside of the traditional setting. Given the premise that it is practically impossible today to maintain a relationship without the use of internet and telephones, it becomes necessary to question the ways in which the online space can become a useful extension of the therapeutic setting. The authors, starting from a consideration regarding the specificity of the online therapeutic relationship, analyze the best ways to use text and email messaging with patients. Furthermore, specific interactions via group chats are presented, for example, to coordinate a therapeutic team involving several professionals. Further, video chat settings are discussed through a clinical case presentation. Lastly, the therapist's management of social networks is debated, underscoring the importance for the therapists that his or her online identity be consistent with the offline image which patients are introduced to in the traditional setting of the therapy room.

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

Impact of Community-Based Approach as Policy Tool: World Health Organization-Designated Safe Communities of Korea and Health Action Zones of the United Kingdom.

PubMed

Kang, Changhyun; Shin, Jihyung; Matthews, Bob

2016-02-01

The aim of this study is to ascertain and identify the effectiveness of area-based initiatives as a policy tool mediated by societal and individual factors in the five World Health Organization (WHO)-designated Safe Communities of Korea and the Health Action Zones of the United Kingdom (UK). The Korean National Hospital discharge in-depth injury survey from the Korea Centers for Disease Control and Prevention and causes of death statistics by the Statistics Korea were used for all analyses. The trend and changes in injury rate and mortality by external causes were compared among the five WHO-designated Safe Communities in Korea. The injury incident rates decreased at a greater level in the Safe Communities compared with the national average. Similar results were shown for the changes in unintentional injury incident rates. In comparison of changes in mortality rate by external causes between 2005 and 2011, the rate increase in Safe Communities was higher than the national average except for Jeju, where the mortality rate by external causes decreased. When the Healthy Action Zones of the UK and the WHO Safe Communities of Korea were examined, the outcomes were interpreted differently among the compared index, regions, and time periods. Therefore, qualitative outcomes, such as bringing the residents' attention to the safety of the communities and promoting participation and coordination of stakeholders, should also be considered as important impacts of the community-based initiatives.

Impact of Community-Based Approach as Policy Tool: World Health Organization-Designated Safe Communities of Korea and Health Action Zones of the United Kingdom

PubMed Central

Kang, Changhyun; Shin, Jihyung; Matthews, Bob

2015-01-01

Objectives The aim of this study is to ascertain and identify the effectiveness of area-based initiatives as a policy tool mediated by societal and individual factors in the five World Health Organization (WHO)-designated Safe Communities of Korea and the Health Action Zones of the United Kingdom (UK). Methods The Korean National Hospital discharge in-depth injury survey from the Korea Centers for Disease Control and Prevention and causes of death statistics by the Statistics Korea were used for all analyses. The trend and changes in injury rate and mortality by external causes were compared among the five WHO-designated Safe Communities in Korea. Results The injury incident rates decreased at a greater level in the Safe Communities compared with the national average. Similar results were shown for the changes in unintentional injury incident rates. In comparison of changes in mortality rate by external causes between 2005 and 2011, the rate increase in Safe Communities was higher than the national average except for Jeju, where the mortality rate by external causes decreased. Conclusion When the Healthy Action Zones of the UK and the WHO Safe Communities of Korea were examined, the outcomes were interpreted differently among the compared index, regions, and time periods. Therefore, qualitative outcomes, such as bringing the residents' attention to the safety of the communities and promoting participation and coordination of stakeholders, should also be considered as important impacts of the community-based initiatives. PMID:26981341

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

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.

Human small bowel as a useful tool to investigate smooth muscle effects of potential therapeutics in organophosphate poisoning.

PubMed

Marquart, Katharina; Prokopchuk, Olga; Worek, Franz; Thiermann, Horst; Martignoni, Marc E; Wille, Timo

2018-09-01

Isolated organs proofed to be a robust tool to study effects of (potential) therapeutics in organophosphate poisoning. Small bowel samples have been successfully used to reveal smooth muscle relaxing effects. In the present study, the effects of obidoxime, TMB-4, HI-6 and MB 327 were investigated on human small bowel tissue and compared with rat data. Hereby, the substances were tested in at least seven different concentrations in the jejunum or ileum both pre-contracted with carbamoylcholine. Additionally, the cholinesterase activity of native tissue was determined. Human small intestine specimens showed classical dose response-curves, similar to rat tissue, with MB 327 exerting the most potent smooth muscle relaxant effect in both species (human EC 50 =0.7×10 -5 M and rat EC 50 =0.7×10 -5 M). The AChE activity for human and rat samples did not differ significantly (rat jejunum=1351±166 mU/mg wet weight; rat ileum=1078±123 mU/mg wet weight; human jejunum=1030±258 mU/mg wet weight; human ileum=1293±243 mU/mg wet weight). Summarizing, our isolated small bowel setup seems to be a solid tool to investigate the effects of (potential) therapeutics on pre-contracted smooth muscle, with data being transferable between rat and humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Safe teleradiology: information assurance as project planning methodology

NASA Astrophysics Data System (ADS)

Collmann, Jeff R.; Alaoui, Adil; Nguyen, Dan; Lindisch, David

2003-05-01

This project demonstrates use of OCTAVE, an information security risk assessment method, as an approach to the safe design and planning of a teleradiology system. By adopting this approach to project planning, we intended to provide evidence that including information security as an intrinsic component of project planning improves information assurance and that using information assurance as a planning tool produces and improves the general system management plan. Several considerations justify this approach to planning a safe teleradiology system. First, because OCTAVE was designed as a method for retrospectively assessing and proposing enhancements for the security of existing information management systems, it should function well as a guide to prospectively designing and deploying a secure information system such as teleradiology. Second, because OCTAVE provides assessment and planning tools for use primarily by interdisciplinary teams from user organizations, not consultants, it should enhance the ability of such teams at the local level to plan safe information systems. Third, from the perspective of sociological theory, OCTAVE explicitly attempts to enhance organizational conditions identified as necessary to safely manage complex technologies. Approaching information system design from the perspective of information security risk management proactively integrates health information assurance into a project"s core. This contrasts with typical approaches that perceive "security" as a secondary attribute to be "added" after designing the system and with approaches that identify information assurance only with security devices and user training. The perspective of health information assurance embraces so many dimensions of a computerized health information system"s design that one may successfully deploy a method for retrospectively assessing information security risk as a prospective planning tool. From a sociological perspective, this approach enhances the

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

PubMed

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

2013-02-14

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

Ayahuasca: Pharmacology, neuroscience and therapeutic potential.

PubMed

Domínguez-Clavé, Elisabet; Soler, Joaquim; Elices, Matilde; Pascual, Juan C; Álvarez, Enrique; de la Fuente Revenga, Mario; Friedlander, Pablo; Feilding, Amanda; Riba, Jordi

2016-09-01

Ayahuasca is the Quechua name for a tea obtained from the vine Banisteriopsis caapi, and used for ritual purposes by the indigenous populations of the Amazon. The use of a variation of the tea that combines B. caapi with the leaves of the shrub Psychotria viridis has experienced unprecedented expansion worldwide for its psychotropic properties. This preparation contains the psychedelic 5-HT 2A receptor agonist N,N-dimethyltryptamine (DMT) from P. viridis, plus β-carboline alkaloids with monoamine-oxidase-inhibiting properties from B. caapi. Acute administration induces a transient modified state of consciousness characterized by introspection, visions, enhanced emotions and recollection of personal memories. A growing body of evidence suggests that ayahuasca may be useful to treat substance use disorders, anxiety and depression. Here we review the pharmacology and neuroscience of ayahuasca, and the potential psychological mechanisms underlying its therapeutic potential. We discuss recent findings indicating that ayahuasca intake increases certain mindfulness facets related to acceptance and to the ability to take a detached view of one's own thoughts and emotions. Based on the available evidence, we conclude that ayahuasca shows promise as a therapeutic tool by enhancing self-acceptance and allowing safe exposure to emotional events. We postulate that ayahuasca could be of use in the treatment of impulse-related, personality and substance use disorders and also in the handling of trauma. More research is needed to assess the full potential of ayahuasca in the treatment of these disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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 ...

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.

Optimizing real time fMRI neurofeedback for therapeutic discovery and development

PubMed Central

Stoeckel, L.E.; Garrison, K.A.; Ghosh, S.; Wighton, P.; Hanlon, C.A.; Gilman, J.M.; Greer, S.; Turk-Browne, N.B.; deBettencourt, M.T.; Scheinost, D.; Craddock, C.; Thompson, T.; Calderon, V.; Bauer, C.C.; George, M.; Breiter, H.C.; Whitfield-Gabrieli, S.; Gabrieli, J.D.; LaConte, S.M.; Hirshberg, L.; Brewer, J.A.; Hampson, M.; Van Der Kouwe, A.; Mackey, S.; Evins, A.E.

2014-01-01

While reducing the burden of brain disorders remains a top priority of organizations like the World Health Organization and National Institutes of Health, the development of novel, safe and effective treatments for brain disorders has been slow. In this paper, we describe the state of the science for an emerging technology, real time functional magnetic resonance imaging (rtfMRI) neurofeedback, in clinical neurotherapeutics. We review the scientific potential of rtfMRI and outline research strategies to optimize the development and application of rtfMRI neurofeedback as a next generation therapeutic tool. We propose that rtfMRI can be used to address a broad range of clinical problems by improving our understanding of brain–behavior relationships in order to develop more specific and effective interventions for individuals with brain disorders. We focus on the use of rtfMRI neurofeedback as a clinical neurotherapeutic tool to drive plasticity in brain function, cognition, and behavior. Our overall goal is for rtfMRI to advance personalized assessment and intervention approaches to enhance resilience and reduce morbidity by correcting maladaptive patterns of brain function in those with brain disorders. PMID:25161891

A comprehensive linear programming tool to optimize formulations of ready-to-use therapeutic foods: an application to Ethiopia.

PubMed

Ryan, Kelsey N; Adams, Katherine P; Vosti, Stephen A; Ordiz, M Isabel; Cimo, Elizabeth D; Manary, Mark J

2014-12-01

Ready-to-use therapeutic food (RUTF) is the standard of care for children suffering from noncomplicated severe acute malnutrition (SAM). The objective was to develop a comprehensive linear programming (LP) tool to create novel RUTF formulations for Ethiopia. A systematic approach that surveyed international and national crop and animal food databases was used to create a global and local candidate ingredient database. The database included information about each ingredient regarding nutrient composition, ingredient category, regional availability, and food safety, processing, and price. An LP tool was then designed to compose novel RUTF formulations. For the example case of Ethiopia, the objective was to minimize the ingredient cost of RUTF; the decision variables were ingredient weights and the extent of use of locally available ingredients, and the constraints were nutritional and product-quality related. Of the new RUTF formulations found by the LP tool for Ethiopia, 32 were predicted to be feasible for creating a paste, and these were prepared in the laboratory. Palatable final formulations contained a variety of ingredients, including fish, different dairy powders, and various seeds, grains, and legumes. Nearly all of the macronutrient values calculated by the LP tool differed by <10% from results produced by laboratory analyses, but the LP tool consistently underestimated total energy. The LP tool can be used to develop new RUTF formulations that make more use of locally available ingredients. This tool has the potential to lead to production of a variety of low-cost RUTF formulations that meet international standards and thereby potentially allow more children to be treated for SAM. © 2014 American Society for Nutrition.

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

PubMed Central

2013-01-01

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

Safe Harbor: a tool to help recover topminnow and pupfish in Arizona

Treesearch

Douglas K. Duncan; Jeremy Voeltz

2005-01-01

The Arizona Game and Fish Department (Department) has developed a Safe Harbor Agreement (SHA) for four native fishes in Arizona. The SHA will allow Gila and Yaqui topminnow (Poeciliopsis occidentalis and P. sonoriensis) and desert and Quitobaquito pupfish (Cyprinodon macularius and C. eremus)...

Prospects for nucleic acid-based therapeutics against hepatitis C virus.

PubMed

Lee, Chang Ho; Kim, Ji Hyun; Lee, Seong-Wook

2013-12-21

In this review, we discuss recent advances in nucleic acid-based therapeutic technologies that target hepatitis C virus (HCV) infection. Because the HCV genome is present exclusively in RNA form during replication, various nucleic acid-based therapeutic approaches targeting the HCV genome, such as ribozymes, aptamers, siRNAs, and antisense oligonucleotides, have been suggested as potential tools against HCV. Nucleic acids are potentially immunogenic and typically require a delivery tool to be utilized as therapeutics. These limitations have hampered the clinical development of nucleic acid-based therapeutics. However, despite these limitations, nucleic acid-based therapeutics has clinical value due to their great specificity, easy and large-scale synthesis with chemical methods, and pharmaceutical flexibility. Moreover, nucleic acid therapeutics are expected to broaden the range of targetable molecules essential for the HCV replication cycle, and therefore they may prove to be more effective than existing therapeutics, such as interferon-α and ribavirin combination therapy. This review focuses on the current status and future prospects of ribozymes, aptamers, siRNAs, and antisense oligonucleotides as therapeutic reagents against HCV.

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

Gaming as a Therapeutic Tool in Adolescence. Experience of Institutional Therapy of CThA, UCL, Brussels, Belgium.

PubMed

Descamps, Guillaume; d'Alcantara, Ann

2016-09-01

This work presents the experience of an Emancipatory action research led at the Therapeutic Center for Adolescents (CThA) at Saint Luc's Clinics (UCL). This research focuses on the practice effects of "Pixels" and "Passerelle" workshops at CThA. It is about the use of video games as a therapeutic tool, mobilizing of the symptomatology of the teenager. "Pixels" workshops use playing according to three specific forms: the paper role-play game, the video game, and the cards playing game. Their specificity is that the participative adult shows a regressive ability strong enough to play with teenagers and is very careful to not interpret what takes place within. "Passerelle" workshops demonstrate the link between the teenager's mind and the use of his own virtual avatar. It allows to evolve from a "play together" to a "talk together", a moment of symbolization and of being able to stand back in regards to his or her own recreational activities. As a discussion, this clinical illustration of Karl recovering from depression and dependency. This setting for speech allowed him to evolve into an impulse mood and to reconnect emotionally.

Safe Use of Acoustic Vestibular-Evoked Myogenic Potential Stimuli: Protocol and Patient-Specific Considerations.

PubMed

Portnuff, Cory D F; Kleindienst, Samantha; Bogle, Jamie M

2017-09-01

Vestibular-evoked myogenic potentials (VEMPs) are commonly used clinical assessments for patients with complaints of dizziness. However, relatively high air-conducted stimuli are required to elicit the VEMP, and ultimately may compromise safe noise exposure limits. Recently, research has reported the potential for noise-induced hearing loss (NIHL) from VEMP stimulus exposure through studies of reduced otoacoustic emission levels after VEMP testing, as well as a recent case study showing permanent sensorineural hearing loss associated with VEMP exposure. The purpose of this report is to review the potential for hazardous noise exposure from VEMP stimuli and to suggest clinical parameters for safe VEMP testing. Literature review with presentation of clinical guidelines and a clinical tool for estimating noise exposure. The literature surrounding VEMP stimulus-induced hearing loss is reviewed, including several cases of overexposure. The article then presents a clinical calculation tool for the estimation of a patient's safe noise exposure from VEMP stimuli, considering stimulus parameters, and includes a discussion of how varying stimulus parameters affect a patient's noise exposure. Finally, recommendations are provided for recognizing and managing specific patient populations who may be at higher risk for NIHL from VEMP stimulus exposure. A sample protocol is provided that allows for safe noise exposure. VEMP stimuli have the potential to cause NIHL due to high sound exposure levels. However, with proper safety protocols in place, clinicians may reduce or eliminate this risk to their patients. Use of the tools provided, including the noise exposure calculation tool and sample protocols, may help clinicians to understand and ensure safe use of VEMP stimuli. American Academy of Audiology

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.

THE ROLE OF LAPAROSCOPY IN BLUNT ABDOMINAL TRAUMA: DIAGNOSTIC, THERAPEUTIC OR BOTH?

PubMed

Koto, M Z; Mosai, F; Matsevych, O Y

2017-06-01

The use of laparoscopy in blunt abdominal trauma is gaining popularity as a useful diagnostic tool to avoid unnecessary laparotomies where there is diagnostic dilemma. But the feasibility of using laparoscopy for therapeutic intervention in these patients has been debated. Even though recent case reports seem to suggest that these patients can be managed using laparoscopy, the practice is not yet wildly adopted. A retrospective analysis of a prospectively collected data was done. All adult patients who presented with abdominal trauma and were offered laparoscopic surgery at Dr George Mukhari Academic Hospital (DGMAH) from 2012 to 2015 were reviewed. Data was retrieved from our departmental database and analysed using descriptive statistics. A total of 318 patients were reviewed and 35 patients had blunt abdominal trauma and were included in the study. All the patients were offered laparoscopy. The median age was 30, with 91% of our patients males. The highest injury severity score calculated was 38. At least 77% of the patients were managed using laparoscopy. This includes 43% who had both diagnostic and therapeutic intervention and 34% who had only diagnostic laparoscopy. Eight patients were converted to open surgery mainly due to active bleeding and complex injuries. We did not have any non-therapeutic laparotomies. There was no documented procedure‑related morbidity and mortality. The positive outcomes seen from the study suggest that laparoscopy can be safe and feasible in both diagnostic and therapeutic interventions in carefully selected blunt abdominal trauma patients. A conversion to open surgery should not be regarded as a failure but rather as a sign of mature and sound clinical judgement acknowledging the limitations of laparoscopy and/or the surgeon.

THE ROLE OF LAPAROSCOPY IN BLUNT ABDOMINAL TRAUMA: DIAGNOSTIC, THERAPEUTIC OR BOTH?

PubMed

Mosai, F

2017-09-01

The use of laparoscopy in blunt abdominal trauma is gaining popularity as a useful diagnostic tool to avoid unnecessary laparotomies where there is diagnostic dilemma. But the feasibility of using laparoscopy for therapeutic intervention in these patients has been debated. Even though recent case reports seem to suggest that these patients can be managed using laparoscopy, the practice is not yet wildly adopted. A retrospective analysis of a prospectively collected data was done. All adult patients who presented with abdominal trauma and were offered laparoscopic surgery at DGMAH from 2012 to 2015 were reviewed. Data was retrieved from our departmental database and analysed using descriptive statistics. A total of 318 patients were reviewed and 35 patients had blunt abdominal trauma and were included in the study. All the patients were offered laparoscopy. The median age was 30, with 91% of our patients being males. The highest injury severity score calculated was 38. At least 77% of the patients were managed using laparoscopy. This includes 43% who had both diagnostic and therapeutic intervention and 34% had only diagnostic laparoscopy. Eight patients were converted to open surgery mainly due to active bleeding and complex injuries. We did not have any non-therapeutic laparotomies, with no documented procedure related morbidity and mortality. The positive outcomes seen from the study suggest that laparoscopy can be safe and feasible in both diagnostic and therapeutic interventions in carefully selected blunt abdominal trauma patients. A conversion to open surgery should not be regarded as a failure but rather as a sign of mature and sound clinical judgement acknowledging the limitations of laparoscopy and/or the surgeon.

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.

Nucleic acid aptamers: research tools in disease diagnostics and therapeutics.

PubMed

Santosh, Baby; Yadava, Pramod K

2014-01-01

Aptamers are short sequences of nucleic acid (DNA or RNA) or peptide molecules which adopt a conformation and bind cognate ligands with high affinity and specificity in a manner akin to antibody-antigen interactions. It has been globally acknowledged that aptamers promise a plethora of diagnostic and therapeutic applications. Although use of nucleic acid aptamers as targeted therapeutics or mediators of targeted drug delivery is a relatively new avenue of research, one aptamer-based drug "Macugen" is FDA approved and a series of aptamer-based drugs are in clinical pipelines. The present review discusses the aspects of design, unique properties, applications, and development of different aptamers to aid in cancer diagnosis, prevention, and/or treatment under defined conditions.

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

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

Implementing AORN recommended practices for a safe environment of care.

PubMed

Hughes, Antonia B

2013-08-01

Providing a safe environment for every patient undergoing a surgical or other invasive procedure is imperative. AORN's "Recommended practices for a safe environment of care" provides guidance on a wide range of topics related to the safety of perioperative patients and health care personnel. The recommendations are intended to provide guidance for establishing best practices and implementing safety measures in all perioperative practice settings. Perioperative nurses should be aware of risks related to musculoskeletal injuries, fire, equipment, latex, and chemicals, among others, and understand strategies for reducing the risks. Evidence-based recommendations can give practitioners the tools to guide safe practice. Copyright © 2013 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Prioritizing therapeutic targets using patient-derived xenograft models

PubMed Central

Lodhia, K.A; Hadley, A; Haluska, P; Scott, C.L

2015-01-01

Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDX) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximise insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design. PMID:25783201

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.

MicroRNAs in Leukemias: Emerging Diagnostic Tools and Therapeutic Targets

PubMed Central

Mian, Yousaf A.; Zeleznik-Le, Nancy J.

2010-01-01

MicroRNAs (miRNA) are small non-coding RNAs of ~22 nucleotides that regulate the translation and stability of mRNA to control different functions of the cell. Misexpression of miRNA has been linked to disruption of normal cellular functions, which results in various disorders including cancers such as leukemias. MicroRNA involvement in disease has been the subject of much attention and is increasing our current understanding of disease biology. Such linkages have been determined by high-throughput studies, which provide a framework for characterizing differential miRNA expression levels correlating to different cytogenetic abnormalities and their corresponding malignancies. In addition, functional studies of particular miRNAs have begun to define the effects of miRNA on predicted mRNA targets. It is clear that miRNAs can serve as molecular markers of leukemias and the hope is that they can also serve as new therapeutic targets. Studies are beginning to elucidate how to deliver therapeutic antagonists to attenuate overexpressed miRNAs and to replace underexpressed miRNAs. In this review, we: i) discuss the current understanding of miRNA function and expression in normal hematopoiesis, ii) provide examples of miRNAs that are misregulated in leukemias, and iii) evaluate the current status and potential future directions for the burgeoning field of antisense oligonucleotides and other therapeutic attempts to intervene in miRNA disregulation in leukemias. PMID:20370647

Strategies and challenges for safe injection practice in developing countries.

PubMed

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, P Ravi; Kumar, Kc Vikash

2013-01-01

Injection is one of the important health care procedures used globally to administer drugs. Its unsafe use can transmit various blood borne pathogens. This article aims to review the history and status of injection practices, its importance, interventions and the challenges for safe injection practice in developing countries. The history of injections started with the discovery of syringe in the early nineteenth century. Safe injection practice in developed countries was initiated in the early twentieth century but has not received adequate attention in developing countries. The establishment of "Safe Injection Global Network (SIGN)" was an milestone towards safe injection practice globally. In developing countries, people perceive injection as a powerful healing tool and do not hesitate to pay more for injections. Unsafe disposal and reuse of contaminated syringe is common. Ensuring safe injection practice is one of the greatest challenges for healthcare system in developing countries. To address the problem, interventions with active involvement of a number of stakeholders is essential. A combination of educational, managerial and regulatory strategies is found to be effective and economically viable. Rational and safe use of injections can save many lives but unsafe practice threatens life. Safe injection practice is crucial in developing countries. Evidence based interventions, with honest commitment and participation from the service provider, recipient and community with aid of policy makers are required to ensure safe injection practice.

Strategies and challenges for safe injection practice in developing countries

PubMed Central

Gyawali, Sudesh; Rathore, Devendra Singh; Shankar, P Ravi; Kumar, KC Vikash

2013-01-01

Injection is one of the important health care procedures used globally to administer drugs. Its unsafe use can transmit various blood borne pathogens. This article aims to review the history and status of injection practices, its importance, interventions and the challenges for safe injection practice in developing countries. The history of injections started with the discovery of syringe in the early nineteenth century. Safe injection practice in developed countries was initiated in the early twentieth century but has not received adequate attention in developing countries. The establishment of “Safe Injection Global Network (SIGN)” was an milestone towards safe injection practice globally. In developing countries, people perceive injection as a powerful healing tool and do not hesitate to pay more for injections. Unsafe disposal and reuse of contaminated syringe is common. Ensuring safe injection practice is one of the greatest challenges for healthcare system in developing countries. To address the problem, interventions with active involvement of a number of stakeholders is essential. A combination of educational, managerial and regulatory strategies is found to be effective and economically viable. Rational and safe use of injections can save many lives but unsafe practice threatens life. Safe injection practice is crucial in developing countries. Evidence based interventions, with honest commitment and participation from the service provider, recipient and community with aid of policy makers are required to ensure safe injection practice. PMID:23662018

33 CFR 150.607 - What are the general safe working requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... machinery, cranes, derricks, portable power tools, and, most importantly, safety gear must be used in a safe... subchapter. (b) All machinery and equipment must be maintained in proper working order or removed. Personal...

33 CFR 150.607 - What are the general safe working requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

... machinery, cranes, derricks, portable power tools, and, most importantly, safety gear must be used in a safe... subchapter. (b) All machinery and equipment must be maintained in proper working order or removed. Personal...

33 CFR 150.607 - What are the general safe working requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

... machinery, cranes, derricks, portable power tools, and, most importantly, safety gear must be used in a safe... subchapter. (b) All machinery and equipment must be maintained in proper working order or removed. Personal...

Extracellular Vesicles as Therapeutic Tools in Cardiovascular Diseases

PubMed Central

Fleury, Audrey; Martinez, Maria Carmen; Le Lay, Soazig

2014-01-01

Extracellular vesicles (EVs), including microvesicles (MVs) and exosomes, are small vesicles secreted from a wide variety of cells. Whereas MVs are particles released by the outward budding of the plasma membrane, exosomes are derived from endocytic compartments. Secretion of EVs can be enhanced by specific stimuli, and increased plasma circulating levels of EVs have been correlated with pathophysiological situations. MVs, already present in the blood of healthy individuals, are considerably elevated in several cardiovascular diseases associated with inflammation, suggesting that they can mediate deleterious effects such as endothelial dysfunction or thrombosis. Nonetheless, very recent studies also demonstrate that MVs may act as biological information vectors transferring proteins or genetic material to maintain cell homeostasis, favor cell repair, or even promote angiogenesis. Additionally, exosomes have also been shown to have pro-angiogenic and cardio-protective properties. These beneficial effects, therefore, reveal the potential therapeutical use of EVs in the field of cardiovascular medicine and regenerative therapy. In this review, we will provide an update of cellular processes modulated by EVs of specific interest in the treatment of cardiovascular pathologies. A special focus will be made on the morphogen sonic hedgehog (Shh) associated with EVs (EVsShh+), which have been shown to mediate many pro-angiogenic effects. In addition to offer a potential source of cardiovascular markers, therapeutical potential of EVs reveal exciting opportunities to deliver specific agents by non-immunogenic means to cardiovascular system. PMID:25136343

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.

Food Safety Posters for Safe Handling of Leafy Greens

ERIC Educational Resources Information Center

Rajagopal, Lakshman; Arendt, Susan W.; Shaw, Angela M.; Strohbehn, Catherine H.; Sauer, Kevin L.

2016-01-01

This article describes food safety educational tools depicting safe handling of leafy greens that are available as downloadable posters to Extension educators and practitioners (www.extension.iastate.edu). Nine visual-based minimal-text colored posters in English, Chinese, and Spanish were developed for use when formally or informally educating…

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.

Translating Discovery in Zebrafish Pancreatic Development to Human Pancreatic Cancer: Biomarkers, Targets, Pathogenesis, and Therapeutics

PubMed Central

Kazi, Abid A.; Yee, Rosemary K.

2013-01-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer. PMID:23682805

Translating discovery in zebrafish pancreatic development to human pancreatic cancer: biomarkers, targets, pathogenesis, and therapeutics.

PubMed

Yee, Nelson S; Kazi, Abid A; Yee, Rosemary K

2013-06-01

Abstract Experimental studies in the zebrafish have greatly facilitated understanding of genetic regulation of the early developmental events in the pancreas. Various approaches using forward and reverse genetics, chemical genetics, and transgenesis in zebrafish have demonstrated generally conserved regulatory roles of mammalian genes and discovered novel genetic pathways in exocrine pancreatic development. Accumulating evidence has supported the use of zebrafish as a model of human malignant diseases, including pancreatic cancer. Studies have shown that the genetic regulators of exocrine pancreatic development in zebrafish can be translated into potential clinical biomarkers and therapeutic targets in human pancreatic adenocarcinoma. Transgenic zebrafish expressing oncogenic K-ras and zebrafish tumor xenograft model have emerged as valuable tools for dissecting the pathogenetic mechanisms of pancreatic cancer and for drug discovery and toxicology. Future analysis of the pancreas in zebrafish will continue to advance understanding of the genetic regulation and biological mechanisms during organogenesis. Results of those studies are expected to provide new insights into how aberrant developmental pathways contribute to formation and growth of pancreatic neoplasia, and hopefully generate valid biomarkers and targets as well as effective and safe therapeutics in pancreatic cancer.

Ontological approach for safe and effective polypharmacy prescription

PubMed Central

Grando, Adela; Farrish, Susan; Boyd, Cynthia; Boxwala, Aziz

2012-01-01

The intake of multiple medications in patients with various medical conditions challenges the delivery of medical care. Initial empirical studies and pilot implementations seem to indicate that generic safe and effective multi-drug prescription principles could be defined and reused to reduce adverse drug events and to support compliance with medical guidelines and drug formularies. Given that ontologies are known to provide well-principled, sharable, setting-independent and machine-interpretable declarative specification frameworks for modeling and reasoning on biomedical problems, we explore here their use in the context of multi-drug prescription. We propose an ontology for modeling drug-related knowledge and a repository of safe and effective generic prescription principles. To test the usability and the level of granularity of the developed ontology-based specification models and heuristic we implemented a tool that computes the complexity of multi-drug treatments, and a decision aid to check the safeness and effectiveness of prescribed multi-drug treatments. PMID:23304299

Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper.

PubMed

Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Börger, Verena; Buzas, Edit; Camussi, Giovanni; Chaput, Nathalie; Chatterjee, Devasis; Court, Felipe A; Del Portillo, Hernando A; O'Driscoll, Lorraine; Fais, Stefano; Falcon-Perez, Juan M; Felderhoff-Mueser, Ursula; Fraile, Lorenzo; Gho, Yong Song; Görgens, André; Gupta, Ramesh C; Hendrix, An; Hermann, Dirk M; Hill, Andrew F; Hochberg, Fred; Horn, Peter A; de Kleijn, Dominique; Kordelas, Lambros; Kramer, Boris W; Krämer-Albers, Eva-Maria; Laner-Plamberger, Sandra; Laitinen, Saara; Leonardi, Tommaso; Lorenowicz, Magdalena J; Lim, Sai Kiang; Lötvall, Jan; Maguire, Casey A; Marcilla, Antonio; Nazarenko, Irina; Ochiya, Takahiro; Patel, Tushar; Pedersen, Shona; Pocsfalvi, Gabriella; Pluchino, Stefano; Quesenberry, Peter; Reischl, Ilona G; Rivera, Francisco J; Sanzenbacher, Ralf; Schallmoser, Katharina; Slaper-Cortenbach, Ineke; Strunk, Dirk; Tonn, Torsten; Vader, Pieter; van Balkom, Bas W M; Wauben, Marca; Andaloussi, Samir El; Théry, Clotilde; Rohde, Eva; Giebel, Bernd

2015-01-01

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed.

Paper-basd surface enhanced Raman spectroscopy of pnenobarbital sodium for point-of-care therapeutic drug monitoring

NASA Astrophysics Data System (ADS)

Yokoyama, Moe; Yamada, Kenji; Nishimura, Takahiro; Kido, Michiko; Jeong, Hieyong; Ohno, Yuko

2015-03-01

Therapeutic drug monitoring (TDM) contributes to safe and effective pharmacotherapy in clinical fields. A simple, rapid, low-cost, and minimally-invasive drug measurement method attracts much interest for point-of-care TDM. Tear fluids can be collected minimally-invasively compared to blood sampling and there is a correlation between a drug concentration in tears and that in bloods. Surface enhanced Raman spectroscopy (SERS) with paper-based substrate is useful for point-of-care TDM owing to inexpensiveness and high-sensitivity. Paper is also a safe tear collection tool. Then we are studying on a paper-based SERS of tear specimen for point-of-care TDM. In this paper, to improve sensitivity in measuring drug concentration in tear fluids, we fabricated a SERS substrate by coating gold nano-rods on a paper substrate and evaluated whether the fabricated substrate can enhance Raman scattering. Sodium phenobarbital (PB), an anti-convulsant agent, was used as a target. In experiment, the fabricated substrate indicated the lower detection limit of PB in a solution than a plain paper substrate. This result showed the potential of the paper based SERS substrate to measure drug concentration in tears simply and inexpensively.

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

Safe Driving Climate among Friends (SDCaF): A new scale.

PubMed

Guggenheim, Noga; Taubman-Ben-Ari, Orit

2018-01-01

Reckless driving among young people, especially young men, is a major cause of injury and fatalities the world over. Like other aspects of this age group, young drivers' driving behaviors and norms are influenced by the accepted social discourse of their peers. Yet despite extensive existing knowledge on young drivers, very few studies have dealt specifically with their characteristic friendship relations. This lacuna in the literature may reflect the absence of specific research tools for examining driving with friends. To fill this gap, we conducted a series of studies with 706 young drivers (aged 17-24) of both sexes aimed at developing and validating a multidimensional scale designed to examine the effect of the social relations of adolescents and young adults on their driving. Entitled Safe Driving Climate among Friends (SDCaF), the final scale consists of 19 items, which tap four dimensions of driving with friends: friends' pressure; social costs of driving with friends; communication with friends about driving; and shared commitment to safe driving. The validity of the scale was established by examining associations between its four dimensions and various variables of personality, friendship, and driving. The findings indicate good reliability and validity, with the three variables of resistance to peer influence, self-disclosure, and personal responsibility for safe driving yielding positive associations with the SDCaF dimensions communication and shared commitment to safe driving, and negative associations with the dimensions friends' pressure and social costs. General tendency to respond to social pressure was positively associated with the dimensions of friends' pressure and social costs, and negatively associated with shared commitment to safe driving. Gender differences were also found, with men scoring higher than women on friends' pressure, and lower than women on shared commitment to safe driving. The SDCaF can serve as a research tool, as well as a

Challenges in validating candidate therapeutic targets in cancer

PubMed Central

Sawyers, Charles L; Hunter, Tony

2018-01-01

More than 30 published articles have suggested that a protein kinase called MELK is an attractive therapeutic target in human cancer, but three recent reports describe compelling evidence that it is not. These reports highlight the caveats associated with some of the research tools that are commonly used to validate candidate therapeutic targets in cancer research. PMID:29417929

Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion

PubMed Central

Lin, Peter P.; Gires, Olivier

2017-01-01

Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to-mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens. PMID:27683128

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.

Applying extracellular vesicles based therapeutics in clinical trials – an ISEV position paper

PubMed Central

Lener, Thomas; Gimona, Mario; Aigner, Ludwig; Börger, Verena; Buzas, Edit; Camussi, Giovanni; Chaput, Nathalie; Chatterjee, Devasis; Court, Felipe A.; del Portillo, Hernando A.; O'Driscoll, Lorraine; Fais, Stefano; Falcon-Perez, Juan M.; Felderhoff-Mueser, Ursula; Fraile, Lorenzo; Gho, Yong Song; Görgens, André; Gupta, Ramesh C.; Hendrix, An; Hermann, Dirk M.; Hill, Andrew F.; Hochberg, Fred; Horn, Peter A.; de Kleijn, Dominique; Kordelas, Lambros; Kramer, Boris W.; Krämer-Albers, Eva-Maria; Laner-Plamberger, Sandra; Laitinen, Saara; Leonardi, Tommaso; Lorenowicz, Magdalena J.; Lim, Sai Kiang; Lötvall, Jan; Maguire, Casey A.; Marcilla, Antonio; Nazarenko, Irina; Ochiya, Takahiro; Patel, Tushar; Pedersen, Shona; Pocsfalvi, Gabriella; Pluchino, Stefano; Quesenberry, Peter; Reischl, Ilona G.; Rivera, Francisco J.; Sanzenbacher, Ralf; Schallmoser, Katharina; Slaper-Cortenbach, Ineke; Strunk, Dirk; Tonn, Torsten; Vader, Pieter; van Balkom, Bas W. M.; Wauben, Marca; Andaloussi, Samir El; Théry, Clotilde; Rohde, Eva; Giebel, Bernd

2015-01-01

Extracellular vesicles (EVs), such as exosomes and microvesicles, are released by different cell types and participate in physiological and pathophysiological processes. EVs mediate intercellular communication as cell-derived extracellular signalling organelles that transmit specific information from their cell of origin to their target cells. As a result of these properties, EVs of defined cell types may serve as novel tools for various therapeutic approaches, including (a) anti-tumour therapy, (b) pathogen vaccination, (c) immune-modulatory and regenerative therapies and (d) drug delivery. The translation of EVs into clinical therapies requires the categorization of EV-based therapeutics in compliance with existing regulatory frameworks. As the classification defines subsequent requirements for manufacturing, quality control and clinical investigation, it is of major importance to define whether EVs are considered the active drug components or primarily serve as drug delivery vehicles. For an effective and particularly safe translation of EV-based therapies into clinical practice, a high level of cooperation between researchers, clinicians and competent authorities is essential. In this position statement, basic and clinical scientists, as members of the International Society for Extracellular Vesicles (ISEV) and of the European Cooperation in Science and Technology (COST) program of the European Union, namely European Network on Microvesicles and Exosomes in Health and Disease (ME-HaD), summarize recent developments and the current knowledge of EV-based therapies. Aspects of safety and regulatory requirements that must be considered for pharmaceutical manufacturing and clinical application are highlighted. Production and quality control processes are discussed. Strategies to promote the therapeutic application of EVs in future clinical studies are addressed. PMID:26725829

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…

Cholinergic drugs as therapeutic tools in inflammatory diseases: participation of neuronal and non-neuronal cholinergic systems.

PubMed

Sales, María Elena

2013-01-01

Acetylcholine (ACh) is synthesized by choline acetyltransferase (ChAT) from acetylcoenzime A and choline. This reaction occurs not only in pre-ganglionic fibers of the autonomic nervous system and post-ganglionic parasympathetic nervous fibers but also in non neuronal cells. This knowledge led to expand the role of ACh as a neurotransmitter and to consider it as a "cytotransmitter" and also to evaluate the existence of a non-neuronal cholinergic system comprising ACh, ChAT, acetylcholinesterase, and the nicotinic and muscarinic ACh receptors, outside the nervous system. This review analyzes the participation of cholinergic system in inflammation and discusses the role of different muscarinic and nicotinic drugs that are being used to treat skin inflammatory disorders, asthma, and chronic obstructive pulmonary disease as well as, intestinal inflammation and systemic inflammatory diseases, among others, to assess the potential application of these compounds as therapeutic tools.

Problem-solving counseling as a therapeutic tool on youth suicidal behavior in the suburban population in Sri Lanka.

PubMed

Perera, E A Ramani; Kathriarachchi, Samudra T

2011-01-01

Suicidal behaviour among youth is a major public health concern in Sri Lanka. Prevention of youth suicides using effective, feasible and culturally acceptable methods is invaluable in this regard, however research in this area is grossly lacking. This study aimed at determining the effectiveness of problem solving counselling as a therapeutic intervention in prevention of youth suicidal behaviour in Sri Lanka. This control trial study was based on hospital admissions with suicidal attempts in a sub-urban hospital in Sri Lanka. The study was carried out at Base Hospital Homagama. A sample of 124 was recruited using convenience sampling method and divided into two groups, experimental and control. Control group was offered routine care and experimental group received four sessions of problem solving counselling over one month. Outcome of both groups was measured, six months after the initial screening, using the visual analogue scale. Individualized outcome measures on problem solving counselling showed that problem solving ability among the subjects in the experimental group had improved after four counselling sessions and suicidal behaviour has been reduced. The results are statistically significant. This Study confirms that problem solving counselling is an effective therapeutic tool in management of youth suicidal behaviour in hospital setting in a developing country.

ePrescribing: Reducing Costs through In-Class Therapeutic Interchange.

PubMed

Stenner, Shane P; Chakravarthy, Rohini; Johnson, Kevin B; Miller, William L; Olson, Julie; Wickizer, Marleen; Johnson, Nate N; Ohmer, Rick; Uskavitch, David R; Bernard, Gordon R; Neal, Erin B; Lehmann, Christoph U

2016-12-14

Spending on pharmaceuticals in the US reached $373.9 billion in 2014. Therapeutic interchange offers potential medication cost savings by replacing a prescribed drug for an equally efficacious therapeutic alternative. Hard-stop therapeutic interchange recommendation alerts were developed for four medication classes (HMG-CoA reductase inhibitors, serotonin receptor agonists, intranasal steroid sprays, and proton-pump inhibitors) in an electronic prescription-writing tool for outpatient prescriptions. Using prescription data from January 2012 to June 2015, the Compliance Ratio (CR) was calculated by dividing the number of prescriptions with recommended therapeutic interchange medications by the number of prescriptions with non-recommended medications to measure effectiveness. To explore potential cost savings, prescription data and medication costs were analyzed for the 45,000 Vanderbilt Employee Health Plan members. For all medication classes, significant improvements were demonstrated - the CR improved (proton-pump inhibitors 2.8 to 5.32, nasal steroids 2.44 to 8.16, statins 2.06 to 5.51, and serotonin receptor agonists 0.8 to 1.52). Quarterly savings through the four therapeutic interchange interventions combined exceeded $200,000 with an estimated annual savings for the health plan of $800,000, or more than $17 per member. A therapeutic interchange clinical decision support tool at the point of prescribing resulted in increased compliance with recommendations for outpatient prescriptions while producing substantial cost savings to the Vanderbilt Employee Health Plan - $17.77 per member per year. Therapeutic interchange rules require rational targeting, appropriate governance, and vigilant content updates.

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.

HEMD: an integrated tool of human epigenetic enzymes and chemical modulators for therapeutics.

PubMed

Huang, Zhimin; Jiang, Haiming; Liu, Xinyi; Chen, Yingyi; Wong, Jiemin; Wang, Qi; Huang, Wenkang; Shi, Ting; Zhang, Jian

2012-01-01

Epigenetic mechanisms mainly include DNA methylation, post-translational modifications of histones, chromatin remodeling and non-coding RNAs. All of these processes are mediated and controlled by enzymes. Abnormalities of the enzymes are involved in a variety of complex human diseases. Recently, potent natural or synthetic chemicals are utilized to establish the quantitative contributions of epigenetic regulation through the enzymes and provide novel insight for developing new therapeutics. However, the development of more specific and effective epigenetic therapeutics requires a more complete understanding of the chemical epigenomic landscape. Here, we present a human epigenetic enzyme and modulator database (HEMD), the database which provides a central resource for the display, search, and analysis of the structure, function, and related annotation for human epigenetic enzymes and chemical modulators focused on epigenetic therapeutics. Currently, HEMD contains 269 epigenetic enzymes and 4377 modulators in three categories (activators, inhibitors, and regulators). Enzymes are annotated with detailed description of epigenetic mechanisms, catalytic processes, and related diseases, and chemical modulators with binding sites, pharmacological effect, and therapeutic uses. Integrating the information of epigenetic enzymes in HEMD should allow for the prediction of conserved features for proteins and could potentially classify them as ideal targets for experimental validation. In addition, modulators curated in HEMD can be used to investigate potent epigenetic targets for the query compound and also help chemists to implement structural modifications for the design of novel epigenetic drugs. HEMD could be a platform and a starting point for biologists and medicinal chemists for furthering research on epigenetic therapeutics. HEMD is freely available at http://mdl.shsmu.edu.cn/HEMD/.

[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.

Awareness tool for safe and responsible driving (OSCAR): a potential educational intervention for increasing interest, openness and knowledge about the abilities required and compensatory strategies among older drivers.

PubMed

Levasseur, Mélanie; Audet, Thérèse; Gélinas, Isabelle; Bédard, Michel; Langlais, Marie-Ève; Therrien, France-Hélène; Renaud, Judith; Coallier, Jean-Claude; D'Amours, Monia

2015-01-01

This pilot study aimed to verify the impact of the awareness tool for safe and responsible driving (OSCAR) on older adults' (1) interest, openness, and knowledge about the abilities and compensatory strategies required for safe driving; (2) awareness of changes that have occurred in their own driving abilities; and (3) actual utilization of compensatory strategies. A preexperimental design, including a pretest (T0) and posttest (T1) 8 to 10 weeks after exposure to the intervention, was used with 48 drivers aged between 67 and 84. The participants had a valid driving license and drove at least once a week. Overall, the results demonstrate that OSCAR increased interest, openness, and knowledge about the abilities and compensatory strategies of older drivers (P <.01). After exposure to OSCAR, the majority of the participants confirmed that changes had occurred in at least one of their abilities. Moreover, half of the older drivers reported having started using 6 or more compensatory strategies. In summary, in addition to increasing older adults' interest, openness, and knowledge to discussion about driving, OSCAR also improved awareness of the changes that could negatively impact safe driving and enhanced utilization of compensatory strategies. While promoting safe driving and the prevention of crashes and injuries, this intervention could ultimately help older adults maintain or increase their transportation mobility. More studies are needed to further evaluate OSCAR and identify ways to improve its effectiveness.

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.

Literature on the Safe and Disruptive Learning Potential of Mobile Technologies

ERIC Educational Resources Information Center

Koszalka, Tiffany A.; Ntloedibe-Kuswani, G. S.

2010-01-01

Worldwide growth in use of mobile phones has fostered the emergence of mobile learning. Mobile technologies are used both in classrooms to support instruction (safe) and as tools that significantly change instructional activities, learner roles, and learning location (disruptive). Learners become less consumers of information and more…

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.

Creativity and improvisation as therapeutic tools within music therapy.

PubMed

Tomaino, Concetta M

2013-11-01

The neuroscience of creativity and music improvisation is a fascinating topic and one with strong implications for clinical music therapy. Music therapists are trained to use musical improvisation as a means to bring their clients into deeper therapeutic relationship as well as free up any inhibitions or limitations that may block recovery. Could recent fMRI studies of jazz musicians showing areas of brain activation during music improvisation provide a new framework to understand underlying mechanisms at work with neurologically impaired individuals? © 2013 New York Academy of Sciences.

Trauma-related dissociative (conversion) disorders in children and adolescents--an overview of assessment tools and treatment principles.

PubMed

Diseth, Trond H; Christie, Helen J

2005-01-01

A high proportion of patients in child and adolescent psychiatry with significant dissociative symptomatology after early childhood traumatization may go undiagnosed, be wrongly diagnosed and/or inappropriately treated. The diagnostics and treatment of dissociative disorders have been limited by lack of comprehensive, reliable and valid instruments and the ongoing polarization and fierce controversy regarding treatment. However, recent neurobiological findings of neurochemical, functional and structural cerebral consequences of early stressful childhood experiences point out a need for active, early and effective identification and treatment interventions. We present an update on assessment tools available in the Nordic countries, and an overview of different appropriate therapeutic intervention models for children and adolescents. A systematic overview of studies of dissociation in children and adolescent published over the last decade disclosed a total of 1019 references. The 465 papers describing aspects of assessment tools and/or treatment were studied in detail. Reliable and valid screening questionnaires and diagnostic interviews for children and adolescents now allow for effective early identification of dissociative disorders. A combination of individual psychotherapy, pharmacotherapy and family therapy are often required to handle dissociative disorders in children and adolescents. Cognitive-behavioural therapy, hypnotherapy, Eye-Movement Desensitization-Reprocessing (EMDR), psychodynamic therapy and an integrated approach are the main described psychotherapeutic approaches, but treatment of dissociation in children and adolescent does not require allegiance to any one particular treatment model. However, achievement of physical safety by providing a safe environment is a primary goal that supersedes any other therapeutic work. Assessments tools are now available, and appropriate therapeutic intervention models may hopefully contribute to reduce the risk

[Eye contact effects: A therapeutic issue?

PubMed

Baltazar, M; Conty, L

2016-12-01

The perception of a direct gaze - that is, of another individual's gaze directed at the observer that leads to eye contact - is known to influence a wide range of cognitive processes and behaviors. We stress that these effects mainly reflect positive impacts on human cognition and may thus be used as relevant tools for therapeutic purposes. In this review, we aim (1) to provide an exhaustive review of eye contact effects while discussing the limits of the dominant models used to explain these effects, (2) to illustrate the therapeutic potential of eye contact by targeting those pathologies that show both preserved gaze processing and deficits in one or several functions that are targeted by the eye contact effects, and (3) to propose concrete ways in which eye contact could be employed as a therapeutic tool. (1) We regroup the variety of eye contact effects into four categories, including memory effects, activation of prosocial behavior, positive appraisals of self and others and the enhancement of self-awareness. We emphasize that the models proposed to account for these effects have a poor predictive value and that further descriptions of these effects is needed. (2) We then emphasize that people with pathologies that affect memory, social behavior, and self and/or other appraisal, and self-awareness could benefit from eye contact effects. We focus on depression, autism and Alzheimer's disease to illustrate our proposal. To our knowledge, no anomaly of eye contact has been reported in depression. Patients suffering from Alzheimer disease, at the early and moderate stage, have been shown to maintain a normal amount of eye contact with their interlocutor. We take into account that autism is controversial regarding whether gaze processing is preserved or altered. In the first view, individuals are thought to elude or omit gazing at another's eyes while in the second, individuals are considered to not be able to process the gaze of others. We adopt the first stance

ePrescribing: Reducing Costs Through In-Class Therapeutic Interchange

PubMed Central

Stenner, Shane P.; Chakravarthy, Rohini; Johnson, Kevin B.; Miller, William L.; Olson, Julie; Wickizer, Marleen; Johnson, Nate N.; Ohmer, Rick; Uskavitch, David R.; Bernard, Gordon R.; Neal, Erin B.

2016-01-01

Summary Introduction Spending on pharmaceuticals in the US reached $373.9 billion in 2014. Therapeutic interchange offers potential medication cost savings by replacing a prescribed drug for an equally efficacious therapeutic alternative. Methods Hard-stop therapeutic interchange recommendation alerts were developed for four medication classes (HMG-CoA reductase inhibitors, serotonin receptor agonists, intranasal steroid sprays, and proton-pump inhibitors) in an electronic prescription-writing tool for outpatient prescriptions. Using prescription data from January 2012 to June 2015, the Compliance Ratio (CR) was calculated by dividing the number of prescriptions with recommended therapeutic interchange medications by the number of prescriptions with non-recommended medications to measure effectiveness. To explore potential cost savings, prescription data and medication costs were analyzed for the 45,000 Vanderbilt Employee Health Plan members. Results For all medication classes, significant improvements were demonstrated – the CR improved (proton-pump inhibitors 2.8 to 5.32, nasal steroids 2.44 to 8.16, statins 2.06 to 5.51, and serotonin receptor agonists 0.8 to 1.52). Quarterly savings through the four therapeutic interchange interventions combined exceeded $200,000 with an estimated annual savings for the health plan of $800,000, or more than $17 per member. Conclusion A therapeutic interchange clinical decision support tool at the point of prescribing resulted in increased compliance with recommendations for outpatient prescriptions while producing substantial cost savings to the Vanderbilt Employee Health Plan – $17.77 per member per year. Therapeutic interchange rules require rational targeting, appropriate governance, and vigilant content updates. PMID:27966005

Use of Virtual Reality Tools for Vestibular Disorders Rehabilitation: A Comprehensive Analysis.

PubMed

Bergeron, Mathieu; Lortie, Catherine L; Guitton, Matthieu J

2015-01-01

Classical peripheral vestibular disorders rehabilitation is a long and costly process. While virtual reality settings have been repeatedly suggested to represent possible tools to help the rehabilitation process, no systematic study had been conducted so far. We systematically reviewed the current literature to analyze the published protocols documenting the use of virtual reality settings for peripheral vestibular disorders rehabilitation. There is an important diversity of settings and protocols involving virtual reality settings for the treatment of this pathology. Evaluation of the symptoms is often not standardized. However, our results unveil a clear effect of virtual reality settings-based rehabilitation of the patients' symptoms, assessed by objectives tools such as the DHI (mean decrease of 27 points), changing symptoms handicap perception from moderate to mild impact on life. Furthermore, we detected a relationship between the duration of the exposure to virtual reality environments and the magnitude of the therapeutic effects, suggesting that virtual reality treatments should last at least 150 minutes of cumulated exposure to ensure positive outcomes. Virtual reality offers a pleasant and safe environment for the patient. Future studies should standardize evaluation tools, document putative side effects further, compare virtual reality to conventional physical therapy, and evaluate economical costs/benefits of such strategies.

Use of Virtual Reality Tools for Vestibular Disorders Rehabilitation: A Comprehensive Analysis

PubMed Central

Bergeron, Mathieu; Lortie, Catherine L.; Guitton, Matthieu J.

2015-01-01

Classical peripheral vestibular disorders rehabilitation is a long and costly process. While virtual reality settings have been repeatedly suggested to represent possible tools to help the rehabilitation process, no systematic study had been conducted so far. We systematically reviewed the current literature to analyze the published protocols documenting the use of virtual reality settings for peripheral vestibular disorders rehabilitation. There is an important diversity of settings and protocols involving virtual reality settings for the treatment of this pathology. Evaluation of the symptoms is often not standardized. However, our results unveil a clear effect of virtual reality settings-based rehabilitation of the patients' symptoms, assessed by objectives tools such as the DHI (mean decrease of 27 points), changing symptoms handicap perception from moderate to mild impact on life. Furthermore, we detected a relationship between the duration of the exposure to virtual reality environments and the magnitude of the therapeutic effects, suggesting that virtual reality treatments should last at least 150 minutes of cumulated exposure to ensure positive outcomes. Virtual reality offers a pleasant and safe environment for the patient. Future studies should standardize evaluation tools, document putative side effects further, compare virtual reality to conventional physical therapy, and evaluate economical costs/benefits of such strategies. PMID:26556560

The role of heparins and nano-heparins as therapeutic tool in breast cancer.

PubMed

Afratis, Nikos A; Karamanou, Konstantina; Piperigkou, Zoi; Vynios, Demitrios H; Theocharis, Achilleas D

2017-06-01

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.

Immunogenicity of therapeutic proteins: the use of animal models.

PubMed

Brinks, Vera; Jiskoot, Wim; Schellekens, Huub

2011-10-01

Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of immunogenicity during drug development and have become vital in studying the mechanisms underlying immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for immunogenicity prediction and summarizes the insights in immunogenicity that they have given so far.

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…

Problem—solving counseling as a therapeutic tool on youth suicidal behavior in the suburban population in Sri Lanka

PubMed Central

Perera, E. A. Ramani; Kathriarachchi, Samudra T.

2011-01-01

Background: Suicidal behaviour among youth is a major public health concern in Sri Lanka. Prevention of youth suicides using effective, feasible and culturally acceptable methods is invaluable in this regard, however research in this area is grossly lacking. Objective: This study aimed at determining the effectiveness of problem solving counselling as a therapeutic intervention in prevention of youth suicidal behaviour in Sri Lanka. Setting and design: This control trial study was based on hospital admissions with suicidal attempts in a sub-urban hospital in Sri Lanka. The study was carried out at Base Hospital Homagama. Materials and Methods: A sample of 124 was recruited using convenience sampling method and divided into two groups, experimental and control. Control group was offered routine care and experimental group received four sessions of problem solving counselling over one month. Outcome of both groups was measured, six months after the initial screening, using the visual analogue scale. Results: Individualized outcome measures on problem solving counselling showed that problem solving ability among the subjects in the experimental group had improved after four counselling sessions and suicidal behaviour has been reduced. The results are statistically significant. Conclusion: This Study confirms that problem solving counselling is an effective therapeutic tool in management of youth suicidal behaviour in hospital setting in a developing country. PMID:21431005

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.

Development of the SAFE Checklist Tool for Assessing Site-Level Threats to Child Protection: Use of Delphi Methods and Application to Two Sites in India.

PubMed

Betancourt, Theresa S; Zuilkowski, Stephanie S; Ravichandran, Arathi; Einhorn, Honora; Arora, Nikita; Bhattacharya Chakravarty, Aruna; Brennan, Robert T

2015-01-01

The child protection community is increasingly focused on developing tools to assess threats to child protection and the basic security needs and rights of children and families living in adverse circumstances. Although tremendous advances have been made to improve measurement of individual child health status or household functioning for use in low-resource settings, little attention has been paid to a more diverse array of settings in which many children in adversity spend time and how context contributes to threats to child protection. The SAFE model posits that insecurity in any of the following fundamental domains threatens security in the others: Safety/freedom from harm; Access to basic physiological needs and healthcare; Family and connection to others; Education and economic security. Site-level tools are needed in order to monitor the conditions that can dramatically undermine or support healthy child growth, development and emotional and behavioral health. From refugee camps and orphanages to schools and housing complexes, site-level threats exist that are not well captured by commonly used measures of child health and well-being or assessments of single households (e.g., SDQ, HOME). The present study presents a methodology and the development of a scale for assessing site-level child protection threats in various settings of adversity. A modified Delphi panel process was enhanced with two stages of expert review in core content areas as well as review by experts in instrument development, and field pilot testing. Field testing in two diverse sites in India-a construction site and a railway station-revealed that the resulting SAFE instrument was sensitive to the differences between the sites from the standpoint of core child protection issues.

Type Safe Extensible Programming

NASA Astrophysics Data System (ADS)

Chae, Wonseok

2009-10-01

Software products evolve over time. Sometimes they evolve by adding new features, and sometimes by either fixing bugs or replacing outdated implementations with new ones. When software engineers fail to anticipate such evolution during development, they will eventually be forced to re-architect or re-build from scratch. Therefore, it has been common practice to prepare for changes so that software products are extensible over their lifetimes. However, making software extensible is challenging because it is difficult to anticipate successive changes and to provide adequate abstraction mechanisms over potential changes. Such extensibility mechanisms, furthermore, should not compromise any existing functionality during extension. Software engineers would benefit from a tool that provides a way to add extensions in a reliable way. It is natural to expect programming languages to serve this role. Extensible programming is one effort to address these issues. In this thesis, we present type safe extensible programming using the MLPolyR language. MLPolyR is an ML-like functional language whose type system provides type-safe extensibility mechanisms at several levels. After presenting the language, we will show how these extensibility mechanisms can be put to good use in the context of product line engineering. Product line engineering is an emerging software engineering paradigm that aims to manage variations, which originate from successive changes in software.

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.

The Importance of Culturally Safe Assessment Tools for Inuit Students

ERIC Educational Resources Information Center

Stoffer, Jasmin

2017-01-01

There are still no major assessment and diagnostic tools that educators can use to properly assess our Inuit students' learning. Cultural safety as it is currently defined in New Zealand educational research (Macfarlane et al., 2007) is necessary in creating a classroom community that encourages the appreciation of culture and worldview, and…

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

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.

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.

Clinical reasoning in nursing: teaching strategies and assessment tools.

PubMed

Carvalho, Emília Campos de; Oliveira-Kumakura, Ana Railka de Souza; Morais, Sheila Coelho Ramalho Vasconcelos

2017-01-01

To present the concept and development of teaching strategies and the assessment tools regarding clinical reasoning for accurate practice. This is a theoretical reflection based on scientific studies. Comprehension of the essential concepts of the thought process and its articulation with the different teaching strategies and the assessment tools which has allowed presenting ways to improve the process of diagnostic or therapeutic clinical reasoning. The use of new strategies and assessment tools should be encouraged in order to contribute to the development of skills that lead to safe and effective decision making. Apresentar o conceito de raciocínio clínico, seu desenvolvimento, as estratégias para seu ensino e os instrumentos de avaliação para uma prática acurada. Trata-se de uma reflexão teórica fundamentada em estudos científicos. A compreensão dos conceitos essenciais do processo de pensamento e sua articulação com as diferentes estratégias de ensino e com os instrumentos de avaliação permitiram exemplificar meios de aprimorar o processo de raciocínio clínico diagnóstico ou terapêutico. A utilização de novas estratégias e instrumentos de avaliação deve ser estimulado para contribuir com o desenvolvimento das habilidades que culminam na tomada de decisão segura e eficaz.

Annual in Therapeutic Recreation. Volume 2.

ERIC Educational Resources Information Center

Crawford, Michael E., Ed.; Card, Jaclyn A., Ed.

This volume focuses on therapeutic recreation, as a subject of inquiry and as a treatment tool. The 11 articles include original field based research, program development initiatives, issue and theory of practice papers, and original tutorials in assessment and research. The article titles are: "The Role of Leisure Education with Family…

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

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.

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.

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.

CRISPR/Cas9 Genome Editing: A Promising Tool for Therapeutic Applications of Induced Pluripotent Stem Cells.

PubMed

Zhang, Yanli; Sastre, Danuta; Wang, Feng

2018-01-01

Induced pluripotent stem cells hold tremendous potential for biological and therapeutic applications. The development of efficient technologies for targeted genome alteration of stem cells in disease models is a prerequisite for utilizing stem cells to their full potential. The revolutionary technology for genome editing known as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) system is recently recognized as a powerful tool for editing DNA at specific loci. The ease of use of the CRISPR-Cas9 technology will allow us to improve our understanding of genomic variation in disease processes via cellular and animal models. More recently, this system was modified to repress (CRISPR interference, CRISPRi) or activate (CRISPR activation, CRISPRa) gene expression without alterations in the DNA, which amplified the scope of applications of CRISPR systems for stem cell biology. Here, we highlight latest advances of CRISPR-associated applications in human pluripotent stem cells. The challenges and future prospects of CRISPR-based systems for human research are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of the SAFE Checklist Tool for Assessing Site-Level Threats to Child Protection: Use of Delphi Methods and Application to Two Sites in India

PubMed Central

Betancourt, Theresa S.; Zuilkowski, Stephanie S.; Ravichandran, Arathi; Einhorn, Honora; Arora, Nikita; Bhattacharya Chakravarty, Aruna; Brennan, Robert T.

2015-01-01

Background The child protection community is increasingly focused on developing tools to assess threats to child protection and the basic security needs and rights of children and families living in adverse circumstances. Although tremendous advances have been made to improve measurement of individual child health status or household functioning for use in low-resource settings, little attention has been paid to a more diverse array of settings in which many children in adversity spend time and how context contributes to threats to child protection. The SAFE model posits that insecurity in any of the following fundamental domains threatens security in the others: Safety/freedom from harm; Access to basic physiological needs and healthcare; Family and connection to others; Education and economic security. Site-level tools are needed in order to monitor the conditions that can dramatically undermine or support healthy child growth, development and emotional and behavioral health. From refugee camps and orphanages to schools and housing complexes, site-level threats exist that are not well captured by commonly used measures of child health and well-being or assessments of single households (e.g., SDQ, HOME). Methods The present study presents a methodology and the development of a scale for assessing site-level child protection threats in various settings of adversity. A modified Delphi panel process was enhanced with two stages of expert review in core content areas as well as review by experts in instrument development, and field pilot testing. Results Field testing in two diverse sites in India—a construction site and a railway station—revealed that the resulting SAFE instrument was sensitive to the differences between the sites from the standpoint of core child protection issues. PMID:26540159

[Video games, a therapeutic mediator for teens].

PubMed

Nickler, Christophe

2015-10-01

Teenagers love video games and other multimedia tools. Sometimes they love them too much, leading to addictive use. A child psychiatry team in Nancy has developed a therapeutic multimedia workshop to contribute to treating teens. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

MicroRNAs in osteosarcoma: diagnostic and therapeutic aspects.

PubMed

Miao, Jinglei; Wu, Song; Peng, Zhi; Tania, Mousumi; Zhang, Chaoyue

2013-08-01

MicroRNAs (miRNAs) are small RNA molecules, which can interfere with the expression of several genes and act as gene regulator. miRNAs have been proved as a successful diagnostic and therapeutic tool in several cancers. In this review, the differential expression of miRNAs in osteosarcoma and their possibility to be used as diagnostic and therapeutic tools have been discussed. Osteosarcoma is the most common primary bone tumor that mainly affects children and adolescents. The current treatment of osteosarcoma remains difficult, and osteosarcoma causes many deaths because of its complex pathogenesis and resistance to conventional treatments. Several studies demonstrated that the differential expression patterns of miRNAs are a promising tool for the diagnosis and treatment of osteosarcoma. Although some aspect of the mechanism of action of miRNAs in controlling osteosarcoma has been identified (e.g., targeting the Notch signaling pathway), it is far beyond to the clear understanding of miRNA targets in osteosarcoma. Identification of the specific target of miRNAs may aid molecular targets for drug development and future relief of osteosarcoma.

Podocytes from the diagnostic and therapeutic point of view.

PubMed

Müller-Deile, Janina; Schiffer, Mario

2017-08-01

The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function. Incubation of cultured human podocyte cell lines with sera from patients with active glomerular diseases is currently also used to identify novel circulating factors with pathophysiological relevance for the glomerular filtration barrier. In addition, treatment of detached urinary podocytes from patients with substances that restore their cytoskeleton might serve as a novel personalized tool to estimate their potential for podocyte recovery ex vivo.

Development of novel cardiovascular therapeutics from small regulatory RNA molecules--an outline of key requirements.

PubMed

Poller, W; Fechner, H

2010-01-01

Understanding of the roles of RNAs within the cell has changed and expanded dramatically during the past few years. Based on fundamentally new insights it is now increasingly possible to employ RNAs as highly valuable tools in molecular biology and medicine. At present, the most important therapeutic strategies are based on non-coding regulatory RNAs inducing RNA interference (RNAi) to silence single genes, and on modulation of cellular microRNAs (miRNAs) to alter complex gene expression patterns in diseased organs. Only recently it became possible to target therapeutic RNAi to specific organs via organotropic viral vector systems and we discuss the most recent strategies in this field, e.g. heart failure treatment by cardiac-targeted RNAi. Due to the peculiar biochemical properties of small RNA molecules, true therapeutic translation of results in vitro is more demanding than with small molecule drugs or proteins. Specifically, there is a critical requirement for extensive studies in animal models of human disease after pre-testing of the RNAi tools in vitro. This requirement likewise applies for miRNA modulations which have complex consequences in the recipient dependent on biochemical stability and distribution of the therapeutic RNA. Problems not yet fully solved are the prediction of targets and specificity of the RNA tools. However, major progress has been made to achieve their tissue-specific and regulatable expression, and breakthroughs in vector technologies from the gene therapy field have fundamentally improved safety and efficacy of RNA-based therapeutic approaches, too. In summary, insight into the molecular mechanisms of action of regulatory RNAs in combination with new delivery tools for RNA therapeutics will significantly expand our cardiovascular therapeutic repertoire beyond classical pharmacology.

Value of diagnostic and therapeutic laparoscopy for patients with blunt abdominal trauma: A 10-year medical center experience

PubMed Central

Chen, Ying-Da; Chen, Shyr-Chyr

2018-01-01

Laparoscopy has been used for the diagnosis and treatment for hemodynamically stable patients with penetrating abdominal trauma. This study evaluated whether diagnostic and therapeutic laparoscopy can be used as effectively in select patients with blunt abdominal trauma. All hemodynamically stable patients undergoing operations for blunt abdominal trauma over a 10-year period (2006–2015) at a tertiary medical center were included. Patients undergoing laparotomy were categorized as group A. Patients who underwent laparoscopy were categorized as group B. The clinical outcomes of the 2 groups were compared. There were 139 patients in group A and 126 patients in group B. Group A patients were more severely injured (mean injury severity score of 23.3 vs. 18.9, P < .001) and had a higher frequency of traumatic brain injuries (25.2% vs. 14.3%, P = .039). The sensitivity and specificity of diagnostic laparoscopy for patients in group B was 99.1% and 100.0%, respectively. No non-therapeutic laparotomies were performed in group B, and the success rate of therapeutic laparoscopy was 92.0% (103/112) for patients with significant intra-abdominal injuries. Patients in the 2 groups had similar perioperative and postoperative outcomes in terms of operation times, blood loss, blood transfusion requirements, mortality, and complications (all, P > .05). Laparoscopy is a feasible and safe tool for the diagnosis and treatment of hemodynamically stable patients with blunt abdominal trauma who require surgery. PMID:29470527

Value of diagnostic and therapeutic laparoscopy for patients with blunt abdominal trauma: A 10-year medical center experience.

PubMed

Lin, Heng-Fu; Chen, Ying-Da; Chen, Shyr-Chyr

2018-01-01

Laparoscopy has been used for the diagnosis and treatment for hemodynamically stable patients with penetrating abdominal trauma. This study evaluated whether diagnostic and therapeutic laparoscopy can be used as effectively in select patients with blunt abdominal trauma. All hemodynamically stable patients undergoing operations for blunt abdominal trauma over a 10-year period (2006-2015) at a tertiary medical center were included. Patients undergoing laparotomy were categorized as group A. Patients who underwent laparoscopy were categorized as group B. The clinical outcomes of the 2 groups were compared. There were 139 patients in group A and 126 patients in group B. Group A patients were more severely injured (mean injury severity score of 23.3 vs. 18.9, P < .001) and had a higher frequency of traumatic brain injuries (25.2% vs. 14.3%, P = .039). The sensitivity and specificity of diagnostic laparoscopy for patients in group B was 99.1% and 100.0%, respectively. No non-therapeutic laparotomies were performed in group B, and the success rate of therapeutic laparoscopy was 92.0% (103/112) for patients with significant intra-abdominal injuries. Patients in the 2 groups had similar perioperative and postoperative outcomes in terms of operation times, blood loss, blood transfusion requirements, mortality, and complications (all, P > .05). Laparoscopy is a feasible and safe tool for the diagnosis and treatment of hemodynamically stable patients with blunt abdominal trauma who require surgery.

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.

Using music as a therapy tool to motivate troubled adolescents.

PubMed

Keen, Alexander W

2004-01-01

Children and adolescents with emotional disorders may often be characterized by having problems in peer and adult relations and in display of inappropriate behaviours. These include suicide attempts, anger, withdrawal from family, social isolation from peers, aggression, school failure, running away, and alcohol and/or drug abuse. A lack of self-concept and self-esteem is often central to these difficulties. Traditional treatment methods with young people usually includes cognitive- behavioural approaches with psychotherapy. Unfortunately these children often lack a solid communication base, creating a block to successful treatment. In my private clinical practice, I have endeavoured to break through these communication barriers by using music as a therapy tool. This paper describes and discusses my use of music as a therapy tool with troubled adolescents. Pre- and post-testing of the effectiveness of this intervention technique by using the Psychosocial Functioning Inventory for Primary School Children (PFI-PSC) has yielded positive initial results, lending support to its continued use. Music has often been successful in helping these adolescents engage in the therapeutic process with minimised resistance as they relate to the music and the therapist becomes a safe and trusted adult. Various techniques such as song discussion, listening, writing lyrics, composing music, and performing music.

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.

RNA therapeutics targeting osteoclast-mediated excessive bone resorption

PubMed Central

Wang, Yuwei; Grainger, David W

2011-01-01

RNA interference (RNAi) is a sequence-specific post-transcriptional gene silencing technique developed with dramatically increasing utility for both scientific and therapeutic purposes. Short interfering RNA (siRNA) is currently exploited to regulate protein expression relevant to many therapeutic applications, and commonly used as a tool for elucidating disease-associated genes. Osteoporosis and their associated osteoporotic fragility fractures in both men and women are rapidly becoming a global healthcare crisis as average life expectancy increases worldwide. New therapeutics are needed for this increasing patient population. This review describes the diversity of molecular targets suitable for RNAi-based gene knock-down in osteoclasts to control osteoclast-mediated excessive bone resorption. We identify strategies for developing targeted siRNA delivery and efficient gene silencing, and describe opportunities and challenges of introducing siRNA as a therapeutic approach to hard and connective tissue disorders. PMID:21945356

Apoptin towards safe and efficient anticancer therapies.

PubMed

Backendorf, Claude; Noteborn, Mathieu H M

2014-01-01

The chicken anemia virus derived protein apoptin harbors cancer-selective cell killing characteristics, essentially based on phosphorylation-mediated nuclear transfer in cancer cells and efficient cytoplasmic degradation in normal cells. Here, we describe a growing set of preclinical experiments underlying the promises of the anti-cancer potential of apoptin. Various non-replicative oncolytic viral vector systems have revealed the safety and efficacy of apoptin. In addition, apoptin enhanced the oncolytic potential of adenovirus, parvovirus and Newcastle disease virus vectors. Intratumoral injection of attenuated Salmonella typhimurium bacterial strains and plasmid-based systems expressing apoptin resulted in significant tumor regression. In-vitro and in-vivo experiments showed that recombinant membrane-transferring PTD4- or TAT-apoptin proteins have potential as a future anticancer therapeutics. In xenografted hepatoma and melanoma mouse models PTD4-apoptin protein entered both cancer and normal cells, but only killed cancer cells. Combinatorial treatment of PTD4-apoptin with various (chemo)therapeutic compounds revealed an additive or even synergistic effect, reducing the side effects of the single (chemo)therapeutic treatment. Degradable polymeric nanocapsules harboring MBP-apoptin fusion-protein induced tumor-selective cell killing in-vitro and in-vivo and revealed the potential of polymer-apoptin protein vehicles as an anticancer agent.Besides its direct use as an anticancer therapeutic, apoptin research has also generated novel possibilities for drug design. The nuclear location domains of apoptin are attractive tools for targeting therapeutic compounds into the nucleus of cancer cells. Identification of cancer-related processes targeted by apoptin can potentially generate novel drug targets. Recent breakthroughs important for clinical applications are reported inferring apoptin-based clinical trials as a feasible reality.

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.

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.

TDM in psychiatry and neurology: A comprehensive summary of the consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology, update 2017; a tool for clinicians^.

PubMed

Schoretsanitis, Georgios; Paulzen, Michael; Unterecker, Stefan; Schwarz, Markus; Conca, Andreas; Zernig, Gerald; Gründer, Gerhard; Haen, Ekkerhard; Baumann, Pierre; Bergemann, Niels; Clement, Hans Willi; Domschke, Katharina; Eckermann, Gabriel; Egberts, Karin; Gerlach, Manfred; Greiner, Christine; Havemann-Reinecke, Ursula; Hefner, Gudrun; Helmer, Renate; Janssen, Ger; Jaquenoud-Sirot, Eveline; Laux, Gerd; Messer, Thomas; Mössner, Rainald; Müller, Matthias J; Pfuhlmann, Bruno; Riederer, Peter; Saria, Alois; Schoppek, Bernd; Silva Gracia, Margarete; Stegmann, Benedikt; Steimer, Werner; Stingl, Julia C; Uhr, Manfred; Ulrich, Sven; Waschgler, Roland; Zurek, Gabriela; Hiemke, Christoph

2018-04-01

Therapeutic drug monitoring (TDM) combines the quantification of drug concentrations in blood, pharmacological interpretation and treatment guidance. TDM introduces a precision medicine tool in times of increasing awareness of the need for personalized treatment. In neurology and psychiatry, TDM can guide pharmacotherapy for patient subgroups such as children, adolescents, pregnant women, elderly patients, patients with intellectual disabilities, patients with substance use disorders, individuals with pharmacokinetic peculiarities and forensic patients. Clear indications for TDM include lack of clinical response in the therapeutic dose range, assessment of drug adherence, tolerability issues and drug-drug interactions. Based upon existing literature, recommended therapeutic reference ranges, laboratory alert levels, and levels of recommendation to use TDM for dosage optimization without specific indications, conversion factors, factors for calculation of dose-related drug concentrations and metabolite-to-parent ratios were calculated. This summary of the updated consensus guidelines by the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie offers the practical and theoretical knowledge for the integration of TDM as part of pharmacotherapy with neuropsychiatric agents into clinical routine. The present guidelines for TDM application for neuropsychiatric agents aim to assist clinicians in enhancing safety and efficacy of treatment.

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.

Embracing Safe Ground Test Facility Operations and Maintenance

NASA Technical Reports Server (NTRS)

Dunn, Steven C.; Green, Donald R.

2010-01-01

Conducting integrated operations and maintenance in wind tunnel ground test facilities requires a balance of meeting due dates, efficient operation, responsiveness to the test customer, data quality, effective maintenance (relating to readiness and reliability), and personnel and facility safety. Safety is non-negotiable, so the balance must be an "and" with other requirements and needs. Pressure to deliver services faster at increasing levels of quality in under-maintained facilities is typical. A challenge for management is to balance the "need for speed" with safety and quality. It s especially important to communicate this balance across the organization - workers, with a desire to perform, can be tempted to cut corners on defined processes to increase speed. Having a lean staff can extend the time required for pre-test preparations, so providing a safe work environment for facility personnel and providing good stewardship for expensive National capabilities can be put at risk by one well-intending person using at-risk behavior. This paper documents a specific, though typical, operational environment and cites management and worker safety initiatives and tools used to provide a safe work environment. Results are presented and clearly show that the work environment is a relatively safe one, though still not good enough to keep from preventing injury. So, the journey to a zero injury work environment - both in measured reality and in the minds of each employee - continues. The intent of this paper is to provide a benchmark for others with operational environments and stimulate additional sharing and discussion on having and keeping a safe work environment.

Safe emergency department removal of a hardened steel penile constriction ring.

PubMed

Peay, Jeremy; Smithson, James; Nelson, James; Witucki, Peter

2009-10-01

Penile constriction devices are used for the enhancement of sexual performance. These devices have the potential to become incarcerated, leading to necrosis and amputation if not removed promptly. This article presents a step-by-step approach for the safe removal of a hardened steel penile constriction device using somewhat unorthodox tools found in a hospital. We present a case of an incarcerated hardened steel penile constriction ring that was not able to be removed with conventional techniques. We describe a novel technique using an electric grinder and laryngoscope blade. The technique described in this article is a valuable and relatively safe technique for the Emergency Physician to facilitate the timely removal of a hardened steel constriction device.

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

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…

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.

Components of practical clinical detox programs--sauna as a therapeutic tool.

PubMed

Crinnion, Walter

2007-01-01

Saunas can be used very effectively for certain cardiovascular problems and as a means to enhance the mobilization of fat-soluble xenobiotics. When saunas are used to reduce blood pressure and enhance blood flow and cardiac functioning, only short sauna sessions (15 minutes) are necessary. When one wants to enhance the mobilization of heavy metals and chemical xenobiotics, longer sessions are needed and those should be medically monitored. But, for either use, saunas are safe and effective and should be used more frequently to benefit the health of our patients and ourselves.

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 ...

Survey of mental health nurses' attitudes towards risk assessment, risk assessment tools and positive risk.

PubMed

Downes, C; Gill, A; Doyle, L; Morrissey, J; Higgins, A

2016-04-01

WHAT IS KNOWN ON THE SUBJECT?: Risk assessment and safety planning are a core aspect of the role of the mental health nurse. Conflicting views exist on the value of risk assessment tools. Few studies have examined mental health nurses' attitudes towards risk, including use of tools and the role of positive risk in recovery. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: Mental health nurses view risk assessment as a core dimension of their role and not merely an exercise to fulfil organizational clinical safety and governance obligations. The majority of nurses hold positive attitudes towards therapeutic or positive risk, and consider creative risk taking as vital to people's recovery. The majority of nurses believe that risk assessment tools facilitate professional decision making, however, some are concerned that tools may negatively impact upon therapeutic relationships. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Ongoing education on the use of risk assessment tools is required to minimize views that their use is incompatible with therapeutic engagement, and to enable nurses to develop confidence to engage with positive risk and to allow service users make decisions and take responsibility. Introduction Risk assessment and safety planning are considered core components of the role of the mental health nurse; however, little is known about nurses' attitudes towards risk assessment, use of tools to assess risk or therapeutic risk taking. Aim This study aimed to explore mental health nurses' attitudes towards completing risk assessments, use of tools as an aid, and therapeutic or positive risk. Method An anonymous survey which included 13 attitudinal statements, rated on a five-point Likert scale, was completed by 381 mental health nurses working in adult services in Ireland. Findings Findings indicate strong support for the practice of risk assessment in mental health practice. The vast majority of nurses believe that risk assessment tools facilitate professional

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

PT-SAFE: a software tool for development and annunciation of medical audible alarms.

PubMed

Bennett, Christopher L; McNeer, Richard R

2012-03-01

Recent reports by The Joint Commission as well as the Anesthesia Patient Safety Foundation have indicated that medical audible alarm effectiveness needs to be improved. Several recent studies have explored various approaches to improving the audible alarms, motivating the authors to develop real-time software capable of comparing such alarms. We sought to devise software that would allow for the development of a variety of audible alarm designs that could also integrate into existing operating room equipment configurations. The software is meant to be used as a tool for alarm researchers to quickly evaluate novel alarm designs. A software tool was developed for the purpose of creating and annunciating audible alarms. The alarms consisted of annunciators that were mapped to vital sign data received from a patient monitor. An object-oriented approach to software design was used to create a tool that is flexible and modular at run-time, can annunciate wave-files from disk, and can be programmed with MATLAB by the user to create custom alarm algorithms. The software was tested in a simulated operating room to measure technical performance and to validate the time-to-annunciation against existing equipment alarms. The software tool showed efficacy in a simulated operating room environment by providing alarm annunciation in response to physiologic and ventilator signals generated by a human patient simulator, on average 6.2 seconds faster than existing equipment alarms. Performance analysis showed that the software was capable of supporting up to 15 audible alarms on a mid-grade laptop computer before audio dropouts occurred. These results suggest that this software tool provides a foundation for rapidly staging multiple audible alarm sets from the laboratory to a simulation environment for the purpose of evaluating novel alarm designs, thus producing valuable findings for medical audible alarm standardization.

Therapeutic target discovery using Boolean network attractors: improvements of kali

PubMed Central

Guziolowski, Carito

2018-01-01

In a previous article, an algorithm for identifying therapeutic targets in Boolean networks modelling pathological mechanisms was introduced. In the present article, the improvements made on this algorithm, named kali, are described. These improvements are (i) the possibility to work on asynchronous Boolean networks, (ii) a finer assessment of therapeutic targets and (iii) the possibility to use multivalued logic. kali assumes that the attractors of a dynamical system, such as a Boolean network, are associated with the phenotypes of the modelled biological system. Given a logic-based model of pathological mechanisms, kali searches for therapeutic targets able to reduce the reachability of the attractors associated with pathological phenotypes, thus reducing their likeliness. kali is illustrated on an example network and used on a biological case study. The case study is a published logic-based model of bladder tumorigenesis from which kali returns consistent results. However, like any computational tool, kali can predict but cannot replace human expertise: it is a supporting tool for coping with the complexity of biological systems in the field of drug discovery. PMID:29515890

The tools of PDT: light sources and devices. Can they help in getting better therapeutic results?

NASA Astrophysics Data System (ADS)

Boucher, Didier

2011-08-01

PDT is a drug and device therapy using photosensitizing drugs activated by laser light, for tissue ablation. PDT light sources must deliver wavelengths matching the absorption of photosensitizers' compound without any side thermal effect. According to applications, these sources need to be: - pled to relatively small optical fibres so as to bring the light energy, of specific wavelength, inside of the body (gastroenterology, head & neck, urology, pneumology), - coupled to a slit lamp adapter to transmit the light to the eye (AMD) - or allow a direct illumination of tissues when large areas must be treated (dermatology). But they also need to be user-friendly with limited investment and installation costs. So as to achieve the required effects, several light sources are available and will be used but practical and economical reasons have limited the number and types of these sources. For PDT oncology applications, besides dermatology, it has also been necessary to develop specific light delivery systems based on optical fibres. These devices allow the treatment: - of circular lumens such as oesophagus, bile ducts, lungs - of solid volumes such as prostate, pancreas - of surfaces such as in head and neck - of empty volumes such as bladder, uterus, cervix. Due to the variety of these treatments, a full family of sources has been developed from original sophisticated costly lasers to more recent easy-to-use diode laser systems. The aim of this presentation is to present the actual state of the art of actual available PDT tools, analyze their qualities and weaknesses, analyze the consequences of a good and/or bad choice or good and/or bad utilization on the quality of the therapeutic results and resulting side effects. It will also evaluate the short and medium term developments of new tools and their effect on the development of the therapy including economical aspects.

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,…

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…

Context-dependent ‘safekeeping’ of foraging tools in New Caledonian crows

PubMed Central

Klump, Barbara C.; van der Wal, Jessica E. M.; St Clair, James J. H.; Rutz, Christian

2015-01-01

Several animal species use tools for foraging, such as sticks to extract embedded arthropods and honey, or stones to crack open nuts and eggs. While providing access to nutritious foods, these behaviours may incur significant costs, such as the time and energy spent searching for, manufacturing and transporting tools. These costs can be reduced by re-using tools, keeping them safe when not needed. We experimentally investigated what New Caledonian crows do with their tools between successive prey extractions, and whether they express tool ‘safekeeping’ behaviours more often when the costs (foraging at height), or likelihood (handling of demanding prey), of tool loss are high. Birds generally took care of their tools (84% of 176 prey extractions, nine subjects), either trapping them underfoot (74%) or storing them in holes (26%)—behaviours we also observed in the wild (19 cases, four subjects). Moreover, tool-handling behaviour was context-dependent, with subjects: keeping their tools safe significantly more often when foraging at height; and storing tools significantly more often in holes when extracting more demanding prey (under these conditions, foot-trapping proved challenging). In arboreal environments, safekeeping can prevent costly tool losses, removing a potentially important constraint on the evolution of habitual and complex tool behaviour. PMID:25994674

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.

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...

Laparoscopic appendicectomy: safe and useful for training.

PubMed Central

Duff, S. E.; Dixon, A. R.

2000-01-01

Debate exists about the benefits of laparoscopic appendicectomy when compared to a conventional open procedure. The majority of appendices are removed by the open route in the UK. We report a series of 132 cases of suspected appendicitis managed laparoscopically: 112 (85%) of the patients had acute appendicitis, the remaining 20 (15%) had non-appendiceal pathology. The median operative time was 30 min and there were no conversions to an open operative procedure. The median postoperative stay was two days. Complications were seen in two patients. The published evidence comparing laparoscopic and open appendicectomy is contradictory. Our series shows that laparoscopic appendicectomy is a safe procedure with low morbidity; it is also an excellent training tool in laparoscopic technique and, with sufficient experience, takes no longer than an open procedure. Negative appendicocecotomies are most common in women of fertile age and can be associated with significant morbidity; therefore, laparoscopy should be used to make the diagnosis and, if appendicitis is the cause, the appendix could safely be removed laparoscopically. However, the choice between open and laparoscopic procedure is a subjective decision for the patient and their surgeon. Laparoscopic appendicectomy cannot be regarded as the gold standard. PMID:11103154

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.

Assessing and Addressing Safe Food Handling Knowledge, Attitudes, and Behaviors of College Undergraduates

ERIC Educational Resources Information Center

Stein, Susan E.; Dirks, Brian P.; Quinlan, Jennifer J.

2010-01-01

The authors determined the food safety knowledge, attitudes, and behaviors of undergraduates (n = 1122) on an urban college campus using a previously piloted survey tool. Data obtained found that while students reported high levels of confidence in their ability to engage in safe food handling practices, their knowledge and self-reported behaviors…

DriveSafe and DriveAware Assessment Tools Are a Measure of Driving-Related Function and Predicts Self-Reported Restriction for Older Drivers.

PubMed

Allan, Claire; Coxon, Kristy; Bundy, Anita; Peattie, Laura; Keay, Lisa

2016-06-01

Safety concerns together with aging of the driving population has prompted research into clinic-based driving assessments. This study investigates the relationship between the DriveSafe and DriveAware assessments and restriction of driving. Community-dwelling adults aged more than 75 (n = 380) were recruited in New South Wales, Australia. Questionnaires were administered to assess driving habits and functional assessments to assess driving-related function. Self-reported restriction was prevalent in this cross-sectional sample (62%) and was related to DriveSafe scores and personal circumstances but not DriveAware scores. DriveSafe scores were correlated with better performance on the Trail-Making Test (TMT; β = -2.94, p < .0001) and better contrast sensitivity (β = 48.70, p < .0001). Awareness was associated with better performance on the TMT (β = 0.08, p < .0001). Our data suggest that DriveSafe and DriveAware are sensitive to deficits in vision and cognition, and drivers with worse DriveSafe scores self-report restricting their driving. © The Author(s) 2015.

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

The Pathway to a Safe and Effective Medication Formulary for Exploration Spaceflight

NASA Technical Reports Server (NTRS)

Daniels, V. R.; Bayuse, T. M.; Mulcahy, R. A.; Mcguire, R. K. M.; Antonsen, E. L.

2017-01-01

PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 “Pharmacy” Gap; defined in the Human Research Program’s (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific

Interactional Practices Used in the Teaching of Conflict Prevention and Resolution Skills in an Innovative Safe School Program at an Elementary School

ERIC Educational Resources Information Center

Shin, Annalise Grace

2010-01-01

Within the framework of language socialization, this dissertation uses conversation analytic and ethnographic methods to examine the interactional practices used by the adult safe school educator at a progressive elementary school to socialize students into beliefs and practices associated with the school's Cool Tools Safe School Program. Cool…

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.

Applications of capillary electrophoresis in characterizing recombinant protein therapeutics.

PubMed

Zhao, Shuai Sherry; Chen, David D Y

2014-01-01

The use of recombinant protein for therapeutic applications has increased significantly in the last three decades. The heterogeneity of these proteins, often caused by the complex biosynthesis pathways and the subsequent PTMs, poses a challenge for drug characterization to ensure its safety, quality, integrity, and efficacy. CE, with its simple instrumentation, superior separation efficiency, small sample consumption, and short analysis time, is a well-suited analytical tool for therapeutic protein characterization. Different separation modes, including CIEF, SDS-CGE, CZE, and CE-MS, provide complementary information of the proteins. The CE applications for recombinant therapeutic proteins from the year 2000 to June 2013 are reviewed and technical concerns are discussed in this article. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications

PubMed Central

Kratz, Jeremy D.; Chaddha, Ashish; Bhattacharjee, Somnath

2016-01-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD. PMID:26809711

Atherosclerosis and Nanotechnology: Diagnostic and Therapeutic Applications.

PubMed

Kratz, Jeremy D; Chaddha, Ashish; Bhattacharjee, Somnath; Goonewardena, Sascha N

2016-02-01

Over the past several decades, tremendous advances have been made in the understanding, diagnosis, and treatment of coronary artery disease (CAD). However, with shifting demographics and evolving risk factors we now face new challenges that must be met in order to further advance are management of patients with CAD. In parallel with advances in our mechanistic appreciation of CAD and atherosclerosis, nanotechnology approaches have greatly expanded, offering the potential for significant improvements in our diagnostic and therapeutic management of CAD. To realize this potential we must go beyond to recognize new frontiers including knowledge gaps between understanding atherosclerosis to the translation of targeted molecular tools. This review highlights nanotechnology applications for imaging and therapeutic advancements in CAD.

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.

Rhomboid protease inhibitors: Emerging tools and future therapeutics.

PubMed

Strisovsky, Kvido

2016-12-01

Rhomboid-family intramembrane serine proteases are evolutionarily widespread. Their functions in different organisms are gradually being uncovered and already suggest medical relevance for infectious diseases and cancer. In contrast to these advances, selective inhibitors that could serve as efficient tools for investigation of physiological functions of rhomboids, validation of their disease relevance or as templates for drug development are lacking. In this review I extract what is known about rhomboid protease mechanism and specificity, examine the currently used inhibitors, their mechanism of action and limitations, and conclude by proposing routes for future development of rhomboid protease inhibitors. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

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

Theiler, James; Yoon, Hyejin; Yusim, Karina

Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraphmore » was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).« less

Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine

DOE PAGES

Theiler, James; Yoon, Hyejin; Yusim, Karina; ...

2016-10-05

Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraphmore » was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).« less

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.

The Expanding Therapeutic Utility of Botulinum Neurotoxins

PubMed Central

Fonfria, Elena; Maignel, Jacquie; Lezmi, Stephane; Martin, Vincent; Splevins, Andrew; Shubber, Saif; Kalinichev, Mikhail; Foster, Keith; Picaut, Philippe; Krupp, Johannes

2018-01-01

Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products. PMID:29783676

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

microRNAs as cancer therapeutics: A step closer to clinical application.

PubMed

Catela Ivkovic, Tina; Voss, Gjendine; Cornella, Helena; Ceder, Yvonne

2017-10-28

During the last decades, basic and translational research has enabled great improvements in the clinical management of cancer. However, scarcity of complete remission and many drug-induced toxicities are still a major problem in the clinics. Recently, microRNAs (miRNAs) have emerged as promising therapeutic targets due to their involvement in cancer development and progression. Their extraordinary regulatory potential, which enables regulation of entire signalling networks within the cells, makes them an interesting tool for the development of cancer therapeutics. In this review we will focus on miRNAs with experimentally proven therapeutic potential, and discuss recent advances in the technical development and clinical evaluation of miRNA-based therapeutic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Update on SLD Engineering Tools Development

NASA Technical Reports Server (NTRS)

Miller, Dean R.; Potapczuk, Mark G.; Bond, Thomas H.

2004-01-01

The airworthiness authorities (FAA, JAA, Transport Canada) will be releasing a draft rule in the 2006 timeframe concerning the operation of aircraft in a Supercooled Large Droplet (SLD) environment aloft. The draft rule will require aircraft manufacturers to demonstrate that their aircraft can operate safely in an SLD environment for a period of time to facilitate a safe exit from the condition. It is anticipated that aircraft manufacturers will require a capability to demonstrate compliance with this rule via experimental means (icing tunnels or tankers) and by analytical means (ice prediction codes). Since existing icing research facilities and analytical codes were not developed to account for SLD conditions, current engineering tools are not adequate to support compliance activities in SLD conditions. Therefore, existing capabilities need to be augmented to include SLD conditions. In response to this need, NASA and its partners conceived a strategy or Roadmap for developing experimental and analytical SLD simulation tools. Following review and refinement by the airworthiness authorities and other international research partners, this technical strategy has been crystallized into a project plan to guide the SLD Engineering Tool Development effort. This paper will provide a brief overview of the latest version of the project plan and technical rationale, and provide a status of selected SLD Engineering Tool Development research tasks which are currently underway.

Powered mobility intervention: understanding the position of tool use learning as part of implementing the ALP tool.

PubMed

Nilsson, Lisbeth; Durkin, Josephine

2017-10-01

To explore the knowledge necessary for adoption and implementation of the Assessment of Learning Powered mobility use (ALP) tool in different practice settings for both adults and children. To consult with a diverse population of professionals working with adults and children, in different countries and various settings; who were learning about or using the ALP tool, as part of exploring and implementing research findings. Classical grounded theory with a rigorous comparative analysis of data from informants together with reflections on our own rich experiences of powered mobility practice and comparisons with the literature. A core category learning tool use and a new theory of cognizing tool use, with its interdependent properties: motivation, confidence, permissiveness, attentiveness and co-construction has emerged which explains in greater depth what enables the application of the ALP tool. The scientific knowledge base on tool use learning and the new theory conveys the information necessary for practitioner's cognizing how to apply the learning approach of the ALP tool in order to enable tool use learning through powered mobility practice as a therapeutic intervention in its own right. This opens up the possibility for more children and adults to have access to learning through powered mobility practice. Implications for rehabilitation Tool use learning through powered mobility practice is a therapeutic intervention in its own right. Powered mobility practice can be used as a rehabilitation tool with individuals who may not need to become powered wheelchair users. Motivation, confidence, permissiveness, attentiveness and co-construction are key properties for enabling the application of the learning approach of the ALP tool. Labelling and the use of language, together with honing observational skills through viewing video footage, are key to developing successful learning partnerships.

A Protocol for Safe Lithiation Reactions Using Organolithium Reagents

PubMed Central

Gau, Michael R.; Zdilla, Michael J.

2016-01-01

Organolithium reagents are powerful tools in the synthetic chemist's toolbox. However, the extreme pyrophoric nature of the most reactive reagents warrants proper technique, thorough training, and proper personal protective equipment. To aid in the training of researchers using organolithium reagents, a thorough, step-by-step protocol for the safe and effective use of tert-butyllithium on an inert gas line or within a glovebox is described. As a model reaction, preparation of lithium tert-butyl amide by the reaction of tert-butyl amine with one equivalent of tert-butyl lithium is presented. PMID:27911386

Nanotechnology solutions for Alzheimer's disease: advances in research tools, diagnostic methods and therapeutic agents.

PubMed

Nazem, Amir; Mansoori, G Ali

2008-03-01

A century of research has passed since the discovery and definition of Alzheimer's disease (AD), the primary common dementing disorder worldwide. However, AD lacks definite diagnostic approaches and effective cure at the present. Moreover, the currently available diagnostic tools are not sufficient for an early screening of AD in order to start preventive approaches. Recently the emerging field of nanotechnology has promised new techniques to solve some of the AD challenges. Nanotechnology refers to the techniques of designing and manufacturing nanosize (1-100 nm) structures through controlled positional and/or self-assembly of atoms and molecules. In this report, we present the promises that nanotechnology brings in research on the AD diagnosis and therapy. They include its potential for the better understanding of the AD root cause molecular mechanisms, AD's early diagnoses, and effective treatment. The advances in AD research offered by the atomic force microscopy, single molecule fluorescence microscopy and NanoSIMS microscopy are examined here. In addition, the recently proposed applications of nanotechnology for the early diagnosis of AD including bio-barcode assay, localized surface plasmon resonance nanosensor, quantum dot and nanomechanical cantilever arrays are analyzed. Applications of nanotechnology in AD therapy including neuroprotections against oxidative stress and anti-amyloid therapeutics, neuroregeneration and drug delivery beyond the blood brain barrier (BBB) are discussed and analyzed. All of these applications could improve the treatment approach of AD and other neurodegenerative diseases. The complete cure of AD may become feasible by a combination of nanotechnology and some other novel approaches, like stem cell technology.

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.

Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Scully, Robert R.

2013-01-01

Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

Therapeutic applications of CRISPR/Cas9 system in gene therapy.

PubMed

Mollanoori, Hasan; Teimourian, Shahram

2018-06-01

Gene therapy is based on the principle of the genetic manipulation of DNA or RNA for treating and preventing human diseases. The clustered regularly interspaced short palindromic repeats/CRISPR associated nuclease9 (CRISPR/Cas9) system, derived from the acquired immune system in bacteria and archaea, has provided a new tool for accurate manipulation of genomic sequence to attain a therapeutic result. The advantage of CRISPR which made it an easy and flexible tool for diverse genome editing purposes is that a single protein (Cas9) complex with 2 short RNA sequences, function as a site-specific endonuclease. Recently, application of CRISPR/Cas9 system has become popular for therapeutic aims such as gene therapy. In this article, we review the fundamental mechanisms of CRISPR-Cas9 function and summarize preclinical CRISPR-mediated gene therapy reports on a wide variety of disorders.

Alternative Splicing in Breast Cancer and the Potential Development of Therapeutic Tools.

PubMed

Martínez-Montiel, Nancy; Anaya-Ruiz, Maricruz; Pérez-Santos, Martín; Martínez-Contreras, Rebeca D

2017-10-05

Alternative splicing is a key molecular mechanism now considered as a hallmark of cancer that has been associated with the expression of distinct isoforms during the onset and progression of the disease. The leading cause of cancer-related deaths in women worldwide is breast cancer, and even when the role of alternative splicing in this type of cancer has been established, the function of this mechanism in breast cancer biology is not completely decoded. In order to gain a comprehensive view of the role of alternative splicing in breast cancer biology and development, we summarize here recent findings regarding alternative splicing events that have been well documented for breast cancer evolution, considering its prognostic and therapeutic value. Moreover, we analyze how the response to endocrine and chemical therapies could be affected due to alternative splicing and differential expression of variant isoforms. With all this knowledge, it becomes clear that targeting alternative splicing represents an innovative approach for breast cancer therapeutics and the information derived from current studies could guide clinical decisions with a direct impact in the clinical advances for breast cancer patients nowadays.

Human cells: new platform for recombinant therapeutic protein production.

PubMed

Swiech, Kamilla; Picanço-Castro, Virgínia; Covas, Dimas Tadeu

2012-07-01

The demand for recombinant therapeutic proteins is significantly increasing. There is a constant need to improve the existing expression systems, and also developing novel approaches to face the therapeutic proteins demands. Human cell lines have emerged as a new and powerful alternative for the production of human therapeutic proteins because this expression system is expected to produce recombinant proteins with post translation modifications more similar to their natural counterpart and reduce the potential immunogenic reactions against nonhuman epitopes. Currently, little information about the cultivation of human cells for the production of biopharmaceuticals is available. These cells have shown efficient production in laboratory scale and represent an important tool for the pharmaceutical industry. This review presents the cell lines available for large-scale recombinant proteins production and evaluates critically the advantages of this expression system in comparison with other expression systems for recombinant therapeutic protein production. Copyright © 2012 Elsevier Inc. All rights reserved.

Critical questions in development of targeted nanoparticle therapeutics.

PubMed

Korsmeyer, Richard

2016-06-01

One of the fourteen Grand Challenges for Engineering articulated by the US National Academy of Engineering is 'Engineer Better Medicines'. Although there are many ways that better medicines could be engineered, one of the most promising ideas is to improve our ability to deliver the therapeutic molecule more precisely to the desired target. Most conventional drug delivery methods (oral absorption, intravenous infusion etc.) result in systemic exposure to the therapeutic molecule, which places severe constraints on the types of molecules that can be used. A molecule administered by systemic delivery must be effective at low concentrations in the target tissue, yet safe everywhere else in the body. If drug carriers could be developed to deliver therapeutic molecules selectively to the desired target, it should be possible to greatly improve safety and efficacy of therapy. Nanoparticles (and related nanostructures, such as liposomes, nanoemulsions, micelles and dendrimers) are an attractive drug carrier concept because they can be made from a variety of materials engineered to have properties that allow loading and precise delivery of bound therapeutic molecules. The field of targeted nanoparticles has been extraordinarily active in the academic realm, with thousands of articles published over the last few years. Many of these publications seem to demonstrate very promising results in in vitro studies and even in animal models. In addition, a handful of human clinical trials are in progress. Yet, the biopharmaceutical industry has been relatively slow to make major investments in targeted nanoparticle development programs, despite a clear desire to introduce innovative new therapies to the market. What is the reason for such caution? Some degree of caution is no doubt due to the use of novel materials and the unproven nature of targeted nanoparticle technology, but many other unproven technologies have generated intense interest at various times. We believe that the

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.

Therapeutic Use of Space: One Agency's Transformation Project

ERIC Educational Resources Information Center

Goelitz, Ann; Stewart-Kahn, Abigail

2007-01-01

The project described in this article addresses the therapeutic use of physical space in an outpatient counseling facility. It was theorized that an improved facility environment could be used as a practice tool when working with a vulnerable population. The authors undertook the project with limited time and finances. The process of the change…

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.

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.

[Mathematical modeling: an essential tool for the study of therapeutic targeting in solid tumors].

PubMed

Saidak, Zuzana; Giacobbi, Anne-Sophie; Morisse, Mony Chenda; Mammeri, Youcef; Galmiche, Antoine

2017-12-01

Recent progress in biology has made the study of the medical treatment of cancer more effective, but it has also revealed the large complexity of carcinogenesis and cell signaling. For many types of cancer, several therapeutic targets are known and in some cases drugs against these targets exist. Unfortunately, the target proteins often work in networks, resulting in functional adaptation and the development of resilience/resistance to medical treatment. The use of mathematical modeling makes it possible to carry out system-level analyses for improved study of therapeutic targeting in solid tumours. We present the main types of mathematical models used in cancer research and we provide examples illustrating the relevance of these approaches in molecular oncobiology. © 2017 médecine/sciences – Inserm.

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.

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 ...

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.

OverView of Space Applications for Environment (SAFE) initiative

NASA Astrophysics Data System (ADS)

Hamamoto, Ko; Fukuda, Toru; Tajima, Yoshimitsu; Takeuchi, Wataru; Sobue, Shinichi; Nukui, Tomoyuki

2014-06-01

Climate change and human activities have a direc or indirect influence on the acceleration of environmental problems and natural hazards such as forest fires, draughts and floods in the Asia-Pacific countries. Satellite technology has become one of the key information sources in assessment, monitoring and mitigation of these disasters and related phenomenon. However, there are still gaps between science and application of satellite technology in real-world usage. Asia-Pacific Regional Space Agency Forum (APRSAF) recommended to initiate the Space Applications for Environment (SAFE) proposal providing opportunity to potential user agencies in the Asia Pacific region to develop prototype applications of satellite technology for number of key issues including forest resources management, coastal monitoring and management, agriculture and food security, water resource management and development user-friendly tools for application of satellite technology. This paper describes the overview of SAFE initiative and outcomes of two selected prototypes; agricultural drought monitoring in Indonesia and coastal management in Sri Lanka, as well as the current status of on-going prototypes.

Exploring the safe and just operating space in an inhomogeneous world

NASA Astrophysics Data System (ADS)

Barfuss, Wolfram; Beronov, Boyan; Wiedermann, Marc; Donges, Jonathan

2015-04-01

The Anthropocene has become reality during the 20th century, implying that our species is pressuring the Earth's ecosystems on a global scale. In the meantime, the challenge of eradicating poverty has not yet ceased to exist. Effectively dealing with these issues requires us to better understand the driving forces, feedback loops and tipping elements in the whole Earth system, constituted by natural and social components. To take a step forward in this direction, we refine an existing conceptual coevolutionary model of social and ecological domains (COPAN:EXPLOIT) by introducing inhomogeneities in the properties of local renewable resource stocks that are abstracted from real-world data. We then propose an analytical framework, 'the safe and just space'- plot, which aligns with the current debate on how to simultaneously stay within planetary boundaries (Rockström et al., 2009) and at the same time ensure that social foundations are met (Raworth, 2012). This plot presents a practical tool for jointly studying global socio-ecological models as well as real-world observations. First results from comparing the model outputs with real-world data indicate that the current state of the world is neither particularly safe nor particularly just. References: Rockström, Johan, et al. "A safe operating space for humanity." Nature 461.7263 (2009): 472-475. Raworth, Kate. "A safe and just space for humanity: can we live within the doughnut?" Oxfam Discussion Papers (2012): 1-26.

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.

Immunogenicity assessment during the development of protein therapeutics.

PubMed

Rosenberg, Amy S; Sauna, Zuben E

2018-05-01

Here we provide a critical review of the state of the art with respect to non-clinical assessments of immunogenicity for therapeutic proteins. The number of studies on immunogenicity published annually has more than doubled in the last 5 years. The science and technology, which have reached a critical mass, provide multiple of non-clinical approaches (computational, in vitro, ex vivo and animal models) to first predict and then to modify or eliminate T-cell or B-cell epitopes via de-immunization strategies. We discuss how these may be used in the context of drug development in assigning the immunogenicity risk of new and marketed therapeutic proteins. Protein therapeutics represents a large share of the pharma market and provide medical interventions for some of the most complex and intractable diseases. Immunogenicity (the development of antibodies to therapeutic proteins) is an important concern for both the safety and efficacy of protein therapeutics as immune responses may neutralize the activity of life-saving and highly effective protein therapeutics and induce hypersensitivity responses including anaphylaxis. The non-clinical computational tools and experimental technologies that offer a comprehensive and increasingly accurate estimation of immunogenic potential are surveyed here. This critical review also discusses technologies which are promising but are not as yet ready for routine use. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

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

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.

Sasquatch Footprint Tool

NASA Technical Reports Server (NTRS)

Bledsoe, Kristin

2013-01-01

The Crew Exploration Vehicle Parachute Assembly System (CPAS) is the parachute system for NASA s Orion spacecraft. The test program consists of numerous drop tests, wherein a test article rigged with parachutes is extracted or released from an aircraft. During such tests, range safety is paramount, as is the recoverability of the parachutes and test article. It is crucial to establish an aircraft release point that will ensure that the article and all items released from it will land in safe locations. A new footprint predictor tool, called Sasquatch, was created in MATLAB. This tool takes in a simulated trajectory for the test article, information about all released objects, and atmospheric wind data (simulated or actual) to calculate the trajectories of the released objects. Dispersions are applied to the landing locations of those objects, taking into account the variability of winds, aircraft release point, and object descent rate. Sasquatch establishes a payload release point (e.g., where the payload will be extracted from the carrier aircraft) that will ensure that the payload and all objects released from it will land in a specified cleared area. The landing locations (the final points in the trajectories) are plotted on a map of the test range. Sasquatch was originally designed for CPAS drop tests and includes extensive information about both the CPAS hardware and the primary test range used for CPAS testing. However, it can easily be adapted for more complex CPAS drop tests, other NASA projects, and commercial partners. CPAS has developed the Sasquatch footprint tool to ensure range safety during parachute drop tests. Sasquatch is well correlated to test data and continues to ensure the safety of test personnel as well as the safe recovery of all equipment. The tool will continue to be modified based on new test data, improving predictions and providing added capability to meet the requirements of more complex testing.

Research Tool Patents--Rumours of their Death are Greatly Exaggerated

ERIC Educational Resources Information Center

Carroll, Peter G.; Roberts, John S.

2006-01-01

Using a patented drug during clinical trials is not infringement [35 U.S.C. 271(e)(1)]. Merck v Integra enlarged this "safe harbour" to accommodate preclinical use of drugs and patented "research tools" if "reasonably related" to FDA approval. The decision allowed lower courts, should they wish, to find any use of a research tool, except for…

Effects of the Smartphone Application "Safe Patients" on Knowledge of Patient Safety Issues Among Surgical Patients.

PubMed

Cho, Sumi; Lee, Eunjoo

2017-12-01

Recently, the patient's role in preventing adverse events has been emphasized. Patients who are more knowledgeable about safety issues are more likely to engage in safety initiatives. Therefore, nurses need to develop techniques and tools that increase patients' knowledge in preventing adverse events. For this reason, an educational smartphone application for patient safety called "Safe Patients" was developed through an iterative process involving a literature review, expert consultations, and pilot testing of the application. To determine the effect of "Safe Patients," it was implemented for patients in surgical units in a tertiary hospital in South Korea. The change in patients' knowledge about patient safety was measured using seven true/false questions developed in this study. A one-group pretest and posttest design was used, and a total of 123 of 190 possible participants were tested. The percentage of correct answers significantly increased from 64.5% to 75.8% (P < .001) after implementation of the "Safe Patients" application. This study demonstrated that the application "Safe Patients" could effectively improve patients' knowledge of safety issues. This will ultimately empower patients to engage in safe practices and prevent adverse events related to surgery.

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 ...

[Anticancer drugs: Which prices for therapeutic innovations?].

PubMed

Gonçalves, Anthony; Maraninchi, Dominique; Marino, Patricia

2016-04-01

The expanding knowledge of the biological mechanisms underlying tumor development made it possible the recent emergence of new therapeutic approaches that are considered as undoubtedly innovative. Yet, to define and to evaluate the magnitude of a drug innovation require an examination of its intrinsic drug properties, medical utility as well as its mode of emergence. Recently, international academic societies, such as ESMO and ASCO, have proposed practical tools that may help quantifying the medical value of a given innovation. Currently, the sustained flux of therapeutic innovations in oncology is associated with an unprecedented growth of costs, the actual determinants of which remain under debate, but raising the critical issue of drugs pricing, and their potential individual or societal "financial toxicity". Copyright © 2016. Published by Elsevier Masson SAS.

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.

[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.

The promises and pitfalls of RNA-interference-based therapeutics

PubMed Central

Castanotto, Daniela; Rossi, John J.

2009-01-01

The discovery that gene expression can be controlled by the Watson–Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence — a process known as RNA interference — has markedly advanced our understanding of eukaryotic gene regulation and function. The ability of short RNA sequences to modulate gene expression has provided a powerful tool with which to study gene function and is set to revolutionize the treatment of disease. Remarkably, despite being just one decade from its discovery, the phenomenon is already being used therapeutically in human clinical trials, and biotechnology companies that focus on RNA-interference-based therapeutics are already publicly traded. PMID:19158789

Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

NASA Astrophysics Data System (ADS)

Kim, Chaekyu; Agasti, Sarit S.; Zhu, Zhengjiang; Isaacs, Lyle; Rotello, Vincent M.

2010-11-01

Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host-guest system featuring diaminohexane-terminated gold nanoparticles (AuNP-NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP-NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP-NH2 was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP-NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications.

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

Escalating role of piezosurgery in dental therapeutics.

PubMed

Agarwal, Esha; Masamatti, Sujata Surendra; Kumar, Ashish

2014-10-01

Dentistry, an art in science and tranquilizer in medicine, has seen a lot of changing concepts over a decade and one such novel innovation is piezosurgery. Piezosurgery is a true revolution in bone surgery as it fulfils both biological and technical criteria. It has a variety of applications ranging from minor surgical procedures to complex implantology, plastic and reconstructive surgeries. Piezosurgery uses a low frequency modulated ultrasonic insert which produces microvibrations in the range of 60-200micro meter/sec and leads to safe and precise bony incision without damaging underlying vital structures like nerves, mucosa and vessels. It overcomes technical difficulties such as visibility by producing bloodless field during surgery and removes debris simultaneously through internal irrigation mechanism. The soft tissues remain safe and biological factors like release of certain cytokines promote bone healing and enhance patients recovery. This critical review outweighs piezosurgery over traditional tools and emphasizes on its clinical and biological aspects contributing to beneficial dental health.

Escalating Role of Piezosurgery in Dental Therapeutics

PubMed Central

Masamatti, Sujata Surendra; Kumar, Ashish

2014-01-01

Dentistry, an art in science and tranquilizer in medicine, has seen a lot of changing concepts over a decade and one such novel innovation is piezosurgery. Piezosurgery is a true revolution in bone surgery as it fulfils both biological and technical criteria. It has a variety of applications ranging from minor surgical procedures to complex implantology, plastic and reconstructive surgeries. Piezosurgery uses a low frequency modulated ultrasonic insert which produces microvibrations in the range of 60-200micro meter/sec and leads to safe and precise bony incision without damaging underlying vital structures like nerves, mucosa and vessels. It overcomes technical difficulties such as visibility by producing bloodless field during surgery and removes debris simultaneously through internal irrigation mechanism. The soft tissues remain safe and biological factors like release of certain cytokines promote bone healing and enhance patients recovery. This critical review outweighs piezosurgery over traditional tools and emphasizes on its clinical and biological aspects contributing to beneficial dental health. PMID:25478473

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

Stem cells as a novel tool for drug screening and treatment of degenerative diseases.

PubMed

Zuba-Surma, Ewa K; Wojakowski, Wojciech; Madeja, Zbigniew; Ratajczak, Mariusz Z

2012-01-01

Degenerative diseases similarly as acute tissue injuries lead to massive cell loss and may cause organ failure of vital organs (e.g., heart, central nervous system). Therefore, they belong to a group of disorders that may significantly benefit from stem cells (SCs)-based therapies. Several stem and progenitor cell populations have already been described as valuable tools for developing therapeutic strategies in regenerative medicine. In particular, pluripotent stem cells (PSCs), including adult-tissue-derived PSCs, neonatal-tissue-derived SCs, embryonic stem cells (ESCs), and recently described induced pluripotent stem cells (iPSCs), are the focus of particular attention because of their capacity to differentiate into all the cell lineages. Although PSCs are predominantly envisioned to be applied for organ regeneration, they may be also successfully employed in drug screening and disease modeling. In particular, adult PSCs and iPSCs derived from patient tissues may not only be a source of cells for autologous therapies but also for individual customized in vitro drug testing and studies on the molecular mechanisms of disease. In this review, we will focus on the potential applications of SCs, especially PSCs i) in regenerative medicine therapies, ii) in studying mechanisms of disease, as well as iii) in drug screening and toxicology tests that are crucial in new drug development. In particular, we will discuss the application of SCs in developing new therapeutic approaches to treat degenerative diseases of the neural system and heart. The advantage of adult PSCs in all the above-mentioned settings is that they can be directly harvested from patient tissues and used not only as a safe non-immunogenic source of cells for therapy but also as tools for personalized drug screening and pharmacological therapies.

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

Proteomics of blood-based therapeutics: a promising tool for quality assurance in transfusion medicine.

PubMed

Thiele, Thomas; Steil, Leif; Völker, Uwe; Greinacher, Andreas

2007-01-01

Blood-based therapeutics are cellular or plasma components derived from human blood. Their production requires appropriate selection and treatment of the donor and processing of cells or plasma proteins. In contrast to clearly defined, chemically synthesized drugs, blood-derived therapeutics are highly complex mixtures of plasma proteins or even more complex cells. Pathogen transmission by the product as well as changes in the integrity of blood constituents resulting in loss of function or immune modulation are currently important issues in transfusion medicine. Protein modifications can occur during various steps of the production process, such as acquisition, enrichment of separate components (e.g. coagulation factors, cell populations), virus inactivation, conservation, and storage. Contemporary proteomic strategies allow a comprehensive assessment of protein modifications with high coverage, offer capabilities for qualitative and even quantitative analysis, and for high-throughput protein identification. Traditionally, proteomics approaches predominantly relied on two-dimensional gel electrophoresis (2-DE). Even if 2-DE is still state of the art, it has inherent limitations that are mainly based on the physicochemical properties of the proteins analyzed; for example, proteins with extremes in molecular mass and hydrophobicity (most membrane proteins) are difficult to assess by 2-DE. These limitations have fostered the development of mass spectrometry centered on non-gel-based separation approaches, which have proven to be highly successful and are thus complementing and even partially replacing 2-DE-based approaches. Although blood constituents have been extensively analyzed by proteomics, this technology has not been widely applied to assess or even improve blood-derived therapeutics, or to monitor the production processes. As proteomic technologies have the capacity to provide comprehensive information about changes occurring during processing and storage of

Salicylic acid derivatives: synthesis, features and usage as therapeutic tools.

PubMed

Ekinci, Deniz; Sentürk, Murat; Küfrevioğlu, Ömer İrfan

2011-12-01

In the field of medicinal chemistry, there is a growing interest in the use of small molecules. Although acetyl salicylic acid is well known for medical applications, little is known about other salicylic acid derivatives, and there is serious lack of data and information on the effects and biological evaluation that connect them. This review covers the synthesis and drug potencies of salicylic acid derivatives. After a brief overview of the information on salicylic acid and its features, a detailed review of salicylic acids as drugs and prodrugs, usage as cyclooxygenase inhibitors, properties in plants, synthesis and recent patents, is developed. Salicylic acid research is still an important area and innovations continue to arise, which offer hope for new therapeutics in related fields. It is anticipated that this review will guide the direction of long-term drug/nutraceutical safety trials and stimulate ideas for future research.

Exploring Oxidative Reactions in Hemoglobin Variants Using Mass Spectrometry: Lessons for Engineering Oxidatively Stable Oxygen Therapeutics

PubMed Central

Strader, Michael Brad

2017-01-01

Abstract Significance: Worldwide demand has driven the development of hemoglobin (Hb)-based oxygen carriers (HBOCs) as potential acellular oxygen therapeutics. HBOCs have the potential to provide an oxygen bridge to patients and minimize current problems associated with supply and storage of donated blood. However, to date, safety and efficacy issues have hampered the approval of viable HBOCs in the United States. These previous efforts have underscored the need for a better molecular understanding of toxicity to design safe and oxidatively stable HBOCs. Recent Advances: High-resolution accurate mass (HRAM) mass spectrometry (MS) has recently become a versatile tool in characterizing oxidative post-translational modifications that occur in Hb. When integrated with other analytical techniques, HRAM data have been invaluable in providing mechanistic insight into the extent of oxidative modification by quantifying oxidation in amino acids near the reactive heme or at specific “oxidative hotspots.” Critical Issues: In addition to providing a deeper understanding of Hb oxidative toxicity, HRAM MS studies are currently being used toward developing suitable HBOCs using a “two-prong” strategy that involves (i) understanding the mechanism of Hb toxicity by evaluating mutant Hbs identified in patients with hemoglobinopathies and (ii) utilizing this information toward designing against (or for) these reactions in acellular oxygen therapeutics that will result in oxidatively stable protein. Future Directions: Future HRAM studies are aimed at fully characterizing engineered candidate HBOCs to determine the most oxidatively stable protein while retaining oxygen carrying function in vivo. Antioxid. Redox Signal. 26, 777–793. PMID:27626360

Ground-penetrating radar: A tool for monitoring bridge scour

USGS Publications Warehouse

Anderson, N.L.; Ismael, A.M.; Thitimakorn, T.

2007-01-01

Ground-penetrating radar (GPR) data were acquired across shallow streams and/or drainage ditches at 10 bridge sites in Missouri by maneuvering the antennae across the surface of the water and riverbank from the bridge deck, manually or by boat. The acquired two-dimensional and three-dimensional data sets accurately image the channel bottom, demonstrating that the GPR tool can be used to estimate and/or monitor water depths in shallow fluvial environments. The study results demonstrate that the GPR tool is a safe and effective tool for measuring and/or monitoring scour in proximity to bridges. The technique can be used to safely monitor scour at assigned time intervals during peak flood stages, thereby enabling owners to take preventative action prior to potential failure. The GPR tool can also be used to investigate depositional and erosional patterns over time, thereby elucidating these processes on a local scale. In certain instances, in-filled scour features can also be imaged and mapped. This information may be critically important to those engaged in bridge design. GPR has advantages over other tools commonly employed for monitoring bridge scour (reflection seismic profiling, echo sounding, and electrical conductivity probing). The tool doesn't need to be coupled to the water, can be moved rapidly across (or above) the surface of a stream, and provides an accurate depth-structure model of the channel bottom and subchannel bottom sediments. The GPR profiles can be extended across emerged sand bars or onto the shore.

Therapeutic Uses of the WebCam in Child Psychiatry

ERIC Educational Resources Information Center

Chlebowski, Susan; Fremont, Wanda

2011-01-01

Objective: The authors provide examples for the use of the WebCam as a therapeutic tool in child psychiatry, discussing cases to demonstrate the application of the WebCam, which is most often used in psychiatry training programs during resident supervision and for case presentations. Method: Six cases illustrate the use of the WebCam in individual…

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.

Genome Editing in Stem Cells for Disease Therapeutics.

PubMed

Song, Minjung; Ramakrishna, Suresh

2018-04-01

Programmable nucleases including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindrome repeats (CRISPR)/CRISPR-associated protein have tremendous potential biological and therapeutic applications as novel genome editing tools. These nucleases enable precise modification of the gene of interest by disruption, insertion, or correction. The application of genome editing technology to pluripotent stem cells or hematopoietic stem cells has the potential to remarkably advance the contribution of this technology to life sciences. Specifically, disease models can be generated and effective therapeutics can be developed with great efficiency and speed. Here we review the characteristics and mechanisms of each programmable nuclease. In addition, we review the applications of these nucleases to stem cells for disease therapies and summarize key studies of interest.

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...

Tools to Enhance Family Engagement in Early Intervention: A Roadmap to Acceptance

ERIC Educational Resources Information Center

Van Nest, Sandra

2017-01-01

Mental health therapists use strategies such as rupture and repair, unconditional positive regard, and managing countertransference to help their clients achieve therapeutic goals. These tools work across disciplines. Teaching parents to use therapeutic techniques increases opportunities to enhance their child's development and builds compliance…

Mechanisms of Change for Children Participating in Therapeutic Horse Riding: A Grounded Theory.

PubMed

Martin, R A; Graham, F P; Taylor, W J; Levack, W M M

2017-12-13

To develop a model for understanding mechanisms of change in health outcomes for riders with disabilities participating in therapeutic horse riding (THR). Using grounded theory methods we collected and analyzed data from interviews with 16 child riders and 18 caregivers, teachers and primary therapists, and from participant-observation during THR sessions. The central concept underpinning the model illustrating mechanisms of change was "gaining the tools to go on." Riders' experiences suggested the THR landscape (i.e., "where the tools are gathered") allowed for an expanded range of experiences in which riders could participate. Riders experienced an expansion of self-concept by learning to move, succeed, connect, and adapt (i.e., "the tools gathered") within the THR landscape. Riders then iteratively translated an expanded view of self into other environments, reflecting "how and where the tools are used." Findings suggest that positive changes in health arise from riders' experiences of learning and agency within the THR therapeutic landscape, and from the influence of these experiences on a child's developing self-concept. This article considers the wider impact of THR on children's health, beyond a focus on changes in physical outcomes.

Safe Tissue Manipulation in Retinal Microsurgery via Motorized Instruments with Force Sensing.

PubMed

Gonenc, Berk; Gehlbach, Peter; Taylor, Russell H; Iordachita, Iulian

2017-01-01

Retinal microsurgery involves careful manipulation of delicate tissues by applying very small amount of forces most of which lie below the tactile sensory threshold of the surgeons. Membrane peeling is a common task in this domain, where application of excessive peeling forces can easily lead to serious complications, hence needs to be avoided. To quantify tool-tissue interaction forces during retinal microsurgery, various force-sensing tools were developed based on fiber Bragg grating sensors, yet the most beneficial way of using the acquired force information is currently unknown. In this study, using a motorized force-sensing micro-forceps tool, we develop an assistive method that enhances safety during membrane peeling by automatically opening the forceps and releasing the tissue based on the detected peeling forces. Through peeling experiments using bandages, we demonstrate that our method can effectively maintain the peeling force at a safe level even in case of non-homogeneous adhesion properties of the membrane.

Development of siRNA expression vector utilizing rock bream beta-actin promoter: a potential therapeutic tool against viral infection in fish.

PubMed

Zenke, Kosuke; Nam, Yoon Kwon; Kim, Ki Hong

2010-01-01

In the present study, we have developed short interfering RNA (siRNA) expression vector utilizing rock bream beta-actin promoter and examined the possible use for the inhibition of highly pathogenic fish virus, rock bream iridovirus (RBIV), replication in vitro. Initially, in order to express siRNA effectively, we added several modifications to wild-type rock bream beta-actin promoter. Next, we succeeded in knocking down the expression of enhanced green fluorescent protein reporter gene expression in fish cells using newly developed vector more effectively than the fugu U6 promoter-driven vector we described previously. Finally, we could observe that cells transfected with modified rock bream beta-actin promoter-driven siRNA expression vector targeting major capsid protein (MCP) gene of RBIV exhibited more resistance to RBIV challenge than other control cells. Our results indicate that this novel siRNA expression vector can be used as a new tool for therapeutics in virus infection in fish species.

Tool and process for miniature explosive joining of tubes

NASA Technical Reports Server (NTRS)

Bement, Laurence J. (Inventor); Bailey, James W. (Inventor)

1987-01-01

A tool and process to be used in the explosive joining of tubes is disclosed. The tool consists of an initiator, a tool form, and a ribbon explosive. The assembled tool is a compact, storable, and safe device suitable for explosive joining of small, lightweight tubes down to 0.20 inch in diameter. The invention is inserted into either another tube or a tube plate. A shim or standoff between the two surfaces to be welded is necessary. Initiation of the explosive inside the tube results in a high velocity, angular collision between the mating surfaces. This collision creates surface melts and collision bonding wherein electron-sharing linkups are formed.

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

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 ...

Cardiovascular RNA interference therapy: the broadening tool and target spectrum.

PubMed

Poller, Wolfgang; Tank, Juliane; Skurk, Carsten; Gast, Martina

2013-08-16

Understanding of the roles of noncoding RNAs (ncRNAs) within complex organisms has fundamentally changed. It is increasingly possible to use ncRNAs as diagnostic and therapeutic tools in medicine. Regarding disease pathogenesis, it has become evident that confinement to the analysis of protein-coding regions of the human genome is insufficient because ncRNA variants have been associated with important human diseases. Thus, inclusion of noncoding genomic elements in pathogenetic studies and their consideration as therapeutic targets is warranted. We consider aspects of the evolutionary and discovery history of ncRNAs, as far as they are relevant for the identification and selection of ncRNAs with likely therapeutic potential. Novel therapeutic strategies are based on ncRNAs, and we discuss here RNA interference as a highly versatile tool for gene silencing. RNA interference-mediating RNAs are small, but only parts of a far larger spectrum encompassing ncRNAs up to many kilobasepairs in size. We discuss therapeutic options in cardiovascular medicine offered by ncRNAs and key issues to be solved before clinical translation. Convergence of multiple technical advances is highlighted as a prerequisite for the translational progress achieved in recent years. Regarding safety, we review properties of RNA therapeutics, which may immunologically distinguish them from their endogenous counterparts, all of which underwent sophisticated evolutionary adaptation to specific biological contexts. Although our understanding of the noncoding human genome is only fragmentary to date, it is already feasible to develop RNA interference against a rapidly broadening spectrum of therapeutic targets and to translate this to the clinical setting under certain restrictions.

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.

Therapeutic role of music listening in stroke rehabilitation.

PubMed

Forsblom, Anita; Laitinen, Sari; Särkämö, Teppo; Tervaniemi, Mari

2009-07-01

We performed two parallel interview studies of stroke patients (n= 20) and professional nurses (n= 5) to gain more insight into the therapeutic role of music listening in stroke rehabilitation. Results suggest that music listening can be used to relax, improve mood, and provide both physical and mental activation during the early stages of recovery from stroke. Thus, music listening could provide a useful clinical tool in stroke rehabilitation.

Green remediation. Tool for safe and sustainable environment: a review

NASA Astrophysics Data System (ADS)

Singh, Mamta; Pant, Gaurav; Hossain, Kaizar; Bhatia, A. K.

2017-10-01

Nowadays, the bioremediation of toxic pollutants is a subject of interest in terms of health issues and environmental cleaning. In the present review, an eco-friendly, cost-effective approach is discussed for the detoxification of environmental pollutants by the means of natural purifier, i.e., blue-green algae over the conventional methods. Industrial wastes having toxic pollutants are not able to eliminate completely by existing the conventional techniques; in fact, these methods can only change their form rather than the entire degradation. These pollutants have an adverse effect on aquatic life, such as fauna and flora, and finally harm human life directly or indirectly. Cyanobacterial approach for the removal of this contaminant is an efficient tool for sustainable development and pollution control. Cyanobacteria are the primary consumers of food chain which absorbed complex toxic compounds from environments and convert them to simple nontoxic compounds which finally protect higher food chain consumer and eliminate risk of pollution. In addition, these organisms have capability to solve secondary pollution, as they can remediate radioactive compound, petroleum waste and degrade toxins from pesticides.

Therapeutic RNA interference for neurodegenerative diseases: From promise to progress.

PubMed

Gonzalez-Alegre, Pedro

2007-04-01

RNA interference (RNAi) has emerged as a powerful tool to manipulate gene expression in the laboratory. Due to its remarkable discriminating properties, individual genes, or even alleles can be targeted with exquisite specificity in cultured cells or living animals. Among its many potential biomedical applications, silencing of disease-linked genes stands out as a promising therapeutic strategy for many incurable disorders. Neurodegenerative diseases represent one of the more attractive targets for the development of therapeutic RNAi. In this group of diseases, the progressive loss of neurons leads to the gradual appearance of disabling neurological symptoms and premature death. Currently available therapies aim to improve the symptoms but not to halt the process of neurodegeneration. The increasing prevalence and economic burden of some of these diseases, such as Alzheimer's disease (AD) or Parkinson's disease (PD), has boosted the efforts invested in the development of interventions, such as RNAi, aimed at altering their natural course. This review will summarize where we stand in the therapeutic application of RNAi for neurodegenerative diseases. The basic principles of RNAi will be reviewed, focusing on features important for its therapeutic manipulation. Subsequently, a stepwise strategy for the development of therapeutic RNAi will be presented. Finally, the different preclinical trials of therapeutic RNAi completed in disease models will be summarized, stressing the experimental questions that need to be addressed before planning application in human disease.

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

PubMed Central

Dostalek, Miroslav; Prueksaritanont, Thomayant; Kelley, Robert F.

2017-01-01

ABSTRACT Pharmacokinetic studies play an important role in all stages of drug discovery and development. Recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. Implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advancing multiple candidates toward clinical development. In this review, we describe tools that should be considered during drug discovery, and discuss approaches that could be included in the pharmacokinetic screening part of the lead candidate generation process to de-risk unexpected pharmacokinetic behaviors of Fc-based therapeutic proteins, with an emphasis on monoclonal antibodies. PMID:28463063

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 ...

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.

The therapeutic use of the relaxation response in stress-related diseases.

PubMed

Esch, Tobias; Fricchione, Gregory L; Stefano, George B

2003-02-01

The objective of this work was to investigate a possible (therapeutic) connection between the relaxation response (RR) and stress-related diseases. Further, common underlying molecular mechanisms and autoregulatory pathways were examined. For the question of (patho)physiology and significance of RR techniques in the treatment of stress-related diseases, we analyzed peer-reviewed references only. The RR has been shown to be an appropriate and relevant therapeutic tool to counteract several stress-related disease processes and certain health-restrictions, particularly in certain immunological, cardiovascular, and neurodegenerative diseases/mental disorders. Further, common underlying molecular mechanisms may exist that represent a connection between the stress response, pathophysiological findings in stress-related diseases, and physiological changes/autoregulatory pathways described in the RR. Here, constitutive or low-output nitric oxide (NO) production may be involved in a protective or ameliorating context, whereas inducible, high-output NO release may facilitate detrimental disease processes. In mild or early disease states, a high degree of biological and physiological flexibility may still be possible (dynamic balance). Here, the therapeutic use of RR techniques may be considered particularly relevant, and the observable (beneficial) effects may be exerted via activation of constitutive NO pathways. RR techniques, regularly part of professional stress management or mind/body medical settings, represent an important tool to be added to therapeutic strategies dealing with stress-related diseases. Moreover, as part of 'healthy' life-style modifications, they may serve primary (or secondary) prevention. Further studies are necessary to elucidate the complex physiology underlying the RR and its impact upon stress-related disease states.

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

GIS learning tool for world's largest earthquakes and their causes

NASA Astrophysics Data System (ADS)

Chatterjee, Moumita

The objective of this thesis is to increase awareness about earthquakes among people, especially young students by showing the five largest and two most predictable earthquake locations in the world and their plate tectonic settings. This is a geographic based interactive tool which could be used for learning about the cause of great earthquakes in the past and the safest places on the earth in order to avoid direct effect of earthquakes. This approach provides an effective way of learning for the students as it is very user friendly and more aligned to the interests of the younger generation. In this tool the user can click on the various points located on the world map which will open a picture and link to the webpage for that point, showing detailed information of the earthquake history of that place including magnitude of quake, year of past quakes and the plate tectonic settings that made this place earthquake prone. Apart from knowing the earthquake related information students will also be able to customize the tool to suit their needs or interests. Students will be able to add/remove layers, measure distance between any two points on the map, select any place on the map and know more information for that place, create a layer from this set to do a detail analysis, run a query, change display settings, etc. At the end of this tool the user has to go through the earthquake safely guidelines in order to be safe during an earthquake. This tool uses Java as programming language and uses Map Objects Java Edition (MOJO) provided by ESRI. This tool is developed for educational purpose and hence its interface has been kept simple and easy to use so that students can gain maximum knowledge through it instead of having a hard time to install it. There are lots of details to explore which can help more about what a GIS based tool is capable of. Only thing needed to run this tool is latest JAVA edition installed in their machine. This approach makes study more fun and

Evaluation of the Missoula-VITAS Quality of Life Index--revised: research tool or clinical tool?

PubMed

Schwartz, Carolyn E; Merriman, Melanie P; Reed, George; Byock, Ira

2005-02-01

Quality of life (QOL) is a central outcome measure in caring for seriously ill patients. The Missoula-VITAS Quality of Life Index (MVQOLI) is a 25-item patient-centered index that weights each of five QOL dimensions (symptoms, function, interpersonal, wellbeing, transcendence) by its importance to the respondent. The measure has been used to assess QOL for hospice patients, and has been found to be somewhat complex to use and analyze. This study aimed to simplify the measure, and evaluate the reliability and validity of a revised version as either a research or clinical tool (i.e., "psychometric" versus "clinimetric"). Two data collection efforts are described. The psychometric study collected QOL data from 175 patients at baseline, 3-5 days, and 21 days later. The implementation study evaluated the feasibility and utility of the MVQOLI-R during over six weeks of use. End-stage renal patients on dialysis, hospice, or long-term care patients participated in the psychometric study. The implementation study was done in hospice, home health, and palliative care settings. The MVQOLI-R and the Memorial Symptom Assessment Scale. The psychometric and implementation studies suggest that the MVQOLI-R performs well as a clinical tool but is not powerful as an outcome research instrument. The MVQOLI-R has the heterogeneous structure of clinimetric tools, and demonstrated both relevance and responsiveness. Additionally, in a clinical setting the MVQOLI-R was useful therapeutically for stimulating communication about the psychosocial and spiritual issues important to the tasks of life completion and life closure. The MVQOLI-R has clinical utility as a patient QOL assessment tool and may have therapeutic utility as a tool for fostering discussion among patients and their clinicians, as well as for helping patients identify sources of suffering and opportunities during this time in their lives.

Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells

PubMed Central

Scarpa, Emanuele-Salvatore; Ninfali, Paolino

2015-01-01

The theory that several carcinogenetic processes are initiated and sustained by cancer stem cells (CSCs) has been validated, and specific methods to identify the CSCs in the entire population of cancer cells have also proven to be effective. This review aims to provide an overview of recently acquired scientific knowledge regarding phytochemicals and herbal extracts, which have been shown to be able to target and kill CSCs. Many genes and proteins that sustain the CSCs’ self-renewal capacity and drug resistance have been described and applications of phytochemicals able to interfere with these signaling systems have been shown to be operatively efficient both in vitro and in vivo. Identification of specific surface antigens, mammosphere formation assays, serial colony-forming unit assays, xenograft transplantation and label-retention assays coupled with Aldehyde dehydrogenase 1 (ALDH1) activity evaluation are the most frequently used techniques for measuring phytochemical efficiency in killing CSCs. Moreover, it has been demonstrated that EGCG, curcumin, piperine, sulforaphane, β-carotene, genistein and the whole extract of some plants are able to kill CSCs. Most of these phytochemicals act by interfering with the canonical Wnt (β-catenin/T cell factor-lymphoid enhancer factor (TCF-LEF)) pathway implicated in the pathogenesis of several cancers. Therefore, the use of phytochemicals may be a true therapeutic strategy for eradicating cancer through the elimination of CSCs. PMID:26184171

Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells.

PubMed

Scarpa, Emanuele-Salvatore; Ninfali, Paolino

2015-07-10

The theory that several carcinogenetic processes are initiated and sustained by cancer stem cells (CSCs) has been validated, and specific methods to identify the CSCs in the entire population of cancer cells have also proven to be effective. This review aims to provide an overview of recently acquired scientific knowledge regarding phytochemicals and herbal extracts, which have been shown to be able to target and kill CSCs. Many genes and proteins that sustain the CSCs' self-renewal capacity and drug resistance have been described and applications of phytochemicals able to interfere with these signaling systems have been shown to be operatively efficient both in vitro and in vivo. Identification of specific surface antigens, mammosphere formation assays, serial colony-forming unit assays, xenograft transplantation and label-retention assays coupled with Aldehyde dehydrogenase 1 (ALDH1) activity evaluation are the most frequently used techniques for measuring phytochemical efficiency in killing CSCs. Moreover, it has been demonstrated that EGCG, curcumin, piperine, sulforaphane, β-carotene, genistein and the whole extract of some plants are able to kill CSCs. Most of these phytochemicals act by interfering with the canonical Wnt (β-catenin/T cell factor-lymphoid enhancer factor (TCF-LEF)) pathway implicated in the pathogenesis of several cancers. Therefore, the use of phytochemicals may be a true therapeutic strategy for eradicating cancer through the elimination of CSCs.

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.

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.…

Alzheimer’s disease: biological aspects, therapeutic perspectives and diagnostic tools

NASA Astrophysics Data System (ADS)

Di Carlo, M.; Giacomazza, D.; San Biagio, P. L.

2012-06-01

Alzheimer’s disease (AD) is the most common form of dementia among older people. Dementia is an irreversible brain disorder that seriously affects a person’s ability to carry out daily activities. It is characterized by loss of cognitive functioning and behavioral abilities, to such an extent that it interferes with the daily life and activities of the affected patients. Although it is still unknown how the disease process begins, it seems that brain damage starts a decade or more before problems become evident. Scientific data seem to indicate that changes in the generation or the degradation of the amyloid-b peptide (Aβ) lead to the formation of aggregated structures that are the triggering molecular events in the pathogenic cascade of AD. This review summarizes some characteristic features of Aβ misfolding and aggregation and how cell damage and death mechanisms are induced by these supramolecular and toxic structures. Further, some interventions for the early diagnosis of AD are described and in the last part the potential therapeutic strategies adoptable to slow down, or better block, the progression of the pathology are reported.

Advancing Biological Understanding and Therapeutics Discovery with Small Molecule Probes

PubMed Central

Schreiber, Stuart L.; Kotz, Joanne D.; Li, Min; Aubé, Jeffrey; Austin, Christopher P.; Reed, John C.; Rosen, Hugh; White, E. Lucile; Sklar, Larry A.; Lindsley, Craig W.; Alexander, Benjamin R.; Bittker, Joshua A.; Clemons, Paul A.; de Souza, Andrea; Foley, Michael A.; Palmer, Michelle; Shamji, Alykhan F.; Wawer, Mathias J.; McManus, Owen; Wu, Meng; Zou, Beiyan; Yu, Haibo; Golden, Jennifer E.; Schoenen, Frank J.; Simeonov, Anton; Jadhav, Ajit; Jackson, Michael R.; Pinkerton, Anthony B.; Chung, Thomas D.Y.; Griffin, Patrick R.; Cravatt, Benjamin F.; Hodder, Peter S.; Roush, William R.; Roberts, Edward; Chung, Dong-Hoon; Jonsson, Colleen B.; Noah, James W.; Severson, William E.; Ananthan, Subramaniam; Edwards, Bruce; Oprea, Tudor I.; Conn, P. Jeffrey; Hopkins, Corey R.; Wood, Michael R.; Stauffer, Shaun R.; Emmitte, Kyle A.

2015-01-01

Small-molecule probes can illuminate biological processes and aid in the assessment of emerging therapeutic targets by perturbing biological systems in a manner distinct from other experimental approaches. Despite the tremendous promise of chemical tools for investigating biology and disease, small-molecule probes were unavailable for most targets and pathways as recently as a decade ago. In 2005, the U.S. National Institutes of Health launched the decade-long Molecular Libraries Program with the intent of innovating in and broadening access to small-molecule science. This Perspective describes how novel small-molecule probes identified through the program are enabling the exploration of biological pathways and therapeutic hypotheses not otherwise testable. These experiences illustrate how small-molecule probes can help bridge the chasm between biological research and the development of medicines, but also highlight the need to innovate the science of therapeutic discovery. PMID:26046436

Intramuscular Heating Characteristics of Multihour Low-Intensity Therapeutic Ultrasound.

PubMed

Rigby, Justin H; Taggart, Rebecca M; Stratton, Kelly L; Lewis, George K; Draper, David O

2015-11-01

The heating characteristics of a stationary device delivering sustained acoustic medicine with low-intensity therapeutic ultrasound (LITUS) are unknown. To measure intramuscular (IM) heating produced by a LITUS device developed for long-duration treatment of musculoskeletal injuries. Controlled laboratory study. University research laboratory. A total of 26 healthy volunteers (16 men, 10 women; age = 23.0 ± 2.1 years, height = 1.74 ± 0.09 m, mass = 73.48 ± 14.65 kg). Participants were assigned randomly to receive active (n = 20) or placebo (n = 6) LITUS at a frequency of 3 MHz and an energy intensity of 0.132 W/cm(2) continuously for 3 hours with a single transducer or dual transducers on the triceps surae muscle. We measured IM temperature using thermocouples inserted at 1.5- and 3-cm depths into muscle. Temperatures were recorded throughout treatment and 30 minutes posttreatment. We used 2-sample t tests to determine the heating curve of the LITUS treatment and differences in final temperatures between depth and number of transducers. A mild IM temperature increase of 1 °C was reached 10 ± 5 minutes into the treatment, and a more vigorous temperature increase of 4 °C was reached 80 ± 10 minutes into the treatment. The maximal steady-state IM temperatures produced during the final 60 minutes of treatment at the 1.5-cm depth were 4.42 °C ± 0.08 °C and 3.92 °C ± 0.06 °C using 1 and 2 transducers, respectively. At the 3.0-cm depth, the maximal steady-state IM temperatures during the final 60 minutes of treatment were 3.05 °C ± 0.09 °C and 3.17 °C ± 0.05 °C using 1 and 2 transducers, respectively. We observed a difference between the temperatures measured at each depth (t78 = -2.45, P = .02), but the number of transducers used to generate heating was not different (t78 = 1.79, P = .08). The LITUS device elicited tissue heating equivalent to traditional ultrasound but could be sustained for multiple hours. It is a safe and effective alternative tool

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.

1st Joint European Conference on Therapeutic Targets and Medicinal Chemistry (TTMC 2015)

PubMed Central

Le Borgne, Marc; Haidar, Samer; Duval, Olivier; Wünsch, Bernhard; Jose, Joachim

2015-01-01

The European Conference on Therapeutic Targets and Medicinal Chemistry is a new two-day meeting on drug discovery that is focused on therapeutic targets and the use of tools to explore all fields of drug discovery and drug design such as molecular modelling, bioorganic chemistry, NMR studies, fragment screening, in vitro assays, in vivo assays, structure activity relationships, autodisplay. Abstracts of keynote lectures, plenary lectures, junior lectures, flash presentations, and posters presented during the meeting are collected in this report. PMID:26712767

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

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2013 CFR

2013-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2014 CFR

2014-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

29 CFR 1926.303 - Abrasive wheels and tools.

Code of Federal Regulations, 2012 CFR

2012-07-01

... and tools. (a) Power. All grinding machines shall be supplied with sufficient power to maintain the spindle speed at safe levels under all conditions of normal operation. (b) Guarding. (1) Grinding machines..., nut, and outer flange may be exposed on machines designed as portable saws. (c) Use of abrasive wheels...

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

Making Safe Surgery Affordable: Design of a Surgical Drill Cover System for Scale.

PubMed

Buchan, Lawrence L; Black, Marianne S; Cancilla, Michael A; Huisman, Elise S; Kooyman, Jeremy J R; Nelson, Scott C; OʼHara, Nathan N; OʼBrien, Peter J; Blachut, Piotr A

2015-10-01

Many surgeons in low-resource settings do not have access to safe, affordable, or reliable surgical drilling tools. Surgeons often resort to nonsterile hardware drills because they are affordable, robust, and efficient, but they are impossible to sterilize using steam. A promising alternative is to use a Drill Cover system (a sterilizable fabric bag plus surgical chuck adapter) so that a nonsterile hardware drill can be used safely for surgical bone drilling. Our objective was to design a safe, effective, affordable Drill Cover system for scale in low-resource settings. We designed our device based on feedback from users at Mulago Hospital (Kampala, Uganda) and focused on 3 main aspects. First, the design included a sealed barrier between the surgical field and hardware drill that withstands pressurized fluid. Second, the selected hardware drill had a maximum speed of 1050 rpm to match common surgical drills and reduce risk of necrosis. Third, the fabric cover was optimized for ease of assembly while maintaining a sterile technique. Furthermore, with the Drill Cover approach, multiple Drill Covers can be provided with a single battery-powered drill in a "kit," so that the drill can be used in back-to-back surgeries without requiring immediate sterilization. The Drill Cover design presented here provides a proof-of-concept for a product that can be commercialized, produced at scale, and used in low-resource settings globally to improve access to safe surgery.

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…

Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges.

PubMed

Köhler, Stephan; Guhn, Anne; Betzler, Felix; Stiglmayr, Christian; Brakemeier, Eva-Lotta; Sterzer, Philipp

2017-01-01

In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT) by so-called "third-wave" strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to "classical CBT," some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a) acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT), (b) the concept of "limited reparenting" as used in Schema Therapy (ST), and (c) disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies.

Therapeutic Self-Disclosure within DBT, Schema Therapy, and CBASP: Opportunities and Challenges

PubMed Central

Köhler, Stephan; Guhn, Anne; Betzler, Felix; Stiglmayr, Christian; Brakemeier, Eva-Lotta; Sterzer, Philipp

2017-01-01

In recent years, various therapeutic interventions have been established that extended behavior and cognitive behavior therapy (CBT) by so-called “third-wave” strategies. In order to address specific therapeutic challenges in certain subgroups of patients who do not sufficiently respond to “classical CBT,” some of these third-wave strategies put particular emphasis on therapist self-disclosure. This article highlights therapeutic self-disclosure as a means to address interpersonal problems by comparing three third-wave strategies: (a) acceptance and change strategies as used in Dialectical Behavioral Therapy (DBT), (b) the concept of “limited reparenting” as used in Schema Therapy (ST), and (c) disciplined personal involvement as used in the Cognitive Behavioral Analysis System of Psychotherapy (CBASP). On the basis of a critical discussion on opportunities and challenges within these three concepts, self-disclosure is proposed to be a promising therapeutic tool that is worth to be investigated in more depth in future studies. PMID:29238317

microRNA Therapeutics in Cancer - An Emerging Concept.

PubMed

Shah, Maitri Y; Ferrajoli, Alessandra; Sood, Anil K; Lopez-Berestein, Gabriel; Calin, George A

2016-10-01

MicroRNAs (miRNAs) are an evolutionarily conserved class of small, regulatory non-coding RNAs that negatively regulate protein coding gene and other non-coding transcripts expression. miRNAs have been established as master regulators of cellular processes, and they play a vital role in tumor initiation, progression and metastasis. Further, widespread deregulation of microRNAs have been reported in several cancers, with several microRNAs playing oncogenic and tumor suppressive roles. Based on these, miRNAs have emerged as promising therapeutic tools for cancer management. In this review, we have focused on the roles of miRNAs in tumorigenesis, the miRNA-based therapeutic strategies currently being evaluated for use in cancer, and the advantages and current challenges to their use in the clinic. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Therapeutic play: preparing the child for the vaccine

PubMed Central

Pontes, Jéssica Etienne Dourado; Tabet, Elaine; Folkmann, Maria Áurea dos Santos; Cunha, Mariana Lucas da Rocha; Almeida, Fabiane de Amorim

2015-01-01

ABSTRACT Objective: To identify and compare behaviors of children during vaccination, who were prepared or not for the procedure using an instructional therapeutic play. Methods: A quasi experimental study, with quantitative approach of 60 children aged 3 to 6 years. The child's reactions were recorded in a checklist. Data were analyzed using descriptive and inferential statistics and Fisher's test. Results: The main reactions in the experimental group were stay still (25;83%) and spontaneously collaborate (24;80%). In the control group, the main reactions were cries and cling to parents (15; 50%), flushing (11;36.67%) and moving the body/agitated (10;33.3%). Conclusion: The reactions of cooperation were more frequent in the experimental group, while low acceptance was observed only in the control group. Therapeutic play has proved an important tool in preparing for the vaccine. PMID:26154545

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.

Safe and secure. How to create an effective OSHA compliance program in your practice.

PubMed

Anderson, Douglas G

2007-08-01

Medical group practice administrators have a responsibility to provide a safe working environment for their employees and patients. You must create an effective Occupational Safety and Health Administration (OSHA) compliance program in your organization. The complexity and diversity of OSHA standards are significant, and developing an effective program requires more than a cut-and-paste approach. This article describes the scope of the task, the steps to take and tools you can use.

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.

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

Fatal hand tool injuries in construction.

PubMed

Trent, R B; Wyant, W D

1990-08-01

Past research on occupational hand tool injuries has generally focused on nonfatal injuries. Most such injuries occur at the point where energy is transferred to the material being worked, eg, at the edge of a saw blade or the point of a drill. Assuming that hand tool injuries that are fatal will differ from nonfatal injuries, 62 Occupation Safety and Health Administration reports were analyzed. Four patterns emerged when the type of contact with energy was used to classify incidents. Fatal injuries occurred when (1) contact was made with energy that supplies power to the hand tool, (2) energy normally transferred to the material being worked is transferred to the worker, (3) workers or materials fall, and (4) potential energy is encountered in the work environment. Analysis showed that almost all such injuries could be prevented by application of existing safe work practices.

Computational methods in preformulation study for pharmaceutical solid dosage forms of therapeutic proteins

NASA Astrophysics Data System (ADS)

Majee, Sutapa Biswas; Biswas, Gopa Roy

2017-06-01

Design and delivery of protein-based biopharmaceuticals needs detailed planning and strict monitoring of intermediate processing steps, storage conditions and container-closure system to ensure a stable, elegant and biopharmaceutically acceptable dosage form. Selection of manufacturing process variables and conditions along with packaging specifications can be achieved through properly designed preformulation study protocol for the formulation. Thermodynamic stability and biological activity of therapeutic proteins depend on folding-unfolding and three-dimensional packing dynamics of amino acid network in the protein molecule. Lack of favourable environment may cause protein aggregation with loss in activity and even fatal immunological reaction. Although lyophilization can enhance the stability of protein-based formulations in the solid state, it can induce protein unfolding leading to thermodynamic instability. Formulation stabilizers such as preservatives can also result in aggregation of therapeutic proteins. Modern instrumental techniques in conjunction with computational tools enable rapid and accurate prediction of amino acid sequence, thermodynamic parameters associated with protein folding and detection of aggregation "hot-spots." Globular proteins pose a challenge during investigations on their aggregation propensity. Biobetter therapeutic monoclonal antibodies with enhanced stability, solubility and reduced immunogenic potential can be designed through mutation of aggregation-prone zones. The objective of the present review article is to focus on the various analytical methods and computational approaches used in the study of thermodynamic stability and aggregation tendency of therapeutic proteins, with an aim to develop optimal and marketable formulation. Knowledge of protein dynamics through application of computational tools will provide the essential inputs and relevant information for successful and meaningful completion of preformulation studies on

Can cannabinoids be a potential therapeutic tool in amyotrophic lateral sclerosis?

PubMed

Giacoppo, Sabrina; Mazzon, Emanuela

2016-12-01

Amyotrophic lateral sclerosis (ALS) is the most common degenerative disease of the motor neuron system. Over the last years, a growing interest was aimed to discovery new innovative and safer therapeutic approaches in the ALS treatment. In this context, the bioactive compounds of Cannabis sativa have shown antioxidant, anti-inflammatory and neuroprotective effects in preclinical models of central nervous system disease. However, most of the studies proving the ability of cannabinoids in delay disease progression and prolong survival in ALS were performed in animal model, whereas the few clinical trials that investigated cannabinoids-based medicines were focused only on the alleviation of ALS-related symptoms, not on the control of disease progression. The aim of this report was to provide a short but important overview of evidences that are useful to better characterize the efficacy as well as the molecular pathways modulated by cannabinoids.

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

More than a Safe Space

ERIC Educational Resources Information Center

Sadowski, Michael

2016-01-01

Over the past three decades, much of the conversation about LGBTQ students in schools has centered on safety--anti-bullying policies, the "safe space" of gay-straight alliances, and "safe zones" marked by rainbow-colored stickers on classroom doors. In this article, Michael Sadowski argues that it's time to move beyond safety…

Protection of therapeutic antibodies from visible light induced degradation: Use safe light in manufacturing and storage.

PubMed

Du, Cheng; Barnett, Gregory; Borwankar, Ameya; Lewandowski, Angela; Singh, Nripen; Ghose, Sanchayita; Borys, Michael; Li, Zheng Jian

2018-06-01

As macromolecules, biologics are susceptible to light exposure, which induces oxidation of multiple amino acid residues including tryptophan, tyrosine, phenylalanine, cysteine and methionine. Pertaining to safety, efficacy and potency, light-induced oxidation of biologics has been widely studied and necessary precautions need to be taken during biologics manufacturing process, drug substance and products handling and storage. Proteins will degrade to varying extents depending on the protein properties, degradation pathways, formulation compositions and type of light source. In addition to UV light, which has been widely known to degrade proteins, visible light from indoor fluorescent lighting also can mediate protein degradation. In this report, we examine and identify wavelengths in the visual spectrum (400-700 nm) that can cause monoclonal antibody and histidine buffer degradation. Installation of safe lights which exclude the identified damaging wavelengths from visible spectra in manufacturing and storage areas can provide a balance between lighting requirement for human operators and their safety and conservation of product quality. Copyright © 2018 Elsevier B.V. All rights reserved.

Liver as a target for oligonucleotide therapeutics.

PubMed

Sehgal, Alfica; Vaishnaw, Akshay; Fitzgerald, Kevin

2013-12-01

Oligonucleotide-based therapeutics are an emerging class of drugs that hold the promise for silencing "un-druggable" targets,thus creating unique opportunities for innovative medicines. As opposed to gene therapy, oligonucleotides are considered to be more akin to small molecule therapeutics because they are small,completely synthetic in origin, do not integrate into the host genome,and have a defined duration of therapeutic activity after which effects recover to baseline. They offer a high degree of specificity at the genetic level, thereby reducing off-target effects.At the same time, they provide a strategy for targeting any gene in the genome, including transcripts that produce mutated proteins.Oligonucleotide-based therapeutics include short interfering RNA (siRNA), that degrade target mRNA through RISC mediated RNAi; anti-miRs, that target miRNAs; miRNA mimics, that regulate target mRNA; antisense oligonucleotides, that may be working through RNAseH mediated mRNA decay; mRNA upregulation,by targeting long non-coding RNAs; and oligonucleotides induced alternative splicing [1]. All these approaches require some minimal degree of homology at the nucleic acid sequence level for them to be functional. The different mechanisms of action and their relevant activity are outlined in Fig. 1. Besides homology,RNA secondary structure has also been exploited in the case of ribozymes and aptamers, which act by binding to nucleic acids or proteins, respectively. While there have been many reports of gene knockdown and gene modulation in cell lines and mice with all these methods, very few have advanced to clinical stages.The main obstacle to date has been the safe and effective intracellular delivery of these compounds in higher species, including humans. Indeed, their action requires direct interaction with DNA/RNA within the target cell so even when one solves the issues of tissue and cellular access, intracellular/intranuclear location represents yet another barrier to

Lipid based delivery and immuno-stimulatory systems: Master tools to combat leishmaniasis.

PubMed

Sabur, Abdus; Asad, Mohammad; Ali, Nahid

2016-11-01

Disease management of leishmaniasis is appalling due to lack of a human vaccine and the toxicity and resistance concerns with limited therapeutic drugs. The challenges in development of a safe vaccine for generation and maintenance of robust antileishmanial protective immunity through a human administrable route of immunization can be addressed through immunomodulation and targeted delivery. The versatility of lipid based particulate system for deliberate delivery of diverse range of molecules including immunomodulators, antigens and drugs have essentially found pivotal role in design of proficient vaccination and therapeutic strategies against leishmaniasis. The prospects of lipid based preventive and curative formulations for leishmaniasis have been highlighted in this review. Copyright © 2016. Published by Elsevier Inc.

Evolution of the Hubble Space Telescope Safing Systems

NASA Technical Reports Server (NTRS)

Pepe, Joyce; Myslinski, Michael

2006-01-01

The Hubble Space Telescope (HST) was launched on April 24 1990, with an expected lifespan of 15 years. Central to the spacecraft design was the concept of a series of on-orbit shuttle servicing missions permitting astronauts to replace failed equipment, update the scientific instruments and keep the HST at the forefront of astronomical discoveries. One key to the success of the Hubble mission has been the robust Safing systems designed to monitor the performance of the observatory and to react to keep the spacecraft safe in the event of equipment anomaly. The spacecraft Safing System consists of a range of software tests in the primary flight computer that evaluate the performance of mission critical hardware, safe modes that are activated when the primary control mode is deemed inadequate for protecting the vehicle, and special actions that the computer can take to autonomously reconfigure critical hardware. The HST Safing System was structured to autonomously detect electrical power system, data management system, and pointing control system malfunctions and to configure the vehicle to ensure safe operation without ground intervention for up to 72 hours. There is also a dedicated safe mode computer that constantly monitors a keep-alive signal from the primary computer. If this signal stops, the safe mode computer shuts down the primary computer and takes over control of the vehicle, putting it into a safe, low-power configuration. The HST Safing system has continued to evolve as equipment has aged, as new hardware has been installed on the vehicle, and as the operation modes have matured during the mission. Along with the continual refinement of the limits used in the safing tests, several new tests have been added to the monitoring system, and new safe modes have been added to the flight software. This paper will focus on the evolution of the HST Safing System and Safing tests, and the importance of this evolution to prolonging the science operations of the

Potential role of bromelain in clinical and therapeutic applications

PubMed Central

Rathnavelu, Vidhya; Alitheen, Noorjahan Banu; Sohila, Subramaniam; Kanagesan, Samikannu; Ramesh, Rajendran

2016-01-01

Pineapple has been used as part of traditional folk medicine since ancient times and it continues to be present in various herbal preparations. Bromelain is a complex mixture of protease extracted from the fruit or stem of the pineapple plant. Although the complete molecular mechanism of action of bromelain has not been completely identified, bromelain gained universal acceptability as a phytotherapeutic agent due to its history of safe use and lack of side effects. Bromelain is widely administered for its well-recognized properties, such as its anti-inflammatory, antithrombotic and fibrinolytic affects, anticancer activity and immunomodulatory effects, in addition to being a wound healing and circulatory improvement agent. The current review describes the promising clinical applications and therapeutic properties of bromelain. PMID:27602208

Managing Cassini Safe Mode Attitude at Saturn

NASA Technical Reports Server (NTRS)

Burk, Thomas A.

2010-01-01

The Cassini spacecraft was launched on October 15, 1997 and arrived at Saturn on June 30, 2004. It has performed detailed observations and remote sensing of Saturn, its rings, and its satellites since that time. In the event safe mode interrupts normal orbital operations, Cassini has flight software fault protection algorithms to detect, isolate, and recover to a thermally safe and commandable attitude and then wait for further instructions from the ground. But the Saturn environment is complex, and safety hazards change depending on where Cassini is in its orbital trajectory around Saturn. Selecting an appropriate safe mode attitude that insures safe operation in the Saturn environment, including keeping the star tracker field of view clear of bright bodies, while maintaining a quiescent, commandable attitude, is a significant challenge. This paper discusses the Cassini safe table management strategy and the key criteria that must be considered, especially during low altitude flybys of Titan, in deciding what spacecraft attitude should be used in the event of safe mode.

Therapeutic communication in nursing students: A Walker & Avant concept analysis

PubMed Central

Abdolrahimi, Mahbobeh; Ghiyasvandian, Shahrzad; Zakerimoghadam, Masoumeh; Ebadi, Abbas

2017-01-01

Background and aim Therapeutic communication, the fundamental component of nursing, is a complex concept. Furthermore, the poor encounters between nursing student and patient demonstrate the necessity of instruction regarding therapeutic communication. The aim of this study was to define and clarify this important concept for including this subject in the nursing curriculum with more emphasis. Methods A literature search was conducted using keywords such as “nursing student”, “patient” and “therapeutic communication” and Persian-equivalent words in Persian databases (including Magiran and Medlib) and English databases (including PubMed, ScienceDirect, Scopus and ProQuest) without time limitation. After extracting concept definitions and determining characteristic features, therapeutic communication in nursing students was defined. Then, sample cases, antecedents, consequences and empirical referents of concept were determined. Results After assessing 30 articles, therapeutic communication defining attributes were as follows: “an important means in building interpersonal relationships”, “a process of information transmission”, “an important clinical competency”, “a structure with two different sections” and “a significant tool in patient centered care”. Furthermore, theoretical and clinical education and receiving educators’ feedback regarding therapeutic communication were considered as antecedents of the concept. Improving physical and psychological health status of patient as well as professional development of nursing students were identified as consequences of the concept. Conclusion Nursing instructors can use these results in order to teach and evaluate therapeutic communication in nursing students and train qualified nurses. Also, nursing students may apply the results to improve the quality of their interactions with patients, perform their various duties and meet patients’ diverse needs. PMID:28979730

"Safe Schools within Safe Communities: A Regional Summit in the Heartland." Policy Briefs Special Report.

ERIC Educational Resources Information Center

Huertas, Aurelio, Jr.; Sullivan, Carol

This report documents the proceedings of a regional policy seminar hosted by the Iowa Department of Education with support from the North Central Regional Educational Laboratory (NCREL) and the Midwest Regional Center for Drug-Free Schools and Communities (MRC). The seminar, "Safe Schools Within Safe Communities," was held on September 19-20,…

Ergonomic glovebox workspace layout tool and associated method of use

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

Roddy, Shannon Howard

The present invention provides an elongate tool that aides in the placement of objects and machinery within a glovebox, such that the objects and machinery can be safely handled by a user. The tool includes a plurality of visual markings (in English units, metric units, other units, grooves, ridges, varying widths, etc.) that indicate distance from the user within the glovebox, optionally broken into placement preference zones that are color coded, grayscale coded, or the like.

Therapeutic gene editing in CD34+ hematopoietic progenitors from Fanconi anemia patients.

PubMed

Diez, Begoña; Genovese, Pietro; Roman-Rodriguez, Francisco J; Alvarez, Lara; Schiroli, Giulia; Ugalde, Laura; Rodriguez-Perales, Sandra; Sevilla, Julian; Diaz de Heredia, Cristina; Holmes, Michael C; Lombardo, Angelo; Naldini, Luigi; Bueren, Juan Antonio; Rio, Paula

2017-11-01

Gene targeting constitutes a new step in the development of gene therapy for inherited diseases. Although previous studies have shown the feasibility of editing fibroblasts from Fanconi anemia (FA) patients, here we aimed at conducting therapeutic gene editing in clinically relevant cells, such as hematopoietic stem cells (HSCs). In our first experiments, we showed that zinc finger nuclease (ZFN)-mediated insertion of a non-therapeutic EGFP-reporter donor in the AAVS1 "safe harbor" locus of FA-A lymphoblastic cell lines (LCLs), indicating that FANCA is not essential for the editing of human cells. When the same approach was conducted with therapeutic FANCA donors, an efficient phenotypic correction of FA-A LCLs was obtained. Using primary cord blood CD34 + cells from healthy donors, gene targeting was confirmed not only in in vitro cultured cells, but also in hematopoietic precursors responsible for the repopulation of primary and secondary immunodeficient mice. Moreover, when similar experiments were conducted with mobilized peripheral blood CD34 + cells from FA-A patients, we could demonstrate for the first time that gene targeting in primary hematopoietic precursors from FA patients is feasible and compatible with the phenotypic correction of these clinically relevant cells. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Safe Use Practices for Pesticides

Science.gov Websites

; Environment Human Health Animal Health Safe Use Practices Food Safety Environment Air Water Soil Wildlife Ingredients Low-Risk Pesticides Organic Pesticide Ingredients Pesticide Incidents Human Exposure Pet Exposure Home Page Pesticide Health and Safety Information Safe Use Practices for Pesticides Related Topics

Is Prevent a Safe Space?

ERIC Educational Resources Information Center

Ramsay, Peter

2017-01-01

In this article, I test the claims of the UK government and universities that the Prevent programme aims to create a safe space for the discussion of "extremist" ideas in universities. I do this by comparing the main elements of the Prevent duty that has been imposed on universities with those of safe spaces as imagined by student…

75 FR 29391 - National Safe Boating Week, 2010

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-26

... Safe Boating Week, 2010 By the President of the United States of America A Proclamation Our Nation's... National Safe Boating Week to practicing safe techniques so boaters of all ages can enjoy this pastime... annually the 7-day period prior to Memorial Day weekend as ``National Safe Boating Week.'' NOW, THEREFORE...

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

PubMed Central

Allen, Patricia J.

2012-01-01

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington’s Disease and Parkinson’s Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. PMID:22465051

Creatine metabolism and psychiatric disorders: Does creatine supplementation have therapeutic value?

PubMed

Allen, Patricia J

2012-05-01

Athletes, body builders, and military personnel use dietary creatine as an ergogenic aid to boost physical performance in sports involving short bursts of high-intensity muscle activity. Lesser known is the essential role creatine, a natural regulator of energy homeostasis, plays in brain function and development. Creatine supplementation has shown promise as a safe, effective, and tolerable adjunct to medication for the treatment of brain-related disorders linked with dysfunctional energy metabolism, such as Huntington's Disease and Parkinson's Disease. Impairments in creatine metabolism have also been implicated in the pathogenesis of psychiatric disorders, leaving clinicians, researchers and patients alike wondering if dietary creatine has therapeutic value for treating mental illness. The present review summarizes the neurobiology of the creatine-phosphocreatine circuit and its relation to psychological stress, schizophrenia, mood and anxiety disorders. While present knowledge of the role of creatine in cognitive and emotional processing is in its infancy, further research on this endogenous metabolite has the potential to advance our understanding of the biological bases of psychopathology and improve current therapeutic strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

30 CFR 77.312 - Fail safe monitoring systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Fail safe monitoring systems. 77.312 Section 77... Thermal Dryers § 77.312 Fail safe monitoring systems. Thermal dryer systems and controls shall be protected by a fail safe monitoring system which will safely shut down the system and any related equipment...

30 CFR 77.312 - Fail safe monitoring systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Fail safe monitoring systems. 77.312 Section 77... Thermal Dryers § 77.312 Fail safe monitoring systems. Thermal dryer systems and controls shall be protected by a fail safe monitoring system which will safely shut down the system and any related equipment...

30 CFR 77.312 - Fail safe monitoring systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Fail safe monitoring systems. 77.312 Section 77... Thermal Dryers § 77.312 Fail safe monitoring systems. Thermal dryer systems and controls shall be protected by a fail safe monitoring system which will safely shut down the system and any related equipment...

30 CFR 77.312 - Fail safe monitoring systems.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Fail safe monitoring systems. 77.312 Section 77... Thermal Dryers § 77.312 Fail safe monitoring systems. Thermal dryer systems and controls shall be protected by a fail safe monitoring system which will safely shut down the system and any related equipment...

30 CFR 77.312 - Fail safe monitoring systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Fail safe monitoring systems. 77.312 Section 77... Thermal Dryers § 77.312 Fail safe monitoring systems. Thermal dryer systems and controls shall be protected by a fail safe monitoring system which will safely shut down the system and any related equipment...

29 CFR 1915.15 - Maintenance of safe conditions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Enclosed Spaces and Other Dangerous Atmospheres in Shipyard Employment § 1915.15 Maintenance of safe... into spaces that have been certified “Safe for Workers” or “Safe for Hot Work” shall be disconnected... certificates. A competent person shall visually inspect and test each space certified as “Safe for Workers” or...

29 CFR 1915.15 - Maintenance of safe conditions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Enclosed Spaces and Other Dangerous Atmospheres in Shipyard Employment § 1915.15 Maintenance of safe... into spaces that have been certified “Safe for Workers” or “Safe for Hot Work” shall be disconnected... certificates. A competent person shall visually inspect and test each space certified as “Safe for Workers” or...

Staying Healthy and Safe at Work

MedlinePlus

... The Prematurity Campaign About us Annual report Our work Community impact Global programs Research Need help? Frequently ... safe at work Staying healthy and safe at work E-mail to a friend Please fill in ...

33 CFR 83.06 - Safe speed (Rule 6).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Safe speed (Rule 6). 83.06... Safe speed (Rule 6). Every vessel shall at all times proceed at a safe speed so that she can take... prevailing circumstances and conditions. In determining a safe speed the following factors shall be among...

33 CFR 83.06 - Safe speed (Rule 6).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Safe speed (Rule 6). 83.06... Safe speed (Rule 6). Every vessel shall at all times proceed at a safe speed so that she can take... prevailing circumstances and conditions. In determining a safe speed the following factors shall be among...

Realistic Testing of the Safe Affordable Fission Engine (SAFE-100) Thermal Simulator Using Fiber Bragg Gratings

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

Stinson-Bagby, Kelly L.; Fielder, Robert S.; Van Dyke, Melissa K.

2004-02-04

The motivation for the reported research was to support NASA space nuclear power initiatives through the development of advanced fiber optic sensors for space-based nuclear power applications. Distributed high temperature measurements were made with 20 FBG temperature sensors installed in the SAFE-100 thermal simulator at the NASA Marshal Space Flight Center. Experiments were performed at temperatures approaching 800 deg. C and 1150 deg. C for characterization studies of the SAFE-100 core. Temperature profiles were successfully generated for the core during temperature increases and decreases. Related tests in the SAFE-100 successfully provided strain measurement data.

Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells.

PubMed

Wang, Meiping; Xie, Fangyuan; Wen, Xikai; Chen, Han; Zhang, Hai; Liu, Junjie; Zhang, He; Zou, Hao; Yu, Yuan; Chen, Yan; Sun, Zhiguo; Wang, Xinxia; Zhang, Guoqing; Yin, Chuan; Sun, Duxin; Gao, Jie; Jiang, Beige; Zhong, Yanqiang; Lu, Ying

2017-05-01

Salinomycin (SAL)-loaded PEG-ceramide nanomicelles (SCM) were prepared to target both liver cancer cells and cancer stem cells. The synergistic ratio of SAL/PEG-ceramide was evaluated to prepare SCM, and the antitumor activity of SCM was examined both in vitro and in vivo. SAL/PEG-ceramide molar ratio of 1:4 was chosen as the synergistic ratio, and SCM showed superior cytotoxic effect and increased apoptosis-inducing activity in both liver cancer cells and cancer stem cells. In vivo, SCM showed the best tumor inhibitory effect with a safety profile. Thus, PEG-ceramide nanomicelles could serve as an effective and safe therapeutic drug carrier to deliver SAL into liver cancer, opening up the avenue of using PEG-ceramide as therapeutic drug carriers.

33 CFR 62.27 - Safe water marks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Safe water marks. 62.27 Section 62.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe...

75 FR 1734 - Children’s Online Privacy Protection Rule Safe Harbor Proposed Self-Regulatory Guidelines; i-SAFE...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-13

...The Federal Trade Commission publishes this notice and request for public comment concerning proposed self-regulatory guidelines submitted by i-SAFE, Inc. under the safe harbor provision of the Children's Online Privacy Protection Rule.

Therapeutic horse back riding of a spinal cord injured veteran: a case study.

PubMed

Asselin, Glennys; Penning, Julius H; Ramanujam, Savithri; Neri, Rebecca; Ward, Constance

2012-01-01

To determine an incomplete spinal cord injured veteran's experience following participation in a therapeutic horseback riding program. Following the establishment of a nationwide therapeutic riding program for America's wounded service veterans in 2007, a Certified Rehabilitation Registered Nurse from the Michael E. DeBakey Veteran Affairs Medical Center worked with an incomplete spinal cord injured veteran who participated in the Horses for Heroes program. This program resulted in many benefits for the veteran, including an increase in balance, muscle strength, and self-esteem. A physical, psychological, and psychosocial benefit of therapeutic horseback riding is shown to have positive results for the spinal cord injured. Therapeutic riding is an emerging field where the horse is used as a tool for physical therapy, emotional growth, and learning. Veterans returning from the Iraq/Afghanistan war with traumatic brain injuries, blast injuries, depression, traumatic amputations, and spinal cord injuries may benefit from this nurse-assisted therapy involving the horse. © 2012 Association of Rehabilitation Nurses.

[Understanding nurses' awareness as to the use of therapeutic play in child care].

PubMed

Maia, Edmara Bazoni Soares; Ribeiro, Circéa Amália; de Borba, Regina Issuzu Hirooka

2011-08-01

The objective of this study was to understand how nurses become aware of the use of therapeutic play as a nursing intervention instrument. Symbolic Interactionism was the theoretical framework and Interpretive Interactionism was used as the methodological framework. Participants were seven nurses working at hospitals and outpatient pediatric units who used the therapeutic play in their practice. Four representative themes emerged: Expanding the way he/she sees the child; Becoming fascinated with a new possibility to provide care; Noticing his/her revalidated action; and Committing himself/herself to the theme development. Such themes revealed that when nurses become acquainted with therapeutic play and use it in his/her practice, they begin on a journey that allows him/her to recognize the benefits of this intervention. By doing so, nurses revalidate their actions more and more, thus valuing play as a nursing intervention tool. The authors believe that teaching about therapeutic play and integrating it to nurses' daily practice are challenges yet to be overcome.

Self-Assembled Peptide-Lanthanide Nanoclusters for Safe Tumor Therapy: Overcoming and Utilizing Biological Barriers to Peptide Drug Delivery.

PubMed

Yan, Jin; He, Wangxiao; Yan, Siqi; Niu, Fan; Liu, Tianya; Ma, Bohan; Shao, Yongping; Yan, Yuwei; Yang, Guang; Lu, Wuyuan; Du, Yaping; Lei, Bo; Ma, Peter X

2018-02-27

Developing a sophisticated nanomedicine platform to deliver therapeutics effectively and safely into tumor/cancer cells remains challenging in the field of nanomedicine. In particular, reliable peptide drug delivery systems capable of overcoming biological barriers are still lacking. Here, we developed a simple, rapid, and robust strategy to manufacture nanoclusters of ∼90 nm in diameter that are self-assembled from lanthanide-doped nanoparticles (5 nm), two anticancer peptides with different targets (BIM and PMI), and one cyclic peptide iNGR targeted to cancer cells. The peptide-lanthanide nanoclusters (LDC-PMI-BIM-iNGR) enhanced the resistance of peptide drugs to proteolysis, disassembled in response to reductive conditions that are present in the tumor microenvironment and inhibited cancer cell growth in vitro and in vivo. Notably, LDC-PMI-BIM-iNGR exhibited extremely low systemic toxicity and side effects in vivo. Thus, the peptide-lanthanide nanocluster may serve as an ideal multifunctional platform for safe, targeted, and efficient peptide drug delivery in cancer therapy.

Memory as a new therapeutic target

PubMed Central

Nader, Karim; Hardt, Oliver; Lanius, Ruth

2013-01-01

This review aims to demonstrate how an understanding of the brain mechanisms involved in memory provides a basis for; (i) reconceptualizing some mental disorders; (ii) refining existing therapeutic tools; and (iii) designing new ones for targeting processes that maintain these disorders. First, some of the stages which a memory undergoes are defined, and the clinical relevance of an understanding of memory processing by the brain is discussed. This is followed by a brief review of some of the clinical studies that have targeted memory processes. Finally, some new insights provided by the field of neuroscience with implications for conceptualizing mental disorders are presented. PMID:24459414

Curiosity's Autonomous Surface Safing Behavior Design

NASA Technical Reports Server (NTRS)

Neilson, Tracy A.; Manning, Robert M.

2013-01-01

The safing routines on all robotic deep-space vehicles are designed to put the vehicle in a power and thermally safe configuration, enabling communication with the mission operators on Earth. Achieving this goal is made a little more difficult on Curiosity because the power requirements for the core avionics and the telecommunication equipment exceed the capability of the single power source, the Multi-Mission Radioisotope Thermoelectric Generator. This drove the system design to create an operational mode, called "sleep mode", where the vehicle turns off most of the loads in order to charge the two Li-ion batteries. The system must keep the vehicle safe from over-heat and under-heat conditions, battery cell failures, under-voltage conditions, and clock failures, both while the computer is running and while the system is sleeping. The other goal of a safing routine is to communicate. On most spacecraft, this simply involves turning on the receiver and transmitter continuously. For Curiosity, Earth is above the horizon only a part of the day for direct communication to the Earth, and the orbiter overpass opportunities only occur a few times a day. The design must robustly place the Rover in a communicable condition at the correct time. This paper discusses Curiosity's autonomous safing behavior and describes how the vehicle remains power and thermally safe while sleeping, as well as a description of how the Rover communicates with the orbiters and Earth at specific times.

Quality and Efficiency Improvement Tools for Every Radiologist.

PubMed

Kudla, Alexei U; Brook, Olga R

2018-06-01

In an era of value-based medicine, data-driven quality improvement is more important than ever to ensure safe and efficient imaging services. Familiarity with high-value tools enables all radiologists to successfully engage in quality and efficiency improvement. In this article, we review the model for improvement, strategies for measurement, and common practical tools with real-life examples that include Run chart, Control chart (Shewhart chart), Fishbone (Cause-and-Effect or Ishikawa) diagram, Pareto chart, 5 Whys, and Root Cause Analysis. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

33 CFR 62.27 - Safe water marks.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

33 CFR 62.27 - Safe water marks.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

33 CFR 62.27 - Safe water marks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to indicate...

SAFE Medication Management for Patients with Physical Impairments of Stroke, Part One.

PubMed

Yetzer, Elizabeth; Blake, Karen; Goetsch, Nancy; Shook, Mary; St Paul, Marilyn

2015-01-01

This article focuses on the extensive impairments of stroke and their influence on medication management. The impairments of motor skills due to paralysis-loss of mobility and balance, lack of hand-to-mouth coordination, and difficulty swallowing-are discussed. A future article will discuss sensory impairments of vision, hearing, cognition, comprehension, communication, and emotional disorders and how these impairments influence medication management. Each of the impairments are presented and discussed, and possible interventions are proposed. Every patient is an individual and requires variable care plans. Intervention strategies that include tools for patient assessment, practice tips, and devices available to assist the patient and family in safe medication management are presented. Patient outcomes and successes vary, but the strategies outlined will return the patient to as close to previous capabilities as possible. Teaching SAFE (Systematic, Accurate, Functional, Effective) medication management to the patient, family, and caregivers will increase medication safety and decrease the number of adverse effects. The rehabilitation nurse is charged with evaluating the patients' needs and developing strategies to assist them to manage their medications. © 2014 Association of Rehabilitation Nurses.

The Principles of Engineering Immune Cells to Treat Cancer

PubMed Central

Lim, Wendell A.; June, Carl H.

2017-01-01

Chimeric antigen receptor (CAR) T cells have proven that engineered immune cells can serve as a powerful new class of cancer therapeutics. Clinical experience has helped to define the major challenges that must be met to make engineered T cells a reliable, safe, and effective platform that can be deployed against a broad range of tumors. The emergence of synthetic biology approaches for cellular engineering is providing us with a broadly expanded set of tools for programming immune cells. We discuss how these tools could be used to design the next generation of smart T cell precision therapeutics. PMID:28187291

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.

Therapeutic Use of Prebiotics, Probiotics, and Postbiotics to Prevent Necrotizing Enterocolitis: What is the Current Evidence?

PubMed Central

Patel, Ravi Mangal; Denning, Patricia Wei

2013-01-01

Synopsis Necrotizing enterocolitis (NEC) is a leading cause of neonatal morbidity and mortality and preventative therapies that are both effective and safe are urgently needed. Current evidence from therapeutic trials suggests that probiotics are effective in decreasing NEC in preterm infants and probiotics are currently the most promising therapy on the horizon for this devastating disease. However, concerns regarding safety and optimal dosing have limited the widespread adoption of routine clinical use of probiotics in preterm infants. In addition, prebiotics and postbiotics may be potential alternatives or adjunctive therapies to the administration of live microorganisms, although studies demonstrating their clinical efficacy in preventing NEC are lacking. This review summarizes the current evidence regarding the use of probiotics, prebiotics and postbiotics in the preterm infant, including its therapeutic role in preventing NEC. PMID:23415261

Removing Hair Safely

MedlinePlus

... For Consumers Home For Consumers Consumer Updates Removing Hair Safely Share Tweet Linkedin Pin it More sharing ... related to common methods of hair removal. Laser Hair Removal In this method, a laser destroys hair ...

A fail-safe CMOS logic gate

NASA Technical Reports Server (NTRS)

Bobin, V.; Whitaker, S.

1990-01-01

This paper reports a design technique to make Complex CMOS Gates fail-safe for a class of faults. Two classes of faults are defined. The fail-safe design presented has limited fault-tolerance capability. Multiple faults are also covered.

Designing a training tool for imaging mental models

NASA Technical Reports Server (NTRS)

Dede, Christopher J.; Jayaram, Geetha

1990-01-01

The training process can be conceptualized as the student acquiring an evolutionary sequence of classification-problem solving mental models. For example a physician learns (1) classification systems for patient symptoms, diagnostic procedures, diseases, and therapeutic interventions and (2) interrelationships among these classifications (e.g., how to use diagnostic procedures to collect data about a patient's symptoms in order to identify the disease so that therapeutic measures can be taken. This project developed functional specifications for a computer-based tool, Mental Link, that allows the evaluative imaging of such mental models. The fundamental design approach underlying this representational medium is traversal of virtual cognition space. Typically intangible cognitive entities and links among them are visible as a three-dimensional web that represents a knowledge structure. The tool has a high degree of flexibility and customizability to allow extension to other types of uses, such a front-end to an intelligent tutoring system, knowledge base, hypermedia system, or semantic network.

Herbs-are they safe enough? an overview.

PubMed

Singh, Divya; Gupta, Rajiv; Saraf, Shubhini A

2012-01-01

Drugs based on herbs have become a common form of therapy as well as for prophylaxis because they are often perceived as being natural and therefore harmless. Today they are one of the hottest trends and most sought after in the field of nutrition or herbal therapeutics. As the use of complementary medicine grows, so does the knowledge that many compounds in common use not only have a significant effect on the body but may also interact with pharmaceuticals and also with other alternative products. Concurrent use of herbs with drugs may mimic, magnify, or oppose the effect of drugs leading to herb-drug interactions. Currently, there is very little information published on herb-herb or herb-drug interactions as compared to the use of herbs which is progressively growing across the world. Many reports of herb-drug interactions are sketchy and lack laboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs and pharmaceutical drugs. The article reviews the recent literature on the adverse effects of herbal remedies including the most widely sold herbal medicinal products, like liquorice, garlic, ginger, green tea, and turmeric, etc., and reinforce the safety aspect of herbal products, which are considered to be relatively safe by common people.

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

PubMed Central

Goode, Travis D.; Kim, Janice J.

2015-01-01

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. PMID:25691517

Safe mobility for older people notebook

DOT National Transportation Integrated Search

1999-04-01

The Safe Mobility for Older People Notebook is a research product of the "Model Driver Screening and Evaluation Program" project sponsored by NHTSA, and is intended as a resource to support program initiatives promoting the safe mobility of older per...

33 CFR 62.27 - Safe water marks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Safe water marks. 62.27 Section 62.27 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO NAVIGATION UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is...

Developing Safe Schools Partnerships with Law Enforcement

ERIC Educational Resources Information Center

Rosiak, John

2009-01-01

Safe schools are the concern of communities throughout the world. If a school is safe, and if children feel safe, students "are better able to learn. But what are the steps to make" this happen? First, it is important to understand the problem: What are the threats to school safety? These include crime-related behaviors that find their way to…

Procedure-Authoring Tool Improves Safety on Oil Rigs

NASA Technical Reports Server (NTRS)

2014-01-01

Dark, cold, and dangerous environments are plentiful in space and on Earth. To ensure safe operations in difficult surroundings, NASA relies heavily on procedures written well ahead of time. Houston-based TRACLabs Inc. worked with Ames Research Center through the SBIR program to create an electronic procedure authoring tool, now used by NASA and companies in the oil and gas industry.

[Regional protocol for adjusting the therapeutic intensity. Southern Metropolitan Area of Barcelona].

PubMed

Fontecha-Gómez, Benito Jesús; Amblàs-Novellas, Jordi; Betancor-Santana, Évora; Rexach-Cano, Lourdes; Ugarte, Marina Isabel; López-Pérez, Araceli; Planas, Kenneth; Gutiérrez Jiménez, Nuria; Casas Floriano, Rosario; García-Fortea, Cristina; Serrano Bermúdez, Gala; Rotllàn-Terradellas, María; Fernández-Ponce, Daniel

2018-02-20

The identification of patients with advanced and complex chronic diseases, and the fragmentation of care towards the end of life, requires the drawing up a long-term therapeutic plan. This should take into account the values and preferences of the patients, as well as the vital and functional prognosis. Having an adjustment tool for determining the diagnostic and therapeutic effort is helpful in the continuity of care, as well as in decision-making in the transitions and dynamic changes of patients as they approach the end of life process. Copyright © 2018 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

Safe haven laws as crime control theater.

PubMed

Hammond, Michelle; Miller, Monica K; Griffin, Timothy

2010-07-01

This article examines safe haven laws, which allow parents to legally abandon their infants. The main objective is to determine whether safe haven laws fit the criteria of crime control theater, a term used to describe public policies that produce the appearance, but not the effect, of crime control, and as such are essentially socially constructed "solutions" to socially constructed crime "problems." The analysis will apply the principles of crime control theater to safe haven laws. Specifically, the term crime control theater applies to laws that are reactionary responses to perceived criminal threats and are often widely supported as a way to address the crime in question. Such laws are attractive because they appeal to mythic narratives (i.e., saving an innocent child from a predator); however they are likely ineffective due to the complexity of the crime. These laws can have deleterious effects when policymakers make false claims of success and stunt public discourse (e.g., drawing attention away from more frequent and preventable crimes). This analysis applies these criteria to safe haven laws to determine whether such laws can be classified as crime control theater. Many qualities inherent to crime control theater are present in safe haven laws. For example, the laws are highly publicized, their intentions lack moral ambiguity, rare cases of success legitimize law enforcement and other agencies, and they appeal to the public sense of responsibility in preventing crime. Yet the goal of saving infant lives may be unattainable. These qualities make the effectiveness of the laws questionable and suggest they may be counterproductive. This analysis determined that safe haven laws are socially constructed solutions to the socially constructed problem of child abandonment. Safe haven laws are appropriately classified as crime control theater. It is imperative that further research be conducted to examine the effectiveness and collateral effects of safe haven laws

Safe Sleep Practices of Kansas Birthing Hospitals

PubMed Central

Ahlers-Schmidt, Carolyn R.; Schunn, Christy; Sage, Cherie; Engel, Matthew; Benton, Mary

2018-01-01

Background Sleep-related death is tied with congenital anomalies as the leading cause of infant mortality in Kansas, and external risk factors are present in 83% of these deaths. Hospitals can impact caregiver intentions to follow risk-reduction strategies. This project assessed the current practices and policies of Kansas hospitals with regard to safe sleep. Methods A cross-sectional survey of existing safe sleep practices and policies in Kansas hospitals was performed. Hospitals were categorized based on reported delivery volume and data were compared across hospital sizes. Results Thirty-one of 73 (42%) contacted hospitals responded. Individual survey respondents represented various hospital departments including newborn/well-baby (68%), neonatal intensive care unit (3%) and other non-nursery departments or administration (29%). Fifty-eight percent of respondents reported staff were trained on infant safe sleep; 44% of these held trainings annually. High volume hospitals tended to have more annual training than low or mid volume birth hospitals. Thirty-nine percent reported a safe sleep policy, though most of these (67%) reported never auditing compliance. The top barrier to safe sleep education, regardless of delivery volume, was conflicting patient and family member beliefs. Conclusions Hospital promotion of infant safe sleep is being conducted in Kansas to varying degrees. High and mid volume birth hospitals may need to work more on formal auditing of safe sleep practices, while low volume hospitals may need more staff training. Low volume hospitals also may benefit from access to additional caregiver education materials. Finally, it is important to note hospitals should not be solely responsible for safe sleep education. PMID:29844848

The effect of therapeutic horseback riding on balance in community-dwelling older adults: a pilot study.

PubMed

Homnick, Tamara D; Henning, Kim M; Swain, Charlene V; Homnick, Douglas N

2015-02-01

Equine assisted activities (hippotherapy and therapeutic riding) improve balance in patients with disabilities such as cerebral palsy, but have not been systematically studied in older adults, at risk of falls due to balance deficits. We conducted a 10-week, single blind, controlled trial of the effect of a therapeutic horseback riding course on measures of balance in community-dwelling adults 65 years and older. Nine riders and six controls completed the trial. Controls were age matched to riders and all participants were recruited from the local community. Both groups showed improvements in balance during the trial, but did not reach statistical significance. Sample size was small, participants had relatively high initial balance scores, and controls tended to increase their physical activities, likely influencing outcomes. No adverse events occurred and the supervised therapeutic riding program appeared to be a safe and effective form of exercise to improve balance in older adults. A power analysis was performed to estimate numbers of participants needed for a larger study. © The Author(s) 2012.

Using Medications Safely

MedlinePlus

... health systems play an important role in preventing medication errors. To make sure you use medicines safely and effectively, ASHP recommends that you: Keep a list of all medications that you take (prescribed drugs, nonprescription medicines, herbal ...

Towards a new era in medicine: therapeutic genome editing.

PubMed

Porteus, Matthew H

2015-12-22

Genome editing is the process of precisely modifying the nucleotide sequence of the genome. It has provided a powerful approach to research questions but, with the development of a new set of tools, it is now possible to achieve frequencies of genome editing that are high enough to be useful therapeutically. Genome editing is being developed to treat not only monogenic diseases but also infectious diseases and diseases that have both a genetic and an environmental component.

Process and outcomes evaluation of older driver screening programs : the Assessment of Driving-Related Skills (ADReS) older-driver screening tool

DOT National Transportation Integrated Search

2009-05-01

Physicians are one resource for identification of older drivers who may be at risk for decreased safe driving ability. However, : physicians have not had the tools to make decisions about the safe driving ability of their patients. With this in mind,...

Test-retest reliability of the safe driving behavior measure for community-dwelling elderly drivers.

PubMed

Song, Chiang-Soon; Lee, Joo-Hyun; Han, Sang-Woo

2016-06-01

[Purpose] The Safe Driving Behavior Measure (SDBM) is a self-report measurement tools that assesses the safe-driving behaviors of the elderly. The purpose of this study was to evaluate the test-retest reliability of the SDBM among community-dwelling elderly drivers. [Subjects and Methods] A total of sixty-one community-dwelling elderly were enrolled to investigate the reliability of the SDBM. The SDBM was assessed in two sessions that were conducted three days apart in a quiet and well-organized assessment room. That test-retest reliability of overall scores and three domain scores of the SDBM were statistically evaluated using intraclass correlation coefficients [ICC (2.1)]. Pearson correlation coefficients were used to quantify bivariate associations among the three domains of the SDBM. [Results] The SDBM demonstrated excellent rest-retest reliability for community-dwelling elderly drivers. The Cronbach alpha coefficients of the three domains of person-vehicle (0.979), person-environment (0.944), and person-vehicle-environment (0.971) of the SDBM indicate high internal consistency. [Conclusion] The results of this study suggest that the SDBM is a reliable measure for evaluating the safe- driving of automobiles by community-dwelling elderly, and is adequate for detecting changes in scores in clinical settings.

Safe prescribing: a titanic challenge

PubMed Central

Routledge, Philip A

2012-01-01

The challenge to achieve safe prescribing merits the adjective ‘titanic’. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the ‘Seven C's’. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. PMID:22738396

Custom-designed proteins as novel therapeutic tools? The case of arrestins

PubMed Central

Gurevich, Vsevolod V.; Gurevich, Eugenia V.

2010-01-01

Multiple genetic disorders can be associated with excessive signalling by mutant G-protein-coupled receptors (GPCRs) that are either constitutively active or have lost sites where phosphorylation by GPCR kinases is necessary for desensitisation by cognate arrestins. Phosphorylation-independent arrestin1 can compensate for defects in phosphorylation of the GPCR rhodopsin in retinal rod cells, facilitating recovery, improving light responsiveness, and promoting photoreceptor survival. These proof-of-principle experiments show that, based on mechanistic understanding of the inner workings of a protein, one can modify its functional characteristics to generate custom-designed mutants that improve the balance of signalling in congenital and acquired disorders. Manipulations of arrestin elements responsible for scaffolding mitogen-activated protein kinase cascades and binding other signalling proteins involved in life-or-death decisions in the cell are likely to yield mutants that affect cell survival and proliferation in the desired direction. Although this approach is still in its infancy, targeted redesign of individual functions of many proteins offers a promise of a completely new therapeutic toolbox with huge potential. PMID:20412604

[Epilepsy-new diagnostic tools, old drugs? : Therapeutic consequences of epilepsy genetics].

PubMed

Tacke, M; Neubauer, B A; Gerstl, L; Roser, T; Rémi, J; Borggraefe, I

2017-12-01

Recent advances in the field of epilepsy genetics have led to an increased fraction of patients with epilepsies where the etiology of the disease could be identified. Nevertheless, there is some criticism regarding the use of epilepsy genetics because in many cases the identification of a pathogenetic mutation does not lead to an adaptation of therapy or to an improved prognosis. In addition, the interpretation of genetic results might be complicated due to the considerable numbers of variants of unclear significance. This publication presents the arguments in favour of a broad use of genetic investigations for children with epilepsies. Several diseases where a genetic diagnosis does in fact have direct therapeutic consequences are mentioned. In addition, the indirect impact of an established etiology, encompassing the avoidance of unnecessary diagnostic measures, possibility of genetic counselling, and the easing of the psychologic burden for the caregivers, should not be underestimated. The arguments in favour of broad genetic diagnostics prevail notwithstanding the lack of relevant new developments regarding the therapy.

Implementation of straight and curved steel girder erection design tools construction : summary.

DOT National Transportation Integrated Search

2010-11-05

Project 0-5574 Curved Plate Girder Design for Safe and Economical Construction, resulted in the : development of two design tools, UT Lift and UT Bridge. UT Lift is a spreadsheet-based program for analyzing : steel girders during lifting while ...

Managing drugs safely.

PubMed

van den Anker, John N

2005-02-01

There is hard data to show that newborn infants are more likely than adults to experience adverse reactions to drugs. Paradoxically, drug-related legislation to ensure safe and effective drug use in humans neglected neonates until 2002, when the Best Pharmaceuticals Act for Children was signed into law in the USA. The situation for neonates should now catch up with that for adults and neonates will be prescribed more licensed drugs in the near future. If we are to be able to analyze the underlying system errors to improve the safe use of drugs in the studied patient population, reporting of adverse drug events and reactions needs to happen in a blame free environment. In addition, computerized physician order entry will certainly further improve the current situation by preventing errors in ordering, transcribing, verifying, and transmitting medication orders.

Exploring Socio-Technical Insights for Safe Nursing Handover.

PubMed

Wong, Ming Chao; Yee, Kwang Chien; Turner, Paul

2017-01-01

Current efforts to improve nursing handover frequently use prescriptive approaches based on research evidence of handover issues within a single nursing ward or nursing specialty. Despite reported handover improvement, few studies adequately consider the transferability of results to other nursing handover environments or acknowledge the unique attributes that supported sustained improvement. With the increasing diffusion of electronic tools it has become even more critical to ensure that socio-technical issues that may impact on the quality and safety of nursing handovers are identified. This paper describes a qualitative research project that examined nursing handover in three different wards - General Medicine, General Surgery and Department of Emergency Medicine in a tertiary teaching hospital. Through conduct of a detailed analysis of nursing handover processes, this paper highlights the similarities and differences in the handover among the three different wards and presents five key socio-technical insights to support safe nursing handover.

Drug Targets for Cardiovascular-Safe Anti-Inflammatory: In Silico Rational Drug Studies

PubMed Central

Shahbazi, Sajad; Sahrawat, Tammanna R.; Ray, Monalisa; Dash, Swagatika; Kar, Dattatreya; Singh, Shikha

2016-01-01

Cyclooxygenase-2 (COX-2) plays an important role in memory consolidation and synaptic activity, the most fundamental functions of the brain. It converts arachidonic acid to prostaglandin endoperoxide H2. In contrast, if over-expressed, it causes inflammation in response to cytokine, pro-inflammatory molecule, and growth factor. Anti-inflammatory agents, by allosteric or competitive inhibition of COX-2, alleviate the symptoms of inflammation. Coxib family drugs, particularly celecoxib, are the most famous anti-inflammatory agents available in the market showing significant inhibitory effect on COX-2 activity. Due to high cardiovascular risk of this drug group, recent researches are focused on the investigation of new safer drugs for anti-inflammatory diseases. Natural compounds, particularly, phytochemicals are found to be good candidates for drug designing and discovery. In the present study, we performed in silico studies to quantitatively scrutinize the molecular interaction of curcumin and its structural analogs with COX-2, COX-1, FXa and integrin αIIbβIII to investigate their therapeutic potential as a cardiovascular-safe anti-inflammatory medicine (CVSAIM). The results of both ADMET and docking study indicated that out of all the 39 compounds studied, caffeic acid had remarkable interaction with proteins involved in inflammatory response. It was also found to inhibit the proteins that are involved in thrombosis, thereby, having the potential to be developed as therapeutic agent. PMID:27258084

An Automated Safe-to-Mate (ASTM) Tester

NASA Technical Reports Server (NTRS)

Nguyen, Phuc; Scott, Michelle; Leung, Alan; Lin, Michael; Johnson, Thomas

2013-01-01

Safe-to-mate testing is a common hardware safety practice where impedance measurements are made on unpowered hardware to verify isolation, continuity, or impedance between pins of an interface connector. A computer-based instrumentation solution has been developed to resolve issues. The ASTM is connected to the circuit under test, and can then quickly, safely, and reliably safe-to-mate the entire connector, or even multiple connectors, at the same time.

The Therapeutic Relationship as Predictor of Change in Music Therapy with Young Children with Autism Spectrum Disorder.

PubMed

Mössler, Karin; Gold, Christian; Aßmus, Jörg; Schumacher, Karin; Calvet, Claudine; Reimer, Silke; Iversen, Gun; Schmid, Wolfgang

2017-09-21

This study examined whether the therapeutic relationship in music therapy with children with Autism Spectrum Disorder predicts generalized changes in social skills. Participants (4-7 years, N = 48) were assessed at baseline, 5 and 12 months. The therapeutic relationship, as observed from session videos, and the generalized change in social skills, as judged by independent blinded assessors and parents, were evaluated using standardized tools (Assessment of the Quality of Relationship; ADOS; SRS). Linear mixed effect models showed significant interaction effects between the therapeutic relationship and several outcomes at 5 and 12 months. We found the music therapeutic relationship to be an important predictor of the development of social skills, as well as communication and language specifically.

SAFE Software and FED Database to Uncover Protein-Protein Interactions using Gene Fusion Analysis.

PubMed

Tsagrasoulis, Dimosthenis; Danos, Vasilis; Kissa, Maria; Trimpalis, Philip; Koumandou, V Lila; Karagouni, Amalia D; Tsakalidis, Athanasios; Kossida, Sophia

2012-01-01

Domain Fusion Analysis takes advantage of the fact that certain proteins in a given proteome A, are found to have statistically significant similarity with two separate proteins in another proteome B. In other words, the result of a fusion event between two separate proteins in proteome B is a specific full-length protein in proteome A. In such a case, it can be safely concluded that the protein pair has a common biological function or even interacts physically. In this paper, we present the Fusion Events Database (FED), a database for the maintenance and retrieval of fusion data both in prokaryotic and eukaryotic organisms and the Software for the Analysis of Fusion Events (SAFE), a computational platform implemented for the automated detection, filtering and visualization of fusion events (both available at: http://www.bioacademy.gr/bioinformatics/projects/ProteinFusion/index.htm). Finally, we analyze the proteomes of three microorganisms using these tools in order to demonstrate their functionality.

SAFE Software and FED Database to Uncover Protein-Protein Interactions using Gene Fusion Analysis

PubMed Central

Tsagrasoulis, Dimosthenis; Danos, Vasilis; Kissa, Maria; Trimpalis, Philip; Koumandou, V. Lila; Karagouni, Amalia D.; Tsakalidis, Athanasios; Kossida, Sophia

2012-01-01

Domain Fusion Analysis takes advantage of the fact that certain proteins in a given proteome A, are found to have statistically significant similarity with two separate proteins in another proteome B. In other words, the result of a fusion event between two separate proteins in proteome B is a specific full-length protein in proteome A. In such a case, it can be safely concluded that the protein pair has a common biological function or even interacts physically. In this paper, we present the Fusion Events Database (FED), a database for the maintenance and retrieval of fusion data both in prokaryotic and eukaryotic organisms and the Software for the Analysis of Fusion Events (SAFE), a computational platform implemented for the automated detection, filtering and visualization of fusion events (both available at: http://www.bioacademy.gr/bioinformatics/projects/ProteinFusion/index.htm). Finally, we analyze the proteomes of three microorganisms using these tools in order to demonstrate their functionality. PMID:22267904

High-intensity focused ultrasound-triggered nanoscale bubble-generating liposomes for efficient and safe tumor ablation under photoacoustic imaging monitoring.

PubMed

Feng, Gang; Hao, Lan; Xu, Chunyan; Ran, Haitao; Zheng, Yuanyi; Li, Pan; Cao, Yang; Wang, Qi; Xia, Jizhu; Wang, Zhigang

2017-01-01

High-intensity focused ultrasound (HIFU) is widely applied to tumors in clinical practice due to its minimally invasive approach. However, several issues lower therapeutic efficiency in some cases. Many synergists such as microbubbles and perfluorocarbon nanoparticles have recently been used to improve HIFU treatment efficiency, but none were determined to be effective and safe in vivo. In this study, nanoscale bubble-generating liposomes (liposomes containing ammonium bicarbonate [Lip-ABC]) were prepared by film hydration followed by sequential extrusion. Their stable nanoscale particle diameter was confirmed, and their bubble-generating capacity after HIFU triggering was demonstrated with ultrasound imaging. Lip-ABC had good stability in vivo and accumulated in the tumor interstitial space based on the enhanced permeability and retention effect evaluated by photoacoustic imaging. When used to synergize HIFU ablation to bovine liver in vitro and implanted breast tumors of BALB/c nude mice, Lip-ABC outperformed the control. Importantly, all mice survived HIFU treatment, suggesting that Lip-ABC is a safe HIFU synergist.

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

PubMed

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

2017-02-01

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

Strategies for safe injections.

PubMed Central

Battersby, A.; Feilden, R.; Stoeckel, P.; Da Silva, A.; Nelson, C.; Bass, A.

1999-01-01

In 1998, faced with growing international concern, WHO set out an approach for achieving injection safety that encompassed all elements from patients' expectations and doctors' prescribing habits to waste disposal. This article follows that lead and describes the implications of the approach for two injection technologies: sterilizable and disposable. It argues that focusing on any single technology diverts attention from the more fundamental need for health services to develop their own comprehensive strategies for safe injections. National health authorities will only be able to ensure that injections are administered safely if they take an approach that encompasses the whole system, and choose injection technologies that fit their circumstances. PMID:10680247

Feeling safe during an inpatient hospitalization: a concept analysis.

PubMed

Mollon, Deene

2014-08-01

This paper aims to explore the critical attributes of the concept feeling safe. The safe delivery of care is a high priority; however; it is not really known what it means to the patient to 'feel safe' during an inpatient hospitalization. This analysis explores the topic of safety from the patient's perspective. Concept analysis. The data bases of CINAHL, Medline, PsychInfo and Google Scholar for the years 1995-2012 were searched using the terms safe and feeling safe. The eight-step concept analysis method of Walker and Avant was used to analyse the concept of feeling safe. Uses and defining attributes, as well as identified antecedents, consequences and empirical referents, are presented. Case examples are provided to assist in the understanding of defining attributes. Feeling safe is defined as an emotional state where perceptions of care contribute to a sense of security and freedom from harm. Four attributes were identified: trust, cared for, presence and knowledge. Relationship, environment and suffering are the antecedents of feeling safe, while control, hope and relaxed or calm are the consequences. Empirical referents and early development of a theory of feeling safe are explored. This analysis begins the work of synthesizing qualitative research already completed around the concept of feeling safe by defining the key attributes of the concept. Support for the importance of developing patient-centred models of care and creating positive environments where patients receive high-quality care and feel safe is provided. © 2014 John Wiley & Sons Ltd.

Tangential gunshot wound with MagSafe ammunition.

PubMed

Rapkiewicz, Amy V; Tamburri, Robert; Basoa, Mark E; Catanese, Charles A

2005-09-01

MagSafe ammunition is a type of unconventional prefragmented ammunition. A fatal tangential gunshot wound involving MagSafe ammunition is presented. The ammunition and wound characteristics are discussed.

Emerging insights into barriers to effective brain tumor therapeutics.

PubMed

Woodworth, Graeme F; Dunn, Gavin P; Nance, Elizabeth A; Hanes, Justin; Brem, Henry

2014-01-01

There is great promise that ongoing advances in the delivery of therapeutics to the central nervous system (CNS) combined with rapidly expanding knowledge of brain tumor patho-biology will provide new, more effective therapies. Brain tumors that form from brain cells, as opposed to those that come from other parts of the body, rarely metastasize outside of the CNS. Instead, the tumor cells invade deep into the brain itself, causing disruption in brain circuits, blood vessel and blood flow changes, and tissue swelling. Patients with the most common and deadly form, glioblastoma (GBM) rarely live more than 2 years even with the most aggressive treatments and often with devastating neurological consequences. Current treatments include maximal safe surgical removal or biopsy followed by radiation and chemotherapy to address the residual tumor mass and invading tumor cells. However, delivering effective and sustained treatments to these invading cells without damaging healthy brain tissue is a major challenge and focus of the emerging fields of nanomedicine and viral and cell-based therapies. New treatment strategies, particularly those directed against the invasive component of this devastating CNS disease, are sorely needed. In this review, we (1) discuss the history and evolution of treatments for GBM, (2) define and explore three critical barriers to improving therapeutic delivery to invasive brain tumors, specifically, the neuro-vascular unit as it relates to the blood brain barrier, the extra-cellular space in regard to the brain penetration barrier, and the tumor genetic heterogeneity and instability in association with the treatment efficacy barrier, and (3) identify promising new therapeutic delivery approaches that have the potential to address these barriers and create sustained, meaningful efficacy against GBM.

Creating Safe Spaces for Music Learning

ERIC Educational Resources Information Center

Hendricks, Karin S.; Smith, Tawnya D.; Stanuch, Jennifer

2014-01-01

This article offers a practical model for fostering emotionally safe learning environments that instill in music students a positive sense of self-belief, freedom, and purpose. The authors examine the implications for music educators of creating effective learning environments and present recommendations for creating a safe space for learning,…

Gas chromatography-mass spectrometry assay method for the therapeutic drug monitoring of the antiepileptic drug tiagabine.

PubMed

Chollet, D F; Castella, E; Goumaz, L; Anderegg, G

1999-11-01

A gas chromatography-mass spectrometry assay method suitable for the therapeutic drug monitoring of the antiepileptic drug tiagabine is described. Tiagabine and its desmethylated analogue used as internal standard were first extracted from serum by liquid-liquid extraction using an ethyl ether-isobutanol 98:2 mixture. Tiagabine and the internal standard were then methylated in the organic phase in presence of methanol by means of a safe and stable diazomethane derivative. After evaporation, the reconstituted extracts were chromatographed on a crosslinked phenyl methyl siloxane capillary column and detected by mass fragmentometry at m/z = 156. No other antiepileptic drug possibly administrated in polytherapy and no metabolite were found to interfere in the assay. The limit of quantification was 5 ng/ml. The precision and the accuracy were found to be suitable for the therapeutic drug monitoring of tiagabine.

Asymptotically safe standard model extensions?

NASA Astrophysics Data System (ADS)

Pelaggi, Giulio Maria; Plascencia, Alexis D.; Salvio, Alberto; Sannino, Francesco; Smirnov, Juri; Strumia, Alessandro

2018-05-01

We consider theories with a large number NF of charged fermions and compute the renormalization group equations for the gauge, Yukawa and quartic couplings resummed at leading order in 1 /NF. We construct extensions of the standard model where SU(2) and/or SU(3) are asymptotically safe. When the same procedure is applied to the Abelian U(1) factor, we find that the Higgs quartic can not be made asymptotically safe and stay perturbative at the same time.

Advancements in nano-enabled therapeutics for neuroHIV management.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood-brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management.

Sulfonamide chalcones: Synthesis and in vitro exploration for therapeutic potential against Brugia malayi.

PubMed

Bahekar, Sandeep P; Hande, Sneha V; Agrawal, Nikita R; Chandak, Hemant S; Bhoj, Priyanka S; Goswami, Kalyan; Reddy, M V R

2016-11-29

Keeping in mind the immense biological potential of chalcones and sulfonamide scaffolds, a library of sulfonamide chalcones has been synthesized and evaluated for in vitro antifilarial assay against human lymphatic filarial parasite Brugia malayi. Experimental evidence showcased for the first time the potential of some sulfonamide chalcones as effective and safe antifilarial lead molecules against human lymphatic filarial parasite B. malayi. Sulfonamide chalcones 4d, 4p, 4q, 4t and 4aa displayed the significantly wide therapeutic window. Particularly chalcones with halogen substitution in aromatic ring proved to be potent antifilarial agents against Brugia malayi. Sulphonamide chalcones with lipophilic methyl moiety (4q and 4aa) at para position of terminal phenyl rings of compounds were found to have remarkable antifilarial activities with therapeutic efficacy. Observed preliminary evidence of apoptosis by effective chalcone derivatives envisaged its fair possibility to inhibit folate pathway with consequent defect in DNA synthesis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Emotional response to a therapeutic technique: The social Broad Minded Affective Coping.

PubMed

Holden, Natasha; Kelly, James; Welford, Mary; Taylor, Peter J

2017-03-01

It has been suggested that savouring positive memories can generate positive emotions. Increasing positive emotion can have a range of benefits including reducing attention to and experiences of threat. This study investigated individuals' emotional reactions to a guided mental imagery task focussing on positive social memory called the 'social Broad Minded Affective Coping (BMAC)' technique. The study examined possible predictors of individuals' responses to this intervention. An internet-based, within-group, repeated-measures design was used. One hundred and twenty-three participants completed self-report measures of self-attacking and social safeness/pleasure. They were then guided through the social BMAC. Participants completed state measures of positive and negative affect and social safeness/pleasure before and after the intervention. Forty-nine participants took part in a 2-week follow-up. It was found that safe/warm positive affect, relaxed positive affect and feelings of social safeness increased following the social BMAC, whilst negative affect decreased. In addition, it was found that people scoring higher on inadequate self-attacking benefited most from this intervention. Changes in affect were not maintained at the 2-week follow-up. The results provide preliminary support for the efficacy of the social BMAC in activating specific types of mood (those associated with safeness rather than drive/reward). This task has potential as part of therapeutic interventions directed at clinical groups, but further evaluation is needed. The social Broad Minded Affective Coping (BMAC) was related to improvements in forms of positive affect linked to the affiliative system. This task may be helpful in inducing these positive mood states within therapy. Further evaluation comparing the BMAC to a control task is needed. Individuals with a greater fear of compassion or more hated-self-criticism may gain less from the task, although effects were small. © 2016 The Authors

THPdb: Database of FDA-approved peptide and protein therapeutics.

PubMed

Usmani, Salman Sadullah; Bedi, Gursimran; Samuel, Jesse S; Singh, Sandeep; Kalra, Sourav; Kumar, Pawan; Ahuja, Anjuman Arora; Sharma, Meenu; Gautam, Ankur; Raghava, Gajendra P S

2017-01-01

THPdb (http://crdd.osdd.net/raghava/thpdb/) is a manually curated repository of Food and Drug Administration (FDA) approved therapeutic peptides and proteins. The information in THPdb has been compiled from 985 research publications, 70 patents and other resources like DrugBank. The current version of the database holds a total of 852 entries, providing comprehensive information on 239 US-FDA approved therapeutic peptides and proteins and their 380 drug variants. The information on each peptide and protein includes their sequences, chemical properties, composition, disease area, mode of activity, physical appearance, category or pharmacological class, pharmacodynamics, route of administration, toxicity, target of activity, etc. In addition, we have annotated the structure of most of the protein and peptides. A number of user-friendly tools have been integrated to facilitate easy browsing and data analysis. To assist scientific community, a web interface and mobile App have also been developed.

Mixed-Methods Evaluation of Real-Time Safety Reporting by Hospitalized Patients and Their Care Partners: The MySafeCare Application.

PubMed

Collins, Sarah A; Couture, Brittany; Smith, Ann DeBord; Gershanik, Esteban; Lilley, Elizabeth; Chang, Frank; Yoon, Cathy; Lipsitz, Stuart; Sheikh, Aziz; Benneyan, James; Bates, David W

2018-04-27

The aims of the study were to evaluate the amount and content of data patients and care partners reported using a real-time electronic safety tool compared with other reporting mechanisms and to understand their perspectives on safety concerns and reporting in the hospital. This study used mixed methods including 20-month preimplementation and postimplementation trial evaluating MySafeCare, a web-based application, which allows hospitalized patients/care partners to report safety concerns in real time. The study compared MySafeCare submission rates for three hospital units (oncology acute care, vascular intermediate care, medical intensive care) with submissions rates of Patient Family Relations (PFR) Department, a hospital service to address patient/family concerns. The study used triangulation of quantitative data with thematic analysis of safety concern submissions and patient/care partner interviews to understand submission content and perspectives on safety reporting. Thirty-two MySafeCare submissions were received with an average rate of 1.7 submissions per 1000 patient-days and a range of 0.3 to 4.8 submissions per 1000 patient-days across all units, indicating notable variation between units. MySafeCare submission rates were significantly higher than PFR submission rates during the postintervention period on the vascular unit (4.3 [95% confidence interval = 2.8-6.5] versus 1.5 [95% confidence interval = 0.7-3.1], Poisson) (P = 0.01). Overall trends indicated a decrease in PFR submissions after MySafeCare implementation. Triangulated data indicated patients preferred to report anonymously and did not want concerns submitted directly to their care team. MySafeCare evaluation confirmed the potential value of providing an electronic, anonymous reporting tool in the hospital to capture safety concerns in real time. Such applications should be tested further as part of patient safety programs.This is an open-access article distributed under the terms of the

Systematic strength training as a model of therapeutic intervention. A controlled trial in postmenopausal women with osteopenia.

PubMed

Hartard, M; Haber, P; Ilieva, D; Preisinger, E; Seidl, G; Huber, J

1996-01-01

Physical exercise is often recommended as a therapeutic tool to combat pre- and postmenopausal loss of bone density. However, the relationship between training dosage (intensity, duration, frequency) and the effect on bone density still is undergoing discussion. Furthermore, the exercise quantification programs are often described so inadequately that they are neither quantitatively nor qualitatively reproducible. The aim of this investigation was to determine whether a clearly defined training of muscle strength, under defined safety aspects, performed only twice weekly, can counteract bone density loss in women with postmenopausal osteopenia. Data from 16 women in the training group (age, 63.6 +/- 6.2 yr) and 15 women in the control group (age, 67.4 +/-9.7 yr), of comparable height and weight, were evaluated. Strength training was performed for 6 mo as continually adapted strength training, providing an intensity of about 70% of each test person's one repetition maximum. Bone mineral density of lumbar vertebrae 2 to 4 and the femoral neck was measured by dual-energy x-ray absorptiometry. Maximum performance in watts and parameters of hemodynamics were controlled with a bicycle ergometer test to maximal effort. In addition, metabolic data were assessed. In the lumbar spine and femoral neck, the training group showed no significant changes, whereas the control group demonstrated a significant loss of bone mineral density, especially in the femoral neck (P<0.05). The strength increase was highly significant in all exercised muscle groups, rising to about 70% above the pretraining status (P<0.001). Heart rate and blood pressure data indicated a slight economization, metabolism was not significantly influenced. Based on these findings, we conclude that continually adapted strength training is an effective, safe, reproducible, and adaptable method of therapeutic strength training, following only two exercise sessions per week.

Diagnostic and therapeutic value of laparoscopy for small bowel blunt injuries: A case report.

PubMed

Addeo, Pietro; Calabrese, Daniela Paola

2011-01-01

Small bowel injuries after blunt abdominal trauma represent both a diagnostic and a therapeutic challenge. Early diagnosis and prompt treatment are necessary in order to avoid a dangerous diagnostic delay. Laparoscopy can represent a diagnostic and therapeutic tool in patients with uncertain clinical symptoms. We report the case of a 25-year-old man, haemodynamically stable, admitted for acute abdominal pain a few hours after a physical assault. Giving the persistence of the abdominal pain and the presence of free fluids at the computed tomography examination, an exploratory laparoscopy was performed. At the laparoscopic exploration, an isolated small bowel perforation was found, 60 cm distal from the ligament of Treitz. The injury was repaired by laparoscopic suturing and the patient was discharged home at postoperative day 3 after an uneventful postoperative course. Laparoscopy represents a valuable tool for patients with small bowel blunt injuries allowing a timely diagnosis and a prompt treatment.

76 FR 30495 - National Safe Boating Week, 2011

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-25

... Safe Boating Week, 2011 By the President of the United States of America A Proclamation As Americans... to watergoers. National Safe Boating Week is an opportunity to highlight the importance of safety... can save lives. Each year for National Safe Boating Week, the United States Coast Guard partners with...

The Internet and the therapeutic education of patients: A systematic review of the literature.

PubMed

Gremeaux, V; Coudeyre, E

2010-12-01

To evaluate from a review of the literature the interest of using the Internet as a tool for the therapeutic education of patients. A systematic review of Pubmed was carried out using the key words: the Internet, or World Wide Web and patient education, or patient preference, or self-care. The search was restricted to articles in English published between 1990 and 2009. References to the selected articles were also analyzed. Only randomized controlled studies were retained. Thirty-nine articles concerning 20 different diseases met the inclusion criteria and were analyzed. Different types of programs were proposed: informative, interactive, cognitive-behavioral and programs concerning self-management of the disease and the treatment. These different approaches were sometimes compared. The use of quality Internet sites made it possible to induce beneficial changes in lifestyle habits, and to diminish subjective and/or objective symptom severity in chronic invalidating diseases when used as a complement to traditional management. By using the Internet, patients were also able to improve decision-making skills to a degree that was at least as good as that obtained using traditional paper documents. The Internet is an effective complementary tool that can contribute to improving therapeutic education. Nonetheless, healthcare professionals should work with patients to create quality sites that correspond more closely to their expectations. It is also essential for learned societies such as the SOFMER to invest in therapeutic education on the Internet to make quality therapeutic education modules based on factual medical data and complying with good practices available on line. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Mechanical Ventilation as a Therapeutic Tool to Reduce ARDS Incidence.

PubMed

Nieman, Gary F; Gatto, Louis A; Bates, Jason H T; Habashi, Nader M

2015-12-01

Trauma, hemorrhagic shock, or sepsis can incite systemic inflammatory response syndrome, which can result in early acute lung injury (EALI). As EALI advances, improperly set mechanical ventilation (MV) can amplify early injury into a secondary ventilator-induced lung injury that invariably develops into overt ARDS. Once established, ARDS is refractory to most therapeutic strategies, which have not been able to lower ARDS mortality below the current unacceptably high 40%. Low tidal volume ventilation is one of the few treatments shown to have a moderate positive impact on ARDS survival, presumably by reducing ventilator-induced lung injury. Thus, there is a compelling case to be made that the focus of ARDS management should switch from treatment once this syndrome has become established to the application of preventative measures while patients are still in the EALI stage. Indeed, studies have shown that ARDS incidence is markedly reduced when conventional MV is applied preemptively using a combination of low tidal volume and positive end-expiratory pressure in both patients in the ICU and in surgical patients at high risk for developing ARDS. Furthermore, there is evidence from animal models and high-risk trauma patients that superior prevention of ARDS can be achieved using preemptive airway pressure release ventilation with a very brief duration of pressure release. Preventing rather than treating ARDS may be the way forward in dealing with this recalcitrant condition and would represent a paradigm shift in the way that MV is currently practiced.

The role of the therapeutic alliance on pain relief in musculoskeletal rehabilitation: A systematic review.

PubMed

Taccolini Manzoni, Ana Carolina; Bastos de Oliveira, Naiane Teixeira; Nunes Cabral, Cristina Maria; Aquaroni Ricci, Natalia

2018-02-05

The aim of this systematic review was to investigate the role of therapeutic alliance in pain relief in patients with musculoskeletal disorders treated by physiotherapy. Manual and database searches (Medline, Embase, ISI Web of Knowledge, CINAHL, PEDro, Lilacs, Cochrane Library, and PsycINFO) were performed with no restrictions of language and publication date. We included prospective studies with samples of patients undergoing physiotherapy for musculoskeletal conditions, with one measure of therapeutic alliance and the outcome pain. Methodological quality was assessed by the Methodological Index for Nonrandomized Studies and the Cochrane tool for risk of bias. Six articles from four studies were included out of the 936 manuscripts identified. All studies used samples composed of patients with chronic low back pain. Two studies applied therapeutic alliance incentive measures during treatment and reported significant improvement in pain. The remaining studies, without alliance incentives, showed divergence regarding the relationship between the therapeutic alliance and pain. Methodological quality analysis determined low risk of bias of the studies. A lack of studies on the therapeutic alliance regarding musculoskeletal physiotherapy was verified. Existing studies fail to provide evidence of a strong relationship between the therapeutic alliance and pain relief.

Safe injection practice among health care workers, Gharbiya, Egypt.

PubMed

Ismail, Nanees A; Aboul Ftouh, Aisha M; El Shoubary, Waleed H

2005-01-01

A cross-sectional study was conducted in 25 health care facilities in Gharbiya governorate to assess safe injection practices among health care workers (HCWs). Two questionnaires, one to collect information about administrative issues related to safe injection and the other to collect data about giving injections, exposure to needle stick injuries, hepatitis B vaccination status and safe injection training. Practices of injections were observed using a standardized checklist. The study revealed that there was lack of both national and local infection control policies and lack of most of the supplies needed for safe injection practices. Many safe practices were infrequent as proper needle manipulation before disposal (41%), safe needle disposal (47.5%), reuse of used syringe & needle (13.2%) and safe syringe disposal (0%). Exposure to needle stick injuries were common among the interviewed HCWs (66.2%) and hand washing was the common post exposure prophylaxis measure (63.4%). Only 11.3% of HCWs had full course hepatitis B vaccination. Infection control -including safe injections- training programs should be afforded to all HCWs.

Nanotechnology Cancer Therapy and Treatment

Cancer.gov

Nanotechnology offers the means to target therapies directly and selectively to cancerous cells and neoplasms. With these tools, clinicians can safely and effectively deliver chemotherapy, radiotherapy, and the next generation of immuno- and gene therapies to the tumor. Futhermore, surgical resection of tumors can be guided and enhanced by way of nanotechnology tools. Find out how nanotechnology will offer the next generation of our therapeutic arsenal to the patient.

Safe handling of antineoplastic drugs.

PubMed

Harrison, B R

1994-07-01

Managers should be aware of the hazardous properties of antineoplastic drugs and of the procedures and equipment commonly recommended to provide a safe working environment for employees, patients, and visitors. Compliance with the many published guidelines should help ensure passage of the inevitable Occupational Safety and Health Administration (OSHA) or Joint Commission inspection. Acute and chronic toxicities of the antineoplastic drugs, the potential for exposure in the workplace, and the basic guidelines for safe handling of these agents are reviewed.

Evolving Role of Natriuretic Peptides from Diagnostic Tool to Therapeutic Modality.

PubMed

Pagel-Langenickel, Ines

2018-01-01

Natriuretic peptides (NP) are widely recognized as key regulators of blood pressure, water and salt homeostasis. In addition, they play a critical role in physiological cardiac growth and mediate a variety of biological effects including antiproliferative and anti-inflammatory effects in other organs and tissues. The cardiac release of NPs ANP and BNP represents an important compensatory mechanism during acute and chronic cardiac overload and during the pathogenesis of heart failure where their actions counteract the sustained activation of renin-angiotensin-aldosterone and other neurohormonal systems. Elevated circulating plasma NP levels correlate with the severity of heart failure and particularly BNP and the pro-peptide, NT-proBNP have been established as biomarkers for the diagnosis of heart failure as well as prognostic markers for cardiovascular risk. Despite activation of the NP system in heart failure it is inadequate to prevent progressive fluid and sodium retention and cardiac remodeling. Therapeutic approaches included administration of synthetic peptide analogs and the inhibition of NP-degrading enzyme neutral endopeptidase (NEP). Of all strategies only the combined NEP/ARB inhibition with sacubitril/valsartan had shown clinical success in reducing cardiovascular mortality and morbidity in patients with heart failure.

SafeNet: a methodology for integrating general-purpose unsafe devices in safe-robot rehabilitation systems.

PubMed

Vicentini, Federico; Pedrocchi, Nicola; Malosio, Matteo; Molinari Tosatti, Lorenzo

2014-09-01

Robot-assisted neurorehabilitation often involves networked systems of sensors ("sensory rooms") and powerful devices in physical interaction with weak users. Safety is unquestionably a primary concern. Some lightweight robot platforms and devices designed on purpose include safety properties using redundant sensors or intrinsic safety design (e.g. compliance and backdrivability, limited exchange of energy). Nonetheless, the entire "sensory room" shall be required to be fail-safe and safely monitored as a system at large. Yet, sensor capabilities and control algorithms used in functional therapies require, in general, frequent updates or re-configurations, making a safety-grade release of such devices hardly sustainable in cost-effectiveness and development time. As such, promising integrated platforms for human-in-the-loop therapies could not find clinical application and manufacturing support because of lacking in the maintenance of global fail-safe properties. Under the general context of cross-machinery safety standards, the paper presents a methodology called SafeNet for helping in extending the safety rate of Human Robot Interaction (HRI) systems using unsafe components, including sensors and controllers. SafeNet considers, in fact, the robotic system as a device at large and applies the principles of functional safety (as in ISO 13489-1) through a set of architectural procedures and implementation rules. The enabled capability of monitoring a network of unsafe devices through redundant computational nodes, allows the usage of any custom sensors and algorithms, usually planned and assembled at therapy planning-time rather than at platform design-time. A case study is presented with an actual implementation of the proposed methodology. A specific architectural solution is applied to an example of robot-assisted upper-limb rehabilitation with online motion tracking. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Advances in therapeutic CRISPR/Cas9 genome editing.

PubMed

Savić, Nataša; Schwank, Gerald

2016-02-01

Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in vivo in animal models and ex vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports. Copyright © 2016 Elsevier Inc. All rights reserved.

Structurally Based Therapeutic Evaluation: A Therapeutic and Practical Approach to Teaching Medicinal Chemistry.

ERIC Educational Resources Information Center

Alsharif, Naser Z.; And Others

1997-01-01

Explains structurally based therapeutic evaluation of drugs, which uses seven therapeutic criteria in translating chemical and structural knowledge into therapeutic decision making in pharmaceutical care. In a Creighton University (Nebraska) medicinal chemistry course, students apply the approach to solve patient-related therapeutic problems in…

77 FR 31147 - National Safe Boating Week, 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... Safe Boating Week, 2012 By the President of the United States of America A Proclamation For generations... friends and family a well- loved tradition. During National Safe Boating Week, we renew our commitment to... mark National Safe Boating Week, let us reflect on that important mission and resolve to do our part to...

Petroleum Jelly: Safe for a Dry Nose?

MedlinePlus

... dryness. Is this safe? Answers from Lawrence E. Gibson, M.D. Petroleum jelly is generally safe to ... several hours of lying down. With Lawrence E. Gibson, M.D. Marchiori E, et al. Exogenous lipoid ...

Taking Medicines Safely: At Your Doctor's Office

MedlinePlus

... on. Feature: Taking Medicines Safely At Your Doctor's Office Past Issues / Summer 2013 Table of Contents Download ... Articles Medicines: Use Them Safely / At Your Doctor's Office / Ask Your Pharmacist / Now, It's Your Turn: How ...

Medication overuse headache: withdrawal and prophylactic therapeutic regimen.

PubMed

Trucco, Marco; Meineri, Piero; Ruiz, Luigi; Gionco, Maurizio

2010-06-01

statistically significant. The protocol was generally effective, safe, and well-tolerated. The results tend to remain stable with time, and seem to be encouraging about long-term use of this therapeutic protocol on a larger number of patients suffering from MOH.

Improving Antibody-Based Cancer Therapeutics Through Glycan Engineering.

PubMed

Yu, Xiaojie; Marshall, Michael J E; Cragg, Mark S; Crispin, Max

2017-06-01

Antibody-based therapeutics has emerged as a major tool in cancer treatment. Guided by the superb specificity of the antibody variable domain, it allows the precise targeting of tumour markers. Recently, eliciting cellular effector functions, mediated by the Fc domain, has gained traction as a means by which to generate more potent antibody therapeutics. Extensive mutagenesis studies of the Fc protein backbone has enabled the generation of Fc variants that more optimally engage the Fcγ receptors known to mediate cellular effector functions such as antibody-dependent cellular cytotoxicity (ADCC) and cellular phagocytosis. In addition to the protein backbone, the homodimeric Fc domain contains two opposing N-linked glycans, which represent a further point of potential immunomodulation, independent of the Fc protein backbone. For example, a lack of core fucose usually attached to the IgG Fc glycan leads to enhanced ADCC activity, whereas a high level of terminal sialylation is associated with reduced inflammation. Significant growth in knowledge of Fc glycosylation over the last decade, combined with advancement in genetic engineering, has empowered glyco-engineering to fine-tune antibody therapeutics. This has culminated in the approval of two glyco-engineered antibodies for cancer therapy: the anti-CCR4 mogamulizumab approved in 2012 and the anti-CD20 obinutuzumab in 2013. We discuss here the technological platforms for antibody glyco-engineering and review the current clinical landscape of glyco-engineered antibodies.

Extended-Interval Gentamicin Dosing in Achieving Therapeutic Concentrations in Malaysian Neonates

PubMed Central

Tan, Sin Li; Wan, Angeline SL

2015-01-01

OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital. METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA. RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13–8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48–0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62–0.68 L/kg), 6.96 hours (95% CI, 6.52–7.40 hours), and 0.11 hour−1 (95% CI, 0.10–0.11 hour−1), respectively. CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates. PMID:25964729

Progression of Ebola Therapeutics During the 2014-2015 Outbreak.

PubMed

Mendoza, Emelissa J; Qiu, Xiangguo; Kobinger, Gary P

2016-02-01

The recent Ebola virus (EBOV) outbreak in West Africa was the deadliest EBOV epidemic in history, highlighting the need for a safe and efficacious treatment against EBOV disease (EVD). In the absence of an approved treatment, experimental drugs were utilized under compassionate grounds hoping to diminish EVD-associated morbidity and mortality. As more data were collected from safety studies, Phase II/III clinical trials were introduced in Guinea, Sierra Leone, and Liberia to test promising candidates, including small-molecule drugs, RNA-based treatments, and antibody-based therapies. In this review, we summarize the use of, and preliminary observations from, current clinical trials with EVD therapeutics, shedding light on experimental drug selection, emergency clinical evaluation, and the impact these factors may have on future infectious disease outbreaks. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Mitochondrial metals as a potential therapeutic target in neurodegeneration

PubMed Central

Grubman, A; White, A R; Liddell, J R

2014-01-01

Transition metals are critical for enzyme function and protein folding, but in excess can mediate neurotoxic oxidative processes. As mitochondria are particularly vulnerable to oxidative damage due to radicals generated during ATP production, mitochondrial biometal homeostasis must therefore be tightly controlled to safely harness the redox potential of metal enzyme cofactors. Dysregulation of metal functions is evident in numerous neurological disorders including Alzheimer's disease, stroke, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis and Friedrich's ataxia. This review describes the mitochondrial metal defects in these disorders and highlights novel metal-based therapeutic approaches that target mitochondrial metal homeostasis in neurological disorders. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24206195

Self-Assembly of pH-Responsive Microspheres for Intestinal Delivery of Diverse Lipophilic Therapeutics.

PubMed

Zhou, Xing; Zhao, Yang; Chen, Siyu; Han, Songling; Xu, Xiaoqiu; Guo, Jiawei; Liu, Mengyu; Che, Ling; Li, Xiaohui; Zhang, Jianxiang

2016-08-08

Targeted delivery of therapeutics to the intestine is preferred for the management of many diseases due to its diverse advantages. Currently, there are still challenges in creating cost-effective and translational pH-responsive microspheres for intestinal delivery of various hydrophobic drugs. Herein we report a multiple noncovalent interactions-mediated assembly strategy in which carboxyl-bearing compounds (CBCs) are guest molecules, while poly(N-isopropylacrylamide) (PNIPAm) serves as a host polymer. Formation of microparticles and therapeutic packaging can be achieved simultaneously by this assembly approach, leading to well-shaped microspheres with extremely higher drug loading capacity as compared to microspheres based on two FDA-approved materials of poly(d,l-lactide-co-glycolide) (PLGA) and an enteric coating polymer EudragitS 100 (S100). Also, carboxyl-deficient hydrophobic drugs can be effectively entrapped. These assembled microspheres, with excellent reconstitution capability as well as desirable scalability, could selectively release drug molecules under intestinal conditions. By significantly enhancing drug dissolution/release in the intestine, these pH-responsive assemblies may notably improve the oral bioavailability of loaded therapeutics. Moreover, the assembled microspheres possessed superior therapeutic performance in rodent models of inflammation and tumor over the control microspheres derived from PLGA and S100. Therapy with newly developed microspheres did not cause undesirable side effects. Furthermore, in vivo evaluation in mice revealed the carrier material PNIPAm was safe for oral delivery at doses as high as 10 g/kg. Collectively, our findings demonstrated that this type of pH-responsive microsphere may function as superior and translational intestine-directed delivery systems for a diverse array of therapeutics.

Functional and Therapeutic Indications of Liposuction: Personal Experience and Review of the Literature.

PubMed

Atiyeh, Bishara; Costagliola, Michel; Illouz, Yves-Gerard; Dibo, Saad; Zgheib, Elias; Rampillon, Florence

2015-08-01

Liposuction is the most common cosmetic surgical procedure worldwide. It has evolved from being designed primarily for body contouring to becoming essential adjunct to various other aesthetic procedures, greatly enhancing their outcome. Despite its hard clear differentiation between an aesthetic and therapeutic indication for some pathologic conditions, liposuction has been increasingly applied to a gamut of disorders as a therapeutic tool or to improve function. In fact, liposuction has ceased to define a specific procedure and became synonymous to a surgical technique or tool same as the surgical knife, laser, electrocautery, suture material, or even wound-dressing products. At present, there seems to be an enormous potential for the application of the basic liposuction technique in ablative and reconstructive surgery outside the realm of purely aesthetic procedures. The present review contemplates the various nonaesthetic applications of liposuction, displaying the enormous potentials of what should be considered a basic surgical technique rather than a specific aesthetic procedure. Implications of this new definition of liposuction should induce third-party public payers and insurance companies to reconsider their remuneration and reimbursement policies.

Safe motherhood -- from advocacy to action.

PubMed

Tinker, A

1991-12-01

Every minute a woman dies from complications related to pregnancy or childbirth. That translates to 500,000 annually, of which, 99% live in developing countries. A woman in Africa has a 1:18 lifetime chance of dying from pregnancy-related causes, compared with a northern European woman who has a 1:10,000 chance. Thus, in 1987 international and regional agencies and national governments started a global program titled the Safe Motherhood Initiative. Its goal is to reduce maternal morbidity and mortality 50% by 2000. The death of a woman during pregnancy or child birth means that her surviving children are much more likely to die. In a bangladesh study it was found that the death of the mother was associated with a 200% increase in mortality for her sons and 350% for her daughters for children up to 10. Family planning is the key, since it is the single best tool of preventing these deaths, by reducing the number of times a woman gets pregnant. Family planning also reduces the number of abortions which are estimated to kill 200,000 women annually in developing countries. Trained midwives who can provide obstetrical emergency assistance will also make a large impact. Risk assessment was once considered very important, but studies have shown that the majority of pregnancy complications develop without being detected. Further, the number of women with risk factors that develop complications is much lower than the number of women who develop complications during pregnancy. So monitoring women with risk factors misses most complications. Regular monitoring and medical examinations are much more effective for preventing complications. Safe motherhood can only be achieved if each program is tailored to the needs of the community. Donor nations are necessary for this program to succeed, but ultimate success rests in the hands of each country. National priorities must be set, resources must be allocated, and programs must be designed to be effective.

Safe and effective prescription of exercise in acute exacerbations of chronic obstructive pulmonary disease: rationale and methods for an integrated knowledge translation study.

PubMed

Camp, Pat; Reid, W Darlene; Yamabayashi, Cristiane; Brooks, Dina; Goodridge, Donna; Chung, Frank; Marciniuk, Darcy D; Neufeld, Andrea; Hoens, Alsion

2013-01-01

Patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) engage in low levels of activity, putting them at risk for relapse and future readmissions. There is little direction for health care providers regarding the parameters for safe exercise during an AECOPD that is effective for increasing activity tolerance before discharge from hospital, especially for patients with associated comorbid conditions. To report the rationale for and methods of a study to develop evidence-informed care recommendations that guide health care providers in the assessment, prescription, monitoring and progression of exercise for patients hospitalized with AECOPD. The present study was a multicomponent knowledge translation project incorporating evidence from systematic reviews of exercise involving populations with chronic obstructive pulmonary disease and⁄or common comorbidities. A Delphi process was then used to obtain expert opinion from clinicians, academics and patients to identify the parameters of safe and effective exercise for patients with AECOPD. Clinical decision-making tool(s) for patients and practitioners supported by a detailed knowledge dissemination, implementation and evaluation framework. The present study addressed an important knowledge gap: the lack of availability of parameters to guide safe and effective exercise prescription for hospitalized patients with AECOPD, with or without comorbid conditions. In the absence of such parameters, health care professionals may adopt an 'activity as tolerated' approach, which may not improve physical activity levels in their patients. The present study synthesizes the best available evidence and expert opinion, and will generate decision-making tools for use by patients and their health care providers.

CRISPR-Cas9 gene editing: Delivery aspects and therapeutic potential.

PubMed

Oude Blenke, Erik; Evers, Martijn J W; Mastrobattista, Enrico; van der Oost, John

2016-12-28

The CRISPR-Cas9 gene editing system has taken the biomedical science field by storm, initiating rumors about future Nobel Prizes and heating up a fierce patent war, but also making significant scientific impact. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), together with CRISPR-associated proteins (Cas) are a part of the prokaryotic adaptive immune system and have successfully been repurposed for genome editing in mammalian cells. The CRISPR-Cas9 system has been used to correct genetic mutations and for replacing entire genes, opening up a world of possibilities for the treatment of genetic diseases. In addition, recently some new CRISPR-Cas systems have been discovered with interesting mechanistic variations. Despite these promising developments, many challenges have to be overcome before the system can be applied therapeutically in human patients and enabling delivery technology is one of the key challenges. Furthermore, the relatively high off-target effect of the system in its current form prevents it from being safely applied directly in the human body. In this review, the transformation of the CRISPR-Cas gene editing systems into a therapeutic modality will be discussed and the currently most realistic in vivo applications will be highlighted. Copyright © 2016 Elsevier B.V. All rights reserved.

Hepatocellular carcinoma and microRNA: new perspectives on therapeutics and diagnostics.

PubMed

Yang, Ningning; Ekanem, Nsikak R; Sakyi, Clement A; Ray, Sidhartha D

2015-01-01

Hepatocellular carcinoma (HCC) remains one of the most lethal forms of cancer in the world. In this arena, utilities of microRNA (miRNA) as a sophisticated tool, in therapeutics and diagnostics, remains a prime focus among the leading researchers. It is well known that viral hepatitis, chronic alcoholism and metabolic syndrome are the prime causes of HCCs. Nevertheless, HCCs are usually diagnosed at late stages by using current serum biomarkers. Most epidemiological studies have found the survival rate in HCC cases to be relatively low. Therefore, development of effective noninvasive biomarkers for early detention of HCC and new strategies for HCC treatment remains a high priority research area on the shoulders of liver oncologists. Accumulating evidence in cancer diagnostics and therapeutics indicates that miRNAs involve in HCC progression, which may serve as sensitive biomarkers for detecting carcinogenesis and monitoring therapies of HCC. This review focuses on the role of miRNAs in the diagnostics and therapeutics of HCC. Copyright © 2014 Elsevier B.V. All rights reserved.

Safe prescribing: a titanic challenge.

PubMed

Routledge, Philip A

2012-10-01

The challenge to achieve safe prescribing merits the adjective 'titanic'. The organisational and human errors leading to poor prescribing (e.g. underprescribing, overprescribing, misprescribing or medication errors) have parallels in the organisational and human errors that led to the loss of the Titanic 100 years ago this year. Prescribing can be adversely affected by communication failures, critical conditions, complacency, corner cutting, callowness and a lack of courage of conviction, all of which were also factors leading to the Titanic tragedy. These issues need to be addressed by a commitment to excellence, the final component of the 'Seven C's'. Optimal prescribing is dependent upon close communication and collaborative working between highly trained health professionals, whose role is to ensure maximum clinical effectiveness, whilst also protecting their patients from avoidable harm. Since humans are prone to error, and the environments in which they work are imperfect, it is not surprising that medication errors are common, occurring more often during the prescribing stage than during dispensing or administration. A commitment to excellence in prescribing includes a continued focus on lifelong learning (including interprofessional learning) in pharmacology and therapeutics. This should be accompanied by improvements in the clinical working environment of prescribers, and the encouragement of a strong safety culture (including reporting of adverse incidents as well as suspected adverse drug reactions whenever appropriate). Finally, members of the clinical team must be prepared to challenge each other, when necessary, to ensure that prescribing combines the highest likelihood of benefit with the lowest potential for harm. © 2012 The Author. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor

PubMed Central

Wu, Chia-Yung; Roybal, Kole T.; Puchner, Elias M.; Onuffer, James; Lim, Wendell A.

2016-01-01

There is growing promise in using engineered cells as therapeutic agents. For example, synthetic Chimeric Antigen Receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, excessive activity and poor control over such engineered T cells can cause severe toxicities. We present the design of “ON-switch” CARs that enable small molecule-control over T cell therapeutic functions, while still retaining antigen specificity. In these split receptors, antigen binding and intracellular signaling components only assemble in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate both cell autonomous recognition and user control. PMID:26405231

Chaperoning G Protein-Coupled Receptors: From Cell Biology to Therapeutics

PubMed Central

Conn, P. Michael

2014-01-01

G protein-coupled receptors (GPCRs) are membrane proteins that traverse the plasma membrane seven times (hence, are also called 7TM receptors). The polytopic structure of GPCRs makes the folding of GPCRs difficult and complex. Indeed, many wild-type GPCRs are not folded optimally, and defects in folding are the most common cause of genetic diseases due to GPCR mutations. Both general and receptor-specific molecular chaperones aid the folding of GPCRs. Chemical chaperones have been shown to be able to correct the misfolding in mutant GPCRs, proving to be important tools for studying the structure-function relationship of GPCRs. However, their potential therapeutic value is very limited. Pharmacological chaperones (pharmacoperones) are potentially important novel therapeutics for treating genetic diseases caused by mutations in GPCR genes that resulted in misfolded mutant proteins. Pharmacoperones also increase cell surface expression of wild-type GPCRs; therefore, they could be used to treat diseases that do not harbor mutations in GPCRs. Recent studies have shown that indeed pharmacoperones work in both experimental animals and patients. High-throughput assays have been developed to identify new pharmacoperones that could be used as therapeutics for a number of endocrine and other genetic diseases. PMID:24661201

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Which therapeutic strategy will achieve a cure for HIV-1?

PubMed

Cillo, Anthony R; Mellors, John W

2016-06-01

Strategies to achieve a cure for HIV-1 infection can be broadly classified into three categories: eradication cure (elimination of all viral reservoirs), functional cure (immune control without reservoir eradication), or a hybrid cure (reservoir reduction with improved immune control). The many HIV-1 cure strategies being investigated include modification of host cells to resist HIV-1, engineered T cells to eliminate HIV-infected cells, broadly HIV-1 neutralizing monoclonal antibodies, and therapeutic vaccination, but the 'kick and kill' strategy to expose latent HIV-1 with latency reversing agents (LRAs) and kill the exposed cells through immune effector functions is currently the most actively pursued. It is unknown, however, whether LRAs can deplete viral reservoirs in vivo or whether current LRAs are sufficiently safe for clinical use. Copyright © 2016. Published by Elsevier B.V.

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

Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

PubMed

Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

2017-07-01

For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

Microgravity as a biological tool to examine host-pathogen interactions and to guide development of therapeutics and preventatives that target pathogenic bacteria.

PubMed

Higginson, Ellen E; Galen, James E; Levine, Myron M; Tennant, Sharon M

2016-11-01

Space exploration programs have long been interested in the effects of spaceflight on biology. This research is important not only in its relevance to future deep space exploration, but also because it has allowed investigators to ask questions about how gravity impacts cell behavior here on Earth. In the 1980s, scientists designed and built the first rotating wall vessel, capable of mimicking the low shear environment found in space. This vessel has since been used to investigate growth of both microorganisms and human tissue cells in low shear modeled microgravity conditions. Bacterial behavior has been shown to be altered both in space and under simulated microgravity conditions. In some cases, bacteria appear attenuated, whereas in others virulence is enhanced. This has consequences not only for manned spaceflight, but poses larger questions about the ability of bacteria to sense the world around them. By using the microgravity environment as a tool, we can exploit this phenomenon in the search for new therapeutics and preventatives against pathogenic bacteria for use both in space and on Earth. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Implementation of Safe-by-Design for Nanomaterial Development and Safe Innovation: Why We Need a Comprehensive Approach

PubMed Central

Kraegeloh, Annette; Suarez-Merino, Blanca; Sluijters, Teun; Micheletti, Christian

2018-01-01

Manufactured nanomaterials (MNMs) are regarded as key components of innovations in various fields with high potential impact (e.g., energy generation and storage, electronics, photonics, diagnostics, theranostics, or drug delivery agents). Widespread use of MNMs raises concerns about their safety for humans and the environment, possibly limiting the impact of the nanotechnology-based innovation. The development of safe MNMs and nanoproducts has to result in a safe as well as functional material or product. Its safe use, and disposal at the end of its life cycle must be taken into account too. However, not all MNMs are similarly useful for all applications, some might bear a higher hazard potential than others, and use scenarios could lead to different exposure probabilities. To improve both safety and efficacy of nanotechnology, we think that a new proactive approach is necessary, based on pre-regulatory safety assessment and dialogue between stakeholders. On the basis of the work carried out in different European Union (EU) initiatives, developing and integrating MNMs Safe-by-Design and Trusted Environments (NANoREG, ProSafe, and NanoReg2), we present our point of view here. This concept, when fully developed, will allow for cost effective industrial innovation, and an exchange of key information between regulators and innovators. Regulators are thus informed about incoming innovations in good time, supporting a proactive regulatory action. The final goal is to contribute to the nanotechnology governance, having faster, cheaper, effective, and safer nano-products on the market. PMID:29661997

Implementation of Safe-by-Design for Nanomaterial Development and Safe Innovation: Why We Need a Comprehensive Approach.

PubMed

Kraegeloh, Annette; Suarez-Merino, Blanca; Sluijters, Teun; Micheletti, Christian

2018-04-14

Manufactured nanomaterials (MNMs) are regarded as key components of innovations in various fields with high potential impact (e.g., energy generation and storage, electronics, photonics, diagnostics, theranostics, or drug delivery agents). Widespread use of MNMs raises concerns about their safety for humans and the environment, possibly limiting the impact of the nanotechnology-based innovation. The development of safe MNMs and nanoproducts has to result in a safe as well as functional material or product. Its safe use, and disposal at the end of its life cycle must be taken into account too. However, not all MNMs are similarly useful for all applications, some might bear a higher hazard potential than others, and use scenarios could lead to different exposure probabilities. To improve both safety and efficacy of nanotechnology, we think that a new proactive approach is necessary, based on pre-regulatory safety assessment and dialogue between stakeholders. On the basis of the work carried out in different European Union (EU) initiatives, developing and integrating MNMs Safe-by-Design and Trusted Environments (NANoREG, ProSafe, and NanoReg2), we present our point of view here. This concept, when fully developed, will allow for cost effective industrial innovation, and an exchange of key information between regulators and innovators. Regulators are thus informed about incoming innovations in good time, supporting a proactive regulatory action. The final goal is to contribute to the nanotechnology governance, having faster, cheaper, effective, and safer nano-products on the market.

Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

NASA Astrophysics Data System (ADS)

Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

2010-02-01

Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

Drosophila eye color mutants as therapeutic tools for Huntington disease.

PubMed

Green, Edward W; Campesan, Susanna; Breda, Carlo; Sathyasaikumar, Korrapati V; Muchowski, Paul J; Schwarcz, Robert; Kyriacou, Charalambos P; Giorgini, Flaviano

2012-01-01

Huntington disease (HD) is a fatal inherited neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein (htt). A pathological hallmark of the disease is the loss of a specific population of striatal neurons, and considerable attention has been paid to the role of the kynurenine pathway (KP) of tryptophan (TRP) degradation in this process. The KP contains three neuroactive metabolites: 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and kynurenic acid (KYNA). 3-HK and QUIN are neurotoxic, and are increased in the brains of early stage HD patients, as well as in yeast and mouse models of HD. Conversely, KYNA is neuroprotective and has been shown to be decreased in HD patient brains. We recently used a Drosophila model of HD to measure the neuroprotective effect of genetic and pharmacological inhibition of kynurenine monoxygenase (KMO)-the enzyme catalyzing the formation of 3-HK at a pivotal branch point in the KP. We found that KMO inhibition in Drosophila robustly attenuated neurodegeneration, and that this neuroprotection was correlated with reduced levels of 3-HK relative to KYNA. Importantly, we showed that KP metabolites are causative in this process, as 3-HK and KYNA feeding experiments modulated neurodegeneration. We also found that genetic inhibition of the upstream KP enzyme tryptophan-2,3-dioxygenase (TDO) was neuroprotective in flies. Here, we extend these results by reporting that genetic impairment of KMO or TDO is protective against the eclosion defect in HD model fruit flies. Our results provide further support for the possibility of therapeutic KP interventions in HD.

Environmentally safe fluid extractor

DOEpatents

Sungaila, Zenon F.

1993-01-01

An environmentally safe fluid extraction device for use in mobile laboratory and industrial settings comprising a pump, compressor, valving system, waste recovery tank, fluid tank, and a exhaust filtering system.

Environmentally safe fluid extractor

DOEpatents

Sungaila, Zenon F.

1993-07-06

An environmentally safe fluid extraction device for use in mobile laboratory and industrial settings comprising a pump, compressor, valving system, waste recovery tank, fluid tank, and a exhaust filtering system.

End-to-End Demonstrator of the Safe Affordable Fission Engine (SAFE) 30: Power Conversion and Ion Engine Operation

NASA Technical Reports Server (NTRS)

Hrbud, Ivana; VanDyke, Melissa; Houts, Mike; Goodfellow, Keith; Schafer, Charles (Technical Monitor)

2001-01-01

The Safe Affordable Fission Engine (SAFE) test series addresses Phase 1 Space Fission Systems issues in particular non-nuclear testing and system integration issues leading to the testing and non-nuclear demonstration of a 400-kW fully integrated flight unit. The first part of the SAFE 30 test series demonstrated operation of the simulated nuclear core and heat pipe system. Experimental data acquired in a number of different test scenarios will validate existing computational models, demonstrated system flexibility (fast start-ups, multiple start-ups/shut downs), simulate predictable failure modes and operating environments. The objective of the second part is to demonstrate an integrated propulsion system consisting of a core, conversion system and a thruster where the system converts thermal heat into jet power. This end-to-end system demonstration sets a precedent for ground testing of nuclear electric propulsion systems. The paper describes the SAFE 30 end-to-end system demonstration and its subsystems.

Therapeutic robotics for children with disabilities: a case study.

PubMed

Drane, James; Safos, Charlotte; Lathan, Corinna E

2009-01-01

The advancement of technology is having a profound effect on enhancing the lives of children with disabilities. As advances in biomedical technology allow research breakthroughs to continue at a steady pace, more and more is being discovered about the nature of different disorders in children. At the same time, partly due to the continuing rapid rate of advancement (and societal acceptance) of robotics technology, researchers, educators, and therapists are exploring the idea that robots might be used as an effective therapeutic and educational tool. Over the past nine years, AnthroTronix has collaborated extensively with therapists, educators, researchers, parents, and children to uncover the therapeutic and educational benefits of including robotics as part of rehabilitation curriculum for children. As a central part of this effort, the company has worked with its colleagues to develop and refine the CosmoBot system, an interactive robotic toolkit designed to enhance therapy, education, and play for children with disabilities.

Preclinical and clinical development of siRNA-based therapeutics

PubMed Central

Ozcan, Gulnihal; Ozpolat, Bulent; Coleman, Robert L.; Sood, Anil K.; Lopez-Berestein, Gabriel

2015-01-01

Discovery of RNA interference, first in plants and C. elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment. PMID:25666164

Results of 30 kWt Safe Affordable Fission Engine (SAFE-30) primary heat transport testing

NASA Astrophysics Data System (ADS)

Pedersen, Kevin; van Dyke, Melissa; Houts, Mike; Godfroy, Tom; Martin, James; Dickens, Ricky; Williams, Eric; Harper, Roger; Salvil, Pat; Reid, Bob

2001-02-01

The use of resistance heaters to simulate heat from fission allows extensive development of fission systems to be performed in non-nuclear test facilities, saving time and money. Resistance heated tests on the Safe Affordable Fission Engine-30 kilowatt (SAFE30) test article are being performed at the Marshall Space Flight Center. This paper discusses the results of these experiments to date, and describes the additional testing that will be performed. Recommendations related to the design of testable space fission power and propulsion systems are made. .

Keeping Campuses Safe.

ERIC Educational Resources Information Center

Kennedy, Mike

1999-01-01

Describes how colleges and universities are using technology, as well as traditional methods, to keep campuses safe and reduce crime. Topics include using free pizza in a successful contest to teach students about campus safety, installing security cameras, using access-control cards, providing adequate lighting, and creating a bicycle patrol…

Development of a therapeutic vaccine for the treatment of cocaine addiction.

PubMed

Fox, B S

1997-12-15

No pharmacotherapies have yet been approved for the treatment of cocaine addiction. One new approach is to block the effects of cocaine with anti-cocaine antibodies induced by a therapeutic cocaine vaccine. A cocaine vaccine has been developed which induces a cocaine-specific antibody response in rodents. The antibody binds to cocaine in the circulation and can be shown to inhibit the ability of cocaine to enter the brain. Furthermore, anti-cocaine antibody can inhibit cocaine self-administration in rats. These data suggest that a cocaine vaccine may be a powerful therapeutic tool. The intent is to immunized motivated patients with the vaccine as part of a comprehensive treatment program. If the patient uses cocaine after being vaccinated, the antibody will inhibit the reinforcing activity of cocaine and decrease the likelihood of relapse.

Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

PubMed

Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

2017-01-06

Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

Safe Hazmat Storage Tips.

ERIC Educational Resources Information Center

Neville, Angela

1996-01-01

Provides a list of recommendations for safely managing hazardous waste containers. Encourages training of employees on the hazards of the wastes they handle and the correct procedures for managing containers. (DDR)

Cyclodextrins: improving the therapeutic response of analgesic drugs: a patent review.

PubMed

de Oliveira, Makson G B; Guimarães, Adriana G; Araújo, Adriano A S; Quintans, Jullyana S S; Santos, Márcio R V; Quintans-Júnior, Lucindo J

2015-01-01

Cyclodextrins (CDs) are cyclic oligosaccharides that have recently been recognized as useful tools for optimizing the delivery of such problematic drugs. CDs can be found in at least 35 pharmaceutical products, such as anticancer agents, analgesic and anti-inflammatory drugs. Besides, several studies have demonstrated that CD-complexed drugs could provide benefits in solubility, stability and also improve pharmacological response when compared with the drug alone. The patent search was conducted in the databases WIPO, Espacenet, USPTO, Derwent and INPI, using the keywords cyclodextrin, pain and its related terms (analgesia, hyperalgesia, hypernociception, nociception, antinociception, antinociceptive). We found 442 patents. Criteria such as the complexation of analgesic agents and evidence of improvement of the therapeutic effect were indispensable for the inclusion of the patent. So, 18 patents were selected. We noticed that some patents are related to the complexation of opioids, NSAIDs, as well as natural products, in different types of CDs. The use of CDs creates the prospect of developing new therapeutic options for the most effective treatment of painful conditions, allowing a reduction of dosage of analgesic drugs and the occurrence of side effects. Thus, CDs can be an important tool to improve the efficacy and pharmacological profile of analgesic drugs.

Novel roles of complement in renal diseases and their therapeutic consequences.

PubMed

Wada, Takehiko; Nangaku, Masaomi

2013-09-01

The complement system functions as a part of the innate immune system. Inappropriate activation of the complement pathways has a deleterious effect on kidneys. Recent advances in complement research have provided new insights into the pathogenesis of glomerular and tubulointerstitial injury associated with complement activation. A new disease entity termed 'C3 glomerulopathy' has recently been proposed and is characterized by isolated C3 deposition in glomeruli without positive staining for immunoglobulins. Genetic and functional studies have demonstrated that several different mutations and disease variants, as well as the generation of autoantibodies, are potentially associated with its pathogenesis. The data from comprehensive analyses suggest that complement dysregulation can also be associated with hemolytic uremic syndrome and more common glomerular diseases, such as IgA nephropathy and diabetic kidney disease. In addition, animal studies utilizing genetically modified mice have begun to elucidate the molecular pathomechanisms associated with the complement system. From a diagnostic point of view, a noninvasive, MRI-based method for detecting C3 has recently been developed to serve as a novel tool for diagnosing complement-mediated kidney diseases. While novel therapeutic tools related to complement regulation are emerging, studies evaluating the precise roles of the complement system in kidney diseases will still be useful for developing new therapeutic approaches.

A photoacoustic tool for therapeutic drug monitoring of heparin (Conference Presentation)

NASA Astrophysics Data System (ADS)

Wang, Junxin; Hartanto, James; Jokerst, Jesse V.

2017-03-01

Heparin is used broadly in cardiac, pulmonary, surgical, and vascular medicine to treat thrombotic disorders with over 500 million doses per year globally. Despite this widespread use, it has a narrow therapeutic window and is one of the top three medication errors. The active partial thromboplastin time (PTT) monitors heparin, but this blood test suffers from long turnaround times, a variable reference range, and limited utility with low molecular weight heparin. Here, we describe an imaging technique that can monitor heparin concentration and activity in real time using photoacoustic spectroscopy via methylene blue as a simple and Federal Drug Agency-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood (R2>0.90). Clinically relevant concentrations were detected in blood with a heparin detection limit of 0.28 U/mL and a low molecular weight heparin (enoxaparin) detection limit of 72 μg/mL. We validated this imaging approach by correlation to the PTT (Pearson's r = 0.86; p<0.05) as well as with protamine sulfate treatment. To the best of our knowledge, this is the first report to use imaging data to monitor anticoagulation.

Shape memory alloy/shape memory polymer tools

DOEpatents

Seward, Kirk P.; Krulevitch, Peter A.

2005-03-29

Micro-electromechanical tools for minimally invasive techniques including microsurgery. These tools utilize composite shape memory alloy (SMA), shape memory polymer (SMP) and combinations of SMA and SMP to produce catheter distal tips, actuators, etc., which are bistable. Applications for these structures include: 1) a method for reversible fine positioning of a catheter tip, 2) a method for reversible fine positioning of tools or therapeutic catheters by a guide catheter, 3) a method for bending articulation through the body's vasculature, 4) methods for controlled stent delivery, deployment, and repositioning, and 5) catheters with variable modulus, with vibration mode, with inchworm capability, and with articulated tips. These actuators and catheter tips are bistable and are opportune for in vivo usage because the materials are biocompatible and convenient for intravascular use as well as other minimal by invasive techniques.

On the advancement of therapeutic penality: therapeutic authority, personality science and the therapeutic community.

PubMed

McBride, Ruari-Santiago

2017-09-01

In this article I examine the advancement of therapeutic penality in the UK, a penal philosophy that reimagines prison policy, practices and environments utilising psychological knowledge. Adopting a historical approach, I show how modern therapeutic penality is linked to the emergence of personality science in the nineteenth century and the development of the democratic therapeutic community (DTC) model in the twentieth century. I outline how at the turn of the twenty-first century a catalytic event generated a moral panic that led the British government to mobilise psychological knowledge and technologies in an attempt to manage dangerous people with severe personality disorder. Tracing subsequent developments, I argue psychological ways of talking, thinking and acting have obtained unparalleled salience in domains of penality and, in turn, radically transformed the conditions of imprisonment. © 2017 Foundation for the Sociology of Health & Illness.

Automatic discrimination between safe and unsafe swallowing using a reputation-based classifier

PubMed Central

2011-01-01

Background Swallowing accelerometry has been suggested as a potential non-invasive tool for bedside dysphagia screening. Various vibratory signal features and complementary measurement modalities have been put forth in the literature for the potential discrimination between safe and unsafe swallowing. To date, automatic classification of swallowing accelerometry has exclusively involved a single-axis of vibration although a second axis is known to contain additional information about the nature of the swallow. Furthermore, the only published attempt at automatic classification in adult patients has been based on a small sample of swallowing vibrations. Methods In this paper, a large corpus of dual-axis accelerometric signals were collected from 30 older adults (aged 65.47 ± 13.4 years, 15 male) referred to videofluoroscopic examination on the suspicion of dysphagia. We invoked a reputation-based classifier combination to automatically categorize the dual-axis accelerometric signals into safe and unsafe swallows, as labeled via videofluoroscopic review. From these participants, a total of 224 swallowing samples were obtained, 164 of which were labeled as unsafe swallows (swallows where the bolus entered the airway) and 60 as safe swallows. Three separate support vector machine (SVM) classifiers and eight different features were selected for classification. Results With selected time, frequency and information theoretic features, the reputation-based algorithm distinguished between safe and unsafe swallowing with promising accuracy (80.48 ± 5.0%), high sensitivity (97.1 ± 2%) and modest specificity (64 ± 8.8%). Interpretation of the most discriminatory features revealed that in general, unsafe swallows had lower mean vibration amplitude and faster autocorrelation decay, suggestive of decreased hyoid excursion and compromised coordination, respectively. Further, owing to its performance-based weighting of component classifiers, the static reputation

Inertial sensing microelectromechanical (MEM) safe-arm device

DOEpatents

Roesler, Alexander W [Tijeras, NM; Wooden, Susan M [Sandia Park, NM

2009-05-12

Microelectromechanical (MEM) safe-arm devices comprise a substrate upon which a sense mass, that can contain an energetic material, is constrained to move along a pathway defined by a track disposed on the surface of the substrate. The pathway has a first end comprising a "safe" position and a second end comprising an "armed" position, whereat the second end the sense mass can be aligned proximal to energetic materials comprising the explosive train, within an explosive component. The sense mass can be confined in the safe position by a first latch, operable to release the sense mass by an acceleration acting in a direction substantially normal to the surface of the substrate. A second acceleration, acting in a direction substantially parallel to the surface of the substrate, can cause the sense mass to traverse the pathway from the safe position to the armed position.

Functional Imaging for Prostate Cancer: Therapeutic Implications

PubMed Central

Aparici, Carina Mari; Seo, Youngho

2012-01-01

Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities CT or MRI (SPECT/CT, PET/CT, and PET/MRI) are promising tools for the management of prostate cancer particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection, to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regards to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, while the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects. PMID:22840598

Telomere biology: Rationale for diagnostics and therapeutics in cancer.

PubMed

Rousseau, Philippe; Autexier, Chantal

2015-01-01

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer.

Telomere biology: Rationale for diagnostics and therapeutics in cancer

PubMed Central

Rousseau, Philippe; Autexier, Chantal

2015-01-01

The key step of carcinogenesis is the malignant transformation which is fundamentally a telomere biology dysfunction permitting cells to bypass the Hayflick limit and to divide indefinitely and uncontrollably. Thus all partners and structures involved in normal and abnormal telomere maintenance, protection and lengthening can be considered as potential anti-cancer therapeutic targets. In this Point of View we discuss, highlight and provide new perspectives from the current knowledge and understanding to position the different aspects of telomere biology and dysfunction as diagnostic, preventive and curative tools in the field of cancer. PMID:26291128

Creating Safe Neighborhoods, Safe Streets, Safe Schools, [and] Safe Workplaces: Using Illinois' Drug Laws.

ERIC Educational Resources Information Center

Illinois Criminal Justice Information Authority, Chicago.

This handbook provides renters, homeowners, teachers, parents, and workers with tools for ridding their communities of illegal drugs. The booklet describes relevant anti-drug laws, and provides examples of how they are being used successfully in one state. The case studies cited almost always involve individuals and community groups working…

Karate: Keep It Safe.

ERIC Educational Resources Information Center

Jordan, David

1981-01-01

Safety guidelines for each phase of a karate practice session are presented to provide an accident-free and safe environment for teaching karate in a physical education or traditional karate training program. (JMF)

Prepare to protect: Operating and maintaining a tornado safe room.

PubMed

Herseth, Andrew; Goldsmith-Grinspoon, Jennifer; Scott, Pataya

2017-06-01

Operating and maintaining a tornado safe room can be critical to the effective continuity of business operations because a firm's most valuable asset is its people. This paper describes aspects of operations and maintenance (O&M) for existing tornado safe rooms as well as a few planning and design aspects that affect the ultimate operation of a safe room for situations where a safe room is planned, but not yet constructed. The information is based on several Federal Emergency Management Agency safe room publications that provide guidance on emergency management and operations, as well as the design and construction of tornado safe rooms.

Review of "Successful, Safe, and Healthy Students"

ERIC Educational Resources Information Center

Glass, Gene V.; Barnett, Steven; Welner, Kevin G.

2010-01-01

The research summary "Successful, Safe, and Healthy Students" presents the research background for the Obama administration's proposals for comprehensive, community-wide services in high-poverty neighborhoods, extended learning time, family engagement and safe schools. While these policies have broad and common-sense appeal, the research…

Engineered magnetic core shell nanoprobes: Synthesis and applications to cancer imaging and therapeutics.

PubMed

Mandal, Samir; Chaudhuri, Keya

2016-02-26

Magnetic core shell nanoparticles are composed of a highly magnetic core material surrounded by a thin shell of desired drug, polymer or metal oxide. These magnetic core shell nanoparticles have a wide range of applications in biomedical research, more specifically in tissue imaging, drug delivery and therapeutics. The present review discusses the up-to-date knowledge on the various procedures for synthesis of magnetic core shell nanoparticles along with their applications in cancer imaging, drug delivery and hyperthermia or cancer therapeutics. Literature in this area shows that magnetic core shell nanoparticle-based imaging, drug targeting and therapy through hyperthermia can potentially be a powerful tool for the advanced diagnosis and treatment of various cancers.

Taking multiple medicines safely

MedlinePlus

... medlineplus.gov/ency/patientinstructions/000883.htm Taking multiple medicines safely To use the sharing features on this ... directed. Why You May Need More Than One Medicine You may take more than one medicine to ...

Monitoring Moving Queries inside a Safe Region

PubMed Central

Al-Khalidi, Haidar; Taniar, David; Alamri, Sultan

2014-01-01

With mobile moving range queries, there is a need to recalculate the relevant surrounding objects of interest whenever the query moves. Therefore, monitoring the moving query is very costly. The safe region is one method that has been proposed to minimise the communication and computation cost of continuously monitoring a moving range query. Inside the safe region the set of objects of interest to the query do not change; thus there is no need to update the query while it is inside its safe region. However, when the query leaves its safe region the mobile device has to reevaluate the query, necessitating communication with the server. Knowing when and where the mobile device will leave a safe region is widely known as a difficult problem. To solve this problem, we propose a novel method to monitor the position of the query over time using a linear function based on the direction of the query obtained by periodic monitoring of its position. Periodic monitoring ensures that the query is aware of its location all the time. This method reduces the costs associated with communications in client-server architecture. Computational results show that our method is successful in handling moving query patterns. PMID:24696652

Safe speed limits for a safe system: The relationship between speed limit and fatal crash rate for different crash types.

PubMed

Doecke, Sam D; Kloeden, Craig N; Dutschke, Jeffrey K; Baldock, Matthew R J

2018-05-19

The objective of this article is to provide empirical evidence for safe speed limits that will meet the objectives of the Safe System by examining the relationship between speed limit and injury severity for different crash types, using police-reported crash data. Police-reported crashes from 2 Australian jurisdictions were used to calculate a fatal crash rate by speed limit and crash type. Example safe speed limits were defined using threshold risk levels. A positive exponential relationship between speed limit and fatality rate was found. For an example fatality rate threshold of 1 in 100 crashes it was found that safe speed limits are 40 km/h for pedestrian crashes; 50 km/h for head-on crashes; 60 km/h for hit fixed object crashes; 80 km/h for right angle, right turn, and left road/rollover crashes; and 110 km/h or more for rear-end crashes. The positive exponential relationship between speed limit and fatal crash rate is consistent with prior research into speed and crash risk. The results indicate that speed zones of 100 km/h or more only meet the objectives of the Safe System, with regard to fatal crashes, where all crash types except rear-end crashes are exceedingly rare, such as on a high standard restricted access highway with a safe roadside design.

Role of Metal and Metal Oxide Nanoparticles as Diagnostic and Therapeutic Tools for Highly Prevalent Viral Infections

PubMed Central

Yadavalli, Tejabhiram; Shukla, Deepak

2016-01-01

Nanotechnology is increasingly playing important roles in various fields including virology. The emerging use of metal or metal oxide nanoparticles in virus targeting formulations shows the promise of improved diagnostic or therapeutic ability of the agents while uniquely enhancing the prospects of targeted drug delivery. Although a number of nanoparticles varying in composition, size, shape, and surface properties have been approved for human use, the candidates being tested or approved for clinical diagnosis and treatment of viral infections are relatively less in number. Challenges remain in this domain due to a lack of essential knowledge regarding the in vivo comportment of nanoparticles during viral infections. This review provides a broad overview of recent advances in diagnostic, prophylactic and therapeutic applications of metal and metal oxide nanoparticles in Human Immunodeficiency Virus, Hepatitis virus, influenza virus and Herpes virus infections. Types of nanoparticles commonly used and their broad applications have been explained in this review. PMID:27575283

Remote control of therapeutic T cells through a small molecule-gated chimeric receptor.

PubMed

Wu, Chia-Yung; Roybal, Kole T; Puchner, Elias M; Onuffer, James; Lim, Wendell A

2015-10-16

There is growing interest in using engineered cells as therapeutic agents. For example, synthetic chimeric antigen receptors (CARs) can redirect T cells to recognize and eliminate tumor cells expressing specific antigens. Despite promising clinical results, these engineered T cells can exhibit excessive activity that is difficult to control and can cause severe toxicity. We designed "ON-switch" CARs that enable small-molecule control over T cell therapeutic functions while still retaining antigen specificity. In these split receptors, antigen-binding and intracellular signaling components assemble only in the presence of a heterodimerizing small molecule. This titratable pharmacologic regulation could allow physicians to precisely control the timing, location, and dosage of T cell activity, thereby mitigating toxicity. This work illustrates the potential of combining cellular engineering with orthogonal chemical tools to yield safer therapeutic cells that tightly integrate cell-autonomous recognition and user control. Copyright © 2015, American Association for the Advancement of Science.

[Complications and postoperative therapeutic strategies in cross-linking].

PubMed

Kohlhaas, M

2017-08-01

The reduced corneal mechanical stability in keratoconus and similar collagen diseases can lead to a progressive and irregular corneal shape and decrease of visual acuity. A progression of keratectatic diseases can be shown with corneal topography. Keratoconus can be treated by photo-oxidative cross-linking of the corneal collagen. In order to achieve a high absorption of irradiation energy in the cornea, riboflavin at a concentration of 0.1% and UVA light at a wavelength of 370 nm corresponding to the relative maximum absorption of riboflavin (vitamin B2) are used. Evidence for corneal cross-linking are the increase of biomechanical stiffness, the increased resistance against enzymatic degradation, a higher shrinkage temperature, a lower swelling rate and an increased diameter of collagen fibers. The currently available data demonstrate that the therapeutic cross-linking procedure is safe when respecting the important theoretical and clinical parameters and that a progression of the keratoconus can be avoided. In 80% of cases an average levelling of the curvature of approximately 2 dpt can be achieved, which leads not only to stabilization but also to an increase in visual acuity of approximately 1.2 lines. In a Cochrane review from 2015 publications about complications and results were reviewed. Complication rates ranged from 1-10% depending on the initial situation, comorbidities and stage of the keratoconus. The most important complications are early epithelial wound healing problems as well as extremely rare perforations. Corneal cross-linking is a well-established and safe procedure but is not free of complications.

Beth Reis and the Safe Schools Coalition

ERIC Educational Resources Information Center

Vaught, Sabina E.

2007-01-01

This article chronicles the formation and organization of the Safe Schools Coalition (SCC) through the experiences of Beth Reis, co-founder and co-Chair. The article suggests ways in which the SCC can serve as a model for both collective and individual work in promoting safe schools.

A new glucocerebrosidase-deficient neuronal cell model provides a tool to probe pathophysiology and therapeutics for Gaucher disease

PubMed Central

Westbroek, Wendy; Nguyen, Matthew; Siebert, Marina; Lindstrom, Taylor; Burnett, Robert A.; Aflaki, Elma; Jung, Olive; Tamargo, Rafael; Rodriguez-Gil, Jorge L.; Acosta, Walter; Hendrix, An; Behre, Bahafta; Tayebi, Nahid; Fujiwara, Hideji; Sidhu, Rohini; Renvoise, Benoit; Ginns, Edward I.; Dutra, Amalia; Pak, Evgenia; Cramer, Carole; Ory, Daniel S.; Pavan, William J.

2016-01-01

ABSTRACT Glucocerebrosidase is a lysosomal hydrolase involved in the breakdown of glucosylceramide. Gaucher disease, a recessive lysosomal storage disorder, is caused by mutations in the gene GBA1. Dysfunctional glucocerebrosidase leads to accumulation of glucosylceramide and glycosylsphingosine in various cell types and organs. Mutations in GBA1 are also a common genetic risk factor for Parkinson disease and related synucleinopathies. In recent years, research on the pathophysiology of Gaucher disease, the molecular link between Gaucher and Parkinson disease, and novel therapeutics, have accelerated the need for relevant cell models with GBA1 mutations. Although induced pluripotent stem cells, primary rodent neurons, and transfected neuroblastoma cell lines have been used to study the effect of glucocerebrosidase deficiency on neuronal function, these models have limitations because of challenges in culturing and propagating the cells, low yield, and the introduction of exogenous mutant GBA1. To address some of these difficulties, we established a high yield, easy-to-culture mouse neuronal cell model with nearly complete glucocerebrosidase deficiency representative of Gaucher disease. We successfully immortalized cortical neurons from embryonic null allele gba−/− mice and the control littermate (gba+/+) by infecting differentiated primary cortical neurons in culture with an EF1α-SV40T lentivirus. Immortalized gba−/− neurons lack glucocerebrosidase protein and enzyme activity, and exhibit a dramatic increase in glucosylceramide and glucosylsphingosine accumulation, enlarged lysosomes, and an impaired ATP-dependent calcium-influx response; these phenotypical characteristics were absent in gba+/+ neurons. This null allele gba−/− mouse neuronal model provides a much-needed tool to study the pathophysiology of Gaucher disease and to evaluate new therapies. PMID:27482815

EUV tools: hydrogen gas purification and recovery strategies

NASA Astrophysics Data System (ADS)

Landoni, Cristian; Succi, Marco; Applegarth, Chuck; Riddle Vogt, Sarah

2015-03-01

The technological challenges that have been overcome to make extreme ultraviolet lithography (EUV) a reality have been enormous1. This vacuum driven technology poses significant purity challenges for the gases employed for purging and cleaning the scanner EUV chamber and source. Hydrogen, nitrogen, argon and ultra-high purity compressed dry air (UHPCDA) are the most common gases utilized at the scanner and source level. Purity requirements are tighter than for previous technology node tools. In addition, specifically for hydrogen, EUV tool users are facing not only gas purity challenges but also the need for safe disposal of the hydrogen at the tool outlet. Recovery, reuse or recycling strategies could mitigate the disposal process and reduce the overall tool cost of operation. This paper will review the types of purification technologies that are currently available to generate high purity hydrogen suitable for EUV applications. Advantages and disadvantages of each purification technology will be presented. Guidelines on how to select the most appropriate technology for each application and experimental conditions will be presented. A discussion of the most common approaches utilized at the facility level to operate EUV tools along with possible hydrogen recovery strategies will also be reported.

Carbon nanotubes (CNTs) based advanced dermal therapeutics: current trends and future potential.

PubMed

Kuche, Kaushik; Maheshwari, Rahul; Tambe, Vishakha; Mak, Kit-Kay; Jogi, Hardi; Raval, Nidhi; Pichika, Mallikarjuna Rao; Kumar Tekade, Rakesh

2018-05-17

The search for effective and non-invasive delivery modules to transport therapeutic molecules across skin has led to the discovery of a number of nanocarriers (viz.: liposomes, ethosomes, dendrimers, etc.) in the last few decades. However, available literature suggests that these delivery modules face several issues including poor stability, low encapsulation efficiency, and scale-up hurdles. Recently, carbon nanotubes (CNTs) emerged as a versatile tool to deliver therapeutics across skin. Superior stability, high loading capacity, well-developed synthesis protocol as well as ease of scale-up are some of the reason for growing interest in CNTs. CNTs have a unique physical architecture and a large surface area with unique surface chemistry that can be tailored for vivid biomedical applications. CNTs have been thus largely engaged in the development of transdermal systems such as tuneable hydrogels, programmable nonporous membranes, electroresponsive skin modalities, protein channel mimetic platforms, reverse iontophoresis, microneedles, and dermal buckypapers. In addition, CNTs were also employed in the development of RNA interference (RNAi) based therapeutics for correcting defective dermal genes. This review expounds the state-of-art synthesis methodologies, skin penetration mechanism, drug liberation profile, loading potential, characterization techniques, and transdermal applications along with a summary on patent/regulatory status and future scope of CNT based skin therapeutics.

Therapeutic drug levels

MedlinePlus

... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

Virus Alert: Ten Steps to Safe Computing.

ERIC Educational Resources Information Center

Gunter, Glenda A.

1997-01-01

Discusses computer viruses and explains how to detect them; discusses virus protection and the need to update antivirus software; and offers 10 safe computing tips, including scanning floppy disks and commercial software, how to safely download files from the Internet, avoiding pirated software copies, and backing up files. (LRW)

16 CFR 312.11 - Safe harbor programs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Safe harbor programs. 312.11 Section 312.11 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS CHILDREN'S ONLINE PRIVACY PROTECTION RULE § 312.11 Safe harbor programs. (a) In general. Industry groups or other persons...

Capturing Essential Information to Achieve Safe Interoperability.

PubMed

Weininger, Sandy; Jaffe, Michael B; Rausch, Tracy; Goldman, Julian M

2017-01-01

In this article, we describe the role of "clinical scenario" information to assure the safety of interoperable systems, as well as the system's ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore, improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheets and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a "patient-controlled analgesia safety interlock" are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a learning health system to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A Web-based research tool for implementing a means of acquiring and managing this information, the Clinical

Speech acts and performances of scientific citizenship: Examining how scientists talk about therapeutic cloning.

PubMed

Marks, Nicola J

2014-07-01

Scientists play an important role in framing public engagement with science. Their language can facilitate or impede particular interactions taking place with particular citizens: scientists' "speech acts" can "perform" different types of "scientific citizenship". This paper examines how scientists in Australia talked about therapeutic cloning during interviews and during the 2006 parliamentary debates on stem cell research. Some avoided complex labels, thereby facilitating public examination of this field. Others drew on language that only opens a space for publics to become educated, not to participate in a more meaningful way. Importantly, public utterances made by scientists here contrast with common international utterances: they did not focus on the therapeutic but the research promises of therapeutic cloning. Social scientists need to pay attention to the performative aspects of language in order to promote genuine citizen involvement in techno-science. Speech Act Theory is a useful analytical tool for this.

Safe Sleep for Babies

MedlinePlus

... Every year, there are thousands of sleep-related deaths among babies. View large image and text description ... 2AZh9Bn Supporting research to better understand sleep-related deaths and strategies to improve safe sleep practices. Healthcare ...

Safe Use of Hydrogen and Hydrogen Systems

NASA Technical Reports Server (NTRS)

Maes, Miguel

2006-01-01

This is a viewgraph presentation that is a course for teaching the safe use of hydrogen. The objectives of the course are 1. To familiarize the student with H2 safety properties 2. To enable the identification, evaluations and addressing of H2 system hazards 3. To teach: a. Safe practices for, b. Design, c. Materials selection, d. H2 system operation, e. Physical principles and empirical observations on which these safe practices are based, f. How to respond to emergency situations involving H2, g How to visualize safety concepts through in-class exercises, h. Identify numerous parameters important to H2 safety.

12 CFR 350.11 - Safe harbor provision.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Safe harbor provision. 350.11 Section 350.11 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY DISCLOSURE OF FINANCIAL AND OTHER INFORMATION BY FDIC-INSURED STATE NONMEMBER BANKS § 350.11 Safe harbor...

MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases.

PubMed

Dua, Kamal; Hansbro, Nicole G; Foster, Paul S; Hansbro, Philip M

2017-02-01

The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.

Use of the Home Safety Self-Assessment Tool (HSSAT) within Community Health Education to Improve Home Safety.

PubMed

Horowitz, Beverly P; Almonte, Tiffany; Vasil, Andrea

2016-10-01

This exploratory research examined the benefits of a health education program utilizing the Home Safety Self-Assessment Tool (HSSAT) to increase perceived knowledge of home safety, recognition of unsafe activities, ability to safely perform activities, and develop home safety plans of 47 older adults. Focus groups in two senior centers explored social workers' perspectives on use of the HSSAT in community practice. Results for the health education program found significant differences between reported knowledge of home safety (p = .02), ability to recognize unsafe activities (p = .01), safely perform activities (p = .04), and develop a safety plan (p = .002). Social workers identified home safety as a major concern and the HSSAT a promising assessment tool. Research has implications for reducing environmental fall risks.

Which non-technical skills do junior doctors require to prescribe safely? A systematic review.

PubMed

Dearden, Effie; Mellanby, Edward; Cameron, Helen; Harden, Jeni

2015-12-01

Prescribing errors are a major source of avoidable morbidity and mortality. Junior doctors write most in-hospital prescriptions and are the least experienced members of the healthcare team. This puts them at high risk of error and makes them attractive targets for interventions to improve prescription safety. Error analysis has shown a background of complex environments with multiple contributory conditions. Similar conditions in other high risk industries, such as aviation, have led to an increased understanding of so-called human factors and the use of non-technical skills (NTS) training to try to reduce error. To date no research has examined the NTS required for safe prescribing. The aim of this review was to develop a prototype NTS taxonomy for safe prescribing, by junior doctors, in hospital settings. A systematic search identified 14 studies analyzing prescribing behaviours and errors by junior doctors. Framework analysis was used to extract data from the studies and identify behaviours related to categories of NTS that might be relevant to safe and effective prescribing performance by junior doctors. Categories were derived from existing literature and inductively from the data. A prototype taxonomy of relevant categories (situational awareness, decision making, communication and team working, and task management) and elements was constructed. This prototype will form the basis of future work to create a tool that can be used for training and assessment of medical students and junior doctors to reduce prescribing error in the future. © 2015 The British Pharmacological Society.

Hemopressin Peptides as Modulators of the Endocannabinoid System and their Potential Applications as Therapeutic Tools.

PubMed

Macedonio, Giorgia; Stefanucci, Azzurra; Maccallini, Cristina; Mirzaie, Sako; Novellino, Ettore; Mollica, Adriano

2016-01-01

The endocannabinoid system (ECS) is activated when natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) bind as lipophilic messengers to cannabinoid receptors CB1 and CB2. The ECS comprises many hydrolytic enzymes responsible for the endocannabinoids cleavage. These hydrolases, such as fatty acid amide hydrolase (FAAH) and monoacylglyceride lipase (MAGL), are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently, a new family of endocannabinoid modulators was discovered; the lead structure of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1. Hemopressin shows several physiological effects, e.g., antinociception, hypophagy, and hypotension. However, it is still a matter of debate whether this peptide, isolated from the brain of rats, is a real neuromodulator of the ECS. Recent evidence indicates that hemopressin could be a by-product formed by chemical degradation of a longer peptide RVD-hemopressin during the extraction from the brain homolysate. Indeed, RVD-hemopressin is more active than hemopressin in certain biological tests and may bind to the same subsite as Rimonabant, which is an inverse agonist of CB1 and a μ-opioid receptor antagonist. These findings have stimulated several studies to verify this hypothesis and to evaluate possible therapeutic applications of hemopressin, its peptidic derivatives, and synthetic analogues, opening new perspectives to the development of novel cannabinoid drugs.

Microelectromechanical safe arm device

DOEpatents

Roesler, Alexander W [Tijeras, NM

2012-06-05

Microelectromechanical (MEM) apparatus and methods for operating, for preventing unintentional detonation of energetic components comprising pyrotechnic and explosive materials, such as air bag deployment systems, munitions and pyrotechnics. The MEM apparatus comprises an interrupting member that can be moved to block (interrupt) or complete (uninterrupt) an explosive train that is part of an energetic component. One or more latching members are provided that engage and prevent the movement of the interrupting member, until the one or more latching members are disengaged from the interrupting member. The MEM apparatus can be utilized as a safe and arm device (SAD) and electronic safe and arm device (ESAD) in preventing unintentional detonations. Methods for operating the MEM apparatus include independently applying drive signals to the actuators coupled to the latching members, and an actuator coupled to the interrupting member.

The Therapeutic Role of Interleukin-1 Inhibition in Idiopathic Recurrent Pericarditis: Current Evidence and Future Challenges

PubMed Central

Lazaros, George; Antonatou, Katerina; Vassilopoulos, Dimitrios

2017-01-01

Recurrent pericarditis is a common complication of acute pericarditis (15–30%) for which, in most cases, no underlying etiology is found [idiopathic recurrent pericarditis (IRP)]. IRP is currently viewed as an autoinflammatory disease with characteristic recurrent episodes of sterile inflammation. According to the most recent Guidelines, the initial treatment regimen consists of a combination of aspirin or non-steroidal anti-inflammatory drugs with colchicine followed by the addition of corticosteroids in resistant or intolerant cases. Despite this treatment approach, a number of patients either do not respond or cannot tolerate the above therapies. For this refractory group, small case series and a recent randomized controlled trial have shown that interleukin-1 inhibition with anakinra is a rapidly acting, highly efficient, steroid-sparing, and safe therapeutic intervention. In this perspective, we discuss the available clinical evidence and our own clinical experience as well as the future prospects of this novel therapeutic approach for patients with IRP. PMID:28660191

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

PubMed

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

2013-09-01

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

Genome Editing: A New Approach to Human Therapeutics.

PubMed

Porteus, Matthew

2016-01-01

The ability to manipulate the genome with precise spatial and nucleotide resolution (genome editing) has been a powerful research tool. In the past decade, the tools and expertise for using genome editing in human somatic cells and pluripotent cells have increased to such an extent that the approach is now being developed widely as a strategy to treat human disease. The fundamental process depends on creating a site-specific DNA double-strand break (DSB) in the genome and then allowing the cell's endogenous DSB repair machinery to fix the break such that precise nucleotide changes are made to the DNA sequence. With the development and discovery of several different nuclease platforms and increasing knowledge of the parameters affecting different genome editing outcomes, genome editing frequencies now reach therapeutic relevance for a wide variety of diseases. Moreover, there is a series of complementary approaches to assessing the safety and toxicity of any genome editing process, irrespective of the underlying nuclease used. Finally, the development of genome editing has raised the issue of whether it should be used to engineer the human germline. Although such an approach could clearly prevent the birth of people with devastating and destructive genetic diseases, questions remain about whether human society is morally responsible enough to use this tool.

A status report on RNAi therapeutics

PubMed Central

2010-01-01

Fire and Mello initiated the current explosion of interest in RNA interference (RNAi) biology with their seminal work in Caenorhabditis elegans. These observations were closely followed by the demonstration of RNAi in Drosophila melanogaster. However, the full potential of these new discoveries only became clear when Tuschl and colleagues showed that 21-22 bp RNA duplexes with 3" overhangs, termed small interfering (si)RNAs, could reliably execute RNAi in a range of mammalian cells. Soon afterwards, it became clear that many different human cell types had endogenous machinery, the RNA-induced silencing complex (RISC), which could be harnessed to silence any gene in the genome. Beyond the availability of a novel way to dissect biology, an important target validation tool was now available. More importantly, two key properties of the RNAi pathway - sequence-mediated specificity and potency - suggested that RNAi might be the most important pharmacological advance since the advent of protein therapeutics. The implications were profound. One could now envisage selecting disease-associated targets at will and expect to suppress proteins that had remained intractable to inhibition by conventional methods, such as small molecules. This review attempts to summarize the current understanding on siRNA lead discovery, the delivery of RNAi therapeutics, typical in vivo pharmacological profiles, preclinical safety evaluation and an overview of the 14 programs that have already entered clinical practice. PMID:20615220

The Triangle Technique: a new evidence-based educational tool for pediatric medication calculations.

PubMed

Sredl, Darlene

2006-01-01

Many nursing student verbalize an aversion to mathematical concepts and experience math anxiety whenever a mathematical problem is confronted. Since nurses confront mathematical problems on a daily basis, they must learn to feel comfortable with their ability to perform these calculations correctly. The Triangle Technique, a new educational tool available to nurse educators, incorporates evidence-based concepts within a graphic model using visual, auditory, and kinesthetic learning styles to demonstrate pediatric medication calculations of normal therapeutic ranges. The theoretical framework for the technique is presented, as is a pilot study examining the efficacy of the educational tool. Statistically significant results obtained by Pearson's product-moment correlation indicate that students are better able to calculate accurate pediatric therapeutic dosage ranges after participation in the educational intervention of learning the Triangle Technique.

Semaphorin3A: A Potential Therapeutic Tool for Lupus Nephritis.

PubMed

Bejar, Jacob; Kessler, Ofra; Sabag, Adi D; Sabo, Edmond; Itzhak, Ofer Ben; Neufeld, Gera; Vadasz, Zahava

2018-01-01

The immune regulatory properties of semaphorin3A (sema3A) (both innate and adaptive) are well established in many in vitro studies. The injection of sema3A into a mice model of rheumatoid arthritis was proven to be highly beneficial, both in attenuating clinical symptoms and in decreasing inflammatory mechanisms. This study was designed in order to assess the possible therapeutic benefits of sema3A following its injection into female NZB/W mice. Forty-eight NZB/W mice were recruited for this study. Thirty mice were treated as a "prevention group" and 18 were used as a "treatment group." Eight-week-old mice were acclimated and then divided into the two abovementioned groups. The injection of sema3A into young mice (at week 12) before the onset of disease (the prevention group) delayed the appearance of proteinuria. Here, the median time to severe proteinuria was 110 days, 95% CI: 88-131. However, in mice in which the empty vector was injected, the median time to severe proteinuria was 63 days, 95% CI: 0-139. sema3A treatment, significantly reduced renal damage, namely, it prevented the deposition of immune complexes in the glomeruli. When sema3A was injected at the onset of proteinuria (the treatment group), aiming to treat rather than to prevent disease in these mice, survival was increased and the deterioration of proteinuria was delayed. Semaphorin3A is highly beneficial in reducing lupus nephritis in NZB/W mice. It delays the appearance and deterioration of proteinuria, and increases the survival rates in these mice. The regulatory mechanisms of sema3A involve both innate and adaptive immune responses. Further studies will establish the idea of applying sema3A in the treatment of lupus nephritis.

Current Challenges in Delivery and Cytosolic Translocation of Therapeutic RNAs

PubMed Central

Lucchino, Marco

2018-01-01

RNA interference (RNAi) is a fundamental cellular process for the posttranscriptional regulation of gene expression. RNAi can exogenously be modulated by small RNA oligonucleotides, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), or by antisense oligonucleotides. These small oligonucleotides provided the scientific community with powerful and versatile tools to turn off the expression of genes of interest, and hold out the promise of new therapeutic solutions against a wide range of gene-associated pathologies. However, unmodified nucleic acids are highly instable in biological systems, and their weak interaction with plasma proteins confers an unfavorable pharmacokinetics. In this review, we first provide an overview of the most efficient chemical strategies that, over the past 30 years, have been used to significantly improve the therapeutic potential of oligonucleotides. Oligonucleotides targeting and delivery technologies are then presented, including covalent conjugates between oligonucleotides and targeting ligand, and noncovalent association with lipid or polymer nanoparticles. Finally, we specifically focus on the endosomal escape step, which represents a major stumbling block for the effective use of oligonucleotides as therapeutic agents. The need for approaches to quantitatively measure endosomal escape and cytosolic arrival of biomolecules is discussed in the context of the development of efficient oligonucleotide targeting and delivery vectors. PMID:29883296

Testosterone and estrogen in multiple sclerosis: from pathophysiology to therapeutics.

PubMed

Collongues, Nicolas; Patte-Mensah, Christine; De Seze, Jérôme; Mensah-Nyagan, Ayikoe-Guy; Derfuss, Tobias

2018-06-01

Neuroprotection and remyelination are two unmet needs in the treatment of multiple sclerosis (MS). Therapeutic potential has been identified with sexual hormones, supported in women by a decrease in MS activity during the pregnancy, in men by a greater severity of symptoms and a faster progression than in women. Areas covered: The therapeutic effect of testosterone and estrogens is reviewed. Both hormones have demonstrated an anti-inflammatory effect. Testosterone has an effect in protecting neurons in culture against glutamate-induced toxicity and oxidative stress, and stimulates myelin formation and regeneration mediated through the neural androgen receptor. In experimental autoimmune encephalomyelitis model, estrogens significantly decrease inflammation in the central nervous system via ERα, while its action on ERβ leads to myelin and axon reparation. Estriol therapy in two phase 2 trials showed a decrease in clinical disease activity and inflammatory parameters in MRI. However, evidence of a therapeutic effect of testosterone is scarce. Expert commentary: Phase 3 trials with estriol as an add-on supplementation are now mandatory. Testosterone is another candidate to be tested in phase 2 trials. These hormones should be considered as an adjunctive therapy. New validated tools are needed to assess their effect on neuroprotection and remyelination.

Physician assessments of the value of therapeutic information delivered via e-mail

PubMed Central

Grad, Roland; Pluye, Pierre; Repchinsky, Carol; Jovaisas, Barbara; Marlow, Bernard; Marques Ricarte, Ivan L.; Galvão, Maria Cristiane Barbosa; Shulha, Michael; de Gaspé Bonar, James

2014-01-01

Abstract Problem addressed Although e-learning programs are popular and access to electronic knowledge resources has improved, raising awareness about updated therapeutic recommendations in practice continues to be a challenge. Objective of program To raise awareness about and document the use of therapeutic recommendations. Program description In 2010, family physicians evaluated e-Therapeutics (e-T) Highlights with a Web-based tool called the Information Assessment Method (IAM). The e-T Highlights consisted of information found in the primary care reference e-Therapeutics+. Each week, family physicians received an e-mail containing a link to 1 Highlight from a different chapter of e-Therapeutics+. Family physicians received continuing medical education credits for each Highlight they rated with the IAM. Of the 5346 participants, 85% of them were full-time or part-time practitioners. A total of 31 429 Highlights ratings were received in 2010 (median of 2 ratings per participant, range 1 to 49). Among participants who rated more than 2 Highlights, the median number of ratings was 7 (mean 11.9). The relevance of the information from individual Highlights varied widely; however, for 90% of the rated Highlights participants indicated total or partial relevance of the information for at least 1 patient. For 41% of rated Highlights, participants expected patient health benefits to result from implementing the recommendation, such as avoiding an unnecessary or inappropriate treatment, or a preventive intervention. Conclusion This continuing medical education program stimulated family physicians to rate therapeutic recommendations that were delivered weekly via e-mail. The process of rating e-T Highlights with the IAM raised awareness about treatment recommendations and documented self-reported use of this information in practice. PMID:24829020

Examining the Factor Structure and Reliability of the Safe Patient Handling Perception Scale: An Initial Validation Study.

PubMed

White-Heisel, Regina; Canfield, James P; Young-Hughes, Sadie