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Sample records for newly emerging therapeutic

  1. Magnetospheric substorms - A newly emerging model

    NASA Technical Reports Server (NTRS)

    Akasofu, S.-I.

    1981-01-01

    A surge of progress in magnetospheric substorm studies is expected by the following three recent developments: (1) the finding of the solar wind-magnetosphere energy coupling function epsilon, (2) the determination of the Pedersen current distribution over the entire polar region, and (3) a new understanding of the auroral potential structure. In this paper, the significance of the three developments and the newly emerging model of magnetospheric substorms is described.

  2. Magnetospheric substorms - A newly emerging model

    NASA Astrophysics Data System (ADS)

    Akasofu, S.-I.

    1981-10-01

    A surge of progress in magnetospheric substorm studies is expected by the following three recent developments: (1) the finding of the solar wind-magnetosphere energy coupling function epsilon, (2) the determination of the Pedersen current distribution over the entire polar region, and (3) a new understanding of the auroral potential structure. In this paper, the significance of the three developments and the newly emerging model of magnetospheric substorms is described.

  3. Out of the reach of children? Young people's health-seeking practices and agency in Africa's newly-emerging therapeutic landscapes.

    PubMed

    Hampshire, Kate R; Porter, Gina; Owusu, Samuel Asiedu; Tanle, Augustine; Abane, Albert

    2011-09-01

    Despite a dominant view within Western biomedicine that children and medicines should be kept apart, a growing literature suggests that children and adolescents often take active roles in health-seeking. Here, we consider young people's health-seeking practices in Ghana: a country with a rapidly-changing therapeutic landscape, characterised by the recent introduction of a National Health Insurance Scheme, mass advertising of medicines, and increased use of mobile phones. Qualitative and quantitative data are presented from eight field-sites in urban and rural Ghana, including 131 individual interviews, focus groups, plus a questionnaire survey of 1005 8-to-18-year-olds. The data show that many young people in Ghana play a major role in seeking healthcare for themselves and others. Young people's ability to secure effective healthcare is often constrained by their limited access to social, economic and cultural resources and information; however, many interviewees actively generated, developed and consolidated such resources in their quest for healthcare. Health insurance and the growth of telecommunications and advertising present new opportunities and challenges for young people's health-seeking practices. We argue that policy should take young people's medical realities as a starting point for interventions to facilitate safe and effective health-seeking. PMID:21824698

  4. Emerging therapeutic aspects in oncology

    PubMed Central

    MacEwan, David J

    2013-01-01

    Cancer remains a peculiarly stubborn disease to treat. Some forms of cancer have seen tremendous advances in the effectiveness of their treatments, whereas other forms have remained resistant to pharmacological control. This lack of hope for success is in part due to the types of drugs that are used in the clinic, and the targeted biological system being based purely on cellular growth rates. However, recent drugs designed to affect specific signalling pathways or proteins have been showing much success. Thanks to the ingenuity of pharmacologists in understanding and targeting these processes, there have been real improvements in treatment. Here we are presented with some of the research into such critical systems that have to be understood, so that they can be conquered. We will also look at the challenges facing cancer pharmacologists and what the field may present to us all in the future. Linked Articles This article is part of a themed section on Emerging Therapeutic Aspects in Oncology. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.169.issue-8 PMID:23889318

  5. Emerging therapeutic options for asthma.

    PubMed

    Colice, Gene L

    2011-04-01

    Asthma is characterized by eosinophilic airway inflammation and elevated serum immunoglobulin E (IgE) levels. Due to these pathologic features, the foundation of asthma treatment has historically been anti-inflammatory therapy with inhaled corticosteroids (ICSs). Numerous factors in addition to IgE and eosinophils, however, likely play important roles in mediating the airway inflammatory response characteristic of asthma. ICSs are effective therapy for some patients with persistent asthma, but clinical trials have shown that even increasing doses of ICSs under carefully controlled situations does not always result in acceptable asthma control. Consequently, other classes of medications, in addition to ICSs, are recommended in those patients with more severe asthma. The class of medication most commonly used in more severe asthma, along with ICSs, is long-acting inhaled beta2-agonists, but leukotriene modifying agents and anti-IgE monoclonal antibodies may also be used. Agents such as tiotropium, a long-acting inhaled anti-muscarinic agent, and those aimed at inhibiting cytokines, such as mepoluzimab, daclizumab, and etanercept, hold promise in the treatment of asthma. Other agents under investigation include phosphodiesterase type 4 inhibitors and oligonucleotides. Bronchial thermoplasty, a nonpharmacologic option, may also be beneficial in patients with poorly controlled asthma. As our understanding of the complex pathophysiology of asthma increases, it will enable the development of novel therapeutic approaches for patients who are not responding well to traditional treatments. Although more studies are necessary to ensure the efficacy and safety of both pharmacologic and nonpharmacologic approaches, there is future promise for therapeutic advances in severe, persistent asthma. PMID:21761958

  6. Emerging therapeutic options in GERD.

    PubMed

    Woodland, Philip; Amarasinghe, Gehanjali; Sifrim, Daniel

    2013-06-01

    Gastroesophageal reflux disease (GERD) is a prevalent problem resulting in a high level of healthcare consultation and expenditure in the Western World. Although standard medical therapy (in the form of proton pump inhibitor drugs) is effective in the majority of cases, there remains a significant proportion who are refractory to treatment. In addition, surgical therapy (in the form of laparoscopic fundoplication) is not always effective, and in some can be associated with significant side-effects, particularly gas-bloat, flatulence and dysphagia. As such there remains an unmet need in GERD to develop new therapies for refractory cases, and to develop alternatives to fundoplication with fewer side-effects. This article discusses the current state of pharmacological and non-pharmacological emerging therapies for GERD. PMID:23998982

  7. Developing and Using Therapeutics for Emerging Infections.

    PubMed

    McCune, Jeannine S; Reynolds, Kellie S

    2015-10-01

    This issue of Clinical Pharmacology & Therapeutics focuses on emerging infections. The outbreaks of the vaccine-preventable diseases (e.g., measles) and the emerging pathogens (e.g., Ebola) show us how small the world has become. These outbreaks also show the pressing need for effective public education and development of novel therapies. This issue covers various aspects of relevant therapeutic topics ranging from preclinical models, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial results, to education efforts in this area. Pharmacokinetic/dynamic modeling had an appreciable role in reducing the morbidity and mortality associated with human immunodeficiency virus and hepatitis C virus, recent emerging infections. However, these gains could be lessened by poor adherence to therapies, which has contributed to the development of multidrug-resistant tuberculosis. We must not forget lessons from previous infections, or they may reemerge. PMID:26179402

  8. Emerging Mitochondrial Therapeutic Targets in Optic Neuropathies.

    PubMed

    Lopez Sanchez, M I G; Crowston, J G; Mackey, D A; Trounce, I A

    2016-09-01

    Optic neuropathies are an important cause of blindness worldwide. The study of the most common inherited mitochondrial optic neuropathies, Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) has highlighted a fundamental role for mitochondrial function in the survival of the affected neuron-the retinal ganglion cell. A picture is now emerging that links mitochondrial dysfunction to optic nerve disease and other neurodegenerative processes. Insights gained from the peculiar susceptibility of retinal ganglion cells to mitochondrial dysfunction are likely to inform therapeutic development for glaucoma and other common neurodegenerative diseases of aging. Despite it being a fast-evolving field of research, a lack of access to human ocular tissues and limited animal models of mitochondrial disease have prevented direct retinal ganglion cell experimentation and delayed the development of efficient therapeutic strategies to prevent vision loss. Currently, there are no approved treatments for mitochondrial disease, including optic neuropathies caused by primary or secondary mitochondrial dysfunction. Recent advances in eye research have provided important insights into the molecular mechanisms that mediate pathogenesis, and new therapeutic strategies including gene correction approaches are currently being investigated. Here, we review the general principles of mitochondrial biology relevant to retinal ganglion cell function and provide an overview of the major optic neuropathies with mitochondrial involvement, LHON and ADOA, whilst highlighting the emerging link between mitochondrial dysfunction and glaucoma. The pharmacological strategies currently being trialed to improve mitochondrial dysfunction in these optic neuropathies are discussed in addition to emerging therapeutic approaches to preserve retinal ganglion cell function. PMID:27288727

  9. Spread of the newly emerging infectious laryngotracheitis viruses in Australia.

    PubMed

    Agnew-Crumpton, Rebecca; Vaz, Paola K; Devlin, Joanne M; O'Rourke, Denise; Blacker-Smith, Hayley Patricia; Konsak-Ilievski, Barbara; Hartley, Carol A; Noormohammadi, Amir H

    2016-09-01

    Infectious laryngotracheitis (ILT) is a significant viral disease of chickens in many countries around the globe. In this report the status of ILT in Australia has been used as a model to evaluate the evolution of the ILT viruses (ILTVs). Due to its geographical isolation, Australia harbored a distinct lineage of ILT viruses (ILTV) up to 2007. However examination of the ILT viruses (ILTV) involved in outbreaks between 2007 and 2009 has revealed that many of the outbreaks were caused by two new viral genotypes, class 8 and class 9. These two recombinant viruses were found to emerge as a result of recombination between previously existing live vaccine strains (SA2 and A20), and another live vaccine strain (Serva) introduced into the country in 2007. The new recombinant ILTVs were also shown to possess significantly higher virulence and replication capacity compared with a previously predominant ILTV, class 2. In the current study, examination of a large number of ILTVs isolated from outbreaks between 2009 and 2015 revealed the emergence of yet another recombinant virus (class 10) that appears to have become a predominant genotype in New South Wales. In Victoria however, the recombinant class 9 gradually became the predominant virus, replacing class 2. Therefore, there was an unusual pattern in geographical spread of the newly emerged viruses in different states of the country. These results suggest that ILTV is fast evolving towards a greater transmissibility and therefore greater capacity to spread into ILTV-free areas. PMID:27223632

  10. Radiation grafted adsorbents for newly emerging environmental applications

    NASA Astrophysics Data System (ADS)

    Mahmoud Nasef, Mohamed; Ting, T. M.; Abbasi, Ali; Layeghi-moghaddam, Alireza; Sara Alinezhad, S.; Hashim, Kamaruddin

    2016-01-01

    Radiation induced grafting (RIG) is acquired to prepare a number of adsorbents for newly emerging environmental applications using a single route involving RIG of glycidymethacrylate (GMA) onto polyethylene-polypropylene (PE-PP) non-woven fabric. The grafted fabric was subjected to one of three functionalization reactions to impart desired ionic characters. This included treatment with (1) N-dimethyl-D-glucamine, (2) triethylamine and (3) triethylamine and alkalisation with KOH. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) were used to study the changes in chemical and physical structures of the obtained fibrous adsorbents. The potential applications of the three adsorbents for removal of boron from solutions, capturing CO2 from CO2/N2 mixtures and catalysing transesterification of triacetin/methanol to methyl acetate (biodiesel) were explored. The obtained fibrous adsorbents provide potential alternatives to granular resins for the investigated applications and require further development.

  11. Newly described or emerging human species of nontuberculous mycobacteria.

    PubMed

    Brown-Elliott, Barbara A; Griffith, David E; Wallace, Richard J

    2002-03-01

    The advent of molecular testing in the laboratory has brought about the recognition of multiple newly characterized mycobacterial species not previously recognizable with most standard techniques. Some of the species are nonpathogenic, but the majority may cause clinical disease. Each is likely to have its own biology, drug susceptibility pattern, and response to drug/surgical therapy. Thus, it is important to try to recognize these new species in the laboratory. A study of the phenotypic and genotypic characteristics of these new species also may help to elucidate the epidemiology and pathogenesis of these organisms. In addition, there are multiple emerging species of nontuberculous mycobacteria including M. ulcerans, M. haemophilum, M. xenopi, and M. malmoense. [table: see text] These species are being recognized increasingly as a cause of human disease and recovered within the laboratory. The clinician must learn about these new pathogens to recognize them clinically and assist the laboratory in their recovery. PMID:11917813

  12. Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy.

    PubMed

    Gauthier, Angela C; Mattson, Richard H

    2015-07-01

    Clobazam is an oral 1,5-benzodiazepine used worldwide for the treatment of many types of epilepsies, although it is currently only approved for Lennox-Gastaut syndrome in the USA. This anticonvulsant and anxiolytic therapeutic has repeatedly demonstrated great efficacy and a high safety profile in refractory epilepsy as well as in a few monotherapy trials in both children and adults. Clobazam allosterically activates the GABAA receptor, and it binds less to subunits that mediate sedative effects than other benzodiazepines. It acts quickly, maintaining a therapeutic effect for a long duration due to its active metabolite, N-desmethylclobazam. Dosage is between 5 mg and 40 mg a day, depending on patient weight, efficacy, and tolerability. Efficacy tolerance has not been a problem in the best studies. Clobazam has provided many benefits to epileptic patients. It should be used by clinicians early as an adjuvant therapy in the treatment of refractory epilepsy and even considered as monotherapy in a broad spectrum of epilepsy syndromes. PMID:25917225

  13. Emerging therapeutics and relevant targets for chronic Hepatitis B.

    PubMed

    Song, Il Han

    2016-05-01

    Chronic hepatitis B virus (HBV) infection is a global health problem for the pursuit of complete virus eradication and immunity acquisition to prevent liver disease progression. Currently, interferon-alpha, with the underlying mechanism of host immunomodulation, and nucleos(t)ide analogs, with the underlying mechanism of inhibition of viral replication, are used for the treatment of patients with chronic hepatitis B. Despite remarkable improvement in the virological, serological, biochemical, and histological response to current therapeutics, we are still far from meeting the therapeutic goals, e.g., clearance of HBV DNA/covalently closed circular DNA (cccDNA) in the serum/liver tissue and seroconversion of hepatitis B surface antigen (HBsAg) to anti-HBs in the present antiviral era. Recently, HBV replication cycle-related, viral RNA interference-based, and host immune-mediated therapeutic targets and relevant anti-HBV agents have been newly introduced and investigated in the preclinical and clinical fields. This review discusses emerging therapeutics and relevant targets in the management of chronic hepatitis B. PMID:27210776

  14. Hα Surges Initiated by Newly-emerging Satellite Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Wang, Jun-feng; Zhou, Tuan-hui; Ji, Hai-sheng

    2014-01-01

    On July 22, 2011 and in the active region NOAA 11259 there ap- peared the event of the ejection of solar atmospheric Hα surges. According to the full-disc Hα observations of the Big Bear Solar Observatory in United States, three consecutive surges at one and the same place in the north of the main spot of the active region were discovered. The trajectories of these three surges exhib- ited the figure of straight lines, and their integral configuration is like an inverted Eiffel Tower. The first two surges are quite similar, and in each of them there appeared two bright points in the northern part of the main spot. After several minutes, the surges appeared in the midst of bright points. When the bright- ness of the bright points attained the maximum value, the surges spouted out from the midst of bright points. And after reaching the maximum altitude, they quickly vanished. Before the ejection of the third surge took place, no bright points appeared. Besides, its maximal altitude is merely one half of that of the first two surges. Via a comparison with the SDO/HMI (Solar Dynamics Obser- vatory/Helioseismic and Magnetic Imager) data of radial magnetic fields, it is found that in more than one hour before the appearance of the first surge there emerged bipolar magnetic fields in the region of ejection. Besides, in several min- utes before the ejection of each Hα surge the magnetic fluxes of positive polarity diminished. Via our analysis it is found that there appeared reconnections be- tween the newly emerging satellite magnetic fields and the preexisting magnetic fields in the spot, and this caused the continuous ejections of Hα surges.

  15. Emerging Issues in Therapeutic Adventure with Families.

    ERIC Educational Resources Information Center

    Burg, James E.

    2001-01-01

    Therapeutic adventure with families is a promising integration of adventure therapy and family therapy. Issues that must be addressed to legitimize the field include licensure and legal scope of practice, developing minimum standards for practitioners, incorporating family development and family therapy theories into practice, and conducting more…

  16. Emerging Therapeutic Approaches to Mitochondrial Diseases

    ERIC Educational Resources Information Center

    Wenz, Tina; Williams, Sion L.; Bacman, Sandra R.; Moraes, Carlos T.

    2010-01-01

    Mitochondrial diseases are very heterogeneous and can affect different tissues and organs. Moreover, they can be caused by genetic defects in either nuclear or mitochondrial DNA as well as by environmental factors. All of these factors have made the development of therapies difficult. In this review article, we will discuss emerging approaches to…

  17. Cell-Specific Aptamers as Emerging Therapeutics

    PubMed Central

    Meyer, Cindy; Hahn, Ulrich; Rentmeister, Andrea

    2011-01-01

    Aptamers are short nucleic acids that bind to defined targets with high affinity and specificity. The first aptamers have been selected about two decades ago by an in vitro process named SELEX (systematic evolution of ligands by exponential enrichment). Since then, numerous aptamers with specificities for a variety of targets from small molecules to proteins or even whole cells have been selected. Their applications range from biosensing and diagnostics to therapy and target-oriented drug delivery. More recently, selections using complex targets such as live cells have become feasible. This paper summarizes progress in cell-SELEX techniques and highlights recent developments, particularly in the field of medically relevant aptamers with a focus on therapeutic and drug-delivery applications. PMID:21904667

  18. SLC Transporters as Therapeutic Targets: Emerging Opportunities

    PubMed Central

    Lin, Lawrence; Yee, Sook Wah; Kim, Richard B.; Giacomini, Kathleen M.

    2015-01-01

    Solute carrier (SLC) transporters — a family of more than 300 membrane-bound proteins that facilitate the transport of a wide array of substrates across biological membranes — have important roles in physiological processes ranging from the cellular uptake of nutrients to the absorption of drugs and other xenobiotics. Several classes of marketed drugs target well-known SLC transporters, such as neurotransmitter transporters, and human genetic studies have provided powerful insight into the roles of more-recently characterized SLC transporters in both rare and common diseases, indicating a wealth of new therapeutic opportunities. This Review summarizes knowledge on the roles of SLC transporters in human disease, describes strategies to target such transporters, and highlights current and investigational drugs that modulate SLC transporters, as well as promising drug targets. PMID:26111766

  19. Phytotherapy: emerging therapeutic option in urologic disease

    PubMed Central

    2012-01-01

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

  20. Emerging Therapeutic Options for Celiac Disease

    PubMed Central

    Bakshi, Anita; Stephen, Sindu; Borum, Marie L.

    2012-01-01

    Celiac disease is an autoimmune disorder of the small intestine that is more common than was previously thought. This disease is caused by an inappropriate immune response to wheat gluten, barley, and rye. Three main pathways cause celiac disease: the environmental trigger (gluten), genetic susceptibility, and unusual gut permeability. The only treatment currently available is a strict gluten-free diet. Unfortunately, a majority of patients have difficulty complying with this diet, and the response to therapy is poor. Therefore, alternative treatments are being developed, and new insights into the pathophysiology of celiac disease have led to research into novel therapies. New treatments include engineering gluten-free grains, decreasing intestinal permeability by blockage of the epithelial zonulin receptor, inducing oral tolerance to gluten with a therapeutic vaccine, and degrading immunodominant gliadin peptides using probiotics with endopeptidases or transglutaminase inhibitors. These nondiet-based therapies provide hope for enhanced, lifelong celiac disease management with improved patient compliance and better quality of life. PMID:23483819

  1. Hypophosphatemia in the emergency department therapeutics.

    PubMed

    Miller, D W; Slovis, C M

    2000-07-01

    Although hypophosphatemia is relatively uncommon, it may be seen in anywhere from 20% to 80% of patients who present to the ED with alcoholic emergencies, diabetic ketoacidosis (DKA), and sepsis. Severe hypophosphatemia, as defined by a serum level below 1.0 mg/dL, may cause acute respiratory failure, myocardial depression, or seizures. Because hypophosphatemia is not as often treated by ED physicians, becoming familiar with a single intravenous phosphate solution and specific guidelines for phosphate repletion are essential. One mL of the most commonly available phosphate solution (K2PO4) contains 4.4 meq of potassium and 3 mmol (93 mgs) of phosphate. Administering K2PO4 at a rate of 1 mL per hour is almost always a very safe and appropriate treatment for hypophosphatemia. This article provides guidelines for phosphate therapy in hypophosphatemic ED patients including those in DKA, those presenting with alcohol-related complaints including alcoholic ketoacidosis and patients with acute exacerbation of asthma and chronic obstructive pulmonary disease. PMID:10919539

  2. Cholera: pathophysiology and emerging therapeutic targets.

    PubMed

    Muanprasat, Chatchai; Chatsudthipong, Varanuj

    2013-05-01

    Cholera is a diarrheal disease that remains an important global health problem with several hundreds of thousands of reported cases each year. This disease is caused by intestinal infection with Vibrio cholerae, which is a highly motile gram-negative bacterium with a single-sheathed flagellum. In the course of cholera pathogenesis, V. cholerae expresses a transcriptional activator ToxT, which subsequently transactivates expressions of two crucial virulence factors: toxin-coregulated pilus and cholera toxin (CT). These factors are responsible for intestinal colonization of V. cholerae and induction of fluid secretion, respectively. In intestinal epithelial cells, CT binds to GM1 ganglioside receptors on the apical membrane and undergoes retrograde vesicular trafficking to endoplasmic reticulum, where it exploits endoplasmic reticulum-associated protein degradation systems to release a catalytic A1 subunit of CT (CT A1) into cytoplasm. CT A1, in turn, catalyzes ADP ribosylation of α subunits of stimulatory G proteins, leading to a persistent activation of adenylate cyclase and an elevation of intracellular cAMP. Increased intracellular cAMP in human intestinal epithelial cells accounts for pathogenesis of profuse diarrhea and severe fluid loss in cholera. This review provides an overview of the pathophysiology of cholera diarrhea and discusses emerging drug targets for cholera, which include V. cholerae virulence factors, V. cholerae motility, CT binding to GM1 receptor, CT internalization and intoxication, as well as cAMP metabolism and transport proteins involved in cAMP-activated Cl(-) secretion. Future directions and perspectives of research on drug discovery and development for cholera are discussed. PMID:23651092

  3. Polymorphic SSR markers for Plasmopara obducens (Peronosporaceae), the newly emergent downy mildew pathogen of Impatiens (Balsaminaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Premise of the study: Microsatellite markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 151.2 Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identi...

  4. Autoimmune therapies targeting costimulation and emerging trends in multivalent therapeutics

    PubMed Central

    Chittasupho, Chuda; Siahaan, Teruna J; Vines, Charlotte M; Berkland, Cory

    2011-01-01

    Proteins participating in immunological signaling have emerged as important targets for controlling the immune response. A multitude of receptor–ligand pairs that regulate signaling pathways of the immune response have been identified. In the complex milieu of immune signaling, therapeutic agents targeting mediators of cellular signaling often either activate an inflammatory immune response or induce tolerance. This review is primarily focused on therapeutics that inhibit the inflammatory immune response by targeting membrane-bound proteins regulating costimulation or mediating immune-cell adhesion. Many of these signals participate in larger, organized structures such as the immunological synapse. Receptor clustering and arrangement into organized structures is also reviewed and emerging trends implicating a potential role for multivalent therapeutics is posited. PMID:21984960

  5. Contributions of T Lymphocyte Abnormalities to Therapeutic Outcomes in Newly Diagnosed Patients with Immune Thrombocytopenia

    PubMed Central

    Yang, Guohua; Zhuang, Yun; Qian, Xifeng; Zhou, Xin; Xiao, Dajiang; Shen, Yunfeng

    2015-01-01

    T cell abnormalities have been reported to play an important role in pathogenesis of immune thrombocytopenia (ITP) besides specific autoantibodies towards platelet. The aim of this study was to explore the clinical importance of T lymphocyte subsets in adult patients with newly diagnosed ITP before and after first-line treatment. Elderly ITP patients were also studied and we tried to analyze the relationships between these items and therapeutic outcomes. The patients were treated with intravenous immunoglobulin (IVIG) plus corticosteroids and therapeutic responses were evaluated. As a result, compared with the controls, absolute lymphocyte counts in ITP patients decreased significantly before treatment. After treatment, lymphocyte counts restored to control level regardless of their treatment outcomes. In addition, we observed increased IgG and CD19+ cell expression and decreased CD4+/CD8+ cell ratio in both whole ITP group and elderly group before treatment. After treatment, the increased IgG and CD19+ cell expression could be reduced in both respond and non-respond group regardless of patient age, while CD4+/CD8+ cell ratio could not be corrected in non-respond ITP patients. In non-respond ITP patients, increased CD8+ cell expression was noticed and could not be corrected by first-line treatment. Furthermore, even lower NK cell expression was found in non-respond elderly patients after treatment when compared with that in controls. Our findings suggest that ITP patients usually had less numbers of peripheral lymphocytes and patients with higher levels of CD8+ cells or lower levels of CD4+/CD8+ cell ratio were less likely to respond to first-line treatment. Lower levels of NK cells made therapies in elderly ITP patients even more difficult. PMID:25978334

  6. Identification of Newly Emerging Influenza Viruses by Surface-Enhanced Raman Spectroscopy.

    PubMed

    Lim, Jae-young; Nam, Jung-soo; Yang, Se-eun; Shin, Hyunku; Jang, Yoon-ha; Bae, Gyu-Un; Kang, Taewook; Lim, Kwang-il; Choi, Yeonho

    2015-12-01

    In this work, we demonstrate in situ virus identification based on surface-enhanced Raman scattering (SERS). We hypothesized that newly emerging influenza viruses possess surface proteins and lipids that can generate distinctive Raman signals. To test this hypothesis, SERS signals were measured from the surface of a noninfluenza virus, two different influenza viruses, and a genetically shuffled influenza virus. To ensure the safety for experimenters we constructed nonreplicating pseudotyped viruses that display main influenza virus surface components. Pseudotype with influenza virus components produced enhanced Raman peaks, on gold nanoparticles, that are easily distinguishable from those of pseudotype with a noninfluenza virus component, vesicular stomatitis virus G protein (VSVG). Furthermore, virus with the surface components of a newly emerging influenza strain, A/California/04/2009 (H1N1), generated Raman peaks different from those of viruses with components of the conventional laboratory-adapted influenza strain, A/WSN/33 (H1N1). Interestingly, the virus simultaneously displaying surface components of both influenza strains, a model mutant with genome reassortment, also produced a Raman signal pattern that is clearly distinguishable from those of each strain. This work highlights that SERS can provide a powerful label-free strategy to quickly identify newly emerging and potentially fatal influenza viruses. PMID:26528878

  7. Siberian subtype tick-borne encephalitis virus in Ixodes ricinus in a newly emerged focus, Finland.

    PubMed

    Jääskeläinen, Anu; Tonteri, Elina; Pieninkeroinen, Ilkka; Sironen, Tarja; Voutilainen, Liina; Kuusi, Markku; Vaheri, Antti; Vapalahti, Olli

    2016-02-01

    The first tick-borne encephalitis (TBE) cases in Kotka, Finland appeared in 2010. Altogether ten human cases have been diagnosed by 2014. Four had long-lasting sequelae. We collected 195 Ixodes ricinus ticks, nine rodents, and eleven shrews from the archipelago of Kotka in 2011. Three Siberian subtype TBE virus (TBEV) strains were isolated from the ticks and three mammals were positive for TBEV antibodies. The archipelago of Kotka is a newly emerged TBE focus of Siberian subtype TBEV circulating notably in I. ricinus. The patients had on average longer hospitalization than reported for the European subtype infection. PMID:26548609

  8. The emerging molecular machinery and therapeutic targets of metastasis

    PubMed Central

    Sun, Yutong; Ma, Li

    2015-01-01

    Metastasis is a 100-year-old research topic. Technological advancements during the past few decades have led to significant progress in our understanding of metastatic disease. However, metastasis remains the leading cause of cancer-related mortalities. The lack of appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are major obstacles in metastasis prevention and treatment. A number of processes, factors, and signaling pathways are involved in regulating metastasis. Here, we discuss recent progress in metastasis research, including epithelial-mesenchymal plasticity, cancer stem cells, emerging molecular determinants and therapeutic targets, and the link between metastasis and therapy resistance. PMID:25939811

  9. Translocation of radiocesium from stems and leaves of plants and the effect on radiocesium concentrations in newly emerged plant tissues.

    PubMed

    Tagami, Keiko; Uchida, Shigeo; Ishii, Nobuyoshi; Kagiya, Shigeo

    2012-09-01

    An accident occurred at the Fukushima Dai-ichi Nuclear Power Plant in March 2011 at which time large amounts of radionuclides were released into the atmosphere and the sea. In early May 2011, it was found that newly emerged tea (Camellia sinensis) leaves contained radiocesium, both (134)Cs and (137)Cs in some areas more than 300 km away from the Fukushima plant. To understand the mechanisms of radiocesium transfer to newly emerged tissues (shoots, leaves and fruits) of other plants in the future, radiocesium concentrations in newly emerged leaves of 14 plant species collected from the sampling areas in and near National Institute of Radiological Sciences in Chiba, Japan. The studied plant types were: (1) herbaceous plants, (2) woody plants with no old leaves at the time of the March accident, and (3) woody plants with old leaves out before the accident. About 40-50 d after the start of the accident, newly emerged leaves from woody plant with old leaves tended to show higher values than other woody or herbaceous plants. Concentrations of radiocesium in newly emerged tissues of trees decreased with time, but they did not decrease to the level of herbaceous plants. The type of the plant and presence of old leaves at the time of the heavy deposition period affected the radiocesium concentrations in newly emerged tissues. PMID:22027214

  10. Suicide epidemics: the impact of newly emerging methods on overall suicide rates - a time trends study

    PubMed Central

    2011-01-01

    Background The impact of newly emerging, popular suicide methods on overall rates of suicide has not previously been investigated systematically. Understanding these effects may have important implications for public health surveillance. We examine the emergence of three novel methods of suicide by gassing in the 20th and 21st centuries and determine the impact of emerging methods on overall suicide rates. Methods We studied the epidemic rises in domestic coal gas (1919-1935, England and Wales), motor vehicle exhaust gas (1975-1992, England and Wales) and barbecue charcoal gas (1999-2006, Taiwan) suicide using Poisson and joinpoint regression models. Joinpoint regression uses contiguous linear segments and join points (points at which trends change) to describe trends in incidence. Results Epidemic increases in the use of new methods of suicide were generally associated with rises in overall suicide rates of between 23% and 71%. The recent epidemic of barbecue charcoal suicides in Taiwan was associated with the largest rise in overall rates (40-50% annual rise), whereas the smallest rise was seen for car exhaust gassing in England and Wales (7% annual rise). Joinpoint analyses were only feasible for car exhaust and charcoal burning suicides; these suggested an impact of the emergence of car exhaust suicides on overall suicide rates in both sexes in England and Wales. However there was no statistical evidence of a change in the already increasing overall suicide trends when charcoal burning suicides emerged in Taiwan, possibly due to the concurrent economic recession. Conclusions Rapid rises in the use of new sources of gas for suicide were generally associated with increases in overall suicide rates. Suicide prevention strategies should include strengthening local and national surveillance for early detection of novel suicide methods and implementation of effective media guidelines and other appropriate interventions to limit the spread of new methods. PMID

  11. A novel Botrytis species is associated with a newly emergent foliar disease in cultivated Hemerocallis.

    PubMed

    Grant-Downton, Robert T; Terhem, Razak B; Kapralov, Maxim V; Mehdi, Saher; Rodriguez-Enriquez, M Josefina; Gurr, Sarah J; van Kan, Jan A L; Dewey, Frances M

    2014-01-01

    Foliar tissue samples of cultivated daylilies (Hemerocallis hybrids) showing the symptoms of a newly emergent foliar disease known as 'spring sickness' were investigated for associated fungi. The cause(s) of this disease remain obscure. We isolated repeatedly a fungal species which proved to be member of the genus Botrytis, based on immunological tests. DNA sequence analysis of these isolates, using several different phyogenetically informative genes, indicated that they represent a new Botrytis species, most closely related to B. elliptica (lily blight, fire blight) which is a major pathogen of cultivated Lilium. The distinction of the isolates was confirmed by morphological analysis of asexual sporulating cultures. Pathogenicity tests on Hemerocallis tissues in vitro demonstrated that this new species was able to induce lesions and rapid tissue necrosis. Based on this data, we infer that this new species, described here as B. deweyae, is likely to be an important contributor to the development of 'spring sickness' symptoms. Pathogenesis may be promoted by developmental and environmental factors that favour assault by this necrotrophic pathogen. The emergence of this disease is suggested to have been triggered by breeding-related changes in cultivated hybrids, particularly the erosion of genetic diversity. Our investigation confirms that emergent plant diseases are important and deserve close monitoring, especially in intensively in-bred plants. PMID:24887415

  12. A Novel Botrytis Species Is Associated with a Newly Emergent Foliar Disease in Cultivated Hemerocallis

    PubMed Central

    Grant-Downton, Robert T.; Terhem, Razak B.; Kapralov, Maxim V.; Mehdi, Saher; Rodriguez-Enriquez, M. Josefina; Gurr, Sarah J.; van Kan, Jan A. L.; Dewey, Frances M.

    2014-01-01

    Foliar tissue samples of cultivated daylilies (Hemerocallis hybrids) showing the symptoms of a newly emergent foliar disease known as ‘spring sickness’ were investigated for associated fungi. The cause(s) of this disease remain obscure. We isolated repeatedly a fungal species which proved to be member of the genus Botrytis, based on immunological tests. DNA sequence analysis of these isolates, using several different phyogenetically informative genes, indicated that they represent a new Botrytis species, most closely related to B. elliptica (lily blight, fire blight) which is a major pathogen of cultivated Lilium. The distinction of the isolates was confirmed by morphological analysis of asexual sporulating cultures. Pathogenicity tests on Hemerocallis tissues in vitro demonstrated that this new species was able to induce lesions and rapid tissue necrosis. Based on this data, we infer that this new species, described here as B. deweyae, is likely to be an important contributor to the development of ‘spring sickness’ symptoms. Pathogenesis may be promoted by developmental and environmental factors that favour assault by this necrotrophic pathogen. The emergence of this disease is suggested to have been triggered by breeding-related changes in cultivated hybrids, particularly the erosion of genetic diversity. Our investigation confirms that emergent plant diseases are important and deserve close monitoring, especially in intensively in-bred plants. PMID:24887415

  13. SIRT3 in cardiovascular diseases: Emerging roles and therapeutic implications.

    PubMed

    Lu, Yi; Wang, Yi-Dong; Wang, Xiao-Ya; Chen, Han; Cai, Zhe-Jun; Xiang, Mei-Xiang

    2016-10-01

    SIRT3 belongs to a highly conserved protein family of histone deacetylases and it is rich in mitochondria. As acetyl-modification is one of the important post-translational modifications that prevail in the mitochondria, it is not surprising that SIRT3 plays a key regulatory role in this organelle. SIRT3 has a wide range of substrates that are involved in the physiological and pathological processes of oxidative stress, ischemia-reperfusion injury, mitochondrial metabolism homeostasis and cellular death. These pathophysiological processes are considered as the underlying mechanisms of diseases like cardiac hypertrophy, myocardial infarction and heart failure, indicating the potential roles of SIRT3 in cardiovascular diseases. In this review, we will summarize the emerging roles and therapeutic implications of SIRT3 in cardiovascular diseases by providing an update on the latest understanding of its functions. PMID:27393852

  14. [Rapidly progressive glomerulonephritis: a diagnostic and therapeutic emergency].

    PubMed

    Halfon, Matthieu; Teta, Daniel; Rotman, Samuel; Pruijm, Menno; Humbert, Antoine

    2014-02-26

    Rapidly progressive glomerulonephritis (RPG) is a rare clinical syndrome characterized by kidney damage that can lead to irreversible kidney failure. RPG can be caused by primary glomerular disease or can be part of a systemic autoimmune disorder. All RPG have a similar pathophysiology (proliferation of cells in Bowman's capsule and formation of crescents) and clinical evolution (rapidly progressive kidney failure with proteinuria and an active urine sediment). Immunosuppressive therapy and sometimes plasma exchanges are required. Overall- and kidney survival are closely linked to the blood creatinine level at presentation, the percentage of damaged glomeruli, and to the underlying cause. RPG is therefore a diagnostic and therapeutic emergency that needs quick referral to a nephrologist. PMID:24665657

  15. Emerging Insights into Barriers to Effective Brain Tumor Therapeutics

    PubMed Central

    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. PMID:25101239

  16. Emergent properties of neural repair: elemental biology to therapeutic concepts.

    PubMed

    Carmichael, S Thomas

    2016-06-01

    Stroke is the leading cause of adult disability. The past decade has seen advances in basic science research of neural repair in stroke. The brain forms new connections after stroke, which have a causal role in recovery of function. Brain progenitors, including neuronal and glial progenitors, respond to stroke and initiate a partial formation of new neurons and glial cells. The molecular systems that underlie axonal sprouting, neurogenesis, and gliogenesis after stroke have recently been identified. Importantly, tractable drug targets exist within these molecular systems that might stimulate tissue repair. These basic science advances have taken the field to its first scientific milestone; the elemental principles of neural repair in stroke have been identified. The next stages in this field involve understanding how these elemental principles of recovery interact in the dynamic cellular systems of the repairing brain. Emergent principles arise out of the interaction of the fundamental or elemental principles in a system. In neural repair, the elemental principles of brain reorganization after stroke interact to generate higher order and distinct concepts of regenerative brain niches in cellular repair, neuronal networks in synaptic plasticity, and the distinction of molecular systems of neuroregeneration. Many of these emergent principles directly guide the development of new therapies, such as the necessity for spatial and temporal control in neural repair therapy delivery and the overlap of cancer and neural repair mechanisms. This review discusses the emergent principles of neural repair in stroke as they relate to scientific and therapeutic concepts in this field. Ann Neurol 2016;79:895-906. PMID:27043816

  17. Polymorphic SSR Markers for Plasmopara obducens (Peronosporaceae), the Newly Emergent Downy Mildew Pathogen of Impatiens (Balsaminaceae)

    DOE PAGESBeta

    Salgado-Salazar, Catalina; Rivera, Yazmín; Veltri, Daniel; Crouch, Jo Anne

    2015-11-10

    Premise of the study: Simple sequence repeat (SSR) markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 202-Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identify 13,483 SSR motifs. Primers were synthesized for 62 marker candidates, of which 37 generated reliable PCR products. Testing of the 37 markers using 96 P. obducens samples showed 96% of the markers were polymorphic, with 2-6 alleles observed. Observed and expected heterozygosity ranged from 0.000-0.892 and 0.023-0.746, respectively. Just 17 markers were sufficientmore » to identify all multilocus genotypes. Conclusions: These are the first SSR markers available for this pathogen, and one of the first molecular resources. These markers will be useful in assessing variation in pathogen populations and determining the factors contributing to the emergence of destructive impatiens downy mildew disease.« less

  18. Cross-protection of newly emerging HPAI H5 viruses by neutralizing human monoclonal antibodies: A viable alternative to oseltamivir.

    PubMed

    Ren, Huanhuan; Wang, Guiqin; Wang, Shuangshuang; Chen, Honglin; Chen, Zhiwei; Hu, Hongxing; Cheng, Genhong; Zhou, Paul

    2016-01-01

    Newly emerging highly pathogenic avian influenza (HPAI) H5N2, H5N3, H5N5, H5N6, H5N8 and H5N9 viruses have been spreading in poultry and wild birds. The H5N6 viruses have also caused 10 human infections with 4 fatal cases in China. Here, we assessed the cross-neutralization and cross-protection of human and mouse monoclonal antibodies against 2 viruses: a HPAI H5N8 virus, A/chicken/Netherlands/14015526/2014 (NE14) and a HPAI H5N6 virus, A/Sichuan/26221/2014 (SC14). The former was isolated from an infected chicken in Netherlands in 2014 and the latter was isolated from an infected human patient in Sichuan, China. We show that antibodies FLA5.10, FLD21.140, 100F4 and 65C6, but not AVFluIgG01, AVFluIgG03, S139/1 and the VRC01 control, potently cross-neutralize the H5N8 NE14 and H5N6 SC14 viruses. Furthermore, we show that a single injection of >1 mg/kg of antibody 100F4 at 4 hours before, or 20 mg/kg antibody 100F4 at 72 hours after, a lethal dose of H5N8 NE14 enables mice to withstand the infection. Finally, we show that a single injection of 0.5 or 1 mg/kg antibody 100F4 prophylactically or 10 mg/kg 100F4 therapeutically outperforms a 5-day course of 10 mg/kg/day oseltamivir treatment against lethal H5N8 NE14 or H5N6 SC14 infection in mice. Our results suggest that further preclinical evaluation of human monoclonal antibodies against newly emerging H5 viruses is warranted. PMID:27167234

  19. Emerging molecular classifications and therapeutic implications for gastric cancer.

    PubMed

    Chen, Tao; Xu, Xiao-Yue; Zhou, Ping-Hong

    2016-01-01

    Gastric cancer (GC) is a highly aggressive and life-threatening malignancy. Even with radical surgical removal and front-line chemotherapy, more than half of GCs locally relapse and metastasize at a distant site. The dismal outcomes reflect the ineffectiveness of a one-size-fits-all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings. The recent comprehensive genomic and molecular profiling has led to our deepened understanding of GC. The emerging molecular classification schemes based on the genetic, epigenetic, and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner. To this end, the Cancer Genome Atlas (TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classification dividing GCs into four subtypes: Epstein-Barr virus-associated tumors, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. This review primarily focuses on the TCGA molecular classification of GCs and discusses the implications on novel targeted therapy strategies. We believe that these fundamental findings will support the future application of targeted therapies and will guide our efforts to develop more efficacious drugs to treat human GCs. PMID:27233623

  20. An infectious disease of ducks caused by a newly emerged Tembusu virus strain in mainland China.

    PubMed

    Yan, Pixi; Zhao, Youshu; Zhang, Xu; Xu, Dawei; Dai, Xiaoguang; Teng, Qiaoyang; Yan, Liping; Zhou, Jiewen; Ji, Xiwen; Zhang, Shumei; Liu, Guangqing; Zhou, Yanjun; Kawaoka, Yoshihiro; Tong, Guangzhi; Li, Zejun

    2011-08-15

    During investigations into an outbreak of egg production decline, retarded growth, and even death among ducks in Southeast China, a novel Tembusu virus strain named Tembusu virus Fengxian 2010 (FX2010) was isolated. This virus replicated in embryonated chicken eggs and caused embryo death. In cross-neutralization tests, antiserum to the partial E protein of Tembusu virus Mm1775 strain neutralized FX2010, whereas antiserum to Japanese encephalitis virus did not. FX2010 is an enveloped RNA virus of approximately 45-50 nm in diameter. Sequence analysis of its E and NS5 genes showed that both genes share up to 99.6% nucleotide sequence identity with Baiyangdian virus, and up to 88% nucleotide sequence identity with their counterparts in Tembusu virus. FX2010 was transmitted without mosquito, and caused systemic infection and lesions in experimentally infected ducks. These results indicate that FX2010 and BYD virus are newly emerged Tembusu virus strains that cause an infectious disease in ducks. PMID:21722935

  1. Sugar administration to newly emerged Aedes albopictus males increases their survival probability and mating performance.

    PubMed

    Bellini, Romeo; Puggioli, Arianna; Balestrino, Fabrizio; Brunelli, Paolo; Medici, Anna; Urbanelli, Sandra; Carrieri, Marco

    2014-04-01

    Aedes albopictus male survival in laboratory cages is no more than 4-5 days when kept without any access to sugar indicating their need to feed on a sugar source soon after emergence. We therefore developed a device to administer energetic substances to newly emerged males when released as pupae as part of a sterile insect technique (SIT) programme, made with a polyurethane sponge 4 cm thick and perforated with holes 2 cm in diameter. The sponge was imbibed with the required sugar solution and due to its high retention capacity the sugar solution was available for males to feed for at least 48 h. When evaluated in lab cages, comparing adults emerged from the device with sugar solution vs the device with water only (as negative control), about half of the males tested positive for fructose using the Van Handel anthrone test, compared to none of males in the control cage. We then tested the tool in semi-field and in field conditions with different sugar concentrations (10%, 15%, and 20%) and compared results to the controls fed with water only. Males were recaptured by a battery operated manual aspirator at 24 and 48 h after pupae release. Rather high share 10-25% of captured males tested positive for fructose in recollections in the vicinity of the control stations, while in the vicinity of the sugar stations around 40-55% of males were positive, though variability between replicates was large. The sugar positive males in the control test may have been released males that had access to natural sugar sources found close to the release station and/or wild males present in the environment. Only a slight increase in the proportion of positive males was obtained by increasing the sugar concentration in the feeding device from 10% to 20%. Surprisingly, modification of the device to add a black plastic inverted funnel above the container reduced rather than increased the proportion of fructose positive males collected around the station. No evidence of difference in the

  2. Porcine circovirus type 2 (PCV2): genetic variation and newly emerging genotypes in China

    PubMed Central

    2010-01-01

    Background Porcine circovirus type 2 (PCV2), the causative agent of postweaning multisystemic wasting syndrome (PMWS), is a serious economic problem for the swine industry in China. In this study, we investigated the genetic variation of PCV2 in China using strains isolated from 2004-2008. Viruses were isolated from samples collected from pigs with multi-systemic lesions and clinical signs of PMWS from different regions of China, and the genomes of these viruses were sequenced. The assembled sequences were used to define the genotypes of these strains; PCR-RFLP methodology was used to distinguish isolates and capture ELISA was used to demonstrate the antigenic changes resulted from ORF2 gene mutation of the isolates. Results We identified 19 PCV2 isolates, including four newly emerging PCV2 mutant strains. The 19 isolates were designated into three genotypes (PCV2a, PCV2b and PCV2d). PCV2d represented a novel genotype and a shift from PCV2a to PCV2b as the predominant genotype in China was identified. This is the first report of 1766 nt PCV2 harboring a base deletion at other new different positions. Amino acid sequence analysis identified two novel ORF2 mutations (resulting in ORF2 sequences 705 and 708 nt in length) in three deletion strains (1766 nt) and one strain with a genome 1767 nt in length. Finding of two amino acids elongation of the ORF2-encoded Cap protein is firstly observed among PCV2 strains all over the world. The isolates were distinguished into different genotypes by PCR-RFLP methodology and antigenic changes were present in Cap protein of mutation isolates by capture ELISA. Conclusions The results of this study provide evidence that PCV2 is undergoing constant genetic variation and that the predominant strain in China as well as the antigenic situation has changed in recent years. Furthermore, the PCR-RFLP method presented here may be useful for the differential identification of PCV2 strains in future studies. PMID:20955622

  3. Newly Emergent Highly Pathogenic H5N9 Subtype Avian Influenza A Virus

    PubMed Central

    Yu, Yang; Wang, Xingbo; Jin, Tao; Wang, Hailong; Si, Weiying; Yang, Hui; Wu, Jiusheng; Yan, Yan; Liu, Guang; Sang, Xiaoyu; Wu, Xiaopeng; Gao, Yuwei; Xia, Xianzhu; Yu, Xinfen; Pan, Jingcao; Gao, George F.

    2015-01-01

    ABSTRACT The novel H7N9 avian influenza virus (AIV) was demonstrated to cause severe human respiratory infections in China. Here, we examined poultry specimens from live bird markets linked to human H7N9 infection in Hangzhou, China. Metagenomic sequencing revealed mixed subtypes (H5, H7, H9, N1, N2, and N9). Subsequently, AIV subtypes H5N9, H7N9, and H9N2 were isolated. Evolutionary analysis showed that the hemagglutinin gene of the novel H5N9 virus originated from A/Muscovy duck/Vietnam/LBM227/2012 (H5N1), which belongs to clade 2.3.2.1. The neuraminidase gene of the novel H5N9 virus originated from human-infective A/Hangzhou/1/2013 (H7N9). The six internal genes were similar to those of other H5N1, H7N9, and H9N2 virus strains. The virus harbored the PQRERRRKR/GL motif characteristic of highly pathogenic AIVs at the HA cleavage site. Receptor-binding experiments demonstrated that the virus binds α-2,3 sialic acid but not α-2,6 sialic acid. Identically, pathogenicity experiments also showed that the virus caused low mortality rates in mice. This newly isolated H5N9 virus is a highly pathogenic reassortant virus originating from H5N1, H7N9, and H9N2 subtypes. Live bird markets represent a potential transmission risk to public health and the poultry industry. IMPORTANCE This investigation confirms that the novel H5N9 subtype avian influenza A virus is a reassortant strain originating from H5N1, H7N9, and H9N2 subtypes and is totally different from the H5N9 viruses reported before. The novel H5N9 virus acquired a highly pathogenic H5 gene and an N9 gene from human-infecting subtype H7N9 but caused low mortality rates in mice. Whether this novel H5N9 virus will cause human infections from its avian host and become a pandemic subtype is not known yet. It is therefore imperative to assess the risk of emergence of this novel reassortant virus with potential transmissibility to public health. PMID:26085150

  4. Ability of newly emerged adult Culex quinquefasciatus (Diptera: Culicidae) mosquitoes to exit belowground stormwater treatment systems via lateral conveyance pipes.

    PubMed

    Metzger, Marco E; Harbison, Justin E; Burns, Joseph E; Hu, Renjie

    2012-03-01

    Culex quinquefasciatus Say mosquitoes flourish in belowground stormwater systems in the southern United States. Recent evidence suggests that oviposition-site-seeking females may have difficulties locating, entering, and ovipositing inside permanent water chambers when surface entry through pickholes in manhole covers are sealed. It remains unknown, however, if newly emerged adults are able to detect cues necessary to exit these partly sealed systems via lateral conveyance pipes or if they perish belowground. Fourth instar Cx. quinquefasciatus were placed within proprietary belowground stormwater treatment systems to determine the percentage of newly emerged adults able to escape treatment chambers via a single lateral conveyance pipe. Overall, 56% of deployed mosquitoes were captured in adult exit traps with an 1:1 male:female ratio. The percentage of adults captured varied significantly among chambers, but was not associated with structural site characteristics such as the chamber depth or the length and course of conveyance pipe to the exit trap. Empirical observations suggested that longbodied cellar spiders, Pholcus phalangioides (Fuesslin), ubiquitous in these structures, may have reduced adult trap capture. Findings demonstrate that newly emerged Cx. quinquefasciatus can exit subterranean chambers under potentially difficult structural conditions but suggest that a portion may perish in the absence of surface exit points in manhole shafts. PMID:22493853

  5. Recent discoveries and emerging therapeutics in eosinophilic esophagitis

    PubMed Central

    Goyal, Aakash; Cheng, Edaire

    2016-01-01

    Eosinophilic esophagitis (EoE) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease (GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor - responsive esophageal eosinophilia (PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for EoE rather than a diagnostic screen to differentiate GERD, PPI-REE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics. PMID:26855809

  6. Recent discoveries and emerging therapeutics in eosinophilic esophagitis.

    PubMed

    Goyal, Aakash; Cheng, Edaire

    2016-02-01

    Eosinophilic esophagitis (EoE) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease (GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor - responsive esophageal eosinophilia (PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for EoE rather than a diagnostic screen to differentiate GERD, PPI-REE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics. PMID:26855809

  7. Therapeutic approach beyond conventional temozolomide for newly diagnosed glioblastoma: Review of the present evidence and future direction

    PubMed Central

    Mallick, Supriya; Gandhi, Ajeet Kumar; Rath, Goura Kishor

    2015-01-01

    Glioblastoma multiforme (GBM) is the most aggressive form of primary brain tumor. Maximal safe surgical resection followed by adjuvant partial brain radiation with concurrent and adjuvant temozolomide (TMZ) (oral alkylating agent) is the standard of care. Five years survival in TMZ treated patient reaches 9.8%. We aimed to summarize the changes in the management of GBM beyond conventional temozolomide based adjuvant treatment. We searched the PUBMED with the following key words: Glioblastoma, phase III trial, Phase II trial, adjuvant treatment in GBM. Clinical research has found a wide range of molecular aberrations in GBM and attempts are being made to further improve survival with the addition of different classes of drugs. Angiogenesis inhibitors, oncolytic vaccines, dose dense TMZ, and anti-epidermal growth factor receptor monoclonal antibody in phase III trials have failed to improve survival. Recent studies have also shown that the management strategies might be different and needs to be customized as per the age of patients such as pediatric and elderly patients. In addition, treatments should be personalized depending on the molecular aberrations. We reviewed all published phase III trials for newly diagnosed GBM as well as also looked into possible future directions in this review. Limited progress has happed beyond conventional TMZ in the adjuvant treatment of GBM. Newer insights are emerging about treatment intensification and introduction of newer molecular targeted drugs with more information about molecular aberrations. PMID:26811592

  8. Notch signaling: an emerging therapeutic target for cancer treatment.

    PubMed

    Yuan, Xun; Wu, Hua; Xu, Hanxiao; Xiong, Huihua; Chu, Qian; Yu, Shiying; Wu, Gen Sheng; Wu, Kongming

    2015-12-01

    The Notch pathway is involved in cell proliferation, differentiation and survival. The Notch signaling pathway is one of the most commonly activated signaling pathways in cancer. Alterations include activating mutations and amplification of the Notch pathway, which play key roles in the progression of cancer. Accumulating evidence suggests that the pharmacological inhibition of this pathway can overcome chemoresistance. Efforts have been taken to develop Notch inhibitors as a single agent or in combination with clinically used chemotherapeutics to treat cancer. Some Notch inhibitors have been demonstrated to have therapeutic efficacy in preclinical studies. This review summarizes the recent studies and clinical evaluations of the Notch inhibitors in cancer. PMID:26341688

  9. Biomaterials and Emerging Anticancer Therapeutics: Engineering the Microenvironment

    PubMed Central

    Gu, Luo; Mooney, David J

    2016-01-01

    The microenvironment is increasingly recognized to play key roles in cancer, and biomaterials provide a means to engineer microenvironments both in vitro and in vivo to study and manipulate cancer. In vitro cancer models using 3D matrices recapitulate key elements of the tumor microenvironment and have revealed new aspects of cancer biology. Cancer vaccines based on some of the same biomaterials have, in parallel, allowed for the engineering of durable prophylactic and therapeutic anticancer activity in preclinical studies, and some of these vaccines have moved to clinical trials. The impact of biomaterials engineering on cancer treatment is expected to further increase in importance in the years to come. PMID:26694936

  10. Emerging Non-Cancer Applications of Therapeutic Ultrasound

    PubMed Central

    O’Reilly, Meaghan A.; Hynynen, Kullervo

    2015-01-01

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

  11. Emerging therapeutic targets for the treatment of hepatic fibrosis.

    PubMed

    Fagone, Paolo; Mangano, Katia; Pesce, Antonio; Portale, Teresa Rosanna; Puleo, Stefano; Nicoletti, Ferdinando

    2016-02-01

    Fibrosis represents a response to chronic injury, aimed at maintaining organ integrity. Hepatic fibrosis is mainly related to chronic viral hepatitis B or C (HBV or HCV), alcoholic and nonalcoholic steatohepatitis (NASH), and biliary diseases. A deep understanding of the cellular and molecular mechanisms underlying liver fibrosis has enabled the development of 'pathogenetic tailored' therapeutic interventions. However, effective drugs to prevent or revert hepatic fibrosis are still lacking. In this review, we discuss the cellular populations and the molecular pathways involved in liver fibrogenesis as well as the novel approaches currently being tested in clinical trials. PMID:26523773

  12. Emerging therapeutic options for myelofibrosis: a Canadian perspective

    PubMed Central

    Gupta, Vikas; Foltz, Lynda; Sirhan, Shireen; Busque, Lambert; Turner, A Robert

    2012-01-01

    Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias, splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory cytokines. MF is associated with decreased survival. The quality of life of patients with MF is similar to other advanced malignancies. Allogeneic hematopoietic cell transplantation is a curative treatment, but is applicable to a minority of patients with MF. None of the conventional therapies are known to alter the natural history of the disease. Significant progress has been made in the last few years in the understanding of disease biology of MF. Discovery of the JAK2V617F mutation paved the way for drug discovery in MF, and the first JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada. Several other JAK1/2 inhibitors are at various stages of clinical development. As a consequence, the therapeutic landscape of MF is changing from a disease where no effective therapies existed to one with several novel treatment options on the horizon. In this report, we assess the changing therapeutic options for MF, and critically analyze the position of novel treatments in the current armamentarium. PMID:23119228

  13. Heterocyclic N-Oxides - An Emerging Class of Therapeutic Agents.

    PubMed

    Mfuh, A M; Larionov, O V

    2015-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  14. Autophagy: an emerging therapeutic target in vascular diseases

    PubMed Central

    Vindis, Cécile

    2015-01-01

    Autophagy is a cellular catabolic process responsible for the destruction of long-lived proteins and organelles via lysosome-dependent pathway. This process is of great importance in maintaining cellular homeostasis, and deregulated autophagy has been implicated in the pathogenesis of a wide range of diseases. A growing body of evidence suggests that autophagy can be activated in vascular disorders such as atherosclerosis. Autophagy occurs under basal conditions and mediates homeostatic functions in cells but in the setting of pathological states up-regulated autophagy can exert both protective and detrimental functions. Therefore, the precise role of autophagy and its relationship with the progression of the disease need to be clarified. This review highlights recent findings regarding autophagy activity in vascular cells and its potential contribution to vascular disorders with a focus on atherogenesis. Finally, whether the manipulation of autophagy represents a new therapeutic approach to treat or prevent vascular diseases is also discussed. PMID:25537552

  15. Emerging Supramolecular Therapeutic Carriers Based on Host-Guest Interactions.

    PubMed

    Karim, Anis Abdul; Dou, Qingqing; Li, Zibiao; Loh, Xian Jun

    2016-05-01

    Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non-covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self-assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site-specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed. PMID:26833861

  16. Emerging therapeutics for the treatment of diabetic nephropathy.

    PubMed

    Brenneman, Jehrod; Hill, Jon; Pullen, Steve

    2016-09-15

    Diabetic nephropathy (DN) is the most common pathology contributing to the development of chronic kidney disease (CKD). DN caused by hypertension and unmitigated inflammation in diabetics, renders the kidneys unable to perform normally, and leads to renal fibrosis and organ failure. The increasing global prevalence of DN has been directly attributed to rising incidences of Type II diabetes, and is now the largest non-communicable cause of death worldwide. Despite the high morbidity, successful new treatments for DN are lacking. This review seeks to provide new insight on emerging clinical candidates under investigation for the treatment of DN. PMID:27520943

  17. Therapeutic Management of Familial Hypercholesterolemia: Current and Emerging Drug Therapies.

    PubMed

    Patel, Roshni S; Scopelliti, Emily M; Savelloni, Julie

    2015-12-01

    Familial hypercholesterolemia (FH) is a genetic disorder characterized by significantly elevated low-density lipoprotein cholesterol (LDL-C) concentrations that result from mutations of the LDL receptor, apolipoprotein B (apo B-100), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Early and aggressive treatment can prevent premature atherosclerotic cardiovascular disease in these high-risk patients. Given that the cardiovascular consequences of FH are similar to typical hypercholesterolemia, traditional therapies are utilized to decrease LDL-C levels. Patients with FH should receive statins as first-line treatment; high-potency statins at high doses are often required. Despite the use of statins, additional treatments are often necessary to achieve appropriate LDL-C lowering in this patient population. Novel drug therapies that target the pathophysiologic defects of the condition are continuously emerging. Contemporary therapies including mipomersen (Kynamro, Genzyme), an oligonucleotide inhibitor of apo B-100 synthesis; lomitapide (Juxtapid, Aegerion), a microsomal triglyceride transfer protein inhibitor; and alirocumab (Praluent, Sanofi-Aventis/Regeneron) and evolocumab (Repatha, Amgen), PCSK9 inhibitors, are currently approved by the U.S. Food and Drug Administration for use in FH. This review highlights traditional as well as emerging contemporary therapies with supporting clinical data to evaluate current recommendations and discuss the future direction of FH management. PMID:26684558

  18. Plant-made therapeutics: an emerging platform in South Africa.

    PubMed

    Rybicki, Edward P; Chikwamba, Rachel; Koch, Muffy; Rhodes, James I; Groenewald, Jan-Hendrik

    2012-01-01

    The field of plant-made therapeutics in South Africa is well established in the form of exploitation of the country's considerable natural plant diversity, both in the use of native plants in traditional herbal medicines over many centuries, and in the more modern extraction of pharmacologically-active compounds from plants, including those known to traditional healers. In recent years, this has been added to by the use of plants for the stable or transient expression of pharmaceutically-important compounds, largely protein-based biologics and vaccines. South Africa has a well-developed plant biotechnology community, as well as a comprehensive legislative framework for the regulation of the exploitation of local botanic resources, and of genetically-modified organisms. The review explores the investigation of both conventional and recombinant plants for pharmaceutical use in South Africa, as well as describing the relevant legislative and regulatory frameworks. Potential opportunities for national projects, as well as factors limiting biopharming in South Africa are discussed. PMID:21839824

  19. The emerging therapeutic roles of κ-opioid agonists.

    PubMed

    Jones, Mark R; Kaye, Alan D; Kaye, Aaron J; Urman, Richard D

    2016-01-01

    The current practice of μ-opioid receptor agonists such as morphine as the primary means of acute and chronic pain relief has several dangerous consequences that limit their effectiveness, including respiratory depression, gastrointestinal motility inhibition, addiction, tolerance, and abuse. Several other opioid receptors, notably the μ-opioid (KOP) receptor, have long been known to play a role in pain relief. Recent discoveries and advancements in laboratory techniques have allowed significant developments of KOP agonists as potential novel therapies for pain relief and other pathological processes. These drugs exhibit none of the classic opioid adverse effects and have displayed pronounced analgesia in several different scenarios. New formulations since 2014 have unveiled increased oral bioavailability, exceptional peripheral versus central selectivity, and a positive safety profile. Continued refinements of established μ-opioid agonist formulations have virtually eliminated the centrally mediated side effects of dysphoria and sedation that limited the applicability of previous KOP agonists. Further research is required to better elucidate the potential of these compounds in pain management, as well as in the mediation or modulation of other complex pathophysiological processes as therapeutic agents. PMID:27194194

  20. The future of osteoarthritis therapeutics: emerging biological therapy.

    PubMed

    Mobasheri, A

    2013-12-01

    Biological therapy is a thriving area of research and development, and is well established for chronic forms of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, there is no clinically validated biological therapy for osteoarthritis (OA). Chronic forms of OA are increasingly viewed as an inflammatory disease. OA was largely regarded as a "wear and tear disease". However, the disease is now believed to involve "low grade" inflammation and the growth of blood vessels and nerves from the subchondral bone into articular cartilage. This realization has focused research effort on the development and evaluation of biological therapy that targets proinflammatory mediators, angiogenic factors and cytokines in articular cartilage, subchondral bone and synovium in chronic forms of OA. This review article provides an overview of emerging biological therapy for OA, and discusses recent molecular targets implicated in angiogenesis and neurogenesis and progress with antibody-based therapy, calcitonin, and kartogenin, the small molecule stimulator of chondrogenesis. PMID:24170255

  1. Activin signaling as an emerging target for therapeutic interventions

    PubMed Central

    Tsuchida, Kunihiro; Nakatani, Masashi; Hitachi, Keisuke; Uezumi, Akiyoshi; Sunada, Yoshihide; Ageta, Hiroshi; Inokuchi, Kaoru

    2009-01-01

    After the initial discovery of activins as important regulators of reproduction, novel and diverse roles have been unraveled for them. Activins are expressed in various tissues and have a broad range of activities including the regulation of gonadal function, hormonal homeostasis, growth and differentiation of musculoskeletal tissues, regulation of growth and metastasis of cancer cells, proliferation and differentiation of embryonic stem cells, and even higher brain functions. Activins signal through a combination of type I and II transmembrane serine/threonine kinase receptors. Activin receptors are shared by multiple transforming growth factor-β (TGF-β) ligands such as myostatin, growth and differentiation factor-11 and nodal. Thus, although the activity of each ligand is distinct, they are also redundant, both physiologically and pathologically in vivo. Activin receptors activated by ligands phosphorylate the receptor-regulated Smads for TGF-β, Smad2 and 3. The Smad proteins then undergo multimerization with the co-mediator Smad4, and translocate into the nucleus to regulate the transcription of target genes in cooperation with nuclear cofactors. Signaling through receptors and Smads is controlled by multiple mechanisms including phosphorylation and other posttranslational modifications such as sumoylation, which affect potein localization, stability and transcriptional activity. Non-Smad signaling also plays an important role in activin signaling. Extracellularly, follistatin and related proteins bind to activins and related TGF-β ligands, and control the signaling and availability of ligands. The functions of activins through activin receptors are pleiotrophic, cell type-specific and contextual, and they are involved in the etiology and pathogenesis of a variety of diseases. Accordingly, activin signaling may be a target for therapeutic interventions. In this review, we summarize the current knowledge on activin signaling and discuss the potential roles of

  2. Protein Kinases: Emerging Therapeutic Targets in Chronic Lymphocytic Leukemia

    PubMed Central

    Balakrishnan, Kumudha; Gandhi, Varsha

    2014-01-01

    Introduction Although protein kinases are primary targets for inhibition in hematological malignancies, until recently their contribution to chronic lymphocytic leukemia (CLL) was poorly understood. Insights into B cell receptor (BCR) signaling and its role in regulating key cellular functions have shed light on candidate protein kinases that are aberrantly activated in CLL. In this regard, protein kinases are now considered as potential drug targets in CLL. Area covered This review has covered signaling pathways and associated protein kinases in CLL and the kinase inhibitors currently available in preclinical and clinical investigations. Individual protein kinases that are abnormally active in CLL and the functional consequences of their inhibition are discussed. Expert opinion A growing body of evidence suggests that protein kinases are druggable targets for patients with CLL. The emergence of novel and bio-available kinase inhibitors and their promising clinical activity in CLL underscore the oncogenic role of kinases in leukemogenesis. Further investigations directed towards their role as single agents or in combinations may provide insight into understanding the substantial role of kinase mediated signal transduction pathways and their inhibition in B- CLL. PMID:22409342

  3. The potential for emerging therapeutic options for Clostridium difficile infection

    PubMed Central

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

    2014-01-01

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

  4. The Cytokine Model of Schizophrenia: Emerging Therapeutic Strategies

    PubMed Central

    Brown, Alan S.

    2014-01-01

    We discuss the rationale for a trial of a novel biologic immunotherapy in schizophrenia (SZ). Available antipsychotic treatments for SZ are often limited by partial effectiveness and significant side effects. Thus, the search for novel medications is of high priority. All current antipsychotics function primarily by blocking D2-type dopamine receptors. An emerging theory of SZ postulates disturbances of cytokines and inflammatory mediators (i.e., the cytokine model), possibly originating in part from infectious exposures. Cytokines are one of the most important components of the immune system that orchestrate the response to infectious and other exogenous insults. Preclinical models of SZ support a convergence between a role for certain cytokines in the pathophysiology of SZ and major neurochemical postulates of the disorder, including the dopamine and glutamate hypotheses. Furthermore, several cytokines are elevated in plasma in SZ, and Positron Emission Tomography (PET) studies have shown active inflammation in the brains of individuals with psychosis. Treatment studies of certain anti-inflammatory agents, such as celecoxib and aspirin, in patients with SZ have provided further support for neuroinflammation in this disorder. The recent development of approved biological therapies for autoimmune diseases provides us with new opportunities to directly target cytokine signaling as a novel treatment strategy in SZ. In addition, advances in imaging, immunology, and psychopharmacology have paved the way for utilizing measures of target engagement of neuroimmune components that would facilitate the identification of patient subgroups who are most likely to benefit from cytokine modulation. PMID:24439555

  5. Emerging innovative therapeutic approaches targeting PCSK9 to lower lipids.

    PubMed

    Shantha, G P S; Robinson, J G

    2016-01-01

    Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015. In addition to robust LDL-C lowering (nearly 50-65% from baseline), they improve other lipid parameters as well. Adverse events associated with these medications are minimal. Importantly, they improve clinical cardiovascular disease outcomes, although long-term study results are awaited. Cost may be an important limiting factor in their use and we propose two possible solutions which can potentially curtail cost. PMID:26492546

  6. Voluntary emergence and water detection in a newly recognized amphibious fish.

    PubMed

    Magellan, K

    2015-06-01

    Galaxias 'nebula', a small fish which has adaptations for air-breathing but is not known to be amphibious, voluntarily emerged from water and, in an unfamiliar environment, moved preferentially towards an alternative water source. Nebula may thus be considered one of the few truly amphibious fishes, and their ability to detect water provides a selective advantage which aids their survival in unpredictable natural environments. PMID:25924804

  7. The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic.

    PubMed

    Scatena, Roberto; Bottoni, Patrizia; Botta, Giorgia; Martorana, Giuseppe E; Giardina, Bruno

    2007-07-01

    In addition to their well-known critical role in energy metabolism, mitochondria are now recognized as the location where various catabolic and anabolic processes, calcium fluxes, various oxygen-nitrogen reactive species, and other signal transduction pathways interact to maintain cell homeostasis and to mediate cellular responses to different stimuli. It is important to consider how pharmacological agents affect mitochondrial biochemistry, not only because of toxicological concerns but also because of potential therapeutic applications. Several potential targets could be envisaged at the mitochondrial level that may underlie the toxic effects of some drugs. Recently, antiviral nucleoside analogs have displayed mitochondrial toxicity through the inhibition of DNA polymerase-gamma (pol-gamma). Other drugs that target different components of mitochondrial channels can disrupt ion homeostasis or interfere with the mitochondrial permeability transition pore. Many known inhibitors of the mitochondrial electron transfer chain act by interfering with one or more of the respiratory chain complexes. Nonsteroidal anti-inflammatory drugs (NSAIDs), for example, may behave as oxidative phosphorylation uncouplers. The mitochondrial toxicity of other drugs seems to depend on free radical production, although the mechanisms have not yet been clarified. Meanwhile, drugs targeting mitochondria have been used to treat mitochondrial dysfunctions. Importantly, drugs that target the mitochondria of cancer cells have been developed recently; such drugs can trigger apoptosis or necrosis of the cancer cells. Thus the aim of this review is to highlight the role of mitochondria in pharmacotoxicology, and to describe whenever possible the main molecular mechanisms underlying unwanted and/or therapeutic effects. PMID:17475665

  8. ‘BRICS without straw’? A systematic literature review of newly emerging economies’ influence in global health

    PubMed Central

    2013-01-01

    Background Since 2010, five newly emerging economies collectively known as ‘BRICS’ (Brazil, India, Russia, China and South Africa) have caught the imagination, and scholarly attention, of political scientists, economists and development specialists. The prospect of a unified geopolitical bloc, consciously seeking to re-frame international (and global) health development with a new set of ideas and values, has also, if belatedly, begun to attract the attention of the global health community. But what influence, if any, do the BRICS wield in global health, and, if they do wield influence, how has that influence been conceptualized and recorded in the literature? Methods We conducted a systematic literature review in (March-December 2012) of documents retrieved from the databases EMBASE, PubMed/Medline, Global Health, and Google Scholar, and the websites of relevant international organisations, research institutions and philanthropic organisations. The results were synthesised using a framework of influence developed for the review from the political science literature. Results Our initial search of databases and websites yielded 887 documents. Exclusion criteria narrowed the number of documents to 71 journal articles and 23 reports. Two researchers using an agreed set of inclusion criteria independently screened the 94 documents, leaving just 7 documents. We found just one document that provided sustained analysis of the BRICS’ collective influence; the overwhelming tendency was to describe individual BRICS countries influence. Although influence was predominantly framed by BRICS countries’ material capability, there were examples of institutional and ideational influence - particularly from Brazil. Individual BRICS countries were primarily ‘opportunity seekers’ and region mobilisers but with potential to become ‘issue leaders’ and region organisers. Conclusion Though small in number, the written output on BRICS influence in global health has

  9. Limited and localized outbreak of newly emergent type 2 vaccine-derived poliovirus in Sichuan, China.

    PubMed

    Yan, Dongmei; Zhang, Yong; Zhu, Shuangli; Chen, Na; Li, Xiaolei; Wang, Dongyan; Ma, Xiaozhen; Zhu, Hui; Tong, Wenbin; Xu, Wenbo

    2014-07-01

    From August 2011 to February 2012, an outbreak caused by type 2 circulating vaccine-derived poliovirus (cVDPV) occurred in Aba County, Sichuan, China. During the outbreak, four type 2 VDPVs (≥0.6% nucleotide divergence in the VP1 region relative to the Sabin 2 strain) were isolated from 3 patients with acute flaccid paralysis (AFP) and one close contact. In addition, a type 2 pre-VDPV (0.3% to 0.5% divergence from Sabin 2) that was genetically related to these type 2 VDPVs was isolated from another AFP patient. These 4 patients were all unimmunized children 0.7 to 1.1 years old. Nucleotide sequencing revealed that the 4 VDPV isolates differed from Sabin 2 by 0.7% to 1.2% in nucleotides in the VP1 region and shared 5 nucleotide substitutions with the pre-VDPV. All 5 isolates were closely related, and all were S2/S3/S2/S3 recombinants sharing common recombination crossover sites. Although the two major determinants of attenuation and temperature sensitivity phenotype of Sabin 2 (A481 in the 5' untranslated region and Ile143 in the VP1 protein) had reverted in all 5 isolates, one VDPV (strain CHN16017) still retained the temperature sensitivity phenotype. Phylogenetic analysis of the third coding position of the complete P1 coding region suggested that the cVDPVs circulated locally for about 7 months following the initiating oral poliovirus vaccine (OPV) dose. Our findings reinforce the point that cVDPVs can emerge and spread in isolated communities with immunity gaps and highlight the emergence risks of type 2 cVDPVs accompanying the trivalent OPV used. To solve this issue, it is recommended that type 2 OPV be removed from the trivalent OPV or that inactivated polio vaccine (IPV) be used instead. PMID:24850620

  10. Structural, Antigenic, and Evolutionary Characterizations of the Envelope Protein of Newly Emerging Duck Tembusu Virus

    PubMed Central

    Huang, Bing; Ma, Xiuli; Li, Yufeng; Yuan, Xiaoyuan; Qin, Zhuoming; Wang, Dan; Chakravarty, Suvobrata; Li, Feng; Song, Minxun; Sun, Huaichang

    2013-01-01

    Since the first reported cases of ducks infected with a previously unknown flavivirus in eastern China in April 2010, the virus, provisionally designated Duck Tembusu Virus (DTMUV), has spread widely in domestic ducks in China and caused significant economic losses to poultry industry. In this study, we examined in detail structural, antigenic, and evolutionary properties of envelope (E) proteins of six DTMUV isolates spanning 2010–2012, each being isolated from individual farms with different geographical locations where disease outbreaks were documented. Structural analysis showed that E proteins of DTMUV and its closely related flavivirus (Japanese Encephalitis Virus) shared a conserved array of predicted functional domains and motifs. Among the six DTMUV strains, mutations were observed only at thirteen amino acid positions across three separate domains of the E protein. Interestingly, these genetic polymorphisms resulted in no detectable change in viral neutralization properties as demonstrated in a serum neutralization assay. Furthermore, phylogenetic analysis of the nucleotide sequences of the E proteins showed that viruses evolved into two distinct genotypes, termed as DTMUV.I and DTMUV.II, with II emerging as the dominant genotype. New findings described here shall give insights into the antigenicity and evolution of this new pathogen and provide guidance for further functional studies of the E protein for which no effective vaccine has yet been developed. PMID:23990944

  11. Newly Emerged Populations of Plasmopara halstedii Infecting Rudbeckia Exhibit Unique Genotypic Profiles and Are Distinct from Sunflower-Infecting Strains.

    PubMed

    Rivera, Yazmín; Salgado-Salazar, Catalina; Gulya, Thomas J; Crouch, Jo Anne

    2016-07-01

    The oomycete Plasmopara halstedii emerged at the onset of the 21st century as a destructive new pathogen causing downy mildew disease of ornamental Rudbeckia fulgida (rudbeckia) in the United States. The pathogen is also a significant global problem of sunflower (Helianthus annuus) and is widely regarded as the cause of downy mildew affecting 35 Asteraceae genera. To determine whether rudbeckia and sunflower downy mildew are caused by the same genotypes, population genetic and phylogenetic analyses were performed. A draft genome assembly of a P. halstedii isolate from sunflower was generated and used to design 15 polymorphic simple sequence repeat (SSR) markers. SSRs and two sequenced phylogenetic markers measured differentiation between 232 P. halstedii samples collected from 1883 to 2014. Samples clustered into two main groups, corresponding to host origin. Sunflower-derived samples separated into eight admixed subclusters, and rudbeckia-derived samples further separated into three subclusters. Pre-epidemic rudbeckia samples clustered separately from modern strains. Despite the observed genetic distinction based on host origin, P. halstedii from rudbeckia could infect sunflower, and exhibited the virulence phenotype of race 734. These data indicate that the newly emergent pathogen populations infecting commercial rudbeckia are a different species from sunflower-infecting strains, notwithstanding cross-infectivity, and genetically distinct from pre-epidemic populations infecting native rudbeckia hosts. PMID:27003506

  12. Isolation and molecular characterization of newly emerging avian reovirus variants and novel strains in Pennsylvania, USA, 2011–2014

    PubMed Central

    Lu, Huaguang; Tang, Yi; Dunn, Patricia A.; Wallner-Pendleton, Eva A.; Lin, Lin; Knoll, Eric A.

    2015-01-01

    Avian reovirus (ARV) infections of broiler and turkey flocks have caused significant clinical disease and economic losses in Pennsylvania (PA) since 2011. Most of the ARV-infected birds suffered from severe arthritis, tenosynovitis, pericarditis and depressed growth or runting-stunting syndrome (RSS). A high morbidity (up to 20% to 40%) was observed in ARV-affected flocks, and the flock mortality was occasionally as high as 10%. ARV infections in turkeys were diagnosed for the first time in PA in 2011. From 2011 to 2014, a total of 301 ARV isolations were made from affected PA poultry. The molecular characterization of the Sigma C gene of 114 field isolates, representing most ARV outbreaks, revealed that only 21.93% of the 114 sequenced ARV isolates were in the same genotyping cluster (cluster 1) as the ARV vaccine strains (S1133, 1733, and 2048), whereas 78.07% of the sequenced isolates were in genotyping clusters 2, 3, 4, 5, and 6 (which were distinct from the vaccine strains) and represented newly emerging ARV variants. In particular, genotyping cluster 6 was a new ARV genotype that was identified for the first time in 10 novel PA ARV variants of field isolates. PMID:26469681

  13. Recent Patents on Emerging Therapeutics for the Treatment of Glaucoma, Age Related Macular Degeneration and Uveitis

    PubMed Central

    Vadlapudi, Aswani Dutt; Patel, Ashaben; Cholkar, Kishore; Mitra, Ashim K.

    2014-01-01

    Advancements in the field and rising interest among pharmaceutical researchers have led to the development of new molecules with enhanced therapeutic activity. Design of new drugs which can target a particular pathway and/or explore novel targets is of immense interest to ocular pharmacologists worldwide. Delivery of suitable pharmacologically active agents at proper dose (within the therapeutic window) to the target tissues without any toxicity to the healthy ocular tissues still remain an elusive task. Moreover, the presence of static and dynamic barriers to drug absorption including the corneal epithelium (lipophilic), corneal and scleral stroma (hydrophilic), conjunctival lymphatics, choroidal vasculature and the blood-ocular barriers also pose a significant challenge for achieving therapeutic drug concentrations at the target site. Although many agents are currently available, new compounds are being introduced for treating various ocular diseases. Deeper understanding of the etiology and complex mechanisms associated with the disease condition would aid in the development of potential therapeutic candidates. Novel small molecules as well as complex biotechnology derived macromolecules with superior efficacy, safety and tolerability are being developed. Therefore, this review article provides an overview of existing drugs, treatment options, advances in emerging therapeutics and related recent patents for the treatment of ocular disorders such as glaucoma, age related macular degeneration (AMD) and uveitis. PMID:25414810

  14. A Budget Impact Analysis of Newly Available Hepatitis C Therapeutics and the Financial Burden on a State Correctional System.

    PubMed

    Nguyen, John T; Rich, Josiah D; Brockmann, Bradley W; Vohr, Fred; Spaulding, Anne; Montague, Brian T

    2015-08-01

    Hepatitis C virus (HCV) infection continues to disproportionately affect incarcerated populations. New HCV drugs present opportunities and challenges to address HCV in corrections. The goal of this study was to evaluate the impact of the treatment costs for HCV infection in a state correctional population through a budget impact analysis comparing differing treatment strategies. Electronic and paper medical records were reviewed to estimate the prevalence of hepatitis C within the Rhode Island Department of Corrections. Three treatment strategies were evaluated as follows: (1) treating all chronically infected persons, (2) treating only patients with demonstrated fibrosis, and (3) treating only patients with advanced fibrosis. Budget impact was computed as the percentage of pharmacy and overall healthcare expenditures accrued by total drug costs assuming entirely interferon-free therapy. Sensitivity analyses assessed potential variance in costs related to variability in HCV prevalence, genotype, estimated variation in market pricing, length of stay for the sentenced population, and uptake of newly available regimens. Chronic HCV prevalence was estimated at 17% of the total population. Treating all sentenced inmates with at least 6 months remaining of their sentence would cost about $34 million-13 times the pharmacy budget and almost twice the overall healthcare budget. Treating inmates with advanced fibrosis would cost about $15 million. A hypothetical 50% reduction in total drug costs for future therapies could cost $17 million to treat all eligible inmates. With immense costs projected with new treatment, it is unlikely that correctional facilities will have the capacity to treat all those afflicted with HCV. Alternative payment strategies in collaboration with outside programs may be necessary to curb this epidemic. In order to improve care and treatment delivery, drug costs also need to be seriously reevaluated to be more accessible and equitable now that HCV

  15. Plant Alkaloids as an Emerging Therapeutic Alternative for the Treatment of Depression

    PubMed Central

    Perviz, Sadia; Khan, Haroon; Pervaiz, Aini

    2016-01-01

    Depression is a heterogeneous mood disorder that has been classified and treated in a variety of ways. Although, a number of synthetic drugs are being used as standard treatment for clinically depressed patients, but they have adverse effects that can compromise the therapeutic treatments and patient's compliance. Unlike, synthetic medications, herbal medicines are widely used across the globe due to their wide applicability and therapeutic efficacy associated with least side effects, which in turn has initiated the scientific research regarding the antidepressant activity. This review is mostly based on the literature of the last decade, aimed at exploring the preclinical profile of plant-based alkaloids (the abundant secondary metabolite) as an emerging therapy for depression. PMID:26913004

  16. Emerging therapeutic targets in metastatic progression: A focus on breast cancer.

    PubMed

    Li, Zhuo; Kang, Yibin

    2016-05-01

    Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor-intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. PMID:27000769

  17. Emerging therapeutic delivery capabilities and challenges utilizing enzyme/protein packaged bacterial vesicles.

    PubMed

    Alves, Nathan J; Turner, Kendrick B; Medintz, Igor L; Walper, Scott A

    2015-07-01

    Nanoparticle-based therapeutics are poised to play a critical role in treating disease. These complex multifunctional drug delivery vehicles provide for the passive and active targeted delivery of numerous small molecule, peptide and protein-derived pharmaceuticals. This article will first discuss some of the current state of the art nanoparticle classes (dendrimers, lipid-based, polymeric and inorganic), highlighting benefits/drawbacks associated with their implementation. We will then discuss an emerging class of nanoparticle therapeutics, bacterial outer membrane vesicles, that can provide many of the nanoparticle benefits while simplifying assembly. Through molecular biology techniques; outer membrane vesicle hijacking potentially allows for stringent control over nanoparticle production allowing for targeted protein packaged nanoparticles to be fully synthesized by bacteria. PMID:26228777

  18. Current and emerging therapeutic options for the treatment of chronic chagasic cardiomyopathy

    PubMed Central

    Muratore, Claudio A; Baranchuk, Adrian

    2010-01-01

    Chagas’ disease is an endemic disease in Latin America caused by a unicellular parasite (Trypanosoma cruzi) that affects almost 18 million people. This condition involves the heart, causing heart failure, arrhythmias, heart block, thromboembolism, stroke, and sudden death. In this article, we review the current and emerging treatment of Chagas’ cardiomyopathy focusing mostly on management of heart failure and arrhythmias. Heart failure therapeutical options including drugs, stem cells and heart transplantation are revised. Antiarrhythmic drugs, catheter ablation, and intracardiac devices are discussed as well. Finally, the evidence for a potential role of specific antiparasitic treatment for the prevention of cardiovascular disease is reviewed. PMID:20730015

  19. Scabies: molecular perspectives and therapeutic implications in the face of emerging drug resistance.

    PubMed

    Mounsey, Kate E; Holt, Deborah C; McCarthy, James; Currie, Bart J; Walton, Shelley F

    2008-02-01

    Limited effective treatments, coupled with recent observations of emerging drug resistance to oral ivermectin and 5% permethrin, raise concerns regarding the future control of scabies, especially in severe cases and in endemic areas where repeated community treatment programs are in place. There is consequently an urgent need to define molecular mechanisms of drug resistance in scabies mites and to develop and assess alternative therapeutic options, such as tea tree oil, in the event of increasing treatment failure. Molecular studies on scabies mites have, until recently, been restricted; however, recent advances are providing new insights into scabies mite biology and genetic mechanisms underlying drug resistance. These may assist in overcoming many of the current difficulties in monitoring treatment efficacy and allow the development of more sensitive tools for monitoring emerging resistance. PMID:18230034

  20. SU-E-T-571: Newly Emerging Integrated Transmission Detector Systems Provide Online Quality Assurance of External Beam Radiation Therapy

    SciTech Connect

    Hoffman, D; Chung, E; Hess, C; Stern, R; Benedict, S

    2015-06-15

    Purpose: Two newly emerging transmission detectors positioned upstream from the patient have been evaluated for online quality assurance of external beam radiotherapy. The prototype for the Integral Quality Monitor (IQM), developed by iRT Systems GmbH (Koblenz, Germany) is a large-area ion chamber mounted on the linac accessory tray to monitor photon fluence, energy, beam shape, and gantry position during treatment. The ion chamber utilizes a thickness gradient which records variable response dependent on beam position. The prototype of Delta4 Discover™, developed by ScandiDos (Uppsala, Sweden) is a linac accessory tray mounted 4040 diode array that measures photon fluence during patient treatment. Both systems are employable for patient specific QA prior to treatment delivery. Methods: Our institution evaluated the reproducibility of measurements using various beam types, including VMAT treatment plans with both the IQM ion chamber and the Delta4 Discover diode array. Additionally, the IQM’s effect on photon fluence, dose response, simulated beam error detection, and the accuracy of the integrated barometer, thermometer, and inclinometer were characterized. The evaluated photon beam errors are based on the annual tolerances specified in AAPM TG-142. Results: Repeated VMAT treatments were measured with 0.16% reproducibility by the IQM and 0.55% reproducibility by the Delta4 Discover. The IQM attenuated 6, 10, and 15 MV photon beams by 5.43±0.02%, 4.60±0.02%, and 4.21±0.03% respectively. Photon beam profiles were affected <1.5% in the non-penumbra regions. The IQM’s ion chamber’s dose response was linear and the thermometer, barometer, and inclinometer agreed with other calibrated devices. The device detected variations in monitor units delivered (1%), field position (3mm), single MLC leaf positions (13mm), and photon energy. Conclusion: We have characterized two new transmissions detector systems designed to provide in-vivo like measurements upstream

  1. Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes

    PubMed Central

    Kimple, Michelle E; Neuman, Joshua C; Linnemann, Amelia K; Casey, Patrick J

    2014-01-01

    The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology. PMID:24946790

  2. Inhibitory G proteins and their receptors: emerging therapeutic targets for obesity and diabetes.

    PubMed

    Kimple, Michelle E; Neuman, Joshua C; Linnemann, Amelia K; Casey, Patrick J

    2014-01-01

    The worldwide prevalence of obesity is steadily increasing, nearly doubling between 1980 and 2008. Obesity is often associated with insulin resistance, a major risk factor for type 2 diabetes mellitus (T2DM): a costly chronic disease and serious public health problem. The underlying cause of T2DM is a failure of the beta cells of the pancreas to continue to produce enough insulin to counteract insulin resistance. Most current T2DM therapeutics do not prevent continued loss of insulin secretion capacity, and those that do have the potential to preserve beta cell mass and function are not effective in all patients. Therefore, developing new methods for preventing and treating obesity and T2DM is very timely and of great significance. There is now considerable literature demonstrating a link between inhibitory guanine nucleotide-binding protein (G protein) and G protein-coupled receptor (GPCR) signaling in insulin-responsive tissues and the pathogenesis of obesity and T2DM. These studies are suggesting new and emerging therapeutic targets for these conditions. In this review, we will discuss inhibitory G proteins and GPCRs that have primary actions in the beta cell and other peripheral sites as therapeutic targets for obesity and T2DM, improving satiety, insulin resistance and/or beta cell biology. PMID:24946790

  3. Targeted therapeutics in SLE: emerging strategies to modulate the interferon pathway

    PubMed Central

    Oon, Shereen; Wilson, Nicholas J; Wicks, Ian

    2016-01-01

    Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by impaired immune tolerance, resulting in the generation of pathogenic autoantibodies and immune complexes. Although autoreactive B lymphocytes have been the first targets for biologic therapies in SLE, the importance of the innate immune system, and in particular, pathways involved in interferon (IFN) signaling, has emerged. There are now data supporting a central role for a plasmacytoid dendritic cell-derived type I IFN pathway in SLE, with a number of biologic therapeutics and small-molecule inhibitors undergoing clinical trials. Monoclonal antibodies targeting IFN-α have completed phase II clinical trials, and an antibody against the type I IFN receptor is entering a phase III trial. However, other IFNs, such as IFN gamma, and the more recently discovered type III IFNs, are also emerging as targets in SLE; and blockade of upstream components of the IFN signaling pathway may enable inhibition of more than one IFN subtype. In this review, we discuss the current understanding of IFNs in SLE, focusing on emerging therapies. PMID:27350879

  4. G protein-coupled receptors as oncogenic signals in glioma: emerging therapeutic avenues

    PubMed Central

    Cherry, Allison E; Stella, Nephi

    2014-01-01

    Gliomas are the most common malignant intracranial tumors. Newly developed targeted therapies for these cancers aim to inhibit oncogenic signals, many of which emanate from receptor tyrosine kinases, including the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR). Unfortunately, the first generation treatments targeting these oncogenic signals provide little survival benefit in both mouse xenograft models and human patients. The search for new treatment options has uncovered several G protein-coupled receptor (GPCR) candidates and generated a growing interest in this class of proteins as alternative therapeutic targets for the treatment of various cancers, including GBM. GPCRs constitute a large family of membrane receptors that influence oncogenic pathways through canonical and non-canonical signaling. Accordingly, evidence indicates that GPCRs display a unique ability to crosstalk with receptor tyrosine kinases, making them important molecular components controlling tumorigenesis. This review summarizes the current research on GPCR functionality in gliomas and explores the potential of modulating these receptors to treat this devastating disease. PMID:25158675

  5. Novel compounds for the treatment of Duchenne muscular dystrophy: emerging therapeutic agents.

    PubMed

    Wilton, Steve D; Fletcher, Sue

    2011-01-01

    The identification of dystrophin and the causative role of mutations in this gene in Duchenne and Becker muscular dystrophies (D/BMD) was expected to lead to timely development of effective therapies. Despite over 20 years of research, corticosteroids remain the only available pharmacological treatment for DMD, although significant benefits and extended life have resulted from advances in the clinical care and management of DMD individuals. Effective treatment of DMD will require dystrophin restitution in skeletal, cardiac, and smooth muscles and nonmuscle tissues; however, modulation of muscle loss and regeneration has the potential to play an important role in altering the natural history of DMD, particularly in combination with other treatments. Emerging biological, molecular, and small molecule therapeutics are showing promise in ameliorating this devastating disease, and it is anticipated that regulatory environments will need to display some flexibility in order to accommodate the new treatment paradigms. PMID:23776365

  6. [The pulmonary-renal syndrome: a diagnostic and therapeutic emergency for the internist and the intensivist].

    PubMed

    Hié, M; Costedoat-Chalumeau, N; Saadoun, D; Azoulay, E

    2013-11-01

    The pulmonary-renal syndrome is a rare and life-threatening condition. It is defined as the association of a diffuse alveolar hemorrhage and a rapidly progressive glomerulonephritis. The characteristic histological lesion common to all underlying diseases is a necrotizing and crescentic glomerulonephritis. The pulmonary-renal syndrome is a diagnostic and therapeutic emergency: any delay in its management will lead to death or serious functional damage as pulmonary and renal impairment. ANCA-associated vasculitis and Goodpasture's disease are the main disorders associated to pulmonary-renal syndrome. More rarely systemic lupus, cryoglobulinaemia, Henoch-Schonlein purpura or subacute endocarditis may induce a pulmonary-renal syndrome. Differential diagnosis can sometimes be difficult, highlighting some ambiguity in the definition of the syndrome. Initial treatment usually associates systemic corticosteroid, cyclophosphamide and plasma exchange. The role of biotherapy as first line therapy remains to be determined. PMID:24140181

  7. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer.

    PubMed

    Qu, Q; Zeng, F; Liu, X; Wang, Q J; Deng, F

    2016-01-01

    Tumor cells exhibit unique metabolic adaptations that are increasingly viewed as potential targets for novel and specific cancer therapies. Among these targets, the carnitine palmitoyltransferase system is responsible for delivering the long-chain fatty acid (FA) from cytoplasm into mitochondria for oxidation, where carnitine palmitoyltransferase I (CPTI) catalyzes the rate-limiting step of fatty acid oxidation (FAO). With increasing understanding of the crucial role had by fatty acid oxidation in cancer, CPTI has received renewed attention as a pivotal mediator in cancer metabolic mechanism. CPTI activates FAO and fuels cancer growth via ATP and NADPH production, constituting an essential part of cancer metabolism adaptation. Moreover, CPTI also functionally intertwines with other key pathways and factors to regulate gene expression and apoptosis of cancer cell. Here, we summarize recent findings and update the current understanding of FAO and CPTI in cancer and provide theoretical basis for this enzyme as an emerging potential molecular target in cancer therapeutic intervention. PMID:27195673

  8. Fatty acid oxidation and carnitine palmitoyltransferase I: emerging therapeutic targets in cancer

    PubMed Central

    Qu, Q; Zeng, F; Liu, X; Wang, Q J; Deng, F

    2016-01-01

    Tumor cells exhibit unique metabolic adaptations that are increasingly viewed as potential targets for novel and specific cancer therapies. Among these targets, the carnitine palmitoyltransferase system is responsible for delivering the long-chain fatty acid (FA) from cytoplasm into mitochondria for oxidation, where carnitine palmitoyltransferase I (CPTI) catalyzes the rate-limiting step of fatty acid oxidation (FAO). With increasing understanding of the crucial role had by fatty acid oxidation in cancer, CPTI has received renewed attention as a pivotal mediator in cancer metabolic mechanism. CPTI activates FAO and fuels cancer growth via ATP and NADPH production, constituting an essential part of cancer metabolism adaptation. Moreover, CPTI also functionally intertwines with other key pathways and factors to regulate gene expression and apoptosis of cancer cell. Here, we summarize recent findings and update the current understanding of FAO and CPTI in cancer and provide theoretical basis for this enzyme as an emerging potential molecular target in cancer therapeutic intervention. PMID:27195673

  9. Recent Patents and Emerging Therapeutics in the Treatment of Allergic Conjunctivitis

    PubMed Central

    Mishra, Gyan P.; Tamboli, Viral; Jwala, Jwala; Mitra, Ashim K.

    2011-01-01

    Ocular allergy is an inflammatory response of the conjunctival mucosa that also affects the cornea and eyelids. Allergic conjunctivitis includes seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), vernal keratoconjunctivitis (VKC), atopic keratoconjunctivitis (AKC) and giant papillary conjunctivitis (GPC). In general, allergic conditions involve mast cell degranulation that leads to release of inflammatory mediators and activation of enzymatic cascades generating pro-inflammatory mediators. In chronic ocular inflammatory disorders associated with mast cell activation such as VKC and AKC constant inflammatory response is observed due to predominance of inflammatory mediators such as eosinophils and Th2-generated cytokines. Antihistamines, mast-cell stabilizers, non-steroidal anti-inflammatory agents, corticosteroids and immunomodulatory agents are commonly indicated for the treatment of acute and chronic allergic conjunctivitis. In recent years newer drug molecules have been introduced in the treatment of allergic conjunctivitis. This article reviews recent patents and emerging therapeutics in the treatment of allergic conjunctivitis. PMID:21171952

  10. Establishing a TaqMan-Based Real-Time PCR Assay for the rapid detection and quantification of the newly emerged duck tembusu virus

    PubMed Central

    2011-01-01

    To establish an accurate, rapid, and a quantifiable method for the detection of the newly emerged duck Tembusu virus (DTMUV) that recently caused a widespread infectious disease in ducks in China, we developed a TaqMan-based real-time PCR assay by using E gene-specific primers and a TaqMan probe. This real-time PCR assay was 100 times more sensitive than the conventional PCR. The reproducibility and specificity of the real-time PCR assay were confirmed using plasmids containing E genes or RNAs and DNAs extracted from well-known viruses causing duck diseases. The reliability of this real-time PCR assay was confirmed in 19 of the 24 swab samples, 22 of the 24 tissue samples collected from experimentally infected ducks, as well as 15 of the 21 clinical samples collected from sick ducks since they were verified as DTMUV-positive. The results reveal that the newly established real-time PCR assay might be a useful diagnostic method for epidemiologically investigating and closely observing the newly emerged DTMUV. PMID:21978536

  11. F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.

    PubMed

    Sukari, Ammar; Muqbil, Irfana; Mohammad, Ramzi M; Philip, Philip A; Azmi, Asfar S

    2016-02-01

    Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. PMID:26804424

  12. Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes.

    PubMed

    Cowan, Elaine; Burch, Kerry J; Green, Brian D; Grieve, David J

    2016-07-01

    Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an α helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain and gastrointestinal motility and also to mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in beta cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with up-regulation of genes associated with beta cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes. PMID:27111465

  13. Uric acid and xanthine oxidase in heart failure - Emerging data and therapeutic implications.

    PubMed

    Doehner, Wolfram; Jankowska, Ewa A; Springer, Jochen; Lainscak, Mitja; Anker, Stefan D

    2016-06-15

    The role of hyperuricaemia as cardiovascular risk factor has exhaustingly been debated for decades. While the association of elevated uric acid (UA) levels with increased mortality risk as convincingly been shown, the question whether UA is independently predictive of just a related effect within a more complex risk factor profile (including metabolic, inflammatory and haemodynamic risk factors) is still a matter of dispute. In heart failure the independent prognostic and functional impact of elevated UA has not only been shown but also the pathophysiologic mechanism(s) and the potential of targeted therapeutic interventions have been investigated in some detail. The emerging picture suggests the increased activity of the enzyme xanthine oxidase (XO) with corresponding increased production of free oxygen radical (ROS) as a main underlying principle with the resulting increase in UA levels being mostly a marker of this up-regulated pathway. While this concept will not diminish the value of UA as a prognostic marker, it provides the basis for a novel metabolic treatment option and the means to identify those patients most eligible for this tailored therapy. This review will summarize the recent evidence on XO as a novel and promising therapeutic target in heart failure. PMID:26318388

  14. [Evolving therapeutic targets in inflammatory Bowel Disease: mucosal healing as an emerging end point].

    PubMed

    Condino, Giovanna; Margagnoni, Giovanna; Aratari, Annalisa; Luchetti, Roberto; Papi, Claudio

    2015-11-01

    In the last years the therapeutic goals of inflammatory bowel disease have changed from control of symptoms only towards long term strategies aimed at modifying the natural history of the disease. In this setting mucosal healing has emerged as an important therapeutic goal both in clinical trials and in clinical practice. Growing evidence suggests that mucosal healing may be associated with lower relapse rates, reduced hospitalizations and reduced need of surgery both in ulcerative colitis and in Crohn's disease. However, a validated definition of mucosal healing is lacking: as a consequence, although several drugs are capable of inducing and maintaining mucosal healing in different clinical settings, the effect size of different treatments is difficult to assess. One of the most important question for clinical practice is if we should systematically assess mucosal healing in all patients and target our treatment strategies to achieve mucosal healing. This review focuses on the definition of mucosal healing and on the ability of different medications to induce and maintain mucosal healing in inflammatory bowel disease. The significance of mucosal healing as a surrogate end point of disease outcome is also discussed. PMID:26668042

  15. The Emerging Role of HMGB1 in Neuropathic Pain: A Potential Therapeutic Target for Neuroinflammation.

    PubMed

    Wan, Wenbin; Cao, Lan; Khanabdali, Ramin; Kalionis, Bill; Tai, Xiantao; Xia, Shijin

    2016-01-01

    Neuropathic pain (NPP) is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1) mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR), receptor for advanced glycation end products (RAGE), C-X-X motif chemokines receptor 4 (CXCR4), and N-methyl-D-aspartate (NMDA) receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP. PMID:27294160

  16. The Emerging Role of HMGB1 in Neuropathic Pain: A Potential Therapeutic Target for Neuroinflammation

    PubMed Central

    Wan, Wenbin; Cao, Lan; Khanabdali, Ramin; Kalionis, Bill; Tai, Xiantao; Xia, Shijin

    2016-01-01

    Neuropathic pain (NPP) is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1) mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR), receptor for advanced glycation end products (RAGE), C-X-X motif chemokines receptor 4 (CXCR4), and N-methyl-D-aspartate (NMDA) receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP. PMID:27294160

  17. A Multi-Method Approach to Curriculum Development for In-Service Training in China’s Newly Established Health Emergency Response Offices

    PubMed Central

    Wang, Yadong; Li, Xiangrui; Yuan, Yiwen; Patel, Mahomed S.

    2014-01-01

    Objective To describe an innovative approach for developing and implementing an in-service curriculum in China for staff of the newly established health emergency response offices (HEROs), and that is generalisable to other settings. Methods The multi-method training needs assessment included reviews of the competency domains needed to implement the International Health Regulations (2005) as well as China’s policies and emergency regulations. The review, iterative interviews and workshops with experts in government, academia, the military, and with HERO staff were reviewed critically by an expert technical advisory panel. Findings Over 1600 participants contributed to curriculum development. Of the 18 competency domains identified as essential for HERO staff, nine were developed into priority in-service training modules to be conducted over 2.5 weeks. Experts from academia and experienced practitioners prepared and delivered each module through lectures followed by interactive problem-solving exercises and desktop simulations to help trainees apply, experiment with, and consolidate newly acquired knowledge and skills. Conclusion This study adds to the emerging literature on China’s enduring efforts to strengthen its emergency response capabilities since the outbreak of SARS in 2003. The multi-method approach to curriculum development in partnership with senior policy-makers, researchers, and experienced practitioners can be applied in other settings to ensure training is responsive and customized to local needs, resources and priorities. Ongoing curriculum development should reflect international standards and be coupled with the development of appropriate performance support systems at the workplace for motivating staff to apply their newly acquired knowledge and skills effectively and creatively. PMID:24971602

  18. Dosimetric characteristics of a newly designed grid block for megavoltage photon radiation and its therapeutic advantage using a linear quadratic model.

    PubMed

    Meigooni, Ali S; Dou, Kai; Meigooni, Navid J; Gnaster, Michael; Awan, Shahid; Dini, Sharifeh; Johnson, Ellis L

    2006-09-01

    Grid radiation therapy with megavoltage x-ray beam has been proven to be an effective technique for management of large, bulky malignant tumors. The clinical advantage of GRID therapy, combined with conventional radiation therapy, has been demonstrated using a prototype GRID block [Mohiuddin, Curtis, Grizos, and Komarnicky, Cancer 66, 114-118 (1990)]. Recently, a new GRID block design with improved dosimetric properties has become commercially available from Radiation Product Design, Inc. (Albertive, MN). This GRID collimator consists of an array of focused apertures in a cerrobend block arranged in a hexagonal pattern having a circular cross-section with a diameter and center-to-center spacing of 14.3 and 21.1 mm, respectively, in the plane of isocenter. In this project, dosimetric characteristics of the newly redesigned GRID block have been investigated for a Varian 21EX linear accelerator (Varian Associates, Palo Alto, CA). These determinations were performed using radiographic films, thermoluminescent dosimeters in Solid Water phantom materials, and an ionization chamber in water. The output factor, percentage depth dose, beam profiles, and isodose distributions of the GRID radiation as a function of field size and beam energy have been measured using both 6 and 18 MV x-ray beams. In addition, the therapeutic advantage obtained from this treatment modality with the new GRID block design for a high, single fraction of dose has been calculated using the linear quadratic model with alpha/beta ratios for typical tumor and normal cells. These biological characteristics of the new GRID block design will also be presented. PMID:17022209

  19. Dosimetric characteristics of a newly designed grid block for megavoltage photon radiation and its therapeutic advantage using a linear quadratic model

    SciTech Connect

    Meigooni, Ali S.; Dou Kai; Meigooni, Navid J.; Gnaster, Michael; Awan, Shahid; Dini, Sharifeh; Johnson, Ellis L.

    2006-09-15

    Grid radiation therapy with megavoltage x-ray beam has been proven to be an effective technique for management of large, bulky malignant tumors. The clinical advantage of GRID therapy, combined with conventional radiation therapy, has been demonstrated using a prototype GRID block [Mohiuddin, Curtis, Grizos, and Komarnicky, Cancer 66, 114-118 (1990)]. Recently, a new GRID block design with improved dosimetric properties has become commercially available from Radiation Product Design, Inc. (Albertive, MN). This GRID collimator consists of an array of focused apertures in a cerrobend block arranged in a hexagonal pattern having a circular cross-section with a diameter and center-to-center spacing of 14.3 and 21.1 mm, respectively, in the plane of isocenter. In this project, dosimetric characteristics of the newly redesigned GRID block have been investigated for a Varian 21EX linear accelerator (Varian Associates, Palo Alto, CA). These determinations were performed using radiographic films, thermoluminescent dosimeters in Solid Water trade mark sign phantom materials, and an ionization chamber in water. The output factor, percentage depth dose, beam profiles, and isodose distributions of the GRID radiation as a function of field size and beam energy have been measured using both 6 and 18 MV x-ray beams. In addition, the therapeutic advantage obtained from this treatment modality with the new GRID block design for a high, single fraction of dose has been calculated using the linear quadratic model with {alpha}/{beta} ratios for typical tumor and normal cells. These biological characteristics of the new GRID block design will also be presented.

  20. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    PubMed Central

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

  1. Application of Emerging Pharmaceutical Technologies for Therapeutic Challenges of Space Exploration Missions

    NASA Technical Reports Server (NTRS)

    Putcha, Lakshmi

    2011-01-01

    An important requirement of therapeutics for extended duration exploration missions beyond low Earth orbit will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and adverse environmental conditions. Availability of sustained, stable and targeted delivery pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepato-renal, musculo-skeletal and immune function are essential to offset adverse effects of space environment beyond low Earth orbit. Specifically, medical needs may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed in space must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nano-carrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of exploration missions. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.

  2. Polymorphic SSR Markers for Plasmopara obducens (Peronosporaceae), the Newly Emergent Downy Mildew Pathogen of Impatiens (Balsaminaceae)

    SciTech Connect

    Salgado-Salazar, Catalina; Rivera, Yazmín; Veltri, Daniel; Crouch, Jo Anne

    2015-11-10

    Premise of the study: Simple sequence repeat (SSR) markers were developed for Plasmopara obducens, the causal agent of the newly emergent downy mildew disease of Impatiens walleriana. Methods and Results: A 202-Mb draft genome assembly was generated from P. obducens using Illumina technology and mined to identify 13,483 SSR motifs. Primers were synthesized for 62 marker candidates, of which 37 generated reliable PCR products. Testing of the 37 markers using 96 P. obducens samples showed 96% of the markers were polymorphic, with 2-6 alleles observed. Observed and expected heterozygosity ranged from 0.000-0.892 and 0.023-0.746, respectively. Just 17 markers were sufficient to identify all multilocus genotypes. Conclusions: These are the first SSR markers available for this pathogen, and one of the first molecular resources. These markers will be useful in assessing variation in pathogen populations and determining the factors contributing to the emergence of destructive impatiens downy mildew disease.

  3. Survival of newly emerged Culex tritaeniorhynchus (Diptera:Culicidae) adults in field cages with or without predators.

    PubMed

    Takagi, M; Sugiyama, A; Maruyama, K

    1996-07-01

    A field experiment was conducted to estimate the survival of Culex tritaeniorhynchus Giles adults before 1st blood feeding under conditions with or without predators in a rice field in central Japan. Adults were counted for 5 d after emerging in cages (2 by 2 and 1.5 m high), which were placed in rice fields during the midseason drying period. Only 10% of the adults survived until day 4 after emergence when exposed to predation, whereas > 60% of the adults survived until day 4 without predation. Lycosidae, hunting spiders, may be an effective predator of Cx. tritaeniorhynchus adults. PMID:8699471

  4. Arginase: The Emerging Therapeutic Target for Vascular Oxidative Stress and Inflammation

    PubMed Central

    Yang, Zhihong; Ming, Xiu-Fen

    2013-01-01

    Oxidative stress and inflammation in the vascular wall are essential mechanisms of atherosclerosis and vascular dysfunctions associated with risk factors such as metabolic diseases, aging, hypertension, etc. Evidence has been provided that activation of the vascular endothelial cells in the presence of the risk factors promotes oxidative stress and vascular inflammatory responses, leading to acceleration of atherosclerotic vascular disease. Increasing number of studies from recent years demonstrates that uncoupling of endothelial nitric oxide synthase (eNOS), whereby the enzyme eNOS produces detrimental amount of superoxide anion O2− instead the vasoprotective nitric oxide (NO⋅), plays a critical role in vascular dysfunction under various pathophysiological conditions and in aging. The mechanisms of eNOS-uncoupling seem multiple and complex. Recent research provides emerging evidence supporting an essential role of increased activity of arginases including arginase-I and arginase-II in causing eNOS-uncoupling, which results in vascular oxidative stress and inflammatory responses, and ultimately leading to vascular diseases. This review article will summarize the most recent findings on the functional roles of arginases in vascular diseases and/or dysfunctions and the underlying mechanisms in relation to oxidative stress and inflammations. Moreover, regulatory mechanisms of arginases in the vasculature are reviewed and the future perspectives of targeting arginases as therapeutic options in vascular diseases are discussed. PMID:23781221

  5. Adenosine, ketogenic diet and epilepsy: the emerging therapeutic relationship between metabolism and brain activity.

    PubMed

    Masino, S A; Kawamura, M; Wasser, C D; Wasser, C A; Pomeroy, L T; Ruskin, D N

    2009-09-01

    For many years the neuromodulator adenosine has been recognized as an endogenous anticonvulsant molecule and termed a "retaliatory metabolite." As the core molecule of ATP, adenosine forms a unique link between cell energy and neuronal excitability. In parallel, a ketogenic (high-fat, low-carbohydrate) diet is a metabolic therapy that influences neuronal activity significantly, and ketogenic diets have been used successfully to treat medically-refractory epilepsy, particularly in children, for decades. To date the key neural mechanisms underlying the success of dietary therapy are unclear, hindering development of analogous pharmacological solutions. Similarly, adenosine receptor-based therapies for epilepsy and myriad other disorders remain elusive. In this review we explore the physiological regulation of adenosine as an anticonvulsant strategy and suggest a critical role for adenosine in the success of ketogenic diet therapy for epilepsy. While the current focus is on the regulation of adenosine, ketogenic metabolism and epilepsy, the therapeutic implications extend to acute and chronic neurological disorders as diverse as brain injury, inflammatory and neuropathic pain, autism and hyperdopaminergic disorders. Emerging evidence for broad clinical relevance of the metabolic regulation of adenosine will be discussed. PMID:20190967

  6. Emerging aspects of nanotoxicology in health and disease: From agriculture and food sector to cancer therapeutics.

    PubMed

    Piperigkou, Zoi; Karamanou, Konstantina; Engin, Ayse Basak; Gialeli, Chrysostomi; Docea, Anca Oana; Vynios, Demitrios H; Pavão, Mauro S G; Golokhvast, Kirill S; Shtilman, Mikhail I; Argiris, Athanassios; Shishatskaya, Ekaterina; Tsatsakis, Aristidis M

    2016-05-01

    Nanotechnology is an evolving scientific field that has allowed the manufacturing of materials with novel physicochemical and biological properties, offering a wide spectrum of potential applications. Properties of nanoparticles that contribute to their usefulness include their markedly increased surface area in relation to mass, surface reactivity and insolubility, ability to agglomerate or change size in different media and enhanced endurance over conventional-scale substance. Here, we review nanoparticle classification and their emerging applications in several fields; from active food packaging to drug delivery and cancer research. Nanotechnology has exciting therapeutic applications, including novel drug delivery for the treatment of cancer. Additionally, we discuss that exposure to nanostructures incorporated to polymer composites, may result in potential human health risks. Therefore, the knowledge of processes, including absorption, distribution, metabolism and excretion, as well as careful toxicological assessment is critical in order to determine the effects of nanomaterials in humans and other biological systems. Expanding the knowledge of nanoparticle toxicity will facilitate designing of safer nanocomposites and their application in a beneficial manner. PMID:26969113

  7. Emergence of Yalom's therapeutic factors in a peer-led, asynchronous, online support group for family caregivers.

    PubMed

    Diefenbeck, Cynthia A; Klemm, Paula R; Hayes, Evelyn R

    2014-01-01

    Support groups fill a critical void in the health care system, harnessing the power of shared experiences to provide support to group members. Likewise, family caregivers fill a void in the health care system, providing billions in unpaid care to the chronically ill. Caregiver support groups offer an opportunity for alleviating the psychological burden of caregiving. The power of any group, including a support group, to foster psychological well-being lies in its ability to cultivate Yalom's therapeutic factors. Gaps in the literature remain regarding the ability of non-prototypical groups to promote therapeutic mechanisms of change. The purpose of this study was to determine if and when Yalom's therapeutic group factors emerged in a peer-led support group delivered in an asynchronous, online format. Qualitative content analysis utilizing deductive category application was employed. Participants' responses were coded and frequency counts were conducted. Results revealed that 9 of 11 therapeutic factors emerged over the course of the group, with Group Cohesiveness, Catharsis, Imparting of Information, and Universality occurring most often. Several factors, including Interpersonal Learning, Corrective Recapitulation of the Primary Family Group, Imitative Behavior, and Development of Socializing Techniques were absent or virtually absent, likely due to the peer-led format of the group. Progression of therapeutic factors over the course of the group is presented. Findings demonstrate the presence of a variety of Yalom's therapeutic factors in an asynchronous, peer-led online support group. PMID:24350748

  8. Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications

    PubMed Central

    De Toro, Julieta; Herschlik, Leticia; Waldner, Claudia; Mongini, Claudia

    2015-01-01

    infectious diseases such as tuberculosis, diphtheria, and toxoplasmosis as well as infections caused by prions or viruses such as HIV. The aim of this review is to disclose the emerging roles of exosomes in normal and pathological conditions and to discuss their potential therapeutic applications. PMID:25999947

  9. Preventing the next 'SARS' - European healthcare workers' attitudes towards monitoring their health for the surveillance of newly emerging infections: qualitative study

    PubMed Central

    2011-01-01

    Background Hospitals are often the epicentres of newly circulating infections. Healthcare workers (HCWs) are at high risk of acquiring infectious diseases and may be among the first to contract emerging infections. This study aims to explore European HCWs' perceptions and attitudes towards monitoring their absence and symptom reports for surveillance of newly circulating infections. Methods A qualitative study with thematic analysis was conducted using focus group methodology. Forty-nine hospital-based HCWs from 12 hospitals were recruited to six focus groups; two each in England and Hungary and one each in Germany and Greece. Results HCWs perceived risk factors for occupationally acquired infectious diseases to be 1.) exposure to patients with undiagnosed infections 2.) break-down in infection control procedures 3.) immuno-naïvety and 4.) symptomatic colleagues. They were concerned that a lack of monitoring and guidelines for infectious HCWs posed a risk to staff and patients and felt employers failed to take a positive interest in their health. Staffing demands and loss of income were noted as pressures to attend work when unwell. In the UK, Hungary and Greece participants felt monitoring staff absence and the routine disclosure of symptoms could be appropriate provided the effectiveness and efficiency of such a system were demonstrable. In Germany, legislation, privacy and confidentiality were identified as barriers. All HCWs highlighted the need for knowledge and structural improvements for timelier recognition of emerging infections. These included increased suspicion and awareness among staff and standardised, homogenous absence reporting systems. Conclusions Monitoring absence and infectious disease symptom reports among HCWs may be a feasible means of surveillance for emerging infections in some settings. A pre-requisite will be tackling the drivers for symptomatic HCWs to attend work. PMID:21740552

  10. Aspects of pathogen genomics, diversity, epidemiology, vector dynamics, and disease management for a newly emerged disease of potato: zebra chip.

    PubMed

    Lin, Hong; Gudmestad, Neil C

    2013-06-01

    An overview is provided for the aspects of history, biology, genomics, genetics, and epidemiology of zebra chip (ZC), a destructive disease of potato (Solanum tuberosum) that represents a major threat to the potato industries in the United States as well as other potato-production regions in the world. The disease is associated with a gram-negative, phloem-limited, insect-vectored, unculturable prokaryote, 'Candidatus Liberibacter solanacearum', that belongs to the Rhizobiaceae family of α-Proteobacteria. The closest cultivated relatives of 'Ca. L. solanacearum' are members of the group of bacteria known as the α-2 subgroup. In spite of the fact that Koch's postulates sensu stricto have not been fulfilled, a great deal of progress has been made in understanding the ZC disease complex since discovery of the disease. Nevertheless, more research is needed to better understand vector biology, disease mechanisms, host response, and epidemiology in the context of vector-pathogen-plant interactions. Current ZC management strategies focus primarily on psyllid control. The ultimate control of ZC likely relies on host resistance. Unfortunately, all commercial potato cultivars are susceptible to ZC. Elucidation of the 'Ca. L. solanacearum' genome sequence has provided insights into the genetic basis of virulence and physiological and metabolic capability of this organism. Finally, the most effective, sustainable management of ZC is likely to be based on integrated strategies, including removal or reduction of vectors or inocula, improvement of host resistance to the presumptive pathogen and psyllid vectors, and novel gene-based therapeutic treatment. PMID:23268582

  11. A Newly Emerged Swine-Origin Influenza A(H3N2) Variant Dampens Host Antiviral Immunity but Induces Potent Inflammasome Activation.

    PubMed

    Cao, Weiping; Mishina, Margarita; Ranjan, Priya; De La Cruz, Juan A; Kim, Jin Hyang; Garten, Rebecca; Kumar, Amrita; García-Sastre, Adolfo; Katz, Jacqueline M; Gangappa, Shivaprakash; Sambhara, Suryaprakash

    2015-12-15

    We compared the innate immune response to a newly emerged swine-origin influenza A(H3N2) variant containing the M gene from 2009 pandemic influenza A(H1N1), termed "A(H3N2)vpM," to the immune responses to the 2010 swine-origin influenza A(H3N2) variant and seasonal influenza A(H3N2). Our results demonstrated that A(H3N2)vpM-induced myeloid dendritic cells secreted significantly lower levels of type I interferon (IFN) but produced significantly higher levels of proinflammatory cytokines and induced potent inflammasome activation. The reduction in antiviral immunity with increased inflammatory responses upon A(H3N2)vpM infection suggest that these viruses have the potential for increased disease severity in susceptible hosts. PMID:26068782

  12. Trading Capsule for Increased Cytotoxin Production: Contribution to Virulence of a Newly Emerged Clade of emm89 Streptococcus pyogenes

    PubMed Central

    Zhu, Luchang; Olsen, Randall J.; Nasser, Waleed; de la Riva Morales, Ivan

    2015-01-01

    ABSTRACT Strains of emm89 Streptococcus pyogenes have become one of the major causes of invasive infections worldwide in the last 10 years. We recently sequenced the genome of 1,125 emm89 strains and identified three major phylogenetic groups, designated clade 1, clade 2, and the epidemic clade 3. Epidemic clade 3 strains, which now cause the great majority of infections, have two distinct genetic features compared to clade 1 and clade 2 strains. First, all clade 3 organisms have a variant 3 nga promoter region pattern, which is associated with increased production of secreted cytolytic toxins SPN (S. pyogenes NADase) and SLO (streptolysin O). Second, all clade 3 strains lack the hasABC locus mediating hyaluronic acid capsule synthesis, whereas this locus is intact in clade 1 and clade 2 strains. We constructed isogenic mutant strains that produce different levels of SPN and SLO toxins and capsule (none, low, or high). Here we report that emm89 strains with elevated toxin production are significantly more virulent than low-toxin producers. Importantly, we also show that capsule production is dispensable for virulence in strains that already produce high levels of SPN and SLO. Our results provide new understanding about the molecular mechanisms contributing to the rapid emergence and molecular pathogenesis of epidemic clade 3 emm89 S. pyogenes. PMID:26443457

  13. Development of a Blocking ELISA for Detection of Serum Neutralizing Antibodies against Newly Emerged Duck Tembusu Virus

    PubMed Central

    Li, Xuesong; Li, Guoxin; Teng, Qiaoyang; Yu, Lei; Wu, Xiaogang; Li, Zejun

    2012-01-01

    Background Since April 2010, domesticated ducks in China have been suffering from an emerging infectious disease characterized by retarded growth, high fever, loss of appetite, decline in egg production, and death. The causative agent was identified as a duck Tembusu virus (DTMUV), a member of the Ntaya virus (NTAV) group within the genus Flavivirus, family Flaviviridae. DTMUV is highly contagious and spreads rapidly in many species of ducks. More than 10 million shelducks have been infected and approximately 1 million died in 2010. The disease remains a constant threat to the duck industry; however, it is not known whether DTMUV can infect humans or other mammalians, despite the fact that the virus has spread widely in southeast China, one of the most densely populated areas in the world. The lack of reliable methods to detect the serum antibodies against DTMUV has limited our ability to conduct epidemiological investigations in various natural hosts and to evaluate the efficiency of vaccines to DTMUV. Methodology/Principal Findings A neutralizing monoclonal antibody (mAb) 1F5 binding specifically to the E protein was developed. Based on the mAb, a blocking enzyme-linked immunosorbent assay (ELISA) was developed for the detection of neutralizing antibodies against DTMUV. The average value of percent inhibition (PI) of 350 duck serum samples obtained from DTMUV-free farms was 1.0% ±5.8% (mean ± SD). The selected cut-off PI values for negative and positive sera were 12.6% (mean +2SD) and 18.4% (mean +3SD), respectively. When compared with a serum neutralizing antibody test (SNT) using chicken embryonated eggs, the rate of coincidence was 70.6% between the blocking ELISA and SNT, based on the titration of 20 duck DTMUV-positive serum samples. Conclusions/Significance The blocking ELISA based on a neutralizing mAb allowed rapid, sensitive, and specific detection of neutralization-related antibodies against DTMUV. PMID:23300851

  14. Identification of Goose-Origin Parvovirus as a Cause of Newly Emerging Beak Atrophy and Dwarfism Syndrome in Ducklings.

    PubMed

    Yu, Kexiang; Ma, Xiuli; Sheng, Zizhang; Qi, Lihong; Liu, Cunxia; Wang, Dan; Huang, Bing; Li, Feng; Song, Minxun

    2016-08-01

    A recent epizootic outbreak, in China, of duck beak atrophy and dwarfism syndrome (BADS) was investigated using electron microscopic, genetic, and virological studies, which identified a parvovirus with a greater similarity to goose parvovirus (GPV) (97% protein homology) than to Muscovy duck parvovirus (MDPV) (90% protein homology). The new virus, provisionally designated GPV-QH15, was found to be antigenically more closely related to GPV than to MDPV in a virus neutralization assay. These findings were further supported by phylogenetic analysis showing that GPV-QH15 evolved from goose lineage parvoviruses, rather than from Muscovy duck- or other duck species-related parvoviruses. In all, two genetic lineages (GPV I and GPV II) were identified from the GPV samples analyzed, and GPV-QH15 was found to be closely clustered with two known goose-origin parvoviruses (GPVa2006 and GPV1995), together forming a distinctive GPV IIa sublineage. Finally, structural modeling revealed that GPV-QH15 and the closely related viruses GPVa2006 and GPV1995 possessed identical clusters of receptor-interacting amino acid residues in the VP2 protein, a major determinant of viral receptor binding and host specificity. Significantly, these three viruses differed from MDPVs and other GPVs at these positions. Taken together, these results suggest that GPV-QH15 represents a new variant of goose-origin parvovirus that currently circulates in ducklings and causes BADS, a syndrome reported previously in Europe. This new finding highlights the need for future surveillance of GPV-QH15 in poultry in order to gain a better understanding of both the evolution and the biology of this emerging parvovirus. PMID:27194692

  15. Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B.

    PubMed

    Cheong, Hui Ting; Ng, Kim Tien; Ong, Lai Yee; Chook, Jack Bee; Chan, Kok Gan; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross

  16. Cross-Border Sexual Transmission of the Newly Emerging HIV-1 Clade CRF51_01B

    PubMed Central

    Cheong, Hui Ting; Ng, Kim Tien; Ong, Lai Yee; Chook, Jack Bee; Chan, Kok Gan; Takebe, Yutaka; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross

  17. A Newly Emerging HIV-1 Recombinant Lineage (CRF58_01B) Disseminating among People Who Inject Drugs in Malaysia

    PubMed Central

    Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B–D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes—subtype B (including subtype B′, the Thai variant of subtype B), CRF01_AE, and CRF33_01B—have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B′ and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention. PMID:24465513

  18. A newly emerging HIV-1 recombinant lineage (CRF58_01B) disseminating among people who inject drugs in Malaysia.

    PubMed

    Chow, Wei Zhen; Takebe, Yutaka; Syafina, Nur Ezreen; Prakasa, Malarvelli Soorya; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2014-01-01

    The HIV epidemic is primarily characterised by the circulation of HIV-1 group M (main) comprising of 11 subtypes and sub-subtypes (A1, A2, B-D, F1, F2, G, H, J, and K) and to date 55 circulating recombinant forms (CRFs). In Southeast Asia, active inter-subtype recombination involving three main circulating genotypes--subtype B (including subtype B', the Thai variant of subtype B), CRF01_AE, and CRF33_01B--have contributed to the emergence of novel unique recombinant forms. In the present study, we conducted the molecular epidemiological surveillance of HIV-1 gag-RT genes among 258 people who inject drugs (PWIDs) in Kuala Lumpur, Malaysia, between 2009 and 2011 whereby a novel CRF candidate was recently identified. The near full-length genome sequences obtained from six epidemiologically unlinked individuals showed identical mosaic structures consisting of subtype B' and CRF01_AE, with six unique recombination breakpoints in the gag-RT, pol, and env regions. Among the high-risk population of PWIDs in Malaysia, which was predominantly infected by CRF33_01B (>70%), CRF58_01B circulated at a low but significant prevalence (2.3%, 6/258). Interestingly, the CRF58_01B shared two unique recombination breakpoints with other established CRFs in the region: CRF33_01B, CRF48_01B, and CRF53_01B in the gag gene, and CRF15_01B (from Thailand) in the env gene. Extended Bayesian Markov chain Monte Carlo sampling analysis showed that CRF58_01B and other recently discovered CRFs were most likely to have originated in Malaysia, and that the recent spread of recombinant lineages in the country had little influence from neighbouring countries. The isolation, genetic characterization, and evolutionary features of CRF58_01B among PWIDs in Malaysia signify the increasingly complex HIV-1 diversity in Southeast Asia that may hold an implication on disease treatment, control, and prevention. PMID:24465513

  19. Emerging antibody-based therapeutic strategies for bladder cancer: A systematic review.

    PubMed

    Azevedo, Rita; Ferreira, José Alexandre; Peixoto, Andreia; Neves, Manuel; Sousa, Nuno; Lima, Aurea; Santos, Lucio Lara

    2015-09-28

    Bladder cancer is the most common malignancy of the urinary tract, presents the highest recurrence rate among solid tumors and is the second leading cause of death in genitourinary cancers. Despite recent advances in understanding of pathophysiology of the disease, the management of bladder cancer patients remains a clinically challenging problem. Particularly, bladder tumors invading the muscularis propria and disseminated disease are often not responsive to currently available therapeutic approaches, which include surgery and conventional chemotherapy. Antibody-based therapeutic strategies have become an established treatment option for over a decade in several types of cancer. However, bladder cancer has remained mostly an "orphan disease" regarding the introduction of these novel therapeutics, which has been translated in few improvements in patients overall survival. In order to shift this paradigm, several clinical studies involving antibody-based therapeutic strategies targeting the most prominent bladder cancer-related biomolecular pathways and immunological mediators are ongoing. This systematic review explores antibody-based therapeutics for bladder cancer undergoing clinical trial and discusses the future perspectives in this field, envisaging the development of more effective guided therapeutics. PMID:26196222

  20. Newly Diagnosed?

    MedlinePlus

    ... Suggestions Examine Your Skin Newly Diagnosed? Understanding Your Pathology Biopsy: The First Step Sentinel Node Biopsy Melanoma ... start this journey: Get a copy of your pathology report. We can help you understand the report ...

  1. Randomized Controlled Trial of Parent Therapeutic Education on Antibiotics to Improve Parent Satisfaction and Attitudes in a Pediatric Emergency Department

    PubMed Central

    Prot-Labarthe, Sonia; Boizeau, Priscilla; Skurnik, David; Morin, Laurence; Mercier, Jean-Christophe; Alberti, Corinne; Bourdon, Olivier

    2013-01-01

    Objective To evaluate therapeutic education delivered in a pediatric emergency department to improve parents’ satisfaction and attitudes about judicious antibiotic use. Methods In an emergency department of a tertiary pediatric hospital, children aged 1 month to 6 years and discharged with an oral antibiotic prescription for an acute respiratory or urinary tract infection were randomized to a patient therapeutic education on antibiotic use (intervention group) or fever control (control group) delivered to the parents (in the presence of the children) by a pharmacist trained in therapeutic education. Education consisted in a 30-minute face-to-face session with four components: educational diagnosis, educational contract, education, and evaluation. The main outcome measure was parent satisfaction about information on antibiotics received at the hospital, as assessed by a telephone interview on day 14. The secondary outcome was attitudes about antibiotic use evaluated on day 14 and at month 6. Results Of the 300 randomized children, 150 per arm, 259 were evaluated on day 14. Parent satisfaction with information on antibiotics was higher in the intervention group (125/129, 96.9%, versus 108/130, 83.0%; P=0.002, exact Fisher test). Intervention Group parents had higher proportions of correct answers on day 14 to questions on attitudes about judicious antibiotic use than did control-group parents (P=0.017, Mann-Whitney U test). Conclusion Therapeutic education delivered by a clinical pharmacist in the pediatric emergency department holds promise for improving the use of antibiotics prescribed to pediatric outpatients. Trial Registration ClinicalTrials.gov NCT00948779 http://clinicaltrials.gov/show/NCT00948779 PMID:24086581

  2. MicroRNAs as emerging biomarkers and therapeutic targets for pancreatic cancer

    PubMed Central

    Gayral, Marion; Jo, Sébastien; Hanoun, Naima; Vignolle-Vidoni, Alix; Lulka, Hubert; Delpu, Yannick; Meulle, Aline; Dufresne, Marlène; Humeau, Marine; Chalret du Rieu, Maël; Bournet, Barbara; Sèlves, Janick; Guimbaud, Rosine; Carrère, Nicolas; Buscail, Louis; Torrisani, Jérôme; Cordelier, Pierre

    2014-01-01

    Despite tremendous efforts from scientists and clinicians worldwide, pancreatic adenocarcinoma (PDAC) remains a deadly disease due to the lack of early diagnostic tools and reliable therapeutic approaches. Consequently, a majority of patients (80%) display an advanced disease that results in a low resection rate leading to an overall median survival of less than 6 months. Accordingly, robust markers for the early diagnosis and prognosis of pancreatic cancer, or markers indicative of survival and/or metastatic disease are desperately needed to help alleviate the dismal prognosis of this cancer. In addition, the discovery of new therapeutic targets is mandatory to design effective treatments. In this review, we will highlight the translational studies demonstrating that microRNAs may soon translate into clinical applications as long-awaited screening tools and therapeutic targets for PDAC. PMID:25170204

  3. The unique chemistry of benzoxaboroles: current and emerging applications in biotechnology and therapeutic treatments.

    PubMed

    Liu, C Tony; Tomsho, John W; Benkovic, Stephen J

    2014-08-15

    Benzoxaboroles have garnered much attention in recent years due to their diverse applications in bio-sensing technology, material science, and therapeutic intervention. Part of the reason arises from the benzoxaboroles' unique chemical properties, especially in comparison to their acyclic boronic acid counterparts. Furthermore, the low bio-toxicity combined with the high target specificity associated with benzoxaboroles make them very attractive as therapeutic agents. Herein, we provide an updated summary on the current knowledge of the fundamental chemical reactivity of benzoxaboroles, followed by highlighting their major applications reported to date. PMID:24864040

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

    PubMed

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

    2016-02-01

    Left ventricular pseudoaneurysm is a rare but serious complication of acute myocardial infarction and cardiac surgery. While surgical intervention is the conventional therapeutic option, transcatheter closure can be considered in selected patients with suitable morphology of the pseudoaneurysm. We report a case of successful transcatheter closure of a left ventricular pseudoaneurysm orifice and isolation of the sac using an Amplatzer septal occluder. PMID:26852302

  5. In the Footsteps of Nature: Nature Therapy as an Emerging Therapeutic-Educational Model.

    ERIC Educational Resources Information Center

    Berger, Ronen

    2003-01-01

    Basic principles of the nature therapy model are described, integrating the author's personal journey and examples from fieldwork and theory. Four aspects are nature as "sacred space"; nature as therapeutic setting; healing potential of nature's physical and aesthetic elements and connections to "universal truths"; and development of a three-way…

  6. The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease.

    PubMed

    Sasser, Jennifer M

    2013-09-15

    Emerging evidence supports a potential therapeutic role of relaxin in fibrotic diseases, including chronic kidney disease. Relaxin is a pleiotropic hormone, best characterized for its role in the reproductive system; however, recent studies have demonstrated a role of relaxin in the cardiorenal system. Both relaxin and its receptor, RXFP1, are expressed in the kidney, and relaxin has been shown to play a role in renal vasodilation, in sodium excretion, and as an antifibrotic agent. Together, these findings suggest that the kidney is a target organ of relaxin. Therefore, the purpose of this review is to describe the functional and structural impacts of relaxin treatment on the kidney and to discuss evidence that relaxin prevents disease progression in several experimental models of kidney disease. In addition, this review will present potential mechanisms that are involved in the therapeutic actions of relaxin. PMID:23883673

  7. The emerging role of relaxin as a novel therapeutic pathway in the treatment of chronic kidney disease

    PubMed Central

    2013-01-01

    Emerging evidence supports a potential therapeutic role of relaxin in fibrotic diseases, including chronic kidney disease. Relaxin is a pleiotropic hormone, best characterized for its role in the reproductive system; however, recent studies have demonstrated a role of relaxin in the cardiorenal system. Both relaxin and its receptor, RXFP1, are expressed in the kidney, and relaxin has been shown to play a role in renal vasodilation, in sodium excretion, and as an antifibrotic agent. Together, these findings suggest that the kidney is a target organ of relaxin. Therefore, the purpose of this review is to describe the functional and structural impacts of relaxin treatment on the kidney and to discuss evidence that relaxin prevents disease progression in several experimental models of kidney disease. In addition, this review will present potential mechanisms that are involved in the therapeutic actions of relaxin. PMID:23883673

  8. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

    PubMed

    Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

    2015-01-12

    We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  9. Combined MYC and P53 Defects Emerge at Medulloblastoma Relapse and Define Rapidly Progressive, Therapeutically Targetable Disease

    PubMed Central

    Hill, Rebecca M.; Kuijper, Sanne; Lindsey, Janet C.; Petrie, Kevin; Schwalbe, Ed C.; Barker, Karen; Boult, Jessica K.R.; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L.; Poon, Evon; Robinson, Simon P.; Ruddle, Ruth; Raynaud, Florence I.; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W.; Wharton, Stephen B.; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S.; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J.; Weiss, William A.; Chesler, Louis; Clifford, Steven C.

    2015-01-01

    Summary We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. PMID:25533335

  10. Why Is Apolipoprotein CIII Emerging as a Novel Therapeutic Target to Reduce the Burden of Cardiovascular Disease?

    PubMed

    Taskinen, Marja-Riitta; Borén, Jan

    2016-10-01

    ApoC-III was discovered almost 50 years ago, but for many years, it did not attract much attention. However, as epidemiological and Mendelian randomization studies have associated apoC-III with low levels of triglycerides and decreased incidence of cardiovascular disease (CVD), it has emerged as a novel and potentially powerful therapeutic approach to managing dyslipidemia and CVD risk. The atherogenicity of apoC-III has been attributed to both direct lipoprotein lipase-mediated mechanisms and indirect mechanisms, such as promoting secretion of triglyceride-rich lipoproteins (TRLs), provoking proinflammatory responses in vascular cells and impairing LPL-independent hepatic clearance of TRL remnants. Encouraging results from clinical trials using antisense oligonucleotide, which selectively inhibits apoC-III, indicate that modulating apoC-III may be a potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk. PMID:27613744

  11. Molecular characterization and infectivity of a Tomato leaf curl New Delhi virus variant associated with newly emerging yellow mosaic disease of eggplant in India

    PubMed Central

    2011-01-01

    Background Begomoviruses have emerged as serious problem for vegetable and fiber crops in the recent past, frequently in tropical and subtropical region of the world. The association of begomovirus with eggplant yellow mosaic disease is hitherto unknown apart from one report from Thailand. A survey in Nagpur, Central India, in 2009-2010 showed severe incidence of eggplant yellow mosaic disease. Here, we have identified and characterized a begomovirus responsible for the newly emerging yellow mosaic disease of eggplant in India. Results The complete DNA-A and DNA-B genomic components of the causative virus were cloned and sequenced. Nucleotide sequence analysis of DNA-A showed that it shared highest 97.6% identity with Tomato leaf curl New Delhi virus-India[India:Udaipur:Okra:2007] and lowest 87.9% identity with Tomato leaf curl New Delhi virus-India[India:NewDelhi:Papaya:2005], while DNA-B showed highest 94.1% identity with ToLCNDV-IN[IN:UD:Ok:07] and lowest 76.2% identity with ToLCNDV-India[India:Lucknow]. Thus, it appears that this begomovirus is a variant of ubiquitous ToLCNDV and hence, we suggest the name ToLCNDV-India[India:Nagpur:Eggplant:2009] for this variant. The pathogenicity of ToLCNDV-IN[IN:Nag:Egg:09] isolate was confirmed by agroinfiltraion and dimeric clones of DNA-A and DNA-B induced characteristic yellow mosaic symptoms in eggplants and leaf curling in tomato plants. Conclusion This is the first report of a ToLCNDV variant moving to a new agriculturally important host, eggplant and causing yellow mosaic disease. This is also a first experimental demonstration of Koch's postulate for a begomovirus associated with eggplant yellow mosaic disease. PMID:21676270

  12. First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China

    PubMed Central

    Zhang, Yibo; Sun, Jingyong; Mi, Chenrong; Li, Wenhui; Zhao, Shengyuan; Wang, Qun; Shi, Dake; Liu, Luo; Ding, Bingyu; Chang, Yung-Fu; Guo, Hongxiong; Guo, XiaoKui; Li, Qingtian; Zhu, Yongzhang

    2015-01-01

    Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2–3 weeks will be also vital for successfully preventing hvKP reinfection or relapse. PMID:26257712

  13. CD20-negative diffuse large B-cell lymphomas: biology and emerging therapeutic options.

    PubMed

    Castillo, Jorge J; Chavez, Julio C; Hernandez-Ilizaliturri, Francisco J; Montes-Moreno, Santiago

    2015-06-01

    CD20-negative diffuse large B-cell lymphoma (DLBCL) is a rare and heterogeneous group of lymphoproliferative disorders. Known variants of CD20-negative DLBCL include plasmablastic lymphoma, primary effusion lymphoma, large B-cell lymphoma arising in human herpesvirus 8-associated multicentric Castleman disease and anaplastic lymphoma kinase-positive DLBCL. Given the lack of CD20 expression, atypical cellular morphology and aggressive clinical behavior characterized by chemotherapy resistance and inferior survival rates, CD20-negative DLBCL represents a challenge from the diagnostic and therapeutic perspectives. The goals of the present review are to summarize the current knowledge on the biology of the distinct variants of CD20-negative DLBCL, provide future therapeutic directions based on the limited preclinical and clinical data available, and increase awareness concerning these rare malignancies among pathologists and clinicians. PMID:25641215

  14. The emergence of precision therapeutics: New challenges and opportunities for Canada's health leaders.

    PubMed

    Slater, Jim; Shields, Laura; Racette, Ray J; Juzwishin, Donald; Coppes, Max

    2015-11-01

    In the era of personalized and precision medicine, the approach to healthcare is quickly changing. Genetic and other molecular information are being increasingly demanded by clinicians and expected by patients for prevention, screening, diagnosis, prognosis, health promotion, and treatment of an increasing number of conditions. As a result of these developments, Canadian health leaders must understand and be prepared to lead the necessary changes associated with these disruptive technologies. This article focuses on precision therapeutics but also provides background on the concepts and terminology related to personalized and precision medicine and explores Canadian health leadership and system issues that may pose barriers to their implementation. The article is intended to inspire, educate, and mobilize Canadian health leaders to initiate dialogue around the transformative changes necessary to ready the healthcare system to realize the benefits of precision therapeutics. PMID:26487734

  15. Human monoclonal antibodies as candidate therapeutics against emerging viruses and HIV-1.

    PubMed

    Zhu, Zhongyu; Prabakaran, Ponraj; Chen, Weizao; Broder, Christopher C; Gong, Rui; Dimitrov, Dimiter S

    2013-04-01

    More than 40 monoclonal antibodies (mAbs) have been approved for a number of disease indications with only one of these (Synagis) - for a viral disease, and not for therapy but for prevention. However, in the last decade novel potent mAbs have been discovered and characterized with potential as therapeutics against viruses of major importance for public health and biosecurity including Hendra virus (HeV), Nipah virus (NiV), severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus (EBOV), West Nile virus (WNV), influenza virus (IFV) and human immunodeficiency virus type 1 (HIV-1). Here, we review such mAbs with an emphasis on antibodies of human origin, and highlight recent results as well as technologies and mechanisms related to their potential as therapeutics. PMID:23575729

  16. 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

  17. Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets

    PubMed Central

    Rucci, Nadia; Sanità, Patrizia; Delle Monache, Simona; Alesse, Edoardo; Angelucci, Adriano

    2014-01-01

    Metastatic occurrence is the principal cause of death in breast cancer patients. The high osteotropism makes breast cancer the most common primary tumor type associated with metastatic bone disease. The peculiar clinical aspects associated with metastases limited to the skeletal system suggest considering these cases as a distinctive subset of metastatic patients with a better prognosis. Because bone is frequently the first metastatic site in disease relapse, it is feasible that the next improvement in therapeutic options for bone metastatic disease could be associated with an improvement of survival expectation and quality of life in breast cancer patients. Study of the molecular basis of bone remodeling and breast cancer osteotropism has allowed identification of several therapeutic candidates involved in formation and progression of bone metastases. These targets are frequently the determinants of positive feedback between the tumor and bone cells whose clinical outcome is osteolytic lesions. In this review, we discuss the physiopathologic features underlying targeted therapeutic strategies aimed at interfering with the aberrant bone remodeling associated with breast cancer metastases. PMID:25114849

  18. Identification of the Critical Therapeutic Entity in Secreted Hsp90α That Promotes Wound Healing in Newly Re-Standardized Healthy and Diabetic Pig Models

    PubMed Central

    Chen, Mei; Wong, Alex K.; Woodley, David T.; Li, Wei

    2014-01-01

    Chronic and non-healing skin wounds represent a significant clinical, economic and social problem worldwide. Currently, there are few effective treatments. Lack of well-defined animal models to investigate wound healing mechanisms and furthermore to identify new and more effective therapeutic agents still remains a major challenge. Pig skin wound healing is close to humans. However, standardized pig wound healing models with demonstrated validity for testing new wound healing candidates are unavailable. Here we report a systematic evaluation and establishment of both acute and diabetic wound healing models in pigs, including wound-creating pattern for drug treatment versus control, measurements of diabetic parameters and the time for detecting delayed wound healing. We find that treatment and control wounds should be on the opposite and corresponding sides of a pig. We demonstrate a strong correlation between duration of diabetic conditions and the length of delay in wound closure. Using these new models, we narrow down the minimum therapeutic entity of secreted Hsp90α to a 27-amino acid peptide, called fragment-8 (F-8). In addition, results of histochemistry and immunohistochemistry analyses reveal more organized epidermis and dermis in Hsp90α-healed wounds than the control. Finally, Hsp90α uses a similar signaling mechanism to promote migration of isolated pig and human keratinocytes and dermal fibroblasts. This is the first report that shows standardized pig models for acute and diabetic wound healing studies and proves its usefulness with both an approved drug and a new therapeutic agent. PMID:25464502

  19. Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

    PubMed Central

    Wolbring, Gregor; Diep, Lucy; Yumakulov, Sophya; Ball, Natalie; Leopatra, Verlyn; Yergens, Dean

    2013-01-01

    So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE). We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a) healthcare, healthcare policy, and healthcare ethics, (b) disability and (c) health consumers and how visible various assessment fields are within Neuro/Cogno/Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers) is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements. PMID:27429129

  20. Therapeutic Targets for Neurodevelopmental Disorders Emerging from Animal Models with Perinatal Immune Activation

    PubMed Central

    Ibi, Daisuke; Yamada, Kiyofumi

    2015-01-01

    Increasing epidemiological evidence indicates that perinatal infection with various viral pathogens enhances the risk for several psychiatric disorders. The pathophysiological significance of astrocyte interactions with neurons and/or gut microbiomes has been reported in neurodevelopmental disorders triggered by pre- and postnatal immune insults. Recent studies with the maternal immune activation or neonatal polyriboinosinic polyribocytidylic acid models of neurodevelopmental disorders have identified various candidate molecules that could be responsible for brain dysfunction. Here, we review the functions of several candidate molecules in neurodevelopment and brain function and discuss their potential as therapeutic targets for psychiatric disorders. PMID:26633355

  1. Emerging use of nanoparticles for the therapeutic ablation of urologic malignancies.

    PubMed

    Stern, Joshua M; Cadeddu, Jeffrey A

    2008-01-01

    Metal nanoshells are a new class of nanoparticle with highly tunable optical properties. Gold nanoshells (GNS) are particularly suitable for use in the surgical arena as their outer shell is composed of a commonly used reduced inert gold. When activated by near infrared light, GNS can raise surrounding temperatures to levels sufficient for cellular ablation. As such, investigators have established both in vitro and in vivo models to examine the role of GNS as a therapeutic modality for the thermal ablation of solid organ tumors. PMID:18190837

  2. Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

    PubMed Central

    Shi, Juan; Chi, Shuhong; Xue, Jing; Yang, Jiali; Li, Feng; Liu, Xiaoming

    2016-01-01

    The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases. PMID:27110577

  3. Evidence for the endothelin system as an emerging therapeutic target for the treatment of chronic pain

    PubMed Central

    Smith, Terika P; Haymond, Tami; Smith, Sherika N; Sweitzer, Sarah M

    2014-01-01

    Many people worldwide suffer from pain and a portion of these sufferers are diagnosed with a chronic pain condition. The management of chronic pain continues to be a challenge, and despite taking prescribed medication for pain, patients continue to have pain of moderate severity. Current pain therapies are often inadequate, with side effects that limit medication adherence. There is a need to identify novel therapeutic targets for the management of chronic pain. One potential candidate for the treatment of chronic pain is therapies aimed at modulating the vasoactive peptide endothelin-1. In addition to vasoactive properties, endothelin-1 has been implicated in pain transmission in both humans and animal models of nociception. Endothelin-1 directly activates nociceptors and potentiates the effect of other algogens, including capsaicin, formalin, and arachidonic acid. In addition, endothelin-1 has been shown to be involved in inflammatory pain, cancer pain, neuropathic pain, diabetic neuropathy, and pain associated with sickle cell disease. Therefore, endothelin-1 may prove a novel therapeutic target for the relief of many types of chronic pain. PMID:25210474

  4. Targeting Bruton's tyrosine kinase signaling as an emerging therapeutic agent of B-cell malignancies

    PubMed Central

    XIA, BING; QU, FULIAN; YUAN, TIAN; ZHANG, YIZHUO

    2015-01-01

    It is becoming increasingly evident that B-cell receptor (BCR) signaling is central to the development and function of B cells. BCR signaling has emerged as a pivotal pathway and a key driver of numerous B-cell lymphomas. Disruption of BCR signaling can be lethal to malignant B cells. Recently, kinase inhibitors that target BCR signaling have induced notable clinical responses. These inhibitors include spleen tyrosine kinase, mammalian target of rapamycin, phosphoinositide 3′-kinase and Bruton's tyrosine kinase (BTK). Ibrutinib, an oral irreversible BTK inhibitor, has emerged as a promising targeted therapy for patients with B-cell malignancies. The present review discusses the current understanding of BTK-mediated BCR signaling in the biology and pathobiology of normal and malignant B cells, and the cellular interaction with the tumor microenvironment. The data on ibrutinib in the preclinical and clinical settings is also discussed, and perspectives for the future use of ibrutinib are outlined. PMID:26788133

  5. Heterocyclic N-Oxides – An Emerging Class of Therapeutic Agents

    PubMed Central

    Mfuh, Adelphe M.; Larionov, Oleg V.

    2016-01-01

    Heterocyclic N-oxides have emerged as potent compounds with anticancer, antibacterial, antihypertensive, antiparasitic, anti-HIV, anti-inflammatory, herbicidal, neuroprotective, and procognitive activities. The N-oxide motif has been successfully employed in a number of recent drug development projects. This review surveys the emergence of this scaffold in the mainstream medicinal chemistry with a focus on the discovery of the heterocyclic N-oxide drugs, N-oxide-specific mechanisms of action, drug-receptor interactions and synthetic avenues to these compounds. As the first review on this subject that covers the developments since 1950s to date, it is expected that it will inspire wider implementation of the heterocyclic N-oxide motif in the rational design of new medicinal agents. PMID:26087764

  6. A Newly Emergent Turkey Arthritis Reovirus Shows Dominant Enteric Tropism and Induces Significantly Elevated Innate Antiviral and T Helper-1 Cytokine Responses

    PubMed Central

    Sharafeldin, Tamer A.; Mor, Sunil K.; Sobhy, Nader M.; Xing, Zheng; Reed, Kent M.; Goyal, Sagar M.; Porter, Robert E.

    2015-01-01

    Newly emergent turkey arthritis reoviruses (TARV) were isolated from tendons of lame 15-week-old tom turkeys that occasionally had ruptured leg tendons. Experimentally, these TARVs induced remarkable tenosynovitis in gastrocnemius tendons of turkey poults. The current study aimed to characterize the location and the extent of virus replication as well as the cytokine response induced by TARV during the first two weeks of infection. One-week-old male turkeys were inoculated orally with TARV (O’Neil strain). Copy numbers of viral genes were estimated in intestines, internal organs and tendons at ½, 1, 2, 3, 4, 7, 14 days Post inoculation (dpi). Cytokine profile was measured in intestines, spleen and leg tendons at 0, 4, 7 and 14 dpi. Viral copy number peaked in jejunum, cecum and bursa of Fabricius at 4 dpi. Copy numbers increased dramatically in leg tendons at 7 and 14 dpi while minimal copies were detected in internal organs and blood during the same period. Virus was detected in cloacal swabs at 1–2 dpi, and peaked at 14 dpi indicating enterotropism of the virus and its early shedding in feces. Elevation of IFN-α and IFN-β was observed in intestines at 7 dpi as well as a prominent T helper-1 response (IFN-γ) at 7 and 14 dpi. IFN-γ and IL-6 were elevated in gastrocnemius tendons at 14 dpi. Elevation of antiviral cytokines in intestines occurred at 7dpi when a significant decline of viral replication in intestines was observed. T helper-1 response in intestines and leg tendons was the dominant T-helper response. These results suggest the possible correlation between viral replication and cytokine response in early infection of TARV in turkeys. Our findings provide novel insights which help elucidate viral pathogenesis in turkey tendons infected with TARV. PMID:26659460

  7. The Emerging Role of the Thrombin Receptor (PAR-1) in Melanoma Metastasis - a Possible Therapeutic Target

    PubMed Central

    Villares, Gabriel J.; Zigler, Maya; Bar-Eli, Menashe

    2011-01-01

    Melanoma remains as the deadliest form of skin cancer with limited and inefficient treatment options available for patients with metastatic disease. Within the last decade, the thrombin receptor, Protease Activated Receptor-1, has been described as an essential gene involved in the progression of human melanoma. PAR-1 is known to activate adhesive, invasive and angiogenic factors to promote melanoma metastasis. It is overexpressed not only in metastatic melanoma cell lines but is also highly expressed in metastatic lesions as compared to primary nevi and normal skin. Recently, PAR-1 has been described to regulate the gap junction protein Connexin 43 and the tumor suppressor gene Maspin to promote the metastatic melanoma phenotype. Herein, we review the role of PAR-1 in the progression of melanoma as well as utilizing PAR-1-regulated genes as potential therapeutic targets for melanoma treatment. PMID:21378407

  8. Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus.

    PubMed

    So, Wing Yan; Leung, Po Sing

    2016-07-01

    Fibroblast growth factor (FGF) 21 is a distinctive member of the FGF family that functions as an endocrine factor. It is expressed predominantly in the liver, but is also found in adipose tissue and the pancreas. Pharmacological studies have shown that FGF21 normalizes glucose and lipid homeostasis, thereby preventing the development of metabolic disorders, such as obesity and diabetes. Despite growing evidence for the therapeutic potential of FGF21, paradoxical increases of FGF21 in different disease conditions point to the existence of FGF21 resistance. In this review, we give a critical appraisal of recent advances in the understanding of the regulation of FGF21 production under various physiological conditions, its antidiabetic actions, and the clinical implications. We also discuss recent preclinical and clinical trials using engineered FGF21 analogs in the management of diabetes, as well as the potential side effects of FGF21 therapy. PMID:27031294

  9. Emerging novel and antimicrobial-resistant respiratory tract infections: new drug development and therapeutic options.

    PubMed

    Zumla, Alimuddin; Memish, Ziad A; Maeurer, Markus; Bates, Matthew; Mwaba, Peter; Al-Tawfiq, Jaffar A; Denning, David W; Hayden, Frederick G; Hui, David S

    2014-11-01

    The emergence and spread of antimicrobial-resistant bacterial, viral, and fungal pathogens for which diminishing treatment options are available is of major global concern. New viral respiratory tract infections with epidemic potential, such as severe acute respiratory syndrome, swine-origin influenza A H1N1, and Middle East respiratory syndrome coronavirus infection, require development of new antiviral agents. The substantial rise in the global numbers of patients with respiratory tract infections caused by pan-antibiotic-resistant Gram-positive and Gram-negative bacteria, multidrug-resistant Mycobacterium tuberculosis, and multiazole-resistant fungi has focused attention on investments into development of new drugs and treatment regimens. Successful treatment outcomes for patients with respiratory tract infections across all health-care settings will necessitate rapid, precise diagnosis and more effective and pathogen-specific therapies. This Series paper describes the development and use of new antimicrobial agents and immune-based and host-directed therapies for a range of conventional and emerging viral, bacterial, and fungal causes of respiratory tract infections. PMID:25189352

  10. PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma

    PubMed Central

    Brault, L; Menter, T; Obermann, E C; Knapp, S; Thommen, S; Schwaller, J; Tzankov, A

    2012-01-01

    Background: PIM serine/threonine kinases are often highly expressed in haematological malignancies. We have shown that PIM inhibitors reduced the survival and migration of leukaemic cells. Here, we investigated PIM kinases in diffuse large B-cell lymphoma (DLBCL) biopsy samples and DLBCL cell lines. Methods: Immunohistochemical staining for PIM kinases and CXCR4 was performed on tissue microarrays from a cohort of 101 DLBCL cases, and the effects of PIM inhibitors on the survival and migration of DLBCL cell lines were determined. Results: PIM1 expression significantly correlated with the activation of signal transducer and activator of transcription (STAT) 3 and 5, P-glycoprotein expression, CXCR4-S339 phosphorylation, and cell proliferation. Whereas most cases exhibited cytoplasmic or cytoplasmic and nuclear PIM1 and PIM2 expression, 12 cases (10 of the non-germinal centre DLBCL type) expressed PIM1 predominately in the nucleus. Interestingly, nuclear expression of PIM1 significantly correlated with disease stage. Exposure of DLBCL cell lines to PIM inhibitors modestly impaired cellular proliferation and CXCR4-mediated migration. Conclusion: This work demonstrates that PIM expression in DLBCL is associated with activation of the JAK/STAT signalling pathway and with the proliferative activity. The correlation of nuclear PIM1 expression with disease stage and the modest response to small-molecule inhibitors suggests that PIM kinases are progression markers rather than primary therapeutic targets in DLBCL. PMID:22722314

  11. The p53 Pathway: Origins, Inactivation in Cancer, and Emerging Therapeutic Approaches.

    PubMed

    Joerger, Andreas C; Fersht, Alan R

    2016-06-01

    Inactivation of the transcription factor p53, through either direct mutation or aberrations in one of its many regulatory pathways, is a hallmark of virtually every tumor. In recent years, screening for p53 activators and a better understanding of the molecular mechanisms of oncogenic perturbations of p53 function have opened up a host of novel avenues for therapeutic intervention in cancer: from the structure-guided design of chemical chaperones to restore the function of conformationally unstable p53 cancer mutants, to the development of potent antagonists of the negative regulators MDM2 and MDMX and other modulators of the p53 pathway for the treatment of cancers with wild-type p53. Some of these compounds have now moved from proof-of-concept studies into clinical trials, with prospects for further, personalized anticancer medicines. We trace the structural evolution of the p53 pathway, from germ-line surveillance in simple multicellular organisms to its pluripotential role in humans. PMID:27145840

  12. The 12/15-lipoxygenase as an emerging therapeutic target for Alzheimer's disease.

    PubMed

    Joshi, Yash B; Giannopoulos, Phillip F; Praticò, Domenico

    2015-03-01

    Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive memory loss. Mutations in genes involved in the production of amyloid-β (Aβ) are linked to the early-onset variant of AD. However, the most common form, sporadic AD, is considered to be the result of an interaction between environmental risk factors and various genes. Among them, recent work has highlighted the potential role that the 12/15-lipoxygenase (12/15LO) pathway may play in AD pathogenesis. 12/15LO is widely distributed in the central nervous system, and its levels are upregulated in patients with AD or mild cognitive impairments. Studies using animal models have implicated 12/15LO in the molecular pathology of AD, including the metabolism of Aβ and tau, synaptic integrity, and cognitive functions. We provide an overview of this pathway and its relevance to AD pathogenesis, discuss the mechanism(s) involved, and provide an assessment of how targeting 12/15LO could lead to novel AD therapeutics. PMID:25708815

  13. Reactive Oxygen-Related Diseases: Therapeutic Targets and Emerging Clinical Indications

    PubMed Central

    Daiber, Andreas; Maghzal, Ghassan J.; Di Lisa, Fabio; Kaludercic, Nina; Leach, Sonia; Cuadrado, Antonio; Jaquet, Vincent; Seredenina, Tamara; Krause, Karl H.; López, Manuela G.; Stocker, Roland

    2015-01-01

    Abstract Significance: Enhanced levels of reactive oxygen species (ROS) have been associated with different disease states. Most attempts to validate and exploit these associations by chronic antioxidant therapies have provided disappointing results. Hence, the clinical relevance of ROS is still largely unclear. Recent Advances: We are now beginning to understand the reasons for these failures, which reside in the many important physiological roles of ROS in cell signaling. To exploit ROS therapeutically, it would be essential to define and treat the disease-relevant ROS at the right moment and leave physiological ROS formation intact. This breakthrough seems now within reach. Critical Issues: Rather than antioxidants, a new generation of protein targets for classical pharmacological agents includes ROS-forming or toxifying enzymes or proteins that are oxidatively damaged and can be functionally repaired. Future Directions: Linking these target proteins in future to specific disease states and providing in each case proof of principle will be essential for translating the oxidative stress concept into the clinic. Antioxid. Redox Signal. 23, 1171–1185. PMID:26583264

  14. Dendritic Cell-Based Vaccination in Cancer: Therapeutic Implications Emerging from Murine Models

    PubMed Central

    Mac Keon, Soledad; Ruiz, María Sol; Gazzaniga, Silvina; Wainstok, Rosa

    2015-01-01

    Dendritic cells (DCs) play a pivotal role in the orchestration of immune responses, and are thus key targets in cancer vaccine design. Since the 2010 FDA approval of the first cancer DC-based vaccine (Sipuleucel-T), there has been a surge of interest in exploiting these cells as a therapeutic option for the treatment of tumors of diverse origin. In spite of the encouraging results obtained in the clinic, many elements of DC-based vaccination strategies need to be optimized. In this context, the use of experimental cancer models can help direct efforts toward an effective vaccine design. This paper reviews recent findings in murine models regarding the antitumoral mechanisms of DC-based vaccination, covering issues related to antigen sources, the use of adjuvants and maturing agents, and the role of DC subsets and their interaction in the initiation of antitumoral immune responses. The summary of such diverse aspects will highlight advantages and drawbacks in the use of murine models, and contribute to the design of successful DC-based translational approaches for cancer treatment. PMID:26042126

  15. Low temperature plasmas as emerging cancer therapeutics: the state of play and thoughts for the future.

    PubMed

    Hirst, Adam M; Frame, Fiona M; Arya, Manit; Maitland, Norman J; O'Connell, Deborah

    2016-06-01

    The field of plasma medicine has seen substantial advances over the last decade, with applications developed for bacterial sterilisation, wound healing and cancer treatment. Low temperature plasmas (LTPs) are particularly suited for medical purposes since they are operated in the laboratory at atmospheric pressure and room temperature, providing a rich source of reactive oxygen and nitrogen species (RONS). A great deal of research has been conducted into the role of reactive species in both the growth and treatment of cancer, where long-established radio- and chemo-therapies exploit their ability to induce potent cytopathic effects. In addition to producing a plethora of RONS, LTPs can also create strong electroporative fields. From an application perspective, it has been shown that LTPs can be applied precisely to a small target area. On this basis, LTPs have been proposed as a promising future strategy to accurately and effectively control and eradicate tumours. This review aims to evaluate the current state of the literature in the field of plasma oncology and highlight the potential for the use of LTPs in combination therapy. We also present novel data on the effect of LTPs on cancer stem cells, and speculatively outline how LTPs could circumvent treatment resistance encountered with existing therapeutics. PMID:26888782

  16. Emerging role of orexin antagonists in insomnia therapeutics: An update on SORAs and DORAs.

    PubMed

    Kumar, Anil; Chanana, Priyanka; Choudhary, Supriti

    2016-04-01

    The pharmacological management of insomnia has lately become a challenge for researchers worldwide. As per the third International Classification of Sleep disorders (ICSD-3) insomnia can be defined as a state with repeated difficulty in sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, and results in some form of daytime impairment. The conventional treatments approved for management of insomnia were benzodiazepines (BZDs) (estazolam, quazepam, triazolam, flurazepam and temazepam) and non-BZDs, also known as z-drugs (zaleplon, zolpidem, and eszopiclone), tricyclic antidepressant (TCA) doxepin as well as melatonin agonists, e.g. ramelteon. But the potential of these agents to address sleep problems has been limited due to substantial side effects associated with them like hangover, dependence and tolerance, rebound insomnia, muscular atonia, inhibition of respiratory system, cognitive dysfunctions, and increased anxiety. Recently, orexin neuropeptides have been identified as regulators of transition between wakefulness and sleep and documented to aid an initial transitory effect towards wakefulness by activating cholinergic/monoaminergic neural pathways of the ascending arousal system. This has led to the development of orexin peptides and receptors, as possible therapeutic targets for the treatment of sleep disorders with the advantage of having lesser side effects as compared to conventional treatments. The present review focuses on the orexin peptides and receptors signifying their physiological profile as well as the development of orexin receptor antagonists as novel strategies in sleep medicine. PMID:26922522

  17. Emerging therapeutic paradigms to target the dysregulated JAK/STAT pathways in hematological malignancies

    PubMed Central

    Mughal, Tariq I.; Girnius, Saulius; Rosen, Steven T.; Kumar, Shaji; Wiestner, Adrian; Abdel-Wahab, Omar; Kiladjian, Jean-Jacques; Wilson, Wyndham H.; Van Etten, Richard A.

    2014-01-01

    Over the past decade, there has been increasing biochemical evidence that the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is aberrantly activated in malignant cells from patients with a wide spectrum of cancers of the blood and immune systems. The emerging availability of small molecule inhibitors of JAK kinases and other signaling molecules in the JAK-STAT pathway has allowed preclinical studies validating an important role of this pathway in the pathogenesis of many hematologic malignancies, and provided motivation for new strategies for treatment of these diseases. Here, a roundtable panel of experts reviews the current preclinical and clinical landscape of the JAK-STAT pathway in acute lymphoid and myeloid leukemias, lymphomas and myeloma, and chronic myeloid neoplasms. PMID:24206094

  18. Therapeutic Approaches for Renal Colic in the Emergency Department: A Review Article

    PubMed Central

    Golzari, Samad EJ; Soleimanpour, Hassan; Rahmani, Farzad; Zamani Mehr, Nahid; Safari, Saeid; Heshmat, Yaghoub; Ebrahimi Bakhtavar, Hanieh

    2014-01-01

    Context: Renal colic is frequently described as the worst pain ever experienced, and management of this intense pain is necessary. The object of our review was to discuss different approaches of pain control for patients with acute renal colic in the emergency department. Evidence Acquisition: Studies that discussed the treatment of renal colic pain were included in this review. We collected articles from reputable internet databases. Results: Our study showed that some new treatment approaches, such as the use of lidocaine or nerve blocks, can be used to control the severe and persistent pain of renal colic. Conclusions: Some new approaches are discussed and their impact on renal colic pain control was compared with traditional therapies. The effectiveness of the new approaches in this review is similar or even better than in traditional treatments. PMID:24701420

  19. New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases

    PubMed Central

    Williams, Jessica A; Manley, Sharon; Ding, Wen-Xing

    2014-01-01

    Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α. PMID:25278688

  20. [Acute therapeutic measures for limb salvage Part 1 : Haemorrhage control, emergency revascularization, compartment syndrome].

    PubMed

    Willy, C; Stichling, M; Engelhardt, M; Vogt, D; Back, D A

    2016-05-01

    The primary care of Gustilo-Anderson type IIIC extremity injuries with relevant vessel lacerations is decisive for the success of a limb salvage procedure. This article shall present substantial emergency procedures for the salvage of the nutritive perfusion of a mangled extremity, based on the current literature. After provisory control of a peripheral haemorrhage (e. g. by manual pressure or tourniquet), an immediate decision must be made about the kind of emergency revascularization to be implemented as the limb salvage procedure. Here, the temporary intravascular shunt will be the fastest technique that can ensure a sufficient tissue perfusion in the case of vessel lacerations. Regarding the treatment of a fracture versus perfusion recovery, a shortening of ischemia time should have priority over fracture stabilization.If an acute compartment syndrome is suspected, a documented monitoring has to be performed in the limb salvage situation for 24 hours with clinical controls every 4 hours. Disproportional pain that does not respond to analgesics, and passive muscle stretching pain can be seen as cardinal symptoms. The positive predictive value of clinical findings is <15 %. During the observation period with an impending but not manifest compartment syndrome, an elevation of the extremity above heart level or its cooling are contraindicated. An intracompartmental pressure measurement is the most important instrument-based supplemental diagnostic method. The open fasciotomy of the affected compartments is the only causal therapy and should be performed as fast as possible. A decision against fasciotomy in cases of non-explicit clinical signs should not be made without a documented intracompartmental pressure measurement. PMID:27160729

  1. Neurotrophic factor small-molecule mimetics mediated neuroregeneration and synaptic repair: emerging therapeutic modality for Alzheimer's disease.

    PubMed

    Kazim, Syed Faraz; Iqbal, Khalid

    2016-01-01

    brain-derived neurotrophic factor (BDNF) expression. It robustly inhibits tau abnormal hyperphosphorylation via increased BDNF mediated decrease in glycogen synthase kinase-3β (GSK-3β, major tau kinase) activity. P021 is a small molecular weight, BBB permeable compound with suitable pharmacokinetics for oral administration, and without adverse effects associated with native CNTF or BDNF molecule. P021 has shown beneficial therapeutic effect in several preclinical studies and has emerged as a highly promising compound for AD drug development. PMID:27400746

  2. Emerging Roles of the Host Defense Peptide LL-37 in Human Cancer and its Potential Therapeutic Applications

    PubMed Central

    Wu, William K.K.; Wang, Guangshun; Coffelt, Seth B.; Betancourt, Aline M.; Lee, Chung W.; Fan, Daiming; Wu, Kaichun; Yu, Jun; Sung, Joseph J.Y.; Cho, Chi H.

    2010-01-01

    Human cathelicidin LL-37, a host defense peptide derived from leukocytes and epithelial cells, plays a crucial role in innate and adaptive immunity. Not only does it eliminate pathogenic microbes directly, LL-37 also modulates host immune responses. Emerging evidence from tumor biology studies indicates that LL-37 plays a prominent and complex role in carcinogenesis. While overexpression of LL-37 has been implicated in the development or progression of many human malignancies, including breast, ovarian and lung cancers, LL-37 suppresses tumorigenesis in gastric cancer. These data are beginning to unveil the intricate and contradictory functions of LL-37. The reasons for the tissue-specific function of LL-37 in carcinogenesis remain to be elucidated. Here, we review the relationship between LL-37, its fragments and cancer progression as well as discuss the potential therapeutic implications of targeting this peptide. PMID:20521250

  3. Emerging roles of the host defense peptide LL-37 in human cancer and its potential therapeutic applications.

    PubMed

    Wu, William K K; Wang, Guangshun; Coffelt, Seth B; Betancourt, Aline M; Lee, Chung W; Fan, Daiming; Wu, Kaichun; Yu, Jun; Sung, Joseph J Y; Cho, Chi H

    2010-10-15

    Human cathelicidin LL-37, a host defense peptide derived from leukocytes and epithelial cells, plays a crucial role in innate and adaptive immunity. Not only does LL-37 eliminate pathogenic microbes directly but also modulates host immune responses. Emerging evidence from tumor biology studies indicates that LL-37 plays a prominent and complex role in carcinogenesis. Although overexpression of LL-37 has been implicated in the development or progression of many human malignancies, including breast, ovarian and lung cancers, LL-37 suppresses tumorigenesis in gastric cancer. These data are beginning to unveil the intricate and contradictory functions of LL-37. The reasons for the tissue-specific function of LL-37 in carcinogenesis remain to be elucidated. Here, we review the relationship between LL-37, its fragments and cancer progression as well as discuss the potential therapeutic implications of targeting this peptide. PMID:20521250

  4. Therapeutic Affordances of Social Media: Emergent Themes From a Global Online Survey of People With Chronic Pain

    PubMed Central

    Gray, Kathleen; Martin-Sanchez, Fernando

    2014-01-01

    Background Research continues to present tenuous suggestions that social media is well suited to enhance management of chronic disease and improve health outcomes. Various studies have presented qualitative reports of health outcomes from social media use and have examined discourse and communication themes occurring through different social media. However, there is an absence of published studies examining and unpacking the underlying therapeutic mechanisms driving social media’s effects. Objective This paper presents a qualitative analysis thoroughly describing what social media therapeutically affords people living with chronic pain who are self-managing their condition. From this therapeutic affordance perspective, we aim to formulate a preliminary conceptual model aimed at better understanding "how" social media can influence patient outcomes. Methods In total, 218 people with chronic pain (PWCP) completed an online survey, investigating patient-reported outcomes (PROs) from social media use. Supplementary to quantitative data collected, participants were also given the opportunity to provide further open commentary regarding their use of social media as part of chronic pain management; 68/218 unique users (31.2%) chose to provide these free-text responses. Through thematic content analysis, 117 free-text responses regarding 10 types of social media were coded. Quotes were extracted and tabulated based on therapeutic affordances that we had previously identified. Inductive analysis was then performed to code defining language and emergent themes central to describing each affordance. Three investigators examined the responses, developed the coding scheme, and applied the coding to the data. Results We extracted 155 quotes from 117 free-text responses. The largest source of quotes came from social network site users (78/155, 50.3%). Analysis of component language used to describe the aforementioned affordances and emergent themes resulted in a final revision

  5. Current and Emerging Therapeutic Strategies for the Treatment of Meibomian Gland Dysfunction (MGD).

    PubMed

    Thode, Adam R; Latkany, Robert A

    2015-07-01

    Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow(®). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested. PMID:26130187

  6. Inflammatory mechanisms and oxidative stress in Peyronie's disease: therapeutic "rationale" and related emerging treatment strategies.

    PubMed

    Paulis, Gianni; Brancato, Tommaso

    2012-02-01

    fibroblasts and myo-fibroblasts and excessive production of collagen between the layers of the tunica albuginea (penile plaque). Referring to the current knowledge of inflammatory and oxidative mechanisms of PD, a possible therapeutic strategy is then analyzed. PMID:22309083

  7. Medical Management of Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage: A Review of Current and Emerging Therapeutic Interventions

    PubMed Central

    Adamczyk, Peter; Amar, Arun Paul; Mack, William J.

    2013-01-01

    Cerebral vasospasm is a major source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Evidence suggests a multifactorial etiology and this concept remains supported by the assortment of therapeutic modalities under investigation. The authors provide an updated review of the literature for previous and recent clinical trials evaluating medical treatments in patients with cerebral vasospasm secondary to aSAH. Currently, the strongest evidence supports use of prophylactic oral nimodipine and initiation of triple-H therapy for patients in cerebral vasospasm. Other agents presented in this report include magnesium, statins, endothelin receptor antagonists, nitric oxide promoters, free radical scavengers, thromboxane inhibitors, thrombolysis, anti-inflammatory agents and neuroprotectants. Although promising data is beginning to emerge for several treatments, few prospective randomized clinical trials are presently available. Additionally, future investigational efforts will need to resolve discrepant definitions and outcome measures for cerebral vasospasm in order to permit adequate study comparisons. Until then, definitive recommendations cannot be made regarding the safety and efficacy for each of these therapeutic strategies and medical management practices will continue to be implemented in a wide-ranging manner. PMID:23691312

  8. Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases

    PubMed Central

    Rogers, J.; Schoepp, R.J.; Schröder, O.; Clements, T.L.; Holland, T.F.; Li, J.Q.; Li, J.; Lewis, L.M.; Dirmeier, R.P.; Frey, G.J.; Tan, X.; Wong, K.; Woodnutt, G.; Keller, M.; Reed, D.S.; Kimmel, B.E.; Tozer, E.C.

    2008-01-01

    Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR™ (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5–4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known. PMID:18480090

  9. Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases.

    PubMed

    Rogers, J; Schoepp, R J; Schröder, O; Clements, T L; Holland, T F; Li, J Q; Li, J; Lewis, L M; Dirmeier, R P; Frey, G J; Tan, X; Wong, K; Woodnutt, G; Keller, M; Reed, D S; Kimmel, B E; Tozer, E C

    2008-08-01

    Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR (human framework reassembly) technology. The best variant (61G4) from this screen showed a 3.5-4-fold improvement in neutralization of SARS-CoV infection in vitro. Finally, using a complete site-saturation mutagenesis methodology focused on the CDR (complementarity determining regions), a single point mutation (51E7) was identified that improved the 80% plaque reduction neutralization of the virus by greater than 8-fold. These discovery and evolution strategies can be applied to any emerging pathogen or toxin where a causative agent is known. PMID:18480090

  10. Emerging Role of PACAP as a New Potential Therapeutic Target in Major Diabetes Complications

    PubMed Central

    Marzagalli, Rubina; Drago, Filippo; Waschek, James A.; Castorina, Alessandro

    2015-01-01

    Enduring diabetes increases the probability of developing secondary damage to numerous systems, and these complications represent a cause of morbidity and mortality. Establishing the causes of diabetes remains the key step to eradicate the disease, but prevention as well as finding therapies to ameliorate some of the major diabetic complications is an equally important step to increase life expectancy and quality for the millions of individuals already affected by the disease or who are likely to develop it before cures become routinely available. In this review, we will firstly summarize some of the major complications of diabetes, including endothelial and pancreatic islets dysfunction, retinopathy, and nephropathy, and then discuss the emerging roles exerted by the neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) to counteract these ranges of pathologies that are precipitated by the prolonged hyperglycemic state. Finally, we will describe the main signalling routes activated by the peptide and propose possible future directions to focus on developing more effective peptide-based therapies to treat the major complications associated with longstanding diabetes. PMID:26074958

  11. Cancer Stem Cells and Therapeutic Targets: An Emerging Field for Cancer Treatment

    PubMed Central

    Vaz, Arokia Priyanka; Ponnusamy, Moorthy P.; Batra, Surinder K.

    2013-01-01

    Recent paradigm in the field of cancer defines its origin from a small population of fast growing cells known as cancer stem cells (CSCs), and they are mainly responsible for disease aggressiveness, drug resistance and tumor relapse. The existence of CSCs has been proven in different types of cancer and possesses characteristic expression of a wide array of cell surface markers specific to the type of cancer. CSCs have been isolated and enriched using several surface markers in different cancer types. Self-renewal, drug resistance and the ability to transition from epithelial to mesenchymal phenotype are the major features attributed to this fraction of mutated stem cells. The CSC hypothesis proposes that these CSCs mimic stem cells by sharing similar pathways, such as Wnt, SHH, Notch and others. Further, the niche, which in this case is the tumor microenvironment, plays a very important role in the maintenance of CSCs. Altogether, this emerging field of research on CSCs is expected to unveil answers to the most difficult issues of one of the most dreadful diseases called cancer. PMID:24077517

  12. Identification and Characterization of Potential Therapeutic Candidates in Emerging Human Pathogen Mycobacterium abscessus: A Novel Hierarchical In Silico Approach

    PubMed Central

    Shanmugham, Buvaneswari; Pan, Archana

    2013-01-01

    Mycobacterium abscessus, a non-tuberculous rapidly growing mycobacterium, is recognized as an emerging human pathogen causing a variety of infections ranging from skin and soft tissue infections to severe pulmonary infections. Lack of an optimal treatment regimen and emergence of multi-drug resistance in clinical isolates necessitate the development of better/new drugs against this pathogen. The present study aims at identification and qualitative characterization of promising drug targets in M. abscessus using a novel hierarchical in silico approach, encompassing three phases of analyses. In phase I, five sets of proteins were mined through chokepoint, plasmid, pathway, virulence factors, and resistance genes and protein network analysis. These were filtered in phase II, in order to find out promising drug target candidates through subtractive channel of analysis. The analysis resulted in 40 therapeutic candidates which are likely to be essential for the survival of the pathogen and non-homologous to host, human anti-targets, and gut flora. Many of the identified targets were found to be involved in different metabolisms (viz., amino acid, energy, carbohydrate, fatty acid, and nucleotide), xenobiotics degradation, and bacterial pathogenicity. Finally, in phase III, the candidate targets were qualitatively characterized through cellular localization, broad spectrum, interactome, functionality, and druggability analysis. The study explained their subcellular location identifying drug/vaccine targets, possibility of being broad spectrum target candidate, functional association with metabolically interacting proteins, cellular function (if hypothetical), and finally, druggable property. Outcome of the present study could facilitate the identification of novel antibacterial agents for better treatment of M. abscesses infections. PMID:23527108

  13. Combating emerging viral threats

    PubMed Central

    Bekerman, Elena; Einav, Shirit

    2015-01-01

    Synopsis Most approved antiviral therapeutics selectively inhibit proteins encoded by a single virus, thereby providing a “one drug-one bug” solution. As a result of this narrow spectrum of coverage and the high cost of drug development, therapies are currently approved for fewer than ten viruses out of the hundreds known to cause human disease. This perspective summarizes progress and challenges in the development of broad-spectrum antiviral therapies. These strategies include targeting enzymatic functions shared by multiple viruses and host cell machinery by newly discovered compounds or by repurposing approved drugs. These approaches offer new practical means for developing therapeutics against existing and emerging viral threats. PMID:25883340

  14. The emerging role of miR-223 as novel potential diagnostic and therapeutic target for inflammatory disorders.

    PubMed

    Aziz, Faisal

    2016-05-01

    Since their discovery of more than a decade ago, microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Specific microRNAs have emerged as key players in disease biology by playing crucial role in disease development and progression. This review draws attention to miR-223 that has been reported to be abnormally expressed in several diseases like diabetes-type2, sepsis, rheumatoid arthritis, viral infections likes' human immunodeficiency virus-1 (HIV-1) and inflammatory disorders. It regulates inflammation by targeting different targets, including cytoplasmic activation/proliferation-associated protein-1 (Caprin-1), Insulin-like growth factor-1 receptor (IGF-1R), heat shock protein 90 (Hsp90), STAT5, artemin, EPB41L3, Ect2, Pknox1, C/EBPα, C/EBPβ, E2F1, FOXO1, NFI-A and other transcription factors. In this review, we summarized the recent studies of miR-223, their mechanisms to develop inflammation diseases and its importance role to use as biomarkers for early diagnosis and therapeutic target against inflammation diseases. PMID:27129807

  15. Allosteric modulation of Ras and the PI3K/AKT/mTOR pathway: emerging therapeutic opportunities

    PubMed Central

    Hubbard, Paul A.; Moody, Colleen L.; Murali, Ramachandran

    2014-01-01

    GTPases and kinases are two predominant signaling modules that regulate cell fate. Dysregulation of Ras, a GTPase, and the three eponymous kinases that form key nodes of the associated phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K)/AKT/mTOR pathway have been implicated in many cancers, including pancreatic cancer, a disease noted for its current lack of effective therapeutics. The K-Ras isoform of Ras is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC) and there is growing evidence linking aberrant PI3K/AKT/mTOR pathway activity to PDAC. Although these observations suggest that targeting one of these nodes might lead to more effective treatment options for patients with pancreatic and other cancers, the complex regulatory mechanisms and the number of sequence-conserved isoforms of these proteins have been viewed as significant barriers in drug development. Emerging insights into the allosteric regulatory mechanisms of these proteins suggest novel opportunities for development of selective allosteric inhibitors with fragment-based drug discovery (FBDD) helping make significant inroads. The fact that allosteric inhibitors of Ras and AKT are currently in pre-clinical development lends support to this approach. In this article, we will focus on the recent advances and merits of developing allosteric drugs targeting these two inter-related signaling pathways. PMID:25566081

  16. Allosteric modulation of Ras and the PI3K/AKT/mTOR pathway: emerging therapeutic opportunities.

    PubMed

    Hubbard, Paul A; Moody, Colleen L; Murali, Ramachandran

    2014-01-01

    GTPases and kinases are two predominant signaling modules that regulate cell fate. Dysregulation of Ras, a GTPase, and the three eponymous kinases that form key nodes of the associated phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K)/AKT/mTOR pathway have been implicated in many cancers, including pancreatic cancer, a disease noted for its current lack of effective therapeutics. The K-Ras isoform of Ras is mutated in over 90% of pancreatic ductal adenocarcinomas (PDAC) and there is growing evidence linking aberrant PI3K/AKT/mTOR pathway activity to PDAC. Although these observations suggest that targeting one of these nodes might lead to more effective treatment options for patients with pancreatic and other cancers, the complex regulatory mechanisms and the number of sequence-conserved isoforms of these proteins have been viewed as significant barriers in drug development. Emerging insights into the allosteric regulatory mechanisms of these proteins suggest novel opportunities for development of selective allosteric inhibitors with fragment-based drug discovery (FBDD) helping make significant inroads. The fact that allosteric inhibitors of Ras and AKT are currently in pre-clinical development lends support to this approach. In this article, we will focus on the recent advances and merits of developing allosteric drugs targeting these two inter-related signaling pathways. PMID:25566081

  17. Sequence type 72 community-associated meticillin-resistant Staphylococcus aureus emerged as a predominant clone of nasal colonization in newly admitted patients.

    PubMed

    Park, S Y; Chung, D R; Yoo, J R; Baek, J Y; Kim, S H; Ha, Y E; Kang, C-I; Peck, K R; Lee, N Y; Song, J-H

    2016-08-01

    Current knowledge of community-associated (CA) meticillin-resistant Staphylococcus aureus (MRSA) carriage in hospitalized patients is incomplete. Genotypic characteristics of 637 nasal MRSA isolates from newly admitted patients in South Korea were investigated. Sequence type (ST) 72 accounted for 52.1%, 46.3%, and 52.8% of the isolates during the periods of 2007-2008, 2009-2010, and 2013-2014, respectively. Instead of classic MRSA clones responsible for healthcare-associated infections, including ST5 and ST239, MRSA with community genotype ST72 was the predominant strain in newly admitted patients regardless of age and home province of the patients. Active strategies are needed to prevent healthcare-associated infection by CA-MRSA. PMID:26874934

  18. S100A12 and the S100/Calgranulins: Emerging Biomarkers for Atherosclerosis and Possibly Therapeutic Targets.

    PubMed

    Oesterle, Adam; Bowman, Marion A Hofmann

    2015-12-01

    Atherosclerosis is mediated by local and systematic inflammation. The multiligand receptor for advanced glycation end products (RAGE) has been studied in animals and humans and is an important mediator of inflammation and atherosclerosis. This review focuses on S100/calgranulin proteins (S100A8, S100A9, and S100A12) and their receptor RAGE in mediating vascular inflammation. Mice lack the gene for S100A12, which in humans is located on chromosome 3 between S100A8 and S100A9. Transgenic mice with smooth muscle cell-targeted expression of S100A12 demonstrate increased coronary and aortic calcification, as well as increased plaque vulnerability. Serum S100A12 has recently been shown to predict future cardiovascular events in a longitudinal population study, underscoring a role for S100A12 as a potential biomarker for coronary artery disease. Genetic ablation of S100A9 or RAGE in atherosclerosis-susceptible apolipoprotein E null mice results in reduced atherosclerosis. Importantly, S100A12 and the RAGE axis can be modified pharmacologically. For example, soluble RAGE reduces murine atherosclerosis and vascular inflammation. Additionally, a class of compounds currently in phase III clinical trials for multiple sclerosis and rheumatologic conditions, the quinoline-3-carboxamides, reduce atherosclerotic plaque burden and complexity in transgenic S100A12 apolipoprotein E null mice, but have not been tested with regards to human atherosclerosis. The RAGE axis is an important mediator for inflammation-induced atherosclerosis, and S100A12 has emerged as biomarker for human atherosclerosis. Decreasing inflammation by inhibiting S100/calgranulin-mediated activation of RAGE attenuates murine atherosclerosis, and future studies in patients with coronary artery disease are warranted to confirm S100/RAGE as therapeutic target for atherosclerosis. PMID:26515415

  19. Molecular detection of HIV-1 subtype B, CRF01_AE, CRF33_01B, and newly emerging recombinant lineages in Malaysia.

    PubMed

    Chook, Jack Bee; Ong, Lai Yee; Takebe, Yutaka; Chan, Kok Gan; Choo, Martin; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-03-01

    A molecular genotyping assay for human immunodeficiency virus type 1 (HIV-1) circulating in Southeast Asia is difficult to design because of the high level of genetic diversity. We developed a multiplex real-time polymerase chain reaction (PCR) assay to detect subtype B, CRF01_AE, CRF33_01B, and three newly described circulating recombinant forms, (CRFs) (CRF53_01B, CRF54_01B, and CRF58_01B). A total of 785 reference genomes were used for subtype-specific primers and TaqMan probes design targeting the gag, pol, and env genes. The performance of this assay was compared and evaluated with direct sequencing and phylogenetic analysis. A total of 180 HIV-infected subjects from Kuala Lumpur, Malaysia were screened and 171 samples were successfully genotyped, in agreement with the phylogenetic data. The HIV-1 genotype distribution was as follows: subtype B (16.7%); CRF01_AE (52.8%); CRF33_01B (24.4%); CRF53_01B (1.1%); CRF54_01B (0.6%); and CRF01_AE/B unique recombinant forms (4.4%). The overall accuracy of the genotyping assay was over 95.0%, in which the sensitivities for subtype B, CRF01_AE, and CRF33_01B detection were 100%, 100%, and 97.7%, respectively. The specificity of genotyping was 100%, inter-subtype specificities were > 95% and the limit of detection of 10(3) copies/mL for plasma. The newly developed real-time PCR assay offers a rapid and cost-effective alternative for large-scale molecular epidemiological surveillance for HIV-1. PMID:25535315

  20. Silver nanoparticles: synthesis, properties, and therapeutic applications

    PubMed Central

    Wei, Liuya; Lu, Jingran; Xu, Huizhong; Patel, Atish; Chen, Zhe-Sheng; Chen, Guofang

    2014-01-01

    Silver nanoparticles (AgNPs) have been widely used in biomedical fields because of their intrinsic therapeutic properties. Here, we introduce methods of synthesizing AgNPs and discuss their physicochemical, localized surface plasmon resonance (LSPR) and toxicity properties. We also review the impact of AgNPs on human health and the environment along with the underlying mechanisms. More importantly, we highlight the newly emerging applications of AgNPs as antiviral agents, photosensitizers and/or radiosensitizers, and anticancer therapeutic agents in the treatment of leukemia, breast cancer, hepatocellular carcinoma, lung cancer, and skin and/or oral carcinoma. PMID:25543008

  1. Recent insights into the molecular pathogenesis of Crohn’s disease: a review of emerging therapeutic targets

    PubMed Central

    Manuc, Teodora-Ecaterina M; Manuc, Mircea M; Diculescu, Mircea M

    2016-01-01

    Chronic inflammatory bowel diseases (IBDs) are a subject of great interest in gastroenterology, due to a pathological mechanism that is difficult to explain and an optimal therapeutic approach still undiscovered. Crohn’s disease (CD) is one of the main entities in IBD, characterized by clinical polymorphism and great variability in the treatment response. Modern theories on the pathogenesis of CD have proven that gut microbiome and environmental factors lead to an abnormal immune response in a genetically predisposed patient. Genome-wide association studies in patients with CD worldwide revealed several genetic mutations that increase the risk of IBD and that predispose to a more severe course of disease. Gut microbiota is considered a compulsory and an essential part in the pathogenesis of CD. Intestinal dysmicrobism with excessive amounts of different bacterial strains can be found in all patients with IBD. The discovery of Escherichia coli entero-invasive on resection pieces in patients with CD now increases the likelihood of antimicrobial or vaccine-type treatments. Recent studies targeting intestinal immunology and its molecular activation pathways provide new possibilities for therapeutics. In addition to antitumor necrosis factor molecules, which were a breakthrough in IBD, improving mucosal healing and resection-free survival rate, other classes of therapeutic agents come to focus. Leukocyte adhesion inhibitors block the leukocyte homing mechanism and prevent cellular immune response. In addition to anti-integrin antibodies, chemokine receptor antagonists and SMAD7 antisense oligonucleotides have shown encouraging results in clinical trials. Micro-RNAs have demonstrated their role as disease biomarkers but it could also become useful for the treatment of IBD. Moreover, cellular therapy is another therapeutic approach under development, aimed for severe refractory CD. Other experimental treatments include intravenous immunoglobulins, exclusive enteral

  2. HDL cholesterol: all hope is not lost after the torcetrapib setback--emerging therapeutic strategies on the horizon.

    PubMed

    Verma, Nitin; Figueredo, Vincent M

    2014-01-01

    Lowering low-density lipoprotein cholesterol (LDL) has been definitely shown to reduce cardiovascular events and improve clinical outcomes in the literature. As a result, LDL lowering has become the cornerstone of therapeutic approaches to cardiovascular disease prevention. Recently, there has been a focus on targeting other lipid fractions to improve the clinical risk profile of patients. Raising high-density lipoprotein (HDL) has received considerable attention. Low HDL levels are often seen in combination with elevated triglyceride levels. New therapeutic modalities are being developed to increase HDL levels. Recent failure of agents such as cholesteryl ester transferase protein inhibitor torcetrapib has highlighted the importance of measuring functionality of HDL particles and not just focus quantitatively on HDL-C levels. The heterogeneity of HDL within the systemic circulation results from constant remodeling of particles in response to several factors. Established dyslipidemia therapies such as stains, fibrates, and niacin have already been well known in the literature to have a substantial benefit. Lifestyle changes such as smoking cessation and moderate alcohol consumption have also shown to have some benefit. Several novel HDL therapies are currently being developed, but only the cholesteryl ester transferase protein inhibitors have received considerable attention. Although torcetrapib has received some negative attention due to adverse effects, this overall class of therapeutic agents still holds a lot of promise. Newer agents without the concerned toxicities are currently being developed. ApoA-1-related peptides, peroxisome proliferator-activated receptor agonists, endothelial lipase inhibitors, and liver X receptor agonists are some of the other novel agents currently in various stages of development. PMID:22967983

  3. MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics

    PubMed Central

    Deiuliis, J A

    2016-01-01

    The prevalence of overweight and obesity in developed and developing countries has greatly increased the risk of insulin resistance and type 2 diabetes mellitus. It is evident from human and animal studies that obesity alters microRNA (miRNA) expression in metabolically important organs, and that miRNAs are involved in changes to normal physiology, acting as mediators of disease. miRNAs regulate multiple pathways including insulin signaling, immune-mediated inflammation, adipokine expression, adipogenesis, lipid metabolism, and food intake regulation. Thus, miRNA-based therapeutics represent an innovative and attractive treatment modality, with non-human primate studies showing great promise. In addition, miRNA measures in plasma or bodily fluids may be used as disease biomarkers and predictors of metabolic disease in humans. This review analyzes the role of miRNAs in obesity and insulin resistance, focusing on the miR-17/92, miR-143-145, miR-130, let-7, miR-221/222, miR-200, miR-223, miR-29 and miR-375 families, as well as miRNA changes by relevant tissue (adipose, liver and skeletal muscle). Further, the current and future applications of miRNA-based therapeutics and diagnostics in metabolic disease are discussed. PMID:26311337

  4. Activation of the Tumor Suppressor PP2A Emerges as a Potential Therapeutic Strategy for Treating Prostate Cancer

    PubMed Central

    Cristóbal, Ion; González-Alonso, Paula; Daoud, Lina; Solano, Esther; Torrejón, Blanca; Manso, Rebeca; Madoz-Gúrpide, Juan; Rojo, Federico; García-Foncillas, Jesús

    2015-01-01

    Protein phosphatase 2A (PP2A) is a tumor suppressor complex that has recently been reported as a novel and highly relevant molecular target in prostate cancer (PCa). However, its potential therapeutic value remains to be fully clarified. We treated PC-3 and LNCaP cell lines with the PP2A activators forskolin and FTY720 alone or combined with the PP2A inhibitor okadaic acid. We examined PP2A activity, cell growth, prostasphere formation, levels of PP2A phosphorylation, CIP2A and SET expression, and AKT and ERK activation. Interestingly, both forskolin and FTY720 dephosphorylated and activated PP2A, impairing proliferation and prostasphere formation and inducing changes in AKT and ERK phosphorylation. Moreover, FTY720 led to reduced CIP2A levels. Treatment with okadaic acid impaired PP2A activation thus demonstrating the antitumoral PP2A-dependent mechanism of action of both forskolin and FTY720. Levels of PP2A phosphorylation together with SET and CIP2A protein expression were studied in 24 PCa patients and both were associated with high Gleason scores and presence of metastatic disease. Altogether, our results suggest that PP2A inhibition could be involved in PCa progression, and the use of PP2A-activating drugs might represent a novel alternative therapeutic strategy for treating PCa patients. PMID:26023836

  5. The emerging role of the thrombin receptor (PAR-1) in melanoma metastasis--a possible therapeutic target.

    PubMed

    Villares, Gabriel J; Zigler, Maya; Bar-Eli, Menashe

    2011-01-01

    Melanoma remains as the deadliest form of skin cancer with limited and inefficient treatment options available for patients with metastatic disease. Within the last decade, the thrombin receptor, Protease Activated Receptor-1, has been described as an essential gene involved in the progression of human melanoma. PAR-1 is known to activate adhesive, invasive and angiogenic factors to promote melanoma metastasis. It is overexpressed not only in metastatic melanoma cell lines but is also highly expressed in metastatic lesions as compared to primary nevi and normal skin. Recently, PAR-1 has been described to regulate the gap junction protein Connexin 43 and the tumor suppressor gene Maspin to promote the metastatic melanoma phenotype. Herein, we review the role of PAR-1 in the progression of melanoma as well as utilizing PAR-1-regulated genes as potential therapeutic targets for melanoma treatment. PMID:21378407

  6. APE1/Ref-1 as an emerging therapeutic target for various human diseases: phytochemical modulation of its functions

    PubMed Central

    Thakur, Shweta; Sarkar, Bibekananda; Cholia, Ravi P; Gautam, Nandini; Dhiman, Monisha; Mantha, Anil K

    2014-01-01

    Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional enzyme involved in the base excision repair (BER) pathway, which repairs oxidative base damage caused by endogenous and exogenous agents. APE1 acts as a reductive activator of many transcription factors (TFs) and has also been named redox effector factor 1, Ref-1. For example, APE1 activates activator protein-1, nuclear factor kappa B, hypoxia-inducible factor 1α, paired box gene 8, signal transducer activator of transcription 3 and p53, which are involved in apoptosis, inflammation, angiogenesis and survival pathways. APE1/Ref-1 maintains cellular homeostasis (redox) via the activation of TFs that regulate various physiological processes and that crosstalk with redox balancing agents (for example, thioredoxin, catalase and superoxide dismutase) by controlling levels of reactive oxygen and nitrogen species. The efficiency of APE1/Ref-1's function(s) depends on pairwise interaction with participant protein(s), the functions regulated by APE1/Ref-1 include the BER pathway, TFs, energy metabolism, cytoskeletal elements and stress-dependent responses. Thus, APE1/Ref-1 acts as a ‘hub-protein' that controls pathways that are important for cell survival. In this review, we will discuss APE1/Ref-1's versatile nature in various human etiologies, including neurodegeneration, cancer, cardiovascular and other diseases that have been linked with alterations in the expression, subcellular localization and activities of APE/Ref-1. APE1/Ref-1 can be targeted for therapeutic intervention using natural plant products that modulate the expression and functions of APE1/Ref-1. In addition, studies focusing on translational applications based on APE1/Ref-1-mediated therapeutic interventions are discussed. PMID:25033834

  7. Aquaporin 1, a potential therapeutic target for migraine with aura

    PubMed Central

    2010-01-01

    The pathophysiology of migraine remains largely unknown. However, evidence regarding the molecules participating in the pathophysiology of migraine has been accumulating. Water channel proteins, known as aquaporins (AQPs), notably AQP-1 and AQP-4, appears to be involved in the pathophysiology of several neurological diseases. This review outlines newly emerging evidence indicating that AQP-1 plays an important role in pain signal transduction and migraine and could therefore serve as a potential therapeutic target for these diseases. PMID:20969805

  8. Manipulating Autophagic Processes in Autoimmune Diseases: A Special Focus on Modulating Chaperone-Mediated Autophagy, an Emerging Therapeutic Target

    PubMed Central

    Wang, Fengjuan; Muller, Sylviane

    2015-01-01

    Autophagy, a constitutive intracellular degradation pathway, displays essential role in the homeostasis of immune cells, antigen processing and presentation, and many other immune processes. Perturbation of autophagy has been shown to be related to several autoimmune syndromes, including systemic lupus erythematosus. Therefore, modulating autophagy processes appears most promising for therapy of such autoimmune diseases. Autophagy can be said non-selective or selective; it is classified into three main forms, namely macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA), the former process being by far the most intensively investigated. The role of CMA remains largely underappreciated in autoimmune diseases, even though CMA has been claimed to play pivotal functions into major histocompatibility complex class II-mediated antigen processing and presentation. Therefore, hereby, we give a special focus on CMA as a therapeutic target in autoimmune diseases, based in particular on our most recent experimental results where a phosphopeptide modulates lupus disease by interacting with CMA regulators. We propose that specifically targeting lysosomes and lysosomal pathways, which are central in autophagy processes and seem to be altered in certain autoimmune diseases such as lupus, could be an innovative approach of efficient and personalized treatment. PMID:26042127

  9. Analytical approaches for the detection of emerging therapeutics and non-approved drugs in human doping controls.

    PubMed

    Thevis, Mario; Schänzer, Wilhelm

    2014-12-01

    The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine. Among these compounds, low- and high-molecular mass substances of peptidic (e.g. modified insulin-like growth factor-1, TB-500, hematide/peginesatide, growth hormone releasing peptides, AOD-9604, etc.) and non-peptidic (selective androgen receptor modulators, hypoxia-inducible factor stabilizers, siRNA, S-107 and ARM036/aladorian, etc.) as well as inorganic (cobalt) nature are considered and discussed in terms of specific requirements originating from physicochemical properties, concentration levels, metabolism, and their amenability for chromatographic-mass spectrometric or alternative detection methods. PMID:24906629

  10. Higher Education, Democracy, and Development: Implications for Newly Industrialized Countries.

    ERIC Educational Resources Information Center

    Altbach, Philip G.

    1992-01-01

    Discusses the university's role in emerging economies of the Pacific Rim's Newly Industrialized Countries, noting that universities are central to educating people for technologically oriented societies, providing a voice to emerging democracies. (SM)

  11. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

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

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

  12. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

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

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

  13. GPBA: a GPCR for bile acids and an emerging therapeutic target for disorders of digestion and sensation

    PubMed Central

    Lieu, T; Jayaweera, G; Bunnett, N W

    2014-01-01

    Bile acids (BAs) are digestive secretions that are necessary for the emulsification and absorption of dietary fats. Given the episodic nature of BA secretion and intestinal re-absorption, the circulating and tissue levels of BAs, like those of the gut hormones, fluctuate in fasting and fed states, and BA levels and forms are markedly affected by disease. BAs exert widespread hormonal-like effects by activating receptors in the nucleus and at the plasma membrane. The nuclear steroid receptors mediate the genomic actions of BAs on BA, glucose and lipid homeostasis. GPBA (TGR5) is a G-protein coupled plasma membrane receptor for BAs that mediates many of the rapid, non-genomic actions of BAs. GPBA has been implicated in the control of glucose homeostasis, inflammation and liver functions. Recent observations have revealed an unexpected role for GPBA in the nervous system. GPBA is expressed by enteric neurons and enterochromaffin cells that control peristalsis, and GPBA mediates the prokinetic actions of BAs in the colon that have been known for millennia. GPBA is also present on primary spinal afferent and spinal neurons that are necessary for sensory transduction. BA-induced activation of GPBA in the sensory nervous system promotes scratching behaviours and analgesia, which may contribute to the pruritus and painless jaundice that are observed in some patients with chronic cholestatic disease, where circulating BA concentrations are markedly increased. Thus, GPBA has emerged as an intriguing target for diverse metabolic, inflammatory, digestive and sensory disorders, where agonists and antagonists may be of value. Linked ArticlesThis article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-5 PMID:24111923

  14. Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer.

    PubMed

    Haque, Absarul; Alam, Qamre; Alam, Mohammad Zubair; Azhar, Esam I; Sait, Khalid Hussain Wali; Anfinan, Nisrin; Mushtaq, Gohar; Kamal, Mohammad Amjad; Rasool, Mahmood

    2016-01-01

    Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors. PMID:27013225

  15. Inhibition of bromodomain and extra-terminal proteins (BET) as a potential therapeutic approach in haematological malignancies: emerging preclinical and clinical evidence

    PubMed Central

    Chaidos, Aristeidis; Caputo, Valentina

    2015-01-01

    Post-translational modifications of the nucleosomal histone proteins orchestrate chromatin organization and gene expression in normal and cancer cells. Among them, the acetylation of N-terminal histone tails represents the fundamental epigenetic mark of open structure chromatin and active gene transcription. The bromodomain and extra-terminal (BET) proteins are epigenetic readers which utilize tandem bromodomains (BRD) modules to recognize and dock themselves on the acetylated lysine tails. The BET proteins act as scaffolds for the recruitment of transcription factors and chromatin organizers required in transcription initiation and elongation. The recent discovery of small molecules capable of blocking their lysine-binding pocket is the first paradigm of successful pharmacological inhibition of epigenetic readers. JQ1 is a prototype benzodiazepine molecule and a specific BET inhibitor with antineoplastic activity both in solid tumours and haematological malignancies. The quinolone I-BET151 and the suitable for clinical development I-BET762 benzodiazepine were introduced in parallel with JQ1 and have also shown potent antitumour activity in preclinical studies. I-BET762 is currently being tested in early phase clinical trials, along with a rapidly growing list of other BET inhibitors. Unlike older epigenetic therapies, the study of BET inhibitors has offered substantial, context-specific, mechanistic insights of their antitumour activity, which will facilitate optimal therapeutic targeting in future. Here, we review the development of this novel class of epigenetic drugs, the biology of BET protein inhibition, the emerging evidence from preclinical work and early phase clinical studies and we discuss their potential role in the treatment of haematological malignancies. PMID:26137204

  16. Nanodevices for the immobilization of therapeutic enzymes.

    PubMed

    Bosio, Valeria E; Islan, Germán A; Martínez, Yanina N; Durán, Nelson; Castro, Guillermo R

    2016-06-01

    Therapeutic enzymes are one of the most promising applications of this century in the field of pharmaceutics. Biocatalyst properties can be improved by enzyme immobilization on nano-objects, thereby increasing stability and reusability and also enhancing the targeting to specific tissues and cells. Therapeutic biocatalyst-nanodevice complexes will provide new tools for the diagnosis and treatment of old and newly emerging pathologies. Among the advantages of this approach are the wide span and diverse range of possible materials and biocatalysts that promise to make the matrix-enzyme combination a unique modality for therapeutic delivery. This review focuses on the most significant techniques and nanomaterials used for enzyme immobilization such as metallic superparamagnetic, silica, and polymeric and single-enzyme nanoparticles. Finally, a review of the application of these nanodevices to different pathologies and modes of administration is presented. In short, since therapeutic enzymes constitute a highly promising alternative for treating a variety of pathologies more effectively, this review is aimed at providing the comprehensive summary needed to understand and improve this burgeoning area. PMID:25641329

  17. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  18. Utility and Applications of Orthotopic Models of Human Non-Small Cell Lung Cancer (NSCLC) for the Evaluation of Novel and Emerging Cancer Therapeutics

    PubMed Central

    Justilien, Verline; Fields, Alan P.

    2014-01-01

    Lung cancer is a leading cause of cancer deaths worldwide. Despite advances in chemotherapy, radiation therapy, and surgery, lung cancer continues to have a low 5-year survival rate. Thus, there is a need to better understand the molecular signaling mechanisms that drive lung tumor formation, maintenance, and progression, and to translate this knowledge into better therapeutic intervention strategies. Mouse models that recapitulate the clinical features of advanced human lung cancer are critical for testing novel therapeutic approaches. This unit describes a highly reproducible, easy-to-establish orthotopic murine model of lung cancer, provides methods for in vivo imaging and monitoring of tumor growth, and discusses the usefulness of this model for translational lung cancer research and the development of therapeutic strategies. PMID:24510718

  19. Newly Deployed Sojourner Rover

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This 8-image mosaic was acquired during the late afternoon (near 5pm LST, note the long shadows) on Sol 2 as part of the predeploy 'insurance panorama' and shows the newly deployed rover sitting on the Martian surface. This color image was generated from images acquired at 530,600, and 750 nm. The insurance panorama was designed as 'insurance' against camera failure upon deployment. Had the camera failed, the losslessly-compressed, multispectral insurance panorama would have been the main source of image data from the IMP.

    However, the camera deployment was successful, leaving the insurance panorama to be downlinked to Earth several weeks later. Ironically enough, the insurance panorama contains some of the best quality image data because of the lossless data compression and relatively dust-free state of the camera and associated lander/rover hardware on Sol 2.

    Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal investigator.

  20. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

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

  1. Newly Diagnosed Acute Promyelocytic Leukemia

    PubMed Central

    Avvisati, Giuseppe

    2011-01-01

    Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA, targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years, rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome. Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up. PMID:22220261

  2. Engineering therapeutic antibodies targeting G-protein–coupled receptors

    PubMed Central

    Jo, Migyeong; Jung, Sang Taek

    2016-01-01

    G-protein–coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution. PMID:26846450

  3. Emerging phleboviruses☆

    PubMed Central

    Elliott, Richard M; Brennan, Benjamin

    2014-01-01

    The Bunyavidae family is the largest grouping of RNA viruses and arguably the most diverse. Bunyaviruses have a truly global distribution and can infect vertebrates, invertebrates and plants. The majority of bunyaviruses are vectored by arthropods and thus have the remarkable capability to replicate in hosts of disparate phylogeny. The family has provided many examples of emerging viruses including Sin Nombre and related viruses responsible for hantavirus cardiopulmonary syndrome in the Americas, first identified in 1993, and Schmallenberg virus which emerged in Europe in 2011, causing foetal malformations in ruminants. In addition, some well-known bunyaviruses like Rift Valley fever and Crimean-Congo haemorrhagic fever viruses continue to emerge in new geographical locations. In this short review we focus on newly identified viruses associated with severe haemorrhagic disease in humans in China and the US. PMID:24607799

  4. Two TIR-like domain containing proteins in a newly emerging zoonotic Staphylococcus aureus strain sequence type 398 are potential virulence factors by impacting on the host innate immune response

    PubMed Central

    Patterson, Nicholas J.; Günther, Juliane; Gibson, Amanda J.; Offord, Victoria; Coffey, Tracey J.; Splitter, Gary; Monk, Ian; Seyfert, Hans-Martin; Werling, Dirk

    2014-01-01

    Staphylococcus aureus, sequence type (ST) 398, is an emerging pathogen and the leading cause of livestock-associated methicillin-resistant S. aureus infections in Europe and North America. This strain is characterized by high promiscuity in terms of host-species and also lacks several traditional S. aureus virulence factors. This does not, however, explain the apparent ease with which it crosses species-barriers. Recently, TIR-domain containing proteins (Tcps) which inhibit the innate immune response were identified in some Gram-negative bacteria. Here we report the presence of two proteins, S. aureus TIR-like Protein 1 (SaTlp1) and S. aureus TIR-like Protein 2 (SaTlp2), expressed by ST398 which contain domain of unknown function 1863 (DUF1863), similar to the Toll/IL-1 receptor (TIR) domain. In contrast to the Tcps in Gram-negative bacteria, our data suggest that SaTlp1 and SaTlp2 increase activation of the transcription factor NF-κB as well as downstream pro-inflammatory cytokines and immune effectors. To assess the role of both proteins as potential virulence factors knock-out mutants were created. These showed a slightly enhanced survival rate in a murine infectious model compared to the wild-type strain at one dose. Our data suggest that both proteins may act as factors contributing to the enhanced ability of ST398 to cross species-barriers. PMID:25538689

  5. [Principles of nutrition in patients with newly appointed stoma].

    PubMed

    Pachocka, Lucyna Małgorzata; Urbanik, Anna

    2016-01-01

    The treatment of intestinal stoma is often a difficult experience for patients and results in numerous problems in the physical, psychological and social aspects. Therefore, post-operative care of the patient with the newly appointed stoma should be taken by therapeutic team consisting of doctors, nurses, physiotherapists, dieticians, psychologists and social workers. Appropriate nutritional education of patients aims to improve their quality of life and to prevent from unpleasant ailments formed after the operation. The specific type of stoma may decide about certain dietary recommendations. The presented work provides a practical dietary recommendations for patients with newly appointed stoma. PMID:27162293

  6. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options--a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference.

    PubMed

    Kirchhof, Paulus; Lip, Gregory Y H; Van Gelder, Isabelle C; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  7. Comprehensive risk reduction in patients with atrial fibrillation: emerging diagnostic and therapeutic options—a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference

    PubMed Central

    Kirchhof, Paulus; Lip, Gregory Y.H.; Van Gelder, Isabelle C.; Bax, Jeroen; Hylek, Elaine; Kaab, Stefan; Schotten, Ulrich; Wegscheider, Karl; Boriani, Giuseppe; Brandes, Axel; Ezekowitz, Michael; Diener, Hans; Haegeli, Laurent; Heidbuchel, Hein; Lane, Deirdre; Mont, Luis; Willems, Stephan; Dorian, Paul; Aunes-Jansson, Maria; Blomstrom-Lundqvist, Carina; Borentain, Maria; Breitenstein, Stefanie; Brueckmann, Martina; Cater, Nilo; Clemens, Andreas; Dobrev, Dobromir; Dubner, Sergio; Edvardsson, Nils G.; Friberg, Leif; Goette, Andreas; Gulizia, Michele; Hatala, Robert; Horwood, Jenny; Szumowski, Lukas; Kappenberger, Lukas; Kautzner, Josef; Leute, Angelika; Lobban, Trudie; Meyer, Ralf; Millerhagen, Jay; Morgan, John; Muenzel, Felix; Nabauer, Michael; Baertels, Christoph; Oeff, Michael; Paar, Dieter; Polifka, Juergen; Ravens, Ursula; Rosin, Ludger; Stegink, W.; Steinbeck, Gerhard; Vardas, Panos; Vincent, Alphons; Walter, Maureen; Breithardt, Günter; Camm, A. John

    2012-01-01

    While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF. PMID:21791573

  8. Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

    PubMed Central

    Ballerini, Andrea; Boccalon, Roberto M; Boncompagni, Giancarlo; Casacchia, Massimo; Margari, Francesco; Minervini, Lina; Righi, Roberto; Russo, Federico; Salteri, Andrea; Frediani, Sonia; Rossi, Andrea; Scatigna, Marco

    2007-01-01

    Background The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance

  9. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  10. Fig4 Deficiency: A Newly Emerged Lysosomal Storage Disorder?

    PubMed Central

    Martyn, Colin; Li, Jun

    2012-01-01

    FIG4 (Sac3 in mammals) is a 5’-phosphoinositide phosphatase that coordinates the turnover of phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), a very low abundance phosphoinositide. Deficiency of FIG4 severely affects the human and mouse nervous systems by causing two distinct forms of abnormal lysosomal storage. The first form occurs in spinal sensory neurons, where vacuolated endolysosomes accumulate in perinuclear regions. A second form occurs in cortical/spinal motor neurons and glia, in which enlarged endolysosomes become filled with electron dense materials in a manner indistinguishable from other lysosomal storage disorders. Humans with a deficiency of FIG4 (known as Charcot-Marie-Tooth disease type 4J or CMT4J) present with clinical and pathophysiological phenotypes indicative of spinal motor neuron degeneration and segmental demyelination. These findings reveal a signaling pathway involving FIG4 that appears to be important for lysosomal function. In this review, we discuss the biology of FIG4 and describe how the deficiency of FIG4 results in lysosomal phenotypes. We also discuss the implications of FIG4/PI(3,5)P2 signaling in understanding other lysosomal storage diseases, neuropathies, and acquired demyelinating diseases. PMID:23165282

  11. Newly Emerging Needs of Children and Youth. Annual Report, 2005

    ERIC Educational Resources Information Center

    International Child Development Initiatives (NJ1), 2005

    2005-01-01

    In global terms, 2005 was not much different from the years before, as it was again not a happy time for the world's children. The trend of many countries sinking further back into poverty continued, with people living shorter lives, fewer children going to school and more children dying than ever before. Wars keep raging on, taking heavy tolls on…

  12. EXPLORATORY OCCURRENCE STUDY OF NEWLY EMERGING PATHOGENS IN POTABLE WATER

    EPA Science Inventory

    Recent attention has focused on the potential transmission via drinking water of two bacterial pathogens, Aeromonas and Helicobacter pylori, both of which are included in the current Contaminant Candidate List. Aeromonas bacteria occur naturally in surface waters and have been i...

  13. Viruses of berry crops: Emerging, newly identified, and getting around

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perennial crops offer great advantages to viruses in terms of adaptation and evolution since they avoid vector imposed evolutionary bottlenecks. There are 30 genera of plant viruses known to infect berry crops with many of the viruses recently identified. It is likely there will be 4 new virus gener...

  14. Zika virus: history of a newly emerging arbovirus.

    PubMed

    Wikan, Nitwara; Smith, Duncan R

    2016-07-01

    Zika virus was originally identified in a sentinel rhesus monkey in the Zika Forest of Uganda in 1947. The virus is a member of the family Flaviviridae, genus Flavivirus, and is transmitted to humans by Aedes species mosquitoes. The first report of Zika virus outside Africa and Asia was in 2007 when the virus was associated with a small outbreak in Yap State, part of the Federated States of Micronesia. Since then, Zika virus infections have been reported around the world, including in southeast Asia; French Polynesia and other islands in the Pacific Ocean; and parts of South, Central, and North America. Symptomatic infection in human beings normally results in a mild and self-limiting febrile disease, although recent reports have suggested a possible association with more serious sequelae such as Guillain-Barré syndrome, and microcephaly in newborn infants of mothers infected with Zika virus during pregnancy. In this Review, we summarise the history of Zika virus from its first detection to its current worldwide distribution. PMID:27282424

  15. Why does A&E attract newly qualified registered nurses?

    PubMed

    Cronin, Gerard; Cronin, Camille

    2006-04-01

    Workforce planning is a particular buzzword that nurse managers must grapple with and now must understand. They must develop strategies to ensure the life and growth of a department while incorporating numerous government targets to ensure the service reaches quality, achieves and meets predetermined goals. To do all this that manager needs a workforce. The recruitment of nursing staff to a specialist area such as Accident & Emergency (A&E) requires a level of creativity and sustained effort. Newly qualified registered nurse working in A&E have, in the past, been considered to be an unusual group of staff to apply to work in A&E. However, many health service managers receive applications from staff in this category and are often encouraged to recruit newly qualified registered nurse's rather than pay for agency workers. Using a qualitative approach this paper explores the key reasons why newly qualified registered nurses choose to work in an Accident & Emergency environment. Data was collected from a sample of 25 newly qualified registered nurses and analysed thematically. Five themes are presented: challenge, teamwork, diversity, support, and learning. These themes have implications for Accident and Emergency units and human resource and workforce planning departments. PMID:16464593

  16. Pigeon therapeutics.

    PubMed

    Harlin, R W

    2000-01-01

    This article examines therapeutics for pigeons, discussing their physiology and reproduction, housing, and nutrition. The author also looks at ways to prevent infection, while discussing treatments for various viral diseases, such as paramyxovirus and pigeon herpesvirus, bacterial infections, such as paratyphoid, and parasitic diseases. Drug dosages are listed for antibiotics, antifungals, antiparasitics, and vaccines. PMID:11228828

  17. Feedlot therapeutics.

    PubMed

    Apley, M D; Fajt, V R

    1998-07-01

    This article discusses therapeutic approaches to conditions commonly encountered in feedlots. Challenges discussed include bovine respiratory complex, tracheal edema, atypical interstitial pneumonia, footrot, toe abscesses, mycoplasma arthritis, cardiovascular disease, lactic acidosis, bloat, coccidiosis, central nervous system diseases, abscesses and cellulitis, pregnancy management and abortion, and ocular disease. PMID:9704416

  18. Career Motivation in Newly Licensed Registered Nurses: What Makes Them Remain

    ERIC Educational Resources Information Center

    Banks, Zarata Mann; Bailey, Jessica H.

    2010-01-01

    Despite vast research on newly licensed registered nurses (RNs), we don't know why some newly licensed registered nurses remain in their current jobs and others leave the nursing profession early in their career. Job satisfaction, the most significant factor emerging from the literature, plays a significant role in nurses' decisions to remain in…

  19. Therapeutic perspectives

    PubMed Central

    Fiore, Carmelo E.; Pennisi, Pietra; Tinè, Marianna

    2008-01-01

    Osteoporosis and atherosclerosis are linked by biological association. This encourages the search for therapeutic strategies having both cardiovascular and skeletal beneficial effects. Among drugs that may concordantly enhance bone density and reduce the progression of atherosclerosis we can include bisphosphonates (BP), statins, β -blockers, and possibly anti-RANKL antibodies. Available data come from experimental animals and human studies. All these treatments however lack controlled clinical studies designed to demonstrate dual-action effects. PMID:22460845

  20. Recurrent pericarditis: new and emerging therapeutic options.

    PubMed

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

    2016-02-01

    Recurrent pericarditis is one of the most common and troublesome complications after an episode of pericarditis, and affects 20-50% of patients treated for pericarditis. In most of these patients, the pericarditis remains idiopathic, although an immune-mediated (either autoimmune or autoinflammatory) pathogenesis is often presumed. The mainstay of therapy for recurrences is aspirin or NSAIDs, with the adjunct of colchicine. Corticosteroids are a second-line option to be considered for specific indications, such as connective tissue disease or pregnancy; contraindications or intolerance to aspirin, NSAIDs, and/or colchicine; or insufficient response to these medications. Furthermore, corticosteroids can be added to NSAIDs and colchicine in patients with persistent symptoms. In patients who do not respond adequately to any of these conventional therapies, alternative treatment options include azathioprine, intravenous human immunoglobulins, and anakinra. An improved understanding of how recurrent pericarditis develops after an initiating event is critical to prevent this complication, and further research is needed into the pathogenesis of recurrences. We discuss the aetiology and diagnosis of recurrent pericarditis, and extensively review the treatment options for this condition. PMID:26259934

  1. Discoidin Domains as Emerging Therapeutic Targets.

    PubMed

    Villoutreix, Bruno O; Miteva, Maria A

    2016-08-01

    Discoidin (DS) domains are found in eukaryotic and prokaryotic extracellular and transmembrane multidomain proteins. These small domains play different functional roles and can interact with phospholipids, glycans, and proteins, including collagens. DS domain-containing proteins are often involved in cellular adhesion, migration, proliferation, and matrix-remodeling events, while some play a major role in blood coagulation. Mutations in DS domains have been associated with various disease conditions. This review provides an update on the structure, function, and modulation of the DS domains, with a special emphasis on two circulating blood coagulation cofactors, factor V and factor VIII, and the transmembrane neuropilin receptors that have been targeted for inhibition by biologics and small chemical compounds. PMID:27372370

  2. Dormancy programs as emerging antimetastasis therapeutic alternatives

    PubMed Central

    Sosa, Maria Soledad

    2016-01-01

    We recently published that the retinoid-responsive gene NR2F1 (nuclear receptor subfamily 2, group F, member 1) mediates postsurgical dormancy of local residual tumor cells and disseminated tumor cells. Importantly, the combination of azacytidine with retinoids induces dormancy of malignant tumor cells by reinstating the NR2F1-regulated gene program. These findings open the door to the development of strategies that may stop minimal residual disease from becoming life-threatening metastases. PMID:27308542

  3. Psychiatric Emergencies.

    PubMed

    Wheat, Santina; Dschida, Dorothy; Talen, Mary R

    2016-06-01

    Psychiatric emergencies are acute disturbances in thought, behavior, mood, or social relationship that require immediate intervention as defined by the patient, family, or social unit to save the patient and/or others from imminent danger. Ensuring the safety of the patient, surrounding persons, and the medical team is the first step of evaluation. Treatment focuses on stabilization of the patient, then on specific symptoms and ultimately the cause of symptoms. There are important legal considerations, particularly regarding involuntary admissions. It is important to debrief with the patient, surrounding family, and the health care team to ensure a continued therapeutic alliance and the emotional health of all involved. PMID:27262012

  4. Emerging Respiratory Viruses: Challenges and Vaccine Strategies

    PubMed Central

    Gillim-Ross, Laura; Subbarao, Kanta

    2006-01-01

    The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from current vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed. PMID:17041137

  5. Therapeutic alliance.

    PubMed

    Fox, Valerie

    2002-01-01

    I have been very fortunate in my journey of mental illness. I respond well to medication, but I don't think that is the complete answer to living successfully with serious, persistent mental illness. I believe a person's environment is also of utmost importance, enabling the person suffering with mental illness to continually grow in life. I found early in my struggle with mental illness a psychiatrist with whom I have always had a very good rapport. Until recently I didn't know that what I have with this psychiatrist is professionally known as a therapeutic alliance. Over the years, when I need someone to talk over anything that is troubling to me, I seek my psychiatrist. A therapeutic alliance is non-judgmental; it is nourishing; and finally it is a relationship of complete trust. Perhaps persons reading this article who have never experienced this alliance will seek it. I believe it can make an insecure person secure; a frightened person less frightened; and allow a person to continue the journey of mental health with a sense of belief in oneself. PMID:12433224

  6. [Therapeutic potential of optogenetic neuromodulation].

    PubMed

    Vandecasteele, Marie; Senova, Yann-Suhan; Palfi, Stéphane; Dugué, Guillaume P

    2015-04-01

    Optogenetic neuromodulation techniques, which have emerged during the last 15 years, have considerably enhanced our ability to probe the functioning of neural circuits by allowing the excitation and inhibition of genetically-defined neuronal populations using light. Having gained tremendous popularity in the field of fundamental neuroscience, these techniques are now opening new therapeutic avenues. Optogenetic neuromodulation is a method of choice for studying the physiopathology of neurological and neuropsychiatric disorders in a range of animal models, and could accelerate the discovery of new therapeutic strategies. New therapeutic protocols employing optogenetic neuromodulation may also emerge in the near future, offering promising alternative approaches for disorders which lack appropriate treatments, such as pharmacoresistant epilepsy and inherited retinal degeneration. PMID:25958759

  7. Lung Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Lung Emergencies People with Marfan syndrome can be at ... should be considered an emergency. Symptoms of sudden lung collapse (pneumothorax) Symptoms of a sudden lung collapse ...

  8. Antisense treatment of caliciviridae: an emerging disease agent of animals and humans.

    PubMed

    Smith, Alvin W; Matson, David O; Stein, David A; Skilling, Douglas E; Kroeker, Andrew D; Berke, Tamas; Iversen, Patrick L

    2002-04-01

    The Earth's oceans are the primary reservoir for an emerging family of RNA viruses, the Caliciviridae, which can cause a spectrum of diseases in marine animals, wildlife, farm animals, pets and humans. Certain members of this family have unusually broad host ranges, and some are zoonotic (transmissible from animals to humans). The RNA virus replicative processes lack effective genetic repair mechanisms, and, therefore, virtually every calicivirus replicate is a mutant. Hence, traditional therapeutics dependent on specific nucleic acid sequences or protein epitopes lack the required diversity of sequence or conformational specificity that would be required to reliably detect, prevent or treat infections from these mutant clusters (quasi-species) of RNA viruses, including the Caliciviridae. Antisense technology using phosphorodiamidate morpholino oligomers shows promise in overcoming these current diagnostic and therapeutic problems inherent with newly emerging viral diseases. PMID:12044040

  9. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  10. Emerging and re-emerging infections.

    PubMed

    Lim, V K

    1999-06-01

    An emerging infection is defined as an infection which has newly appeared in a population while a re-emerging infection is one which has existed in the past but its incidence is rapidly increasing. The reasons for the emergence and re-emergence of infections are not well understood but appear to be associated with factors that involve the pathogen, the host and the environment. These factors are often inter-related and act together in a complex manner to bring about changes in patterns of infection. Pathogens are extremely resourceful and possess mechanisms to adapt to new hosts and environments as well as to acquire new virulence traits. Host factors include herd immunity, social behaviour and demographics. Environmental factors like the climate, deforestation and new technologies have an impact on the emergence of infections. The challenge is to contain an infection when it emerges but more importantly to prevent its emergence in the first place. As the emergence of an infection is complex and multifactorial, a multidisciplinary approach is required. Health based strategies alone are insufficient. Social, economic and environmental measures and the political will to implement appropriate policies are equally important. PMID:10972048

  11. Eye Emergencies

    MedlinePlus

    ... Emergencies Cardiac Emergencies Eye Emergencies Lung Emergencies Surgeries Eye Emergencies Marfan syndrome significantly increases your risk of ... light-sensitive membrane in the back of the eye (the retina) from its supporting layers. It is ...

  12. Emerging strategies for the treatment of pulmonary tuberculosis: promise and limitations?

    PubMed Central

    Yew, Wing Wai; Koh, Won-Jung

    2016-01-01

    A worsening scenario of drug-resistant tuberculosis has increased the need for new treatment strategies to tackle this worldwide emergency. There is a pressing need to simplify and shorten the current 6-month treatment regimen for drug-susceptible tuberculosis. Rifamycins and fluoroquinolones, as well as several new drugs, are potential candidates under evaluation. At the same time, treatment outcomes of patients with drug-resistant tuberculosis should be improved through optimizing the use of fluoroquinolones, repurposed agents and newly developed drugs. In this context, the safety and tolerance of new therapeutic approaches must be addressed. PMID:26767853

  13. Epigenomes as therapeutic targets.

    PubMed

    Hamm, Christopher A; Costa, Fabricio F

    2015-07-01

    Epigenetics is a molecular phenomenon that pertains to heritable changes in gene expression that do not involve changes in the DNA sequence. Epigenetic modifications in a whole genome, known as the epigenome, play an essential role in the regulation of gene expression in both normal development and disease. Traditional epigenetic changes include DNA methylation and histone modifications. Recent evidence reveals that other players, such as non-coding RNAs, may have an epigenetic regulatory role. Aberrant epigenetic signaling is becoming to be known as a central component of human disease, and the reversible nature of the epigenetic modifications provides an exciting opportunity for the development of clinically relevant therapeutics. Current epigenetic therapies provide a clinical benefit through disrupting DNA methyltransferases or histone deacetylases. However, the emergence of next-generation epigenetic therapies provides an opportunity to more effectively disrupt epigenetic disease states. Novel epigenetic therapies may improve drug targeting and drug delivery, optimize dosing schedules, and improve the efficacy of preexisting treatment modalities (chemotherapy, radiation, and immunotherapy). This review discusses the epigenetic mechanisms that contribute to the disease, available epigenetic therapies, epigenetic therapies currently in development, and the potential future use of epigenetic therapeutics in a clinical setting. PMID:25797698

  14. Pharmacogenetics approach to therapeutics.

    PubMed

    Koo, Seok Hwee; Lee, Edmund Jon Deoon

    2006-01-01

    1. Pharmacogenetics refers to the study of genetically controlled variations in drug response. Functional variants caused by single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolising enzymes, transporters, ion channels and drug receptors have been known to be associated with interindividual and interethnic variation in drug response. Genetic variations in these genes play a role in influencing the efficacy and toxicity of medications. 2. Rapid, precise and cost-effective high-throughput technological platforms are essential for performing large-scale mutational analysis of genetic markers involved in the aetiology of variable responses to drug therapy. 3. The application of a pharmacogenetics approach to therapeutics in general clinical practice is still far from being achieved today owing to various constraints, such as limited accessibility of technology, inadequate knowledge, ambiguity of the role of variants and ethical concerns. 4. Drug actions are determined by the interplay of several genes encoding different proteins involved in various biochemical pathways. With rapidly emerging SNP discovery technological platforms and widespread knowledge on the role of SNPs in disease susceptibility and variability in drug response, the pharmacogenetics approach to therapeutics is anticipated to take off in the not-too-distant future. This will present profound clinical, economic and social implications for health care. PMID:16700889

  15. Hypertensive emergencies.

    PubMed

    Murphy, C

    1995-11-01

    Hypertensive emergencies are uncommon and physiologically diverse. Consequently, it is difficult for most physicians to develop a familiarity with all the different hypertensive crises and with all drugs available for treating them (Table 4). Clinicians should not agonize over which is the perfect therapeutic agent for a particular emergency, but instead, they should focus on scrupulous monitoring and familiarize themselves with a few agents that will serve in most situations. Generally, these agents will be sodium nitroprusside and nitroglycerin. Vigilant neurologic monitoring is mandatory in all hypertensive emergencies. The early symptoms and signs of cerebral hypoperfusion can be vague and subtle, but if recognized, serious complications of therapy can be avoided. Remember, the patient may still be hypertensive. Avoid acute (during the first hour) reductions in MAP of more than 20% whenever possible; subsequent reductions should be gradual. In patients known to have markedly elevated ICP and who need acute reductions in their BP, serious consideration should be given to direct monitoring of the ICP so that CPP can be maintained within safe limits. In general, oral agents should not be used for the treatment of hypertensive emergencies. Intravenous Labetalol and intravenous nicardipine are not suitable for general use in hypertensive emergencies. In special situations (e.g., perioperative hypertension and subarachnoid hemorrhage), however, they may be employed. Their role may expand with further study. Trimethaphan may be superior to nitroprusside for hypertension complicated by elevated ICP or cerebral dysfunction. Realistically, most physicians will continue to use nitroprusside. Intense neurologic monitoring is more important than the specific agent used. Nitroglycerin is the agent of choice for acute ischemic heart disease complicated by severe hypertension; if it fails, use nitroprusside. For aortic dissection, the combination of nitroprusside and IV

  16. Therapeutic approaches for celiac disease

    PubMed Central

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  17. Myc proteins as therapeutic targets

    PubMed Central

    Gustafson, WC; Weiss, WA

    2010-01-01

    Myc proteins (c-myc, Mycn and Mycl) target proliferative and apoptotic pathways vital for progression in cancer. Amplification of the MYCN gene has emerged as one of the clearest indicators of aggressive and chemotherapy-refractory disease in children with neuroblastoma, the most common extracranial solid tumor of childhood. Phosphorylation and ubiquitin-mediated modulation of Myc protein influence stability and represent potential targets for therapeutic intervention. Phosphorylation of Myc proteins is controlled in-part by the receptor tyrosine kinase/phosphatidylinositol 3-kinase/Akt/mTOR signaling, with additional contributions from Aurora A kinase. Myc proteins regulate apoptosis in part through interactions with the p53/Mdm2/Arf signaling pathway. Mutation in p53 is commonly observed in patients with relapsed neuroblastoma, contributing to both biology and therapeutic resistance. This review examines Myc function and regulation in neuroblastoma, and discusses emerging therapies that target Mycn. PMID:20101214

  18. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  19. Generational differences among newly licensed registered nurses.

    PubMed

    Keepnews, David M; Brewer, Carol S; Kovner, Christine T; Shin, Juh Hyun

    2010-01-01

    Responses of 2369 newly licensed registered nurses from 3 generational cohorts-Baby Boomers, Generation X, and Generation Y-were studied to identify differences in their characteristics, work-related experiences, and attitudes. These responses revealed significant differences among generations in: job satisfaction, organizational commitment, work motivation, work-to-family conflict, family-to-work conflict, distributive justice, promotional opportunities, supervisory support, mentor support, procedural justice, and perceptions of local job opportunities. Health organizations and their leaders need to anticipate intergenerational differences among newly licensed nurses and should provide for supportive working environments that recognize those differences. Orientation and residency programs for newly licensed nurses should be tailored to the varying needs of different generations. Future research should focus on evaluating the effectiveness of orientation and residency programs with regard to different generations so that these programs can be tailored to meet the varying needs of newly licensed nurses at the start of their careers. PMID:20494691

  20. Current and Emerging Aspects of Diabetes Mellitus in Acromegaly.

    PubMed

    Frara, Stefano; Maffezzoni, Filippo; Mazziotti, Gherardo; Giustina, Andrea

    2016-07-01

    Diabetes mellitus is a frequent complication of acromegaly, a disease characterized by chronic hypersecretion of growth hormone (GH) by a pituitary adenoma. Diabetes occurs commonly but not only as a consequence of an insulin-resistant state induced by GH excess. The development of diabetes in patients with acromegaly is clinically relevant, since such a complication is thought to increase the already elevated cardiovascular morbidity and mortality risk of the disease. Emerging data suggest that a specific cardiomyopathy can be identified in acromegaly patients with diabetes. Moreover, the presence of diabetes may also influence therapeutic decision making in acromegaly, since traditional and newly developed drugs used in this clinical setting may impact glucose metabolism regardless of control of GH hypersecretion. PMID:27229934

  1. Chemotherapy in newly diagnosed primary central nervous system lymphoma

    PubMed Central

    Hashemi-Sadraei, Nooshin; Peereboom, David M.

    2010-01-01

    Primary central nervous system lymphoma (PCNSL) accounts for only 3% of brain tumors. It can involve the brain parenchyma, leptomeninges, eyes and the spinal cord. Unlike systemic lymphoma, durable remissions remain uncommon. Although phase III trials in this rare disease are difficult to perform, many phase II trials have attempted to define standards of care. Treatment modalities for patients with newly diagnosed PCNSL include radiation and/or chemotherapy. While the role of radiation therapy for initial management of PCNSL is controversial, clinical trials will attempt to improve the therapeutic index of this modality. Routes of chemotherapy administration include intravenous, intraocular, intraventricular or intra-arterial. Multiple trials have outlined different methotrexate-based chemotherapy regimens and have used local techniques to improve drug delivery. A major challenge in the management of patients with PCNSL remains the delivery of aggressive treatment with preservation of neurocognitive function. Because PCNSL is rare, it is important to perform multicenter clinical trials and to incorporate detailed measurements of long-term toxicities. In this review we focus on different chemotherapeutic approaches for immunocompetent patients with newly diagnosed PCNSL and discuss the role of local drug delivery in addition to systemic therapy. We also address the neurocognitive toxicity of treatment. PMID:21789140

  2. Chemical Emergency

    MedlinePlus

    ... Emergency App Find our Emergency App in the Apple Store or Google Play Aplicación de Emergencias - ahora ... Lifesaving Blood Get Assistance Types of Emergencies Be Red Cross Ready Mobile Apps Workplaces & Organizations Resources For ...

  3. Emergency Contraception

    MedlinePlus

    ... contraception are available: emergency contraceptive pills and the copper-containing intrauterine device (IUD). Emergency contraceptive pills include ... for emergency use, talk to your doctor. The copper-containing IUD (brand name: Paragard) is a small, ...

  4. 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 ...

  5. Recently emerging signaling landscape of ataxia-telangiectasia mutated (ATM) kinase.

    PubMed

    Farooqi, Ammad Ahmad; Attar, Rukset; Arslan, Belkis Atasever; Romero, Mirna Azalea; ul Haq, Muhammad Fahim; Qadir, Muhammad Imran

    2014-01-01

    Research over the years has progressively and sequentially provided near complete resolution of regulators of the DNA repair pathways which are so important for cancer prevention. Ataxia-telangiectasia mutated kinase (ATM), a high-molecular-weight PI3K-family kinase has emerged as a master regulator of DNA damage signaling and extensive cross-talk between ATM and downstream proteins forms an interlaced signaling network. There is rapidly growing scientific evidence emphasizing newly emerging paradigms in ATM biology. In this review, we provide latest information regarding how oxidative stress induced activation of ATM can be utilized as a therapeutic target in different cancer cell lines and in xenografted mice. Moreover, crosstalk between autophagy and ATM is also discussed with focus on how autophagy inhibition induces apoptosis in cancer cells. PMID:25169474

  6. The Florida Survey of Newly Legalized Persons.

    ERIC Educational Resources Information Center

    Schilit, Jeffrey; Nimnicht, Glen

    This study was conducted to gather more definitive information about aliens who were newly legalized under the Immigration Reform and Control Act of 1986. Two groups of eligible legal aliens were interviewed in Florida: those residing in the United States before 1982 (PRE-82s) and special agricultural workers (SAWs). The 1,300 subjects were asked…

  7. Anxiety and the Newly Returned Adult Student

    ERIC Educational Resources Information Center

    Cleary, Michelle Navarre

    2012-01-01

    Based on interviews with students who had recently returned to school, this essay demonstrates the need for, challenges of, and ways to respond to the writing anxiety many adults bring with them back to school. Jessica and Sam were two of twenty-five newly returned adult students whom the author spent over sixty hours interviewing in the fall of…

  8. Rice blast evaluation of newly introduced germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic resistance to the rice blast fungus, Magnaporthe oryzae (anamorph Pyricularia grisea oryzae) was identified in newly introduced rice germplasm through quarantine when tested in artificially inoculated greenhouse and field nursery tests during the 2007 growing season. Of 229 accessions, 31 we...

  9. Newly diagnosed immune thrombocytopenia: update on diagnosis and management.

    PubMed

    Bansal, Deepak; Rajendran, Aruna; Singhi, Sunit

    2014-10-01

    Immune thrombocytopenia (ITP) continues to intrigue pediatricians and hematologists alike. Patients can have a dramatic presentation with wide-spread bleeds over a few days. There is an aura and fear of intra-cranial hemorrhage that drives the physician to recommend and the patient's family to accept drug treatment. Difference of opinion among physicians in the recommendations for treatment is not uncommon, even though recent evidence-based guidelines recommend a conservative, observation-based approach for the majority of patients with newly diagnosed childhood ITP. It is important to note that a specific 'platelet cut-off count', is no longer suggested as an indication by itself to recommend drug therapy. The manuscript is an update on newly diagnosed ITP in children. Recent changes in definitions and recommendations for treatment are highlighted. Pros and cons of 1st line drugs, including corticosteroids, intravenous immunoglobulin and anti-D are listed. Adjunctive therapies for the management of epistaxis and menorrhagia are described. Role of splenic artery embolization and emergency splenectomy in the backdrop of severe thrombocytopenia is discussed. Realistic case scenarios, common errors and frequently asked questions are included for a practical and easy reading. PMID:24091868

  10. Ethics seminars: the ethical debate on practicing procedures on the newly dead.

    PubMed

    Schmidt, Terri A; Abbott, Jean T; Geiderman, Joel M; Hughes, Jason A; Johnson, Catherine X; McClure, Katie B; McKay, Mary P; Razzak, Junaid A; Salo, David; Schears, Raquel M; Solomon, Robert C

    2004-09-01

    Emergency medicine and its academic teaching programs face an ethical dilemma surrounding the question of practicing procedures on the newly dead. For many years, procedures have been practiced on the newly dead, but few institutions have had policies addressing the practice. This article considers the ethical arguments both for and against practicing procedures on the newly dead without consent, reviews the empirical studies on the subject, and presents the positions of other professional societies, before concluding with the position of the Society for Academic Emergency Medicine (SAEM). SAEM strongly encourages all emergency medicine training programs to develop a policy and make that policy available to the institution, educators, trainees, and the public. The practice should not occur behind closed doors or on an ad hoc basis without clearly articulated guidelines. With improvements in technology, including patient simulation and virtual reality, the need for the practice may decrease, but there is no current evidence that is compelling regarding the best methods of teaching procedural skills. Given the importance of protecting trust in the profession of medicine and the existing evidence that the public would expect that consent be obtained, SAEM recommends that families be asked for consent prior to practicing procedures on the newly dead. PMID:15347547

  11. International intellectual property strategies for therapeutic antibodies

    PubMed Central

    2011-01-01

    Therapeutic antibodies need international patent protection as their markets expand to include industrialized and emerging countries. Because international intellectual property strategies are frequently complex and costly, applicants require sound information as a basis for decisions regarding the countries in which to pursue patents. While the most important factor is the size of a given market, other factors should also be considered. PMID:22123063

  12. Zika Virus: Diagnosis, Therapeutics, and Vaccine.

    PubMed

    Shan, Chao; Xie, Xuping; Barrett, Alan D T; Garcia-Blanco, Mariano A; Tesh, Robert B; Vasconcelos, Pedro Fernando da Costa; Vasilakis, Nikos; Weaver, Scott C; Shi, Pei-Yong

    2016-03-11

    The current explosive epidemic of Zika virus in South and Central America, as well as the Caribbean, poses a global public health emergency. Here we comment on the challenges on development of better diagnosis and potential therapeutics and vaccine for Zika virus. PMID:27623030

  13. Liberation Therapeutics: Consciousness Raising as a Problem.

    ERIC Educational Resources Information Center

    Lasch-Quinn, Elisabeth

    2002-01-01

    Questions the content and form of consciousness raising as a mode of purveying knowledge or bringing about change by considering its emergence in the civil rights movement. Examines such books as "Black Rage" (William Grierand Price Cobbs), "Triumph of the Therapeutic" (Philip Reiff), "Where Do We Go From Here: Chaos or Community?" (Martin Luther…

  14. International intellectual property strategies for therapeutic antibodies.

    PubMed

    Storz, Ulrich

    2011-01-01

    Therapeutic antibodies need international patent protection as their markets expand to include industrialized and emerging countries. Because international intellectual property strategies are frequently complex and costly, applicants require sound information as a basis for decisions regarding the countries in which to pursue patents. While the most important factor is the size of a given market, other factors should also be considered. PMID:22123063

  15. Digesting dietary miRNA therapeutics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hippocrates famously advised, "Let food be thy medicine and thy medicine be thy food." Numerous plant-derived compounds are used as cancer therapeutics including antimitotics, topoisomerase inhibitors, and kinase inhibitors. Here we will review emerging evidence suggesting that diet derived small RN...

  16. Therapeutic radionuclides: Making the right choice

    SciTech Connect

    Srivastava, S.C.

    1996-08-01

    Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article.

  17. Emergency contraception

    MedlinePlus

    Morning-after pill; Postcoital contraception; Birth control - emergency; Plan B ... Emergency contraception most likely prevents pregnancy in the same way as regular birth control pills: By preventing or delaying ...

  18. Emergency Contraception

    MedlinePlus

    f AQ FREQUENTLY ASKED QUESTIONS FAQ114 CONTRACEPTION Emergency Contraception • What is emergency contraception (EC)? • How does EC work? • What are the different types of EC? • What is the most ...

  19. Radiation Emergencies

    MedlinePlus

    ... day from sources such as sunlight. A radiation emergency would involve larger amounts of radiation and could ... are no guarantees of safety during a radiation emergency, you can take actions to protect yourself. You ...

  20. Heat emergencies

    MedlinePlus

    Heat emergencies or illnesses are caused by exposure to extreme heat and sun. Heat illnesses can be prevented by ... to regulate the temperature, and make a heat emergency more likely: Drinking alcohol before or during exposure ...

  1. Emergent Expertise?

    ERIC Educational Resources Information Center

    McGivern, Patrick

    2014-01-01

    The concept of emergence appears in various places within the literature on expertise and expert practice. Here, I examine some of these applications of emergence in the light of two prominent accounts of emergence from the philosophy of science and philosophy of mind. I evaluate these accounts with respect to several specific contexts in which…

  2. Childhood Emergencies

    MedlinePlus

    ... Fitness Tracker Save Your Life in the ER? Abdominal Pain Resources Home Safety Checklist ACEP Coloring Book Download the Coloring Book » Emergency Care For You American College of Emergency Phycisians Copyright © American College of Emergency Physicians 2016 Privacy Policy Terms of Use

  3. Antibody Engineering and Therapeutics Conference

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Scott, Jamie; Larrick, James W; Plückthun, Andreas; Veldman, Trudi; Adams, Gregory P; Parren, Paul WHI; Chester, Kerry A; Bradbury, Andrew; Reichert, Janice M; Huston, James S

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Biology), who will discuss a systems approach for studying disease that is enabled by emerging technology; Douglas Lauffenburger (Massachusetts Institute of Technology), who will discuss systems analysis of cell communication network dynamics for therapeutic biologics design; David Baker (University of Washington), who will describe computer-based design of smart protein therapeutics; and William Schief (The Scripps Research Institute), who will discuss epitope-focused immunogen design.   In this preview of the conference, the workshop and session chairs share their thoughts on what conference participants may learn in sessions on: (1) three-dimensional structure antibody modeling; (2) identifying clonal lineages from next-generation data sets of expressed VH gene sequences; (3) antibodies in cardiometabolic medicine; (4) the effects of antibody gene variation and usage on the antibody response; (5) directed evolution; (6) antibody pharmacokinetics, distribution and off-target toxicity; (7) use of knowledge-based design to guide development of complementarity-determining regions and epitopes to engineer or elicit the desired antibody; (8) optimizing antibody formats for immunotherapy; (9) antibodies in a complex environment; (10) polyclonal, oligoclonal and bispecific antibodies; (11) antibodies to watch in 2014; and (12) polyreactive antibodies and polyspecificity.

  4. The Use of Therapeutic Metaphor among Members of the AAMFT.

    ERIC Educational Resources Information Center

    Bryant, Lou; And Others

    1988-01-01

    Explored use of therapeutic metaphor among marriage and family therapists (N=102) belonging to the American Association of Marriage and Family Therapy. Three major themes emerged, including metaphors pertaining to the process of change, those relevant to stages in family life cycle, and methods by which therapeutic metaphors can be constructed and…

  5. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  6. Chicanoizing the Therapeutic Community

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  7. Cytokines and therapeutic oligonucleotides.

    PubMed

    Hartmann, G; Bidlingmaier, M; Eigler, A; Hacker, U; Endres, S

    1997-12-01

    Therapeutic oligonucleotides - short strands of synthetic nucleic acids - encompass antisense and aptamer oligonucleotides. Antisense oligonucleotides are designed to bind to target RNA by complementary base pairing and to inhibit translation of the target protein. Antisense oligonucleotides enable specific inhibition of cytokine synthesis. In contrast, aptamer oligonucleotides are able to bind directly to specific proteins. This binding depends on the sequence of the oligonucleotide. Aptamer oligonucleotides with CpG motifs can exert strong immunostimulatory effects. Both kinds of therapeutic oligonucleotides - antisense and aptamer oligonucleotides - provide promising tools to modulate immunological functions. Recently, therapeutic oligonucleotides have moved towards clinical application. An antisense oligonucleotide directed against the proinflammatory intercellular adhesion molecule 1 (ICAM-1) is currently being tested in clinical trials for therapy of inflammatory disease. Immunostimulatory aptamer oligonucleotides are in preclinical development for immunotherapy. In the present review we summarize the application of therapeutic oligonucleotides to modulate immunological functions. We include technological aspects as well as current therapeutic concepts and clinical studies. PMID:9740353

  8. Emerging targets in neurodegeneration: new opportunities for Alzheimer's disease treatment?

    PubMed

    Rampa, Angela; Gobbi, Silvia; Belluti, Federica; Bisi, Alessandra

    2013-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain associated with memory impairment, progressive cognitive decline and changes in personality and behavior, with rising incidence among elderly people. Reflecting the world population ageing, the scenario is expected to worsen in the next decades if novel drugs or mechanisms that help to counteract neurodegeneration will not be identified. The complex neuropathology of AD is characterized by cholinergic loss, extracellular deposition of amyloid-β plaques, formation of intracellular neurofibrillary tangles, chronic brain inflammation and oxidative damage. To date, there are no effective treatments that can slow or halt the disease, and currently approved drugs only seem to act as palliative by temporary ameliorating cognitive impairment. On the other hand, the role played by other biological systems in the pathogenetic process is now clearly growing and, as knowledge on how AD develops and triggers brain damage proceeds, drug discovery attempts to identify new potential therapeutic targets. This review will focus on these emerging strategies, some of which could open new therapeutic perspectives in Alzheimer's disease, adding new elements for the medicinal chemist to handle and combine for the design of novel multi-target-directed ligands able to simultaneously modulate 'old classic' and newly identified targets. PMID:23931436

  9. Reporting therapeutic discourse in a therapeutic community.

    PubMed

    Chapman, G E

    1988-03-01

    Research in nurses' communications has concentrated on nurse to patient interactions. Those few studies which focus on nurse to nurse communications seem to be generated by a pragmatic and normative concern with effective information sharing. In this paper, which describes one aspect of a larger case study of a hospital-based therapeutic community, the description and analysis of nurses' reports flows not from a normative model of professional practice, but rather an exploration of how professional practice is articulated as discourse in nurses' written accounts. Foucault's ideas about therapeutic discourse inform the theoretical framework of the research. Ethnomethodological concerns with the importance of documentary analysis provide the methodological rationale for examining nurses' 24-hour report documents, as official discourse, reflecting therapeutic practice in this setting. A content analysis of nurses' reports, collected over a period of 4 months, demonstrated the importance of domesticity and ordinary everyday activities in nurses' accounts of hospital life. Disruption to the 'life as usual' domesticity in the community seemed to be associated with admission to and discharge from the hospital when interpersonal and interactional changes between patients occur. It is suggested that nurses in general hospital wards and more orthodox psychiatric settings might usefully consider the impact of admissions and discharges on the group of patients they manage, and make this a discursive focus of their work. PMID:3372900

  10. Value of a newly sequenced bacterial genome.

    PubMed

    Barbosa, Eudes Gv; Aburjaile, Flavia F; Ramos, Rommel Tj; Carneiro, Adriana R; Le Loir, Yves; Baumbach, Jan; Miyoshi, Anderson; Silva, Artur; Azevedo, Vasco

    2014-05-26

    Next-generation sequencing (NGS) technologies have made high-throughput sequencing available to medium- and small-size laboratories, culminating in a tidal wave of genomic information. The quantity of sequenced bacterial genomes has not only brought excitement to the field of genomics but also heightened expectations that NGS would boost antibacterial discovery and vaccine development. Although many possible drug and vaccine targets have been discovered, the success rate of genome-based analysis has remained below expectations. Furthermore, NGS has had consequences for genome quality, resulting in an exponential increase in draft (partial data) genome deposits in public databases. If no further interests are expressed for a particular bacterial genome, it is more likely that the sequencing of its genome will be limited to a draft stage, and the painstaking tasks of completing the sequencing of its genome and annotation will not be undertaken. It is important to know what is lost when we settle for a draft genome and to determine the "scientific value" of a newly sequenced genome. This review addresses the expected impact of newly sequenced genomes on antibacterial discovery and vaccinology. Also, it discusses the factors that could be leading to the increase in the number of draft deposits and the consequent loss of relevant biological information. PMID:24921006

  11. Nanoformulation and antimicrobial evaluation of newly synthesized thiouracil derivatives.

    PubMed

    Fadda, Ahmed A; Bayoumy, Nesma M; El-Sherbiny, Ibrahim M

    2016-07-01

    The present work reports the synthesis of a new series of pyridopyrimidine derivatives. The newly synthesized compounds were characterized by various analytical and spectral techniques. In addition, their antimicrobial activity was evaluated as well as modeling studies were performed to investigate their ability to recognize and bind to the biotin carboxylase (BC)-active site. The results showed a broad spectrum antibacterial and antifungal profile of the synthesized derivatives. Docking results demonstrated that all members of this class of new derivatives were able to recognize the active site of Escherichia coli BC and form different types of bonding interactions with key active site amino acid residues. Besides the compounds with promising antimicrobial activity in addition to 6-aminothiouracil, as control, were incorporated into polycaprolactone nanoparticles to improve their water solubility, permeability through physiological barriers and consequently enhanced therapeutic efficacy. The compounds-loaded nanoparticles were prepared using single emulsion-solvent evaporation technique, and their diameters were found to be in the range 136 ± 30 to 213 ± 28 nm. Transmission electron microscopy (TEM) showed a spherical and dense morphology of the nanoparticles. The results also showed high entrapment efficiency of the synthesized bioactive compounds in the nanoparticles (85 ± 5% to 91 ± 2%) with a desirable in vitro biodegradation and release profiles. PMID:26559404

  12. [Hypertensive emergency and urgency: clinical update].

    PubMed

    Milan, Alberto; Puglisi, Elisabetta; Ferrari, Giovanni; Fabbri, Ambra; Rabbia, Franco; Mulatero, Paolo; Veglio, Franco

    2010-11-01

    Hypertensive crises (i.e., blood pressure > 180/120 mmHg) are common issues in the emergency department. This term is used to indicate both emergencies and urgencies, characterized by presence and absence of target organ damage, respectively. A wide range of therapeutic options are available. The aim of this article is to review current knowledge and treatment trends in the literature to provide clinicians with diagnostic and therapeutic tools. PMID:21348321

  13. New therapeutic approaches in PV

    PubMed Central

    Falchi, Lorenzo; Newberry, Kate J.; Verstovsek, Srdan

    2015-01-01

    Polycytemia vera (PV) is one of the three Philadelphia-negative myeloproliferative neoplasms. Clinically, PV is an indolent disease but its course can be complicated by arterial and venous vascular accidents, evolution to myelofibrosis or leukemic transformation. Treatment of PV is, therefore, aimed at preventing such acute complications. The cornerstone of therapy of low-risk patients remains strict control of cardiovascular risk factors, the use of phlebotomy and low dose aspirin. Higher risk patients should also receive cytoreductive treatments. Hydroxyurea and interferon-α represent standard first-line options for newly diagnosed high-risk PV patients. Recommendations for patients who fail these therapies are less clearly defined. The discovery of a mutation in the Janus kinase 2 gene (V617F) in almost all cases of PV has prompted the development of molecularly targeted agents for the treatment of these patients. In this review we will discuss key clinical aspects, the current therapeutic armamentarium and data on the use of novel agents in patients with PV. PMID:26297275

  14. Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches

    PubMed Central

    Swiecicki, Paul L; Malloy, Kelly M; Worden, Francis P

    2016-01-01

    Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease. PMID:26862488

  15. Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction

    PubMed Central

    Zhu, Ping; Liu, Jianfeng; Shi, Jinxin; Zhou, Qian; Liu, Jie; Zhang, Xianwei; Du, Zhiyan; Liu, Qiaowei; Guo, Yuanyuan

    2015-01-01

    Myocardial infarction (MI) is a major cause of death and disability worldwide. In the last decade, mesenchymal stem cells (MSCs) based cell therapy has emerged as a promising therapeutic strategy. Although great advance have been made using MSCs to treat MI, the low viability of transplanted MSCs severely limits the efficiency of MSCs therapy. Here, we show evidence that ex vivo pre-treatment with melatonin, an endogenous hormone with newly found anti-oxidative activity, could improve survival and function of adipose tissue derived MSCs (ADSCs) in vitro as well as in vivo. ADSCs with 5 μM melatonin pre-treatment for 24 hrs showed increased expression of the antioxidant enzyme catalase and Cu/Zn superoxide dismutase (SOD-1), as well as pro-angiogenic and mitogenic factors like insulin-like growth factor 1, basic fibroblast growth factor, hepatocyte growth factor (HGF), epidermal growth factor. Furthermore, melatonin pre-treatment protected MSCs from reactive oxygen species (ROS) induced apoptosis both directly by promoting anti-apoptosis kinases like p-Akt as well as blocking caspase cascade, and indirectly by restoring the ROS impaired cell adhesion. Using a rat model of MI, we found that melatonin pre-treatment enhanced the viability of engrafted ADSCs, and promoted their therapeutic potency. Hopefully, our results may shed light on the design of more effective therapeutic strategies treating MI by MSCs in clinic. PMID:26081690

  16. Melatonin protects ADSCs from ROS and enhances their therapeutic potency in a rat model of myocardial infarction.

    PubMed

    Zhu, Ping; Liu, Jianfeng; Shi, Jinxin; Zhou, Qian; Liu, Jie; Zhang, Xianwei; Du, Zhiyan; Liu, Qiaowei; Guo, Yuanyuan

    2015-09-01

    Myocardial infarction (MI) is a major cause of death and disability worldwide. In the last decade, mesenchymal stem cells (MSCs) based cell therapy has emerged as a promising therapeutic strategy. Although great advance have been made using MSCs to treat MI, the low viability of transplanted MSCs severely limits the efficiency of MSCs therapy. Here, we show evidence that ex vivo pre-treatment with melatonin, an endogenous hormone with newly found anti-oxidative activity, could improve survival and function of adipose tissue derived MSCs (ADSCs) in vitro as well as in vivo. ADSCs with 5 μM melatonin pre-treatment for 24 hrs showed increased expression of the antioxidant enzyme catalase and Cu/Zn superoxide dismutase (SOD-1), as well as pro-angiogenic and mitogenic factors like insulin-like growth factor 1, basic fibroblast growth factor, hepatocyte growth factor (HGF), epidermal growth factor. Furthermore, melatonin pre-treatment protected MSCs from reactive oxygen species (ROS) induced apoptosis both directly by promoting anti-apoptosis kinases like p-Akt as well as blocking caspase cascade, and indirectly by restoring the ROS impaired cell adhesion. Using a rat model of MI, we found that melatonin pre-treatment enhanced the viability of engrafted ADSCs, and promoted their therapeutic potency. Hopefully, our results may shed light on the design of more effective therapeutic strategies treating MI by MSCs in clinic. PMID:26081690

  17. Common Emergencies in Pet Birds.

    PubMed

    Stout, Jane D

    2016-05-01

    Treating avian emergencies can be a challenging task. Pet birds often mask signs of illness until they are critically ill and require quick initiation of supportive care with minimal handling to stabilize them. This article introduces the clinician to common avian emergency presentations and details initial therapeutics and diagnostics that can be readily performed in the small-animal emergency room. Common disease presentations covered include respiratory and extrarespiratory causes of dyspnea, gastrointestinal signs, reproductive disease, neurologic disorders, trauma, and toxin exposure. The duration and severity of the avian patient's disease and the clinician's initiation of appropriate therapy often determines clinical outcome. PMID:26948267

  18. Engineering antibody therapeutics.

    PubMed

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  19. The newly-found Rheticus lectures.

    NASA Astrophysics Data System (ADS)

    Kraai, J.

    This article discusses a hitherto unknown set of lectures presumably given by Georg Joachim Rheticus, and taken down by several students in Wittenberg. These lectures offer considerable insight into Rheticus' teaching activities shortly before the publication of De Revolutionibus (1543). The most salient aspects of this newly-found text may be summarized as follows: a) Rheticus was known among the students in Wittenberg as Joachimus Heliopolitanus, i.e. Joachim of the City of the Sun - a clear reference to Rheticus' stay in Frauenburg with Copernicus, b) Rheticus returned from his stay with Copernicus to Wittenberg for a short period of time in 1540 to fulfill his professorial obligations, and c) we have 155 folio pages which document Rheticus' introductory lectures on astronomy.

  20. Understanding the newly observed heavy pentaquark candidates

    NASA Astrophysics Data System (ADS)

    Liu, Xiao-Hai; Wang, Qian; Zhao, Qiang

    2016-06-01

    We find that several thresholds can contribute to the enhancements of the newly observed heavy pentaquark candidates Pc+ (4380) and Pc+ (4450) via the anomalous triangle singularity (ATS) transitions in the specific kinematics of Λb → J / ψK- p. Apart from the observed two peaks we find that another peaks around 4.5 GeV can also be produced by the ATS. We also show that the Σc(*) can be produced at leading order in Λb decay. This process is different from the triangle diagram and its threshold enhancement only appears as CUSP effects if there is no pole structure or the ATS involved. The threshold interaction associated with the presence of the ATS turns out to be a general phenomenon and plays a crucial role in the understanding of candidates for exotic states.

  1. Michael Maier--nine newly discovered letters.

    PubMed

    Lenke, Nils; Roudet, Nicolas; Tilton, Hereward

    2014-02-01

    The authors provide a transcription, translation, and evaluation of nine newly discovered letters from the alchemist Michael Maier (1568-1622) to Gebhardt Johann von Alvensleben (1576-1631), a noble landholder in the vicinity of Magdeburg. Stemming from the final year of his life, this correspondence casts new light on Maier's biography, detailing his efforts to secure patronage amid the financial crisis of the early Thirty Years' War. While his ill-fated quest to perfect potable gold continued to form the central focus of his patronage suits, Maier also offered his services in several arts that he had condemned in his printed works, namely astrology and "supernatural" magic. Remarks concerning his previously unknown acquaintance with Heinrich Khunrath call for a re-evaluation of Maier's negotiation of the discursive boundaries between Lutheran orthodoxy and Paracelsianism. The letters also reveal Maier's substantial contribution to a work previously ascribed solely to the English alchemist Francis Anthony. PMID:25241502

  2. Are therapeutic communities therapeutic for women?

    PubMed Central

    Eliason, Michele J

    2006-01-01

    This paper addresses the growing phenomena of therapeutic community (TC) treatment approaches for women in correctional settings. Although rapidly increasing in number across the country, there is very little empirical research to support the effectiveness of TC treatment for women. Therefore, the literature on the efficacy and effectiveness of TC treatment for women is reviewed in relation to the literature on women's treatment issues. The literature review highlights the gaps where TC treatment ignores or exacerbates issues that are common to addicted women, or uses methods that may be contradictory to women's recovery. PMID:16722560

  3. Contextual Emergence

    NASA Astrophysics Data System (ADS)

    Atmanspacher, Harald

    The concept of contextual emergence has been proposed as a nonreductive, yet well-defined relation between different levels of description of physical and other systems. It yields a formally sound and empirically applicable procedure to translate between descriptive levels in an overall consistent fashion. This will be discussed for the contextual emergence of mental states from a neural level of description.

  4. [Therapeutic neuromodulation in primary headaches].

    PubMed

    May, A; Jürgens, T P

    2011-06-01

    Neuromodulatory techniques have developed rapidly in the therapeutic management of refractory headaches. Invasive procedures comprise peripheral nerve stimulation (particularly occipital nerve stimulation), vagus nerve stimulation, cervical spinal cord stimulation and hypothalamic deep brain stimulation. Transcutaneous electrical nerve stimulation, repetitive transcranial magnetic stimulation and transcranial direct current stimulation are noninvasive variants. Based on current neuroimaging, neurophysiological and clinical studies occipital nerve stimulation and hypothalamic deep brain stimulation are recommended for patients with chronic cluster headache. Less convincing evidence can be found for their use in other refractory headaches such as chronic migraine. No clear recommendation can be given for the other neuromodulatory techniques. The emerging concept of intermittent stimulation of the sphenopalatine ganglion is nonetheless promising. Robust randomized and sham-controlled multicenter studies are needed before these therapeutic approaches are widely implemented. Due to the experimental nature all patients should be treated in clinical studies. It is essential to confirm the correct headache diagnosis and the refractory nature before an invasive approach is considered. Patients should generally be referred to specialized interdisciplinary outpatient departments which closely collaborate with neurosurgeons who are experienced in the implantation of neuromodulatory devices. It is crucial to ensure a competent postoperative follow-up with optimization of stimulation parameters and adjustment of medication. PMID:20972665

  5. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  6. Therapeutic innovations in inflammatory bowel diseases.

    PubMed

    Vanhove, W; Nys, K; Vermeire, S

    2016-01-01

    Inflammatory bowel disease (IBD) is a spectrum of complex multifactorial immune disorders characterized by chronic inflammation of the gut. Significant advances have been made in unraveling the pathogenesis of this disease spectrum, which have spurred the discovery of new therapeutic targets and strategies. In this review, we highlight the emerging new classes of IBD therapeutics under clinical evaluation and their method of action, including JAK inhibitors, anti-SMAD7 oligonucleotides, and cell-based therapies. Moreover, we discuss how an approach based on unique molecular insights in a given patient will, in the future, lead to a truly individualized/tailored disease management, starting at diagnosis, aiding in prognosis, and resulting in a personalized therapeutic approach. PMID:26509246

  7. Microbial synthetic biology for human therapeutics.

    PubMed

    Jain, Aastha; Bhatia, Pooja; Chugh, Archana

    2012-06-01

    The emerging field of synthetic biology holds tremendous potential for developing novel drugs to treat various human conditions. The current study discusses the scope of synthetic biology for human therapeutics via microbial approach. In this context, synthetic biology aims at designing, engineering and building new microbial synthetic cells that do not pre-exist in nature as well as re-engineer existing microbes for synthesis of therapeutic products. It is expected that the construction of novel microbial genetic circuitry for human therapeutics will greatly benefit from the data generated by 'omics' approaches and multidisciplinary nature of synthetic biology. Development of novel antimicrobial drugs and vaccines by engineering microbial systems are a promising area of research in the field of synthetic biology for human theragnostics. Expression of plant based medicinal compounds in the microbial system using synthetic biology tools is another avenue dealt in the present study. Additionally, the study suggest that the traditional medicinal knowledge can do value addition for developing novel drugs in the microbial systems using synthetic biology tools. The presented work envisions the success of synthetic biology for human therapeutics via microbial approach in a holistic manner. Keeping this in view, various legal and socio-ethical concerns emerging from the use of synthetic biology via microbial approach such as patenting, biosafety and biosecurity issues have been touched upon in the later sections. PMID:23730360

  8. Urologic Emergencies.

    PubMed

    Ludvigson, Adam E; Beaule, Lisa T

    2016-06-01

    The diagnosis and management of urologic emergencies are incorporated into the basic training of all urology residents. In institutions without access to urologic services, it is usually left to the General Surgeon or Emergency Medicine physician to provide timely care. This article discusses diagnoses that are important to recognize and treatment that is practically meaningful for the non-Urologist to identify and treat. The non-Urology provider, after reading this article, will have a better understanding and a higher comfort level with treating patients with urologic emergencies. PMID:27261785

  9. Therapeutic potential of cannabinoid medicines.

    PubMed

    Robson, P J

    2014-01-01

    Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. PMID:24006213

  10. Quantifying Therapeutic and Diagnostic Efficacy in 2D Microvascular Images

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Vickerman, Mary B.; Keith, Patricia A.

    2009-01-01

    VESGEN is a newly automated, user-interactive program that maps and quantifies the effects of vascular therapeutics and regulators on microvascular form and function. VESGEN analyzes two-dimensional, black and white vascular images by measuring important vessel morphology parameters. This software guides the user through each required step of the analysis process via a concise graphical user interface (GUI). Primary applications of the VESGEN code are 2D vascular images acquired as clinical diagnostic images of the human retina and as experimental studies of the effects of vascular regulators and therapeutics on vessel remodeling.

  11. A therapeutic group for parents of transgender adolescents.

    PubMed

    Menvielle, Edgardo J; Rodnan, Leslie A

    2011-10-01

    Therapy for transgender, transsexual, and gender variant persons has traditionally assisted individuals in the process of adjusting to their newly adopted gender role. Increasingly, younger gender variant patients,teens and preteens, present to the clinical consultation raising the need to develop therapeutic interventions that better address the psychosocial needs of minors. The Gender and Sexuality Development Program at Children's National Medical Center (CNMC) in Washington,DC (http://www.childrensnational.org/gendervariance), provides outpatient psychosocial evaluations and therapeutic services for children,adolescents, and their families. PMID:22051009

  12. Emerging treatments in Castleman disease – a critical appraisal of siltuximab

    PubMed Central

    Koff, Jean L; Lonial, Sagar

    2016-01-01

    Castleman disease (CD) is a rare, heterogeneous lymphoproliferative disorder for which no standard of care currently exists. Evidence that the pathophysiology of CD is fueled by excessive interleukin-6 (IL-6) has led to considerable interest in therapeutic targeting of this cytokine. Siltuximab, a chimeric monoclonal antibody to IL-6, has thus emerged as a promising treatment option in a disease lacking efficacious therapy. Here, we review the findings of recent studies evaluating single-agent siltuximab treatment in CD, including the first-ever randomized clinical trial in this disease. Although much more work is needed to establish a standardized treatment approach, siltuximab appears to be a safe and effective treatment for patients with newly diagnosed and previously treated CD. PMID:26869762

  13. Rheumatologic emergencies.

    PubMed

    Gutiérrez-González, Luis Arturo

    2015-12-01

    Rheumatological conditions can sometimes present as emergencies. These can occur due to the disease process or infection; contrary to what many people think, rheumatologic emergencies like a pain, rheumatic crisis, or attack gout do not compromise the patient's life. This article mentioned only true emergencies: catastrophic antiphospholipid syndrome (cAPS), kidney-lung syndrome, central nervous system (CNS) vasculitis, anti-Ro syndrome (neonatal lupus), and macrophage activation syndrome (MAS). The management of above emergencies includes critical care, immunosuppression when indicated, and use of a diagnostic flowchart as well as fast laboratory profile for making decisions. Anticoagulants have to be used in the management of antiphospholipid syndrome. A good understanding of these conditions is of paramount importance for proper management. PMID:26099604

  14. Ear emergencies

    MedlinePlus

    ... from an explosion, blow to the head, flying, scuba diving, falling while water skiing, or being slapped on ... Byyny RL, Shockley LW. Scuba diving and dysbarism. In: Marx JA, ... Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ...

  15. Thoracic emergencies.

    PubMed

    Worrell, Stephanie G; Demeester, Steven R

    2014-02-01

    This article discusses thoracic emergencies, including the anatomy, pathophysiology, clinical presentation, examination, diagnosis, technique, management, and treatment of acute upper airway obstruction, massive hemoptysis, spontaneous pneumothorax, and pulmonary empyema. PMID:24267505

  16. Patterns of Nonadherence to Antiepileptic Drug Therapy in Children With Newly Diagnosed Epilepsy

    PubMed Central

    Modi, Avani C.; Rausch, Joseph R.; Glauser, Tracy A.

    2012-01-01

    Context Because of epilepsy’s common occurrence, the narrow therapeutic and safety margins of antiepileptic medications, and the recognized complications of medication nonadherence in adults with epilepsy, identifying the rates, patterns, and predictors of nonadherence in children with epilepsy is imperative. The onset and evolution of antiepileptic drug nonadherence in children with newly diagnosed epilepsy remains unknown. Objectives To identify and characterize trajectories of adherence in children with newly diagnosed epilepsy over the first 6 months of therapy and to determine sociodemographic and epilepsy-specific predictors of adherence trajectories. Design, Setting, and Patients Prospective, longitudinal observational study of antiepileptic drug adherence in a consecutive cohort of 124 children (2–12 years old) with newly diagnosed epilepsy at Cincinnati Children’s Hospital Medical Center. Patients were recruited from April 2006 through March 2009, and final data collection occurred in September 2009. Main Outcome Measure Objective adherence measured using electronic monitors. Results Fifty-eight percent of children with newly diagnosed epilepsy demonstrated persistent nonadherence during the first 6 months of therapy. Group-based trajectory models identified 5 differential adherence patterns (Bayesian information criterion=−23611.8): severe early nonadherence (13%; 95% confidence interval [CI], 8%–20%), severe delayed nonadherence (7%; 95% CI, 3%–12%), moderate nonadherence (13%; 95% CI, 8%–20%), mild nonadherence (26%; 95% CI, 19%–34%), and near-perfect adherence (42%; 95% CI, 33%–50%). The adherence pattern of most patients was established by the first month of therapy. Socioeconomic status was the sole predictor of adherence trajectory group status (χ42=19.3 [n = 115]; P < .001; partial r2 = 0.25), with lower socioeconomic status associated with higher nonadherence. Conclusion Five trajectory patterns were identified that captured the

  17. [New features in the recommendations of the Second Hungarian Therapeutic Consensus Conference].

    PubMed

    Pados, Gyula; Karádi, István; Paragh, György; Halmy, László; Jermendy, György; Zámolyi, Károly; Kiss, István

    2006-07-16

    The First Hungarian Therapeutic Consensus Conference took place on 3rd Nov. 2003 with the participation of 9 medical societies. Over the past 2 years the results of new major studies have been published and the American ATP III has also updated its guidelines issued in 2004. Based on the above proposals, the Second Hungarian Therapeutic Consensus Conference held on 3rd Nov. 2005 partly confirmed its earlier suggestions, but made some changes as well. Within the high risk category the Conference optionally created a very high risk group from those patients who - in addition to their cardiovascular disease--have either diabetes or metabolic syndrome or acut coronaria syndrome or who are chain smokers. We have included - as a complement - into the asymptomatic high risk category such newly emerging risk factors, one of which already in itself means high risk: ankle/arm index < or = 0.9, GFR <60 ml/min, microalbuminuria (30-300 mg), preclinical atherosclerosis (plaque). Besides, 4 other risk factors were also categorised such as Lp/a (> or = 30 mg/dl), CRP (> or = 3mg/l), homocysteine (> or = 12 micromol), familiarity--atherogenic gene constellation, but only the presence of at least two of these verify high risk. In very high risk group the goals of 3.5 mmol/l and 1.8 mmol/l were determined as therapeutic option. The goal in obese patients--expressed earlier only in BMI--can now be equally determined by the abdominal circumference (94 cm for men, 80 cm for women respectively). ACE inhibitors were recommended earlier as a preventive therapy in case of dysfunction of the left ventricle, while at present they are suggested for all patients with cardiovascular disease. In the recent recommendations guidelines related to nutrition, smoking, exercise have also been included. PMID:16999015

  18. Anorectal emergencies

    PubMed Central

    Lohsiriwat, Varut

    2016-01-01

    Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

  19. Anorectal emergencies.

    PubMed

    Lohsiriwat, Varut

    2016-07-14

    Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

  20. Emergency contraception.

    PubMed

    Grimes, David A; Raymond, Elizabeth G

    2002-08-01

    Emergency contraception is used to prevent pregnancy after a coital act not adequately protected by a regular method of contraception. In contrast to early medical abortion, emergency contraception prevents a pregnancy from starting and does not disrupt an established pregnancy. The most commonly used approaches consist of two oral doses of contraceptive steroids. The levonorgestrel-only regimen (levonorgestrel, 0.75 mg, repeated in 12 hours) appears to be more effective and better tolerated than the Yuzpe regimen (ethinyl estradiol, 100 microg, and levonorgestrel, 0.5 mg, repeated in 12 hours). In the largest randomized, controlled trial to date, levonorgestrel prevented about 85% of pregnancies that would have occurred without its use. Hormonal emergency contraception has no known medical contraindications, although it is not indicated for suspected or confirmed pregnancy. However, if hormonal emergency contraception is inadvertently taken in early pregnancy, neither the woman nor the fetus will be harmed. Nausea and vomiting associated with the Yuzpe regimen can be reduced by prophylactic use of meclizine. A strong medical and legal case exists for making hormonal emergency contraception available over the counter, as has happened in countries other than the United States. Easier access to and wider use of emergency contraception could dramatically lower the high rates of unintended pregnancy and induced abortion in the United States. PMID:12160366

  1. Arsenic behavior in newly drilled wells

    USGS Publications Warehouse

    Kim, M.-J.; Nriagu, J.; Haack, S.

    2003-01-01

    In the present paper, inorganic arsenic species and chemical parameters in groundwater were determined to investigate the factors related to the distribution of arsenic species and their dissolution from rock into groundwater. For the study, groundwater and core samples were taken at different depths of two newly drilled wells in Huron and Lapeer Counties, Michigan. Results show that total arsenic concentrations in the core samples varied, ranging from 0.8 to 70.7 mg/kg. Iron concentration in rock was about 1800 times higher than that of arsenic, and there was no correlation between arsenic and iron occurrences in the rock samples. Arsenic concentrations in groundwater ranged from <1 to 171 ??g/l. The arsenic concentration in groundwater depended on the amount of arsenic in aquifer rocks, and as well decreased with increasing depth. Over 90% of arsenic existed in the form of As(III), implying that the groundwater systems were in the reduced condition. The results such as high ferrous ion, low redox potential and low dissolved oxygen supported the observed arsenic species distribution. There was no noticeable difference in the total arsenic concentration and arsenic species ratio between unfiltered and filtered (0.45 ??m) waters, indicating that the particulate form of arsenic was negligible in the groundwater samples. There were correlations between water sampling depth and chemical parameters, and between arsenic concentration and chemical parameters, however, the trends were not always consistent in both wells. ?? 2003 Elsevier Science Ltd. All rights reserved.

  2. Therapeutic management of cutaneous and genital warts.

    PubMed

    Ockenfels, Hans Michael

    2016-09-01

    During their lifetime, at least 10 % of the population will be infected by human papillomaviruses (HPV), clinically characterized by the formation of cutaneous or genital warts. Although warts are ubiquitous, there are no defined treatments. Especially in the first six months, warts frequently resolve without therapeutic intervention. This complicates the interpretation of study data, given that many studies do not differentiate between newly infected patients and those with infections that have persisted for a long time. Similarly, most studies do not take location, size, and thickness of lesions into account, either. The objective of the present review article is to analyze the study data currently available, taking into consideration both subtypes and locations - factors exceedingly crucial in clinical practice. In particular, the distinction between new-onset and chronic recalcitrant warts is reflected in a therapeutic algorithm. In the case of genital warts, the algorithm is more clearly determined by the extent of the area affected rather than the longevity of lesions. In immunocompetent individuals, any therapeutic intervention must be aimed at achieving complete resolution. PMID:27607030

  3. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  4. Therapeutics for cognitive aging

    PubMed Central

    Shineman, Diana W.; Salthouse, Timothy A.; Launer, Lenore J.; Hof, Patrick R.; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J.; Small, Gary W.; Aisen, Paul S.; Lowe, David A.; Fillit, Howard M.

    2011-01-01

    This review summarizes the scientific talks presented at the conference “Therapeutics for Cognitive Aging,” hosted by the New York Academy of Sciences and the Alzheimer’s Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people—approximately 200 in all—the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease. PMID:20392284

  5. Advances in Therapeutic Cholangioscopy

    PubMed Central

    Moura, Renata Nobre; de Moura, Eduardo Guimarães Hourneaux

    2016-01-01

    Nowadays, cholangioscopy is an established modality in diagnostic and treatment of pancreaticobiliary diseases. The more widespread use and the recent development of new technologies and accessories had renewed the interest of endoscopic visualization of the biliary tract, increasing the range of indications and therapeutic procedures, such as diagnostic of indeterminate biliary strictures, lithotripsy of difficult bile duct stones, ablative techniques for intraductal malignancies, removal of foreign bodies and gallbladder drainage. These endoscopic interventions will probably be the last frontier in the near future. This paper presents the new advances in therapeutic cholangioscopy, focusing on the current clinical applications and on research areas. PMID:27403156

  6. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

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

    2009-01-01

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

  7. An update on hypertensive emergencies and urgencies.

    PubMed

    Muiesan, Maria Lorenza; Salvetti, Massimo; Amadoro, Valentina; di Somma, Salvatore; Perlini, Stefano; Semplicini, Andrea; Borghi, Claudio; Volpe, Massimo; Saba, Pier Sergio; Cameli, Matteo; Ciccone, Marco Matteo; Maiello, Maria; Modesti, Pietro Amedeo; Novo, Salvatore; Palmiero, Pasquale; Scicchitano, Pietro; Rosei, Enrico Agabiti; Pedrinelli, Roberto

    2015-05-01

    Severe acute arterial hypertension is usually defined as 'hypertensive crisis', although 'hypertensive emergencies' or 'hypertensive urgencies', as suggested by the Joint National Committee and the European Society of Hypertension, have completely different diagnostic and therapeutic approaches.The prevalence and demographics of hypertensive emergencies and urgencies have changed over the last four decades, but hypertensive emergencies and urgencies are still associated with significant morbidity and mortality.Different scientific societies have repeatedly produced up-to-date guidelines; however, the treatment of hypertensive emergencies and urgencies is still inappropriate, with potential clinical implications.This review focuses on hypertensive emergencies and urgencies management and treatment, as suggested by recent data. PMID:25575271

  8. Health status of newly arrived refugees in Toronto, Ont

    PubMed Central

    Redditt, Vanessa J.; Janakiram, Praseedha; Graziano, Daniela; Rashid, Meb

    2015-01-01

    Abstract Objective To determine the prevalence of selected infectious diseases among newly arrived refugee patients and whether there is variation by key demographic factors. Design Retrospective chart review. Setting Primary care clinic for refugee patients in Toronto, Ont. Participants A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. Main outcome measures Demographic information (age, sex, and region of birth); prevalence of HIV, hepatitis B, hepatitis C, Strongyloides, Schistosoma, intestinal parasites, gonorrhea, chlamydia, and syphilis infections; and varicella immune status. Results The median age of patients was 29 years and 56% were female. Refugees were born in 87 different countries. Approximately 33% of patients were from Africa, 28% were from Europe, 14% were from the Eastern Mediterranean Region, 14% were from Asia, and 8% were from the Americas (excluding 4% born in Canada or the United States). The overall rate of HIV infection was 2%. The prevalence of hepatitis B infection was 4%, with a higher rate among refugees from Asia (12%, P < .001). Hepatitis B immunity was 39%, with higher rates among Asian refugees (64%, P < .001) and children younger than 5 years (68%, P < .001). The rate of hepatitis C infection was less than 1%. Strongyloides infection was found in 3% of tested patients, with higher rates among refugees from Africa (6%, P = .003). Schistosoma infection was identified in 15% of patients from Africa. Intestinal parasites were identified in 16% of patients who submitted stool samples. Approximately 8% of patients were varicella nonimmune, with higher rates in patients from the Americas (21%, P < .001). Conclusion This study highlights the importance of screening for infectious diseases among refugee patients to provide timely preventive and curative care. Our data also point to possible policy and clinical implications, such as targeted screening approaches and improved access to vaccinations and

  9. [Renal colic: new care in emergency centers].

    PubMed

    Morandi, Eléonore; Kherad, Omar; Chollet, Yves; Dussoix, Philippe

    2016-02-01

    The prevalence of renal colic is increasing in industrialized countries, representing a frequent reason for consultation in emergencies. Most patients have simple renal colic that will require analgesia and ambulatory monitoring. Doctors working in emergency centers play a key role in the diagnosis, care and guidance of these patients. They must identify factors of gravity and request urological advice if necessary. This article summarizes the recent diagnostic and therapeutic innovations in the management and guidance of renal colic in emergency centers. PMID:26999995

  10. Alzheimer's Disease Mechanisms and Emerging Roads to Novel Therapeutics.

    PubMed

    Sala Frigerio, Carlo; De Strooper, Bart

    2016-07-01

    Ten years of remarkable progress in understanding the fundamental biochemistry of Alzheimer's disease have been followed by ten years of remarkable and increasing clinical insight into the natural progression of the disorder. The concept of a long, intermediary, prodromal phase between the first appearance of amyloid plaques and tangles and the manifestation of dementia is now well established. The major challenge for the next decade is to chart the many cellular processes that underlie this phase and link the biochemical alterations to the clinical manifestation of Alzheimer's disease. We discuss here how genetics, new cell culture systems, and improved animal models will fuel this work. We anticipate that the resulting novel insights will provide a basis for further drug development for this terrible disease. PMID:27050320

  11. Pathogenesis, Emerging therapeutic targets and Treatment in Sialidosis

    PubMed Central

    d’Azzo, Alessandra; Machado, Eda; Annunziata, Ida

    2015-01-01

    Introduction Sialidosis is a neurosomatic, lysosomal storage disease (LSD) caused by mutations in the NEU1 gene, encoding the lysosomal sialidase NEU1. Deficient enzyme activity results in impaired processing/degradation of sialo-glycoproteins, and accumulation of oversialylated metabolites. Sialidosis is considered an orphan disorder for which no therapy is currently available. Areas covered The review describes the clinical forms of sialidosis and the NEU1 mutations so far identified; NEU1 requirement to complex with the protective protein/cathepsin A for stability and activation; and the pathogenic effects of NEU1 deficiency. Studies of the molecular mechanisms of pathogenesis in animal models uncovered basic cellular pathways downstream of NEU1 and its substrates, which may be implicated in more common adult (neurodegenerative) diseases. The development of a Phase I/II clinical trial for patients with galactosialidosis may prove suitable for sialidosis patients with the attenuated form of the disease. Expert opinion Recently, there has been a renewed interest in the development of therapies for orphan LSDs, like sialidosis. Given the small number of potentially eligible patients, the way to treat sialidosis would be through the coordinated effort of clinical centers, which provide diagnosis and care for these patients, and the basic research labs that work towards understanding the disease pathogenesis. PMID:26949572

  12. Emerging therapeutic targets and strategies in Crohn's disease.

    PubMed

    Furfaro, Federica; Fiorino, Gionata; Allocca, Mariangela; Gilardi, Daniela; Danese, Silvio

    2016-06-01

    Crohn's disease (CD) is an immune-mediated inflammatory bowel disease, in which inflammation is driven by a complex interaction between the microbiota, immune cells, genes and mediators. New mechanisms of action and several cytokines have been identified as factors involved in the inflammatory process in CD, and many new molecules have been developed to treat this complex disease. New agents have been developed that target leukocyte trafficking, block or adhesion molecules for example, as well as the development of antibodies against classic inflammatory cytokines or therapies directed against IL-12/23 and Janus kinases. The development of selective mechanisms of action and targeting of different cytokines or inflammatory mediators for each patient presents the biggest challenge for the future in CD therapy. Such agents are currently at different phases of development. We aim to review the current literature data on a targeted approach in CD, which could be promising alternative approach for CD patients in the near future. PMID:26766496

  13. Sirtuins in vascular diseases: Emerging roles and therapeutic potential.

    PubMed

    D'Onofrio, Nunzia; Vitiello, Milena; Casale, Rosario; Servillo, Luigi; Giovane, Alfonso; Balestrieri, Maria Luisa

    2015-07-01

    Silent information regulator-2 (Sir-2) proteins, or sirtuins, are a highly conserved protein family of histone deacetylases that promote longevity by mediating many of the beneficial effects of calorie restriction which extends life span and reduces the incidence of cancer, cardiovascular disease (CVD), and diabetes. Here, we review the role of sirtuins (SIRT1-7) in vascular homeostasis and diseases by providing an update on the latest knowledge about their roles in endothelial damage and vascular repair mechanisms. Among all sirtuins, in the light of the numerous functions reported on SIRT1 in the vascular system, herein we discuss its roles not only in the control of endothelial cells (EC) functionality but also in other cell types beyond EC, including endothelial progenitor cells (EPC), smooth muscle cells (SMC), and immune cells. Furthermore, we also provide an update on the growing field of compounds under clinical evaluation for the modulation of SIRT1 which, at the state of the art, represents the most promising target for the development of novel drugs against CVD, especially when concomitant with type 2 diabetes. PMID:25766107

  14. Biologics and Pediatric Generalized Pustular Psoriasis: An Emerging Therapeutic Trend

    PubMed Central

    Mattes, Monica

    2016-01-01

    Generalized pustular psoriasis (GPP) is a rare form of childhood psoriasis, often requiring systemic therapy, which is challenging as there is a paucity of randomized controlled trials and standardized guidelines. Biologic agents have been used in adults and in pediatric plaque psoriasis, but evidence regarding their efficacy in pediatric GPP has slowly become available. The objective of this study is to summarize and compare the efficacy and safety of biologic agents, such as etanercept, infliximab, and adalimumab, in the treatment of pediatric GPP. A PubMed literature review was conducted and 12 studies met the inclusion criteria for analysis. After reviewing the efficacy of these drugs in pediatric GPP patients and their safety in the use of other pediatric conditions, etanercept was identified as a possible first-line biologic agent for pediatric psoriasis, including GPP, followed by infliximab and adalimumab. In conclusion, several case reports have documented the successful use of biologic agents in refractory cases of pediatric GPP, but clinical trials are needed to gain a better understanding of the efficacy and side effect profile in this population. PMID:27462478

  15. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    SciTech Connect

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  16. Treatment of inflammatory myopathy: emerging therapies and therapeutic targets

    PubMed Central

    Moghadam-Kia, Siamak; Aggarwal, Rohit; Oddis, Chester V

    2016-01-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy and myositis-associated interstitial lung disease. Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. First-line conventional immunosuppressive drugs include either methotrexate or azathioprine, and when they fail, more aggressive therapy includes mycophenolate mofetil, tacrolimus or cyclosporine, intravenous immunoglobulin, rituximab, or cyclophosphamide, used alone or in various combinations. Further investigations are required to assess the role of more novel therapies in the treatment of myositis and myositis-associated interstitial lung disease. PMID:26313852

  17. Emerging Therapeutic Strategies and Future Challenges in Clinical Periodontics.

    PubMed

    Shin, Daniel; Hamada, Yusuke; John, Vanchit

    2016-01-01

    Currently, the protocol for treating periodontitis follows a standardized and straightforward algorithm: 1) review and reinforce oral hygiene; 2) perform scaling and root planing; 3) proceed to periodontal surgery if the disease process has not been arrested; then 4) enroll the patient in a customized periodontal maintenance recall program to maintain the health of the reduced periodontium. Multiple longitudinal studies have demonstrated that the aforementioned treatment regimen can arrest the progression of periodontitis and can increase the likelihood of tooth retention and periodontal stability. PMID:26939412

  18. Emerging therapeutic options for sporadic inclusion body myositis

    PubMed Central

    Alfano, Lindsay N; Lowes, Linda P

    2015-01-01

    Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. PMID:26445546

  19. Lysosomal storage disorders: emerging therapeutic options require early diagnosis.

    PubMed

    Meikle, Peter J; Hopwood, John J

    2003-12-01

    Lysosomal storage disorders have been recognised as one of the major groups of genetic disorders affecting children and adults. With over 40 different disorders and a combined prevalence of up to 1:5000 births, this group of disorders is a major public health problem and places an enormous burden on the individuals and families affected. Since the introduction of enzyme replacement therapy for Gaucher disease over 10 years ago there has been considerable progress in the development of enzyme based therapies for other disorders, in addition to alternate therapies including substrate deprivation and gene based therapies. Early diagnosis of these disorders before the onset of irreversible pathologies will lead to better outcomes for current and proposed therapies. In this review we describe the strategies and technology being used for the development of newborn screening for lysosomal storage disorders and discuss the future requirements for the early diagnosis and effective therapy of this group of disorders. PMID:14610674

  20. Newly qualified teachers' visions of science learning and teaching

    NASA Astrophysics Data System (ADS)

    Roberts, Deborah L.

    2011-12-01

    This study investigated newly qualified teachers' visions of science learning and teaching. The study also documented their preparation in an elementary science methods course. The research questions were: What educational and professional experiences influenced the instructor's visions of science learning and teaching? What visions of science learning and teaching were promoted in the participants' science methods course? What visions of science learning and teaching did these newly qualified teachers bring with them as they graduated from their teacher preparation program? How did these visions compare with those advocated by reform documents? Data sources included participants' assignments, weekly reflections, and multi-media portfolio finals. Semi-structured interviews provided the emic voice of participants, after graduation but before they had begun to teach. These data were interpreted via a combination of qualitative methodologies. Vignettes described class activities. Assertions supported by excerpts from participants' writings emerged from repeated review of their assignments. A case study of a typical participant characterized weekly reflections and final multi-media portfolio. Four strands of science proficiency articulated in a national reform document provided a framework for interpreting activities, assignments, and interview responses. Prior experiences that influenced design of the methods course included an inquiry-based undergraduate physics course, participation in a reform-based teacher preparation program, undergraduate and graduate inquiry-based science teaching methods courses, participation in a teacher research group, continued connection to the university as a beginning teacher, teaching in diverse Title 1 schools, service as the county and state elementary science specialist, participation in the Carnegie Academy for the Scholarship of Teaching and Learning, service on a National Research Council committee, and experience teaching a

  1. Emerging and Re-Emerging Zoonoses of Dogs and Cats.

    PubMed

    Chomel, Bruno B

    2014-01-01

    Since the middle of the 20th century, pets are more frequently considered as "family members" within households. However, cats and dogs still can be a source of human infection by various zoonotic pathogens. Among emerging or re-emerging zoonoses, viral diseases, such as rabies (mainly from dog pet trade or travel abroad), but also feline cowpox and newly recognized noroviruses or rotaviruses or influenza viruses can sicken our pets and be transmitted to humans. Bacterial zoonoses include bacteria transmitted by bites or scratches, such as pasteurellosis or cat scratch disease, leading to severe clinical manifestations in people because of their age or immune status and also because of our closeness, not to say intimacy, with our pets. Cutaneous contamination with methicillin-resistant Staphylococcus aureus, Leptospira spp., and/or aerosolization of bacteria causing tuberculosis or kennel cough are also emerging/re-emerging pathogens that can be transmitted by our pets, as well as gastro-intestinal pathogens such as Salmonella or Campylobacter. Parasitic and fungal pathogens, such as echinococcosis, leishmaniasis, onchocercosis, or sporotrichosis, are also re-emerging or emerging pet related zoonoses. Common sense and good personal and pet hygiene are the key elements to prevent such a risk of zoonotic infection. PMID:26480316

  2. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  3. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  4. Dynamics of newly established elk populations

    USGS Publications Warehouse

    Sargeant, G.A.; Oehler, M.W., Sr.

    2007-01-01

    The dynamics of newly established elk (Cervus elaphus) populations can provide insights about maximum sustainable rates of reproduction, survival, and increase. However, data used to estimate rates of increase typically have been limited to counts and rarely have included complementary estimates of vital rates. Complexities of population dynamics cannot be understood without considering population processes as well as population states. We estimated pregnancy rates, survival rates, age ratios, and sex ratios for reintroduced elk at Theodore Roosevelt National Park, North Dakota, USA; combined vital rates in a population projection model; and compared model projections with observed elk numbers and population ratios. Pregnancy rates in January (early in the second trimester of pregnancy) averaged 54.1% (SE = 5.4%) for subadults and 91.0% (SE = 1.7%) for adults, and 91.6% of pregnancies resulted in recruitment at 8 months. Annual survival rates of adult females averaged 0.96 (95% CI = 0.94-0.98) with hunting included and 0.99 (95% CI = 0.97-0.99) with hunting excluded from calculations. Our fitted model explained 99.8% of past variation in population estimates and represents a useful new tool for short-term management planning. Although we found no evidence of temporal variation in vital rates, variation in population composition caused substantial variation in projected rates of increase (??=1.20-1.36). Restoring documented hunter harvests and removals of elk by the National Park Service led to a potential rate of ?? = 1.26. Greater rates of increase substantiated elsewhere were within the expected range of chance variation, given our model and estimates of vital rates. Rates of increase realized by small elk populations are too variable to support inferences about habitat quality or density dependence.

  5. Newly Identified Pathogens Associated with Periodontitis

    PubMed Central

    Pérez-Chaparro, P.J.; Gonçalves, C.; Figueiredo, L.C.; Faveri, M.; Lobão, E.; Tamashiro, N.; Duarte, P.; Feres, M.

    2014-01-01

    There is substantial evidence supporting the role of certain oral bacteria species in the onset and progression of periodontitis. Nevertheless, results of independent-culture diagnostic methods introduced about a decade ago have pointed to the existence of new periodontal pathogens. However, the data of these studies have not been evaluated together, which may generate some misunderstanding on the actual role of these microorganisms in the etiology of periodontitis. The aim of this systematic review was to determine the current weight of evidence for newly identified periodontal pathogens based on the results of “association” studies. This review was conducted and reported in accordance with the PRISMA statement. The MEDLINE, EMBASE, and Cochrane databases were searched up to September 2013 for studies (1) comparing microbial data of subgingival plaque samples collected from subjects with periodontitis and periodontal health and (2) evaluating at least 1 microorganism other than the already-known periodontal pathogens. From 1,450 papers identified, 41 studies were eligible. The data were extracted and registered in predefined piloted forms. The results suggested that there is moderate evidence in the literature to support the association of 17 species or phylotypes from the phyla Bacteroidetes, Candidatus Saccharibacteria, Firmicutes, Proteobacteria, Spirochaetes, and Synergistetes. The phylum Candidatus Saccharibacteria and the Archaea domain also seem to have an association with disease. These data point out the importance of previously unidentified species in the etiology of periodontitis and might guide future investigations on the actual role of these suspected new pathogens in the onset and progression of this infection. PMID:25074492

  6. Newly Identified Rydberg Emission Lines in Novae

    NASA Astrophysics Data System (ADS)

    Lynch, David K.; Rudy, R. J.; Bernstein, L. S.

    2008-09-01

    Newly Identified Rydberg Emission Lines in Novae David K. Lynch, Richard. J. Rudy (The Aerospace Corporation) & Lawrence S. Bernstein (Spectral Sciences, Inc.) Novae spectra in the near infrared frequently show a set of six emission lines that have not been positively identified (Williams, Longmore, & Geballe 1996, MNRAS, 279, 804; Lynch et al. 2001, AJ, 122, 2013; Rudy et al. 2002 ApJ, 573, 794; Lynch et al. 2004 Astron. J. 127, 1089-1097). These lines are at 0.8926, 1.1114, 1.1901, 1.5545, 2.0996 and 2.425 µm ± 0.005 µm. Krautter et al. (1984 A&A 137, 304) suggested that three of the lines were due to rydberg (hydrogenic) transitions in an unspecified atomic species that was in the 4th or 5th ionization stage (core charge = 4 & 5). We believe that Krautter et al.'s explanation is correct based on 4 additional lines that we have identified in the visible and near infrared spectrum of V723 Cassiopeiae. The observed Rydberg lines appear to originate from high angular momentum states with negligible quantum defects. The species cannot be determined with any certainty because in rydberg states, the outer electron sees a nucleus shielded by the inner electrons and together the inner atom appears to have a charge of +1, like hydrogen. As a result, the atom looks hydrogenic and species such as CV, NV, OV, MgV, SiV, etc. have their rydberg transitions at very similar wavelengths. All the lines represent permitted transitions, most likely formed by recombination. Atoms with core charges 4, 5 & 6 are rarely seen in the astrophysical environment because an extremely hot radiation field is necessary to ionize them. Thermonuclear runaways on the surface of a white dwarf can reach millions of degrees K, and thus there are enough X-ray photons available to achieve the necessary high ionization levels.

  7. Vitamin C nutriture in newly diagnosed diabetes.

    PubMed

    Shim, Jae Eun; Paik, Hee Young; Shin, Chan Soo; Park, Kyong Soo; Lee, Hong Kyu

    2010-01-01

    This study was performed to investigate the relationship between serum L-ascorbic acid, vitamin C intake, and diabetes in a nested case-control study. A cross-sectional survey of diet and health was conducted in 2,048 adults with an age of 30 y or older in Yonchon County, Korea. An oral glucose tolerance test was administered to all participants. One hundred cases of newly diagnosed diabetes were identified. Two healthy controls for each case matched with age, gender, drinking status, and smoking status were selected among the survey participants. L-Ascorbic acid levels were analyzed in fasting serum samples and one 24-h dietary recall was performed. Dietary vitamin C intake of persons with diabetes was 50.1±47.6 mg/d and that of controls was 55.1±41.1 mg/d. People with diabetes (22.3±16.8 µmol/L) have lower serum ascorbic acid levels than their controls (26.3±17.0 µmol/L) and the difference was significant by paired t-test (p<0.01). The association between diabetes and serum ascorbic acid level was still significant in non-smokers (24.2±17.8 µmol/L for the diabetes group and 29.5±16.7 µmol/L for the control group, p<0.01) but not in smokers (19.4±15.7 µmol/L for the diabetes group and 21.2±16.0 µmol/L for the control group). Our results suggest that diabetes and smoking interactively affect serum ascorbic acid levels. Since this population had poor nutritional status of vitamin C, further investigation of association between serum ascorbic acid level and diabetes and smoking by the level of vitamin C consumption is warranted. PMID:20924142

  8. Emerging therapies for multiple myeloma

    PubMed Central

    Podar, Klaus; Tai, Yu-Tzu; Hideshima, Teru; Vallet, Sonia; Richardson, Paul G; Anderson, Kenneth C

    2011-01-01

    Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 – 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents – small molecules as well as therapeutic antibodies – that hold promise to further improve outcome in MM. PMID:19249983

  9. Emerging therapies for multiple myeloma.

    PubMed

    Podar, Klaus; Tai, Yu-Tzu; Hideshima, Teru; Vallet, Sonia; Richardson, Paul G; Anderson, Kenneth C

    2009-03-01

    Multiple myeloma (MM) is a clonal plasma cell malignancy clinically characterized by osteolytic lesions, immunodeficiency, and renal disease. There are an estimated 750,000 people diagnosed with MM worldwide, with a median overall survival of 3 - 5 years. Besides chromosomal aberrations, translocations, and mutations in essential growth and tumor-suppressor genes, accumulating data strongly highlight the pathophysiologic role of the bone marrow (BM) microenvironment in MM pathogenesis. Based on this knowledge, several novel agents have been identified, and treatment options in MM have fundamentally changed during the last decade. Thalidomide, bortezomib, and lenalidomide have been incorporated into conventional cytotoxic and transplantation regimens, first in relapsed and refractory and now also in newly diagnosed MM. Despite these significant advances, there remains an urgent need for more efficacious and tolerable drugs. Indeed, a plethora of preclinical agents awaits translation from the bench to the bedside. This article reviews the scientific rationale of new therapy regimens and newly identified therapeutic agents - small molecules as well as therapeutic antibodies - that hold promise to further improve outcome in MM. PMID:19249983

  10. A trend towards increasing viral load in newly diagnosed HIV-infected inpatients in southeast China.

    PubMed

    Chen, Y; Wang, Z; Huang, A; Yuan, J; Wei, D; Ye, H

    2016-06-01

    Peripheral blood viral load is an important indicator of viral production and clearance. Previous studies have suggested that viral load might predict the rate of decrease in CD4+ cell count and progression to AIDS and death. Here, we conducted a retrospective analysis of the trends in HIV-1 viral load in southeast China. Among inpatients newly diagnosed with HIV infection, we found that viral load has increased over the past decade from 4·20 log10 copies/ml in 2002 to 6·61 log10 copies/ml in 2014, with a mean increase of 0·19 log10 copies/ml each year. However, the CD4+ cell count was stable and insensitive to changes in viral load. Thus, increasing viral load appears to be an emerging trend in newly diagnosed HIV-infected inpatients. PMID:26732896

  11. Longitudinal trends and subgroup analysis in publication patterns for preclinical data of newly approved drugs.

    PubMed

    Köster, Ursula; Nolte, Ingo; Michel, Martin C

    2016-02-01

    Having observed a large variation in the number and type of original preclinical publications for newly registered drugs, we have explored whether longitudinal trends and/or factors specific for certain drugs or their manufacturers may explain such variation. Our analysis is based on 1954 articles related to 170 newly approved drugs. The number of preclinical publications per compound declined from a median of 10.5 in 1991 to 3 in 2011. A similar trend was observed for the number of in vivo studies in general, but not in the subset of in vivo studies in animal models of disease. The percentage of compounds with studies using isolated human cells or cell lines almost doubled over time from 37 to 72%. Number of publications did not exhibit major differences between compounds intended for human versus veterinary use, therapeutic areas, small molecules versus biologicals, or innovator versus follow-up compounds; however, some companies may publish fewer studies per compound than others. However, there were qualitative differences in the types of models being used depending on the therapeutic area; specifically, compounds for use in oncology very often used isolated cells and cell lines, often from human origin. We conclude that the large variation in number and type of reported preclinical data is not easily explained. We propose that pharmaceutical companies should consistently provide a comprehensive documentation of the preclinical data they generate as part of their development programs in the public domain to enable a better understanding of the drugs they intend to market. PMID:26612506

  12. Emergency contraception.

    PubMed

    Gold, M A

    2000-01-01

    High rates of adolescent pregnancy remain a challenge for health care providers. For most sexually active adolescents, pregnancy is unintended. Emergency contraception, also called the "morning-after-pill" or postcoital contraception, is a way to prevent pregnancy after unprotected intercourse. In the United States, three forms of emergency contraception currently are available: high-dose combination estrogen and progestin pills, high-dose progestin-only pills, and postcoital insertion of a copper intrauterine device. The postcoital intrauterine device is used infrequently. When emergency contraceptive pills (ECPs) are taken within 72 hours of unprotected intercourse, they reduce the risk of pregnancy by at least 75%. However, they are most effective if taken within 24 hours of coitus. Eleven brands of pills currently are marketed in the United States that conform to the regimens approved by the Food and Drug Administration (FDA) for this indication. Recently, two prepackaged ECPs were approved by the FDA. The only medical contraindication to prescribing ECPs is pregnancy. The most common side effects are nausea and vomiting, followed by menstrual disturbances, breast tenderness, abdominal cramping, dizziness, headache, and mood changes. Because vomiting can compromise the efficacy of ECPs, routine pretreatment with an antiemetic is recommended. Primary care providers can reduce unintended adolescent pregnancy by routinely counseling adolescents at all office visits about the existence of emergency contraception and by prescribing it in advance and over the telephone. PMID:10959448

  13. Emerging Scholars

    ERIC Educational Resources Information Center

    Anyaso, Hilary Hurd; Rolo, Mark Anthony; Roach, Ronald; Delos, Robin Chen; Branch-Brioso, Karen; Miranda, Maria Eugenia; Seymour, Add, Jr.; Grossman, Wendy; Nealy, Michelle J.; Lum, Lydia

    2009-01-01

    This year's group of "emerging scholars" is a force to be reckoned with. This diverse group of young (under-40) crusaders is pushing the boundaries of research, technology and public policy in ways never imagined and reaching new heights of accomplishments. The Class of 2009 includes a physiologist who devised an artificial pancreas to produce the…

  14. Radiation Emergencies

    MedlinePlus

    ... over a short period can cause burns or radiation sickness. If the exposure is large enough, it can cause premature aging or even death. Although there are no guarantees of safety during a radiation emergency, you can take actions to protect yourself. ...

  15. Chemical Emergencies

    MedlinePlus

    ... agents such as sarin and VX. Many hazardous chemicals are used in industry - for example, chlorine, ammonia, and benzene. Some can be made from everyday items such as household cleaners. Although there are no guarantees of safety during a chemical emergency, you can take actions to protect yourself. ...

  16. Emerging Options for Emergency Contraception

    PubMed Central

    Koyama, Atsuko; Hagopian, Laura; Linden, Judith

    2013-01-01

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

  17. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches. PMID:26149015

  18. Therapeutic antibodies against cancer

    PubMed Central

    Adler, Mark J.; Dimitrov, Dimiter S.

    2012-01-01

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

  19. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  20. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

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

  1. Strategies for therapeutic hypometabothermia

    PubMed Central

    Liu, Shimin; Chen, Jiang-Fan

    2013-01-01

    Although therapeutic hypothermia and metabolic suppression have shown robust neuroprotection in experimental brain ischemia, systemic complications have limited their use in treating acute stroke patients. The core temperature and basic metabolic rate are tightly regulated and maintained in a very stable level in mammals. Simply lowering body temperature or metabolic rate is actually a brutal therapy that may cause more systemic as well as regional problems other than providing protection. These problems are commonly seen in hypothermia and barbiturate coma. The main innovative concept of this review is to propose thermogenically optimal and synergistic reduction of core temperature and metabolic rate in therapeutic hypometabothermia using novel and clinically practical approaches. When metabolism and body temperature are reduced in a systematically synergistic manner, the outcome will be maximal protection and safe recovery, which happen in natural process, such as in hibernation, daily torpor and estivation. PMID:24179563

  2. Management of hypertension emergencies.

    PubMed

    Elliott, William J

    2003-12-01

    Although they have become less common, hypertensive emergencies occur with an incidence of approximately 1 to 2/100,000 people per year. Our knowledge about this problem, its pathophysiology, risk factors, and appropriate treatment options has expanded during the past decade. A hypertensive emergency can be declared when an elevated blood pressure is associated with acute target-organ damage. Rapid evaluation and treatment (typically with an intravenously administered agent) should be instituted, usually in an intensive care unit setting, and the patient should be observed carefully during acute blood-pressure lowering. When properly treated, the prognosis for these patients is not nearly as dismal as it was more than 60 years ago, and the initial level of function of target organs (brain, heart, kidneys) is more indicative of an emergency than the actual level of blood pressure. Therapeutic options include the time-tested sodium nitroprusside (which has toxic metabolic products and is contraindicated in pregnancy, tobacco amblyopia, and Leber's optic atrophy); fenoldopam mesylate; and nicardipine. When properly treated, "malignant hypertension" need be considered malignant no longer. PMID:14594569

  3. Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection.

    PubMed

    Varmuzova, Karolina; Kubasova, Tereza; Davidova-Gerzova, Lenka; Sisak, Frantisek; Havlickova, Hana; Sebkova, Alena; Faldynova, Marcela; Rychlik, Ivan

    2016-01-01

    Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID:27379083

  4. Composition of Gut Microbiota Influences Resistance of Newly Hatched Chickens to Salmonella Enteritidis Infection

    PubMed Central

    Varmuzova, Karolina; Kubasova, Tereza; Davidova-Gerzova, Lenka; Sisak, Frantisek; Havlickova, Hana; Sebkova, Alena; Faldynova, Marcela; Rychlik, Ivan

    2016-01-01

    Since poultry is a very common source of non-typhoid Salmonella for humans, different interventions aimed at decreasing the prevalence of Salmonella in chickens are understood as an effective measure for decreasing the incidence of human salmonellosis. One such intervention is the use of probiotic or competitive exclusion products. In this study we tested whether microbiota from donor hens of different age will equally protect chickens against Salmonella Enteritidis infection. Newly hatched chickens were therefore orally inoculated with cecal extracts from 1-, 3-, 16-, 28-, and 42-week-old donors and 7 days later, the chickens were infected with S. Enteritidis. The experiment was terminated 4 days later. In the second experiment, groups of newly hatched chickens were inoculated with cecal extracts of 35-week-old hens either on day 1 of life followed by S. Enteritidis infection on day 2 or were infected with S. Enteritidis infection on day 1 followed by therapeutic administration of the cecal extract on day 2 or were inoculated on day 1 of life with a mixture of the cecal extract and S. Enteritidis. This experiment was terminated when the chickens were 5 days old. Both Salmonella culture and chicken gene expression confirmed that inoculation of newly hatched chickens with microbiota from 3-week-old or older chickens protected them against S. Enteritidis challenge. On the other hand, microbiota from 1-week-old donors failed to protect chickens against S. Enteritidis challenge. Microbiota from 35-week-old hens protected chickens even 24 h after administration. However, simultaneous or therapeutic microbiota administration failed to protect chickens against S. Enteritidis infection. Gut microbiota can be used as a preventive measure against S. Enteritidis infection but its composition and early administration is critical for its efficacy. PMID:27379083

  5. Polycyclic peptide therapeutics.

    PubMed

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases. PMID:23355488

  6. The emergence and cross species transmission of newly discovered tick-borne Bunyavirus in China.

    PubMed

    Zhang, Yong-Zhen; Xu, Jianguo

    2016-02-01

    A novel tick-borne Bunyavirus, discovered in China and later in South Korea and Japan, is now known as Huaiyangshan virus or severe fever with thrombocytopenia syndrome virus and has been identified as the causative agent of a hemorrhagic fever-like disease. Of five species of ticks carrying Huaiyangshan viruses, Haemaphysalis longicornis was the most abundant in regions where the virus was endemic. Its usual hosts (cattle, goats, dogs, rats and chickens) tested positive for Huaiyangshan virus RNA and had a high seroprevalence. The distribution of H. longicornis and the migratory routes of four wild fowl across China, South Korea and Japan are coincident. Thus a tick and migratory bird model for the transmission of the Huaiyangshan virus was proposed. PMID:26949898

  7. The Acquisition of Newly Emerging Sociophonetic Variation: /str-/ in American English

    ERIC Educational Resources Information Center

    Rutter, Ben

    2014-01-01

    Eight children aged 4;1-8;1 and their primary caregivers participated in a study designed to evaluate their use of the onset cluster /str-/ in both read and conversational speech. The cluster is currently undergoing a reported sound change in many varieties of English, with the initial /s/ being retracted to [?]. The study compared the initial…

  8. Better colonisation of newly emerged Bordetella pertussis in the co-infection mouse model study.

    PubMed

    Safarchi, Azadeh; Octavia, Sophie; Luu, Laurence Don Wai; Tay, Chin Yen; Sintchenko, Vitali; Wood, Nicholas; Marshall, Helen; McIntyre, Peter; Lan, Ruiting

    2016-07-25

    Molecular epidemiological data indicates that the resurgence of pertussis (whooping cough) in populations with high vaccine coverage is associated with genomic adaptation of Bordetella pertussis, the causative agent of the disease, to vaccine selection pressure. We have previously shown that in the period after the introduction of acellular pertussis vaccine (ACV), the majority of circulating strains in Australia switched to single nucleotide polymorphism (SNP) cluster I (carrying ptxP3/prn2), replacing SNP cluster II (carrying ptxP1/prn3). In this study, we carried out an in vivo competition assay using a mouse model infected with SNP cluster I and II B. pertussis strains from Australia. We found that the SNP cluster I strain colonised better than the SNP cluster II strain, in both naïve and immunised mice, suggesting that SNP cluster I strains had better fitness regardless of immunisation status of the host, consistent with SNP cluster I strains replacing SNP cluster II. Nevertheless, we found that ACV enhanced clearance of both SNP cluster I and II strains from the mouse respiratory tract. PMID:27346304

  9. Seasonal climate effects anemotaxis in newly emerged adult anopheles gambiae giles in Mali, West Africa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The direction and magnitude of movement of the malaria vector Anopheles gambiae Giles has been of great interest to medical entomologists for over 70 years. This direction of movement is likely to be affected by many factors, from environmental conditions and stage of life history of the mosquito to...

  10. Gluconobacter as well as Asaia species, newly emerging opportunistic human pathogens among acetic acid bacteria.

    PubMed

    Alauzet, Corentine; Teyssier, Corinne; Jumas-Bilak, Estelle; Gouby, Anne; Chiron, Raphael; Rabaud, Christian; Counil, François; Lozniewski, Alain; Marchandin, Hélène

    2010-11-01

    Acetic acid bacteria (AAB) are broadly used in industrial food processing. Among them, members of the genera Asaia, Acetobacter, and Granulibacter were recently reported to be human opportunistic pathogens. We isolated AAB from clinical samples from three patients and describe here the clinical and bacteriological features of these cases. We report for the first time (i) the isolation of a Gluconobacter sp. from human clinical samples; (ii) the successive isolation of different AAB, i.e., an Asaia sp. and two unrelated Gluconobacter spp., from a cystic fibrosis patient; and (iii) persistent colonization of the respiratory tract by a Gluconobacter sp. in this patient. We reviewed the main clinical features associated with AAB isolation identified in the 10 documented reports currently available in the literature. Albeit rare, infections as well as colonization with AAB are increasingly reported in patients with underlying chronic diseases and/or indwelling devices. Clinicians as well as medical microbiologists should be aware of these unusual opportunistic pathogens, which are difficult to detect during standard medical microbiological investigations and which are multiresistant to antimicrobial agents. Molecular methods are required for identification of genera of AAB, but the results may remain inconclusive for identification to the species level. PMID:20826638

  11. Molecular characterization of newly emerged blaKPC-2-producing Klebsiella pneumoniae in Singapore.

    PubMed

    Balm, Michelle N D; Ngan, Grace; Jureen, Roland; Lin, Raymond T P; Teo, Jeanette

    2012-02-01

    In Asia, bla(KPC) detection has been limited to East Asia and not yet seen in Southeast Asia. We report four bla(KPC-2)-containing Klebsiella pneumoniae isolates from two different hospitals in Singapore. All isolates belonged to strain type 11 (ST11) and were indistinguishable by pulsed-field gel electrophoresis (PFGE). bla(KPC-2) was located on nonconjugative plasmids and flanked by mobile genetic structures composed of a partial Tn4401 transposon and a Tn3-based transposon which previously have been described only in Chinese isolates. PMID:22116160

  12. A newly-emerged (August 2013) artificially-triggered fumarole near the Fiumicino airport, Rome, Italy

    NASA Astrophysics Data System (ADS)

    Sella, Pio; Billi, Andrea; Mazzini, Ilaria; De Filippis, Luigi; Pizzino, Luca; Sciarra, Alessandra; Quattrocchi, Fedora

    2014-06-01

    Early in the morning of 24 August, 2013, following by hours the drilling of a shallow borehole in the same spot, a new fumarole producing emissions of CO2-rich gas, water, and mud suddenly appeared at a crossroad along the fenced area of the Fiumicino international airport of Rome, Italy. Similar episodes have been scientifically documented or simply reported in recent and past years. To understand why gases are easily entrapped in the shallow subsurface of the Fiumicino area, we used five borehole cores drilled by us, analyzed the stratigraphy of these and other nearby cores, acquired a 2D seismic refraction tomogram, and performed chemical and isotopic analyses of water samples collected from aquifers intercepted by two drilled boreholes. Our boreholes were realized with proper anti-gas measures as, while drilling, we recorded the presence of pressurized gases at a specific permeable gravel level. Results show that, in the study area, gases become mainly entrapped in a mid-Pleistocene gravel horizon at about 40-50 m depth. This horizon contains a confined aquifer that stores the endogenous upwelling gases. The gravel is interposed between two silty-clayey units. The lower unit, very hard and overconsolidated, is affected by fractures that allow ascending gases to bypass the otherwise impermeable shale, permeate the gravel, and dissolve into the aquifer. In contrast, the upper unit is impermeable to fluids and seals the gas-pressurized aquifer, which therefore constitutes a source of hazard during human activities such as well drilling, quarrying, and various building-related excavations. As the stratigraphy of the Fiumicino area is very common in large portions of the densely populated Roman area and as the adjacent volcanic districts are hydrothermally active, we conclude that phenomena similar to that observed at Fiumicino could again occur both at Fiumicino and elsewhere in the surrounding region. As a prompt confirmation of our conclusion, we signal that, while writing this paper, new artificially-triggered degassing phenomena occurred off Fiumicino in connection with the construction of the new harbor.

  13. 21 CFR 868.5915 - Manual emergency ventilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual emergency ventilator. 868.5915 Section 868...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5915 Manual emergency ventilator. (a) Identification. A manual emergency ventilator is a device, usually incorporating a bag and valve, intended...

  14. Materials innovation for co-delivery of diverse therapeutic cargos

    PubMed Central

    Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

    2014-01-01

    Co-delivery is a rapidly growing sector of drug delivery that aspires to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes with synergistic activities. It requires the design of carriers capable of simultaneously transporting to and releasing multiple therapeutics at a disease site. Co-delivery has arisen from the emerging trend of combination therapy, where treatment with two or more therapeutics at the same time can succeed where single therapeutics fail. However, conventional combination therapy offers little control over achieving an optimized therapeutic ratio at the target site. Co-delivery via inclusion of multiple therapeutic cargos within the same carrier addresses this issue by not only ensuring delivery of both therapeutics to the same cell, but also offering a platform for control of the delivery process, from loading to release. Co-delivery systems have been formulated using a number of carriers previously developed for single-therapeutic delivery. Liposomes, polymeric micelles, PLGA nanoparticles, and dendrimers have all been adapted for co-delivery. Much of the effort focuses on dealing with drugs having dissimilar properties, increasing loading efficiencies, and controlling loading and release ratios. In this review, we highlight the innovations in carrier designs and formulations to deliver combination cargoes of drug/drug, drug/siRNA, and drug/pDNA toward disease therapy. With rapid advances in mechanistic understanding of interrelating molecular pathways and development of molecular medicine, the future of co-delivery will become increasingly promising and prominent. PMID:24818000

  15. Advances in sarcoma genomics and new therapeutic targets

    PubMed Central

    Taylor, Barry S.; Barretina, Jordi; Maki, Robert G.; Antonescu, Cristina R.; Singer, Samuel; Ladanyi, Marc

    2012-01-01

    Preface Increasingly, human mesenchymal malignancies are classified by the abnormalities that drive their pathogenesis. While many of these aberrations are highly prevalent within particular sarcoma subtypes, few are currently targeted therapeutically. Indeed, most subtypes of sarcoma are still treated with traditional therapeutic modalities and in many cases are resistant to adjuvant therapies. In this Review, we discuss the core molecular determinants of sarcomagenesis and emphasize the emerging genomic and functional genetic approaches that, coupled to novel therapeutic strategies, have the potential to transform the care of patients with sarcoma. PMID:21753790

  16. RNA-based Therapeutics- Current Progress and Future Prospects

    PubMed Central

    Burnett, John C.; Rossi, John J.

    2012-01-01

    Summary Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprecedented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes. PMID:22284355

  17. 40 CFR 268.38 - Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 27 2014-07-01 2014-07-01 false Waste specific prohibitions-newly identified organic toxicity characteristic wastes and newly listed coke by-product and chlorotoluene production wastes. 268.38 Section 268.38 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) LAND...

  18. Determinants of immunogenic response to protein therapeutics.

    PubMed

    Singh, Satish K; Cousens, Leslie P; Alvarez, David; Mahajan, Pramod B

    2012-09-01

    Protein therapeutics occupy a very significant position in the biopharmaceutical market. In addition to the preclinical, clinical and post marketing challenges common to other drugs, unwanted immunogenicity is known to affect efficacy and/or safety of most biotherapeutics. A standard set of immunogenicity risk factors are routinely used to inform monitoring strategies in clinical studies. A number of in-silico, in vivo and in vitro approaches have also been employed to predict immunogenicity of biotherapeutics, but with limited success. Emerging data also indicates the role of immune tolerance mechanisms and impact of several product-related factors on modulating host immune responses. Thus, a comprehensive discussion of the impact of innate and adaptive mechanisms and molecules involved in induction of host immune responses on immunogenicity of protein therapeutics is needed. A detailed understanding of these issues is essential in order to fully exploit the therapeutic potential of this class of drugs. This Roundtable Session was designed to provide a common platform for discussing basic immunobiological and pharmacological issues related to the role of biotherapeutic-associated risk factors, as well as host immune system in immunogenicity against protein therapeutics. The session included overview presentations from three speakers, followed by a panel discussion with audience participation. PMID:22770604

  19. Perspective of power in therapeutic relationships.

    PubMed

    van Mens-Verhulst, J

    1991-04-01

    Therapists can have several reasons to reflect on the helping process from a perspective of power. In effect, they all use a theory of power, be it implicit or explicit. If this theory is meant to support therapeutic thoughts and actions, it has to meet several requirements. First, it must recognize the human qualities of therapists, clients, and other people involved. Second, it must account for the complexity and dynamics of therapeutic situations; it must, for example, high-light possible shifts in power differences. Third, it must be applicable to a variety of therapeutic circumstances and systems. This means that the familiar paradigm of control, predictability, simple causality, full rationality and linearity of action must be replaced by an evolutionary paradigm that assumes continuous flows of changes between actors and factors. Some of the emerging patterns get fixed, spontaneously or artificially and become visible as shorter--or longer-lasting--stable patterns on micro- and macro-levels. Power is focussed on by an anarchistic decision-making approach. The (combinations of) people involved are depicted as living, i.e., evolving and learning systems: all actors are supposed to have their own intentions, resources, strategies, interpretations, opportunities, and development. One has to look for power inequalities between the actors on operational, organizational, structural, and cultural decision-making levels. The result is a multi-actor, multidimensional decision-making model for the therapeutic relationship that opens up new possibilities for intervention. PMID:2069201

  20. Molecular therapeutics in pancreas cancer

    PubMed Central

    Narayanan, Vignesh; Weekes, Colin D

    2016-01-01

    The emergence of the “precision-medicine” paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  1. Molecular therapeutics in pancreas cancer.

    PubMed

    Narayanan, Vignesh; Weekes, Colin D

    2016-04-15

    The emergence of the "precision-medicine" paradigm in oncology has ushered in tremendous improvements in patient outcomes in a wide variety of malignancies. However, pancreas ductal adenocarcinoma (PDAC) has remained an obstinate challenge to the oncology community and continues to be associated with a dismal prognosis with 5-year survival rates consistently less than 5%. Cytotoxic chemotherapy with gemcitabine-based regimens has been the cornerstone of treatment in PDAC especially because most patients present with inoperable disease. But in recent years remarkable basic science research has improved our understanding of the molecular and genetic basis of PDAC. Whole genomic analysis has exemplified the genetic heterogeneity of pancreas cancer and has led to ingenious efforts to target oncogenes and their downstream signaling cascades. Novel stromal depletion strategies have been devised based on our enhanced recognition of the complex architecture of the tumor stroma and the various mechanisms in the tumor microenvironment that sustain tumorigenesis. Immunotherapy using vaccines and immune checkpoint inhibitors has also risen to the forefront of therapeutic strategies against PDAC. Furthermore, adoptive T cell transfer and strategies to target epigenetic regulators are being explored with enthusiasm. This review will focus on the recent advances in molecularly targeted therapies in PDAC and offer future perspectives to tackle this lethal disease. PMID:27096032

  2. [Future therapeutics in celiac disease].

    PubMed

    Lerner, Aaron

    2012-06-01

    Celiac disease is a common autoimmune disease affecting 1% of the Western populations. It is an inappropriate immune response, in genetically susceptible patients to dietary wheat, rye, barley and oats. Treatment involves a Lifelong gluten-free diet that predisposes to low compliance due to limited variety, high cost and low palatability, imposing social pressure and affecting quality of life. The result is an urgent need for alternative therapeutic strategies. Based on the growing actual knowledge on the intestinal inflammatory cascade, mucosal immunology and genetics of celiac disease, new attractive potential therapies are emerging. Possibilities include: searching for low immunogenic wheat variants or strains pretreated with enzymes or binders for lower toxicity. Other strategies involve decreasing transepithelial uptake or dampening of the adaptive immune response by transglutaminase inhibitors or blockage of the HLA groove and immune modulation to shift the TH1 to TH2 profile. Developing biological therapy aims to decrease intestinal homing, adhesion and activity of inflammatory cells, counteract the pro-inflammatory cytokines, clonal intestinal T cells or mesenchymal stem cell replacement or mitogenic intestinal repair safety, cost, affordability and clinical effectiveness are of prime concern. Most of the above strategies showed promising results ex-vivo. The future will highlight the in-vivo winner. PMID:22991867

  3. Thyroid Emergencies.

    PubMed

    Leung, Angela M

    2016-01-01

    Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states-which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively-is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting. PMID:27598067

  4. Emerging jets

    NASA Astrophysics Data System (ADS)

    Schwaller, Pedro; Stolarski, Daniel; Weiler, Andreas

    2015-05-01

    In this work, we propose a novel search strategy for new physics at the LHC that utilizes calorimeter jets that (i) are composed dominantly of displaced tracks and (ii) have many different vertices within the jet cone. Such emerging jet signatures are smoking guns for models with a composite dark sector where a parton shower in the dark sector is followed by displaced decays of dark pions back to SM jets. No current LHC searches are sensitive to this type of phenomenology. We perform a detailed simulation for a benchmark signal with two regular and two emerging jets, and present and implement strategies to suppress QCD backgrounds by up to six orders of magnitude. At the 14 TeV LHC, this signature can be probed with mediator masses as large as 1.5 TeV for a range of dark pion lifetimes, and the reach is increased further at the high-luminosity LHC. The emerging jet search is also sensitive to a broad class of long-lived phenomena, and we show this for a supersymmetric model with R-parity violation. Possibilities for discovery at LHCb are also discussed.

  5. Nitric Oxide Release Part II. Therapeutic Applications

    PubMed Central

    Carpenter, Alexis W.; Schoenfisch, Mark H.

    2012-01-01

    Summary A wide range of nitric oxide (NO)-releasing materials have emerged as potential therapeutics that exploit NO’s vast biological roles. Macromolecular NO-releasing scaffolds are particularly promising due to their ability to store and deliver larger NO payloads in a more controlled and effective manner compared to low molecular weight NO donors. While a variety of scaffolds (e.g., particles, dendrimers, and polymers/films) have been cleverly designed, the ultimate clinical utility of most NO-releasing macromolecules remains unrealized. Although not wholly predictive of clinical success, in vitro and in vivo investigations have enabled a preliminary evaluation of the therapeutic potential of such materials. Herein, we review the application of macromolecular NO therapies for cardiovascular disease, cancer, bacterial infections, and wound healing. PMID:22362384

  6. Psychodynamic Perspective on Therapeutic Boundaries

    PubMed Central

    Bridges, Nancy A.

    1999-01-01

    Discussion of boundaries in therapeutic work most often focuses on boundary maintenance, risk management factors, and boundary violations. The psychodynamic meaning and clinical management of boundaries in therapeutic relationships remains a neglected area of discourse. Clinical vignettes will illustrate a psychodynamic, developmental-relational perspective using boundary dilemmas to deepen and advance the therapeutic process. This article contributes to the dialogue about the process of making meaning and constructing therapeutically useful and creative boundaries that further the psychotherapeutic process. PMID:10523432

  7. Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology

    PubMed Central

    Yu, Xiaofei; Guo, Chunqing; Fisher, Paul B.; Subjeck, John R.; Wang, Xiang-Yang

    2015-01-01

    Scavenger receptors constitute a large family of evolutionally conserved protein molecules that are structurally and functionally diverse. Although scavenger receptors were originally identified based on their capacity to scavenge modified lipoproteins, these molecules have been shown to recognize and bind to a broad spectrum of ligands, including modified and unmodified host-derived molecules or microbial components. As a major subset of innate pattern recognition receptors, scavenger receptors are mainly expressed on myeloid cells and function in a wide range of biological processes, such as endocytosis, adhesion, lipid transport, antigen presentation, and pathogen clearance. In addition to playing a crucial role in maintenance of host homeostasis, scavenger receptors have been implicated in the pathogenesis of a number of diseases, e.g., atherosclerosis, neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal these receptor molecules as important regulators of tumor behavior and host immune responses to cancer. This review summarizes our current understanding on the newly identified, distinct functions of scavenger receptors in cancer biology and immunology. The potential of scavenger receptors as diagnostic biomarkers and novel targets for therapeutic interventions to treat malignancies is also highlighted. PMID:26216637

  8. Frankincense--therapeutic properties.

    PubMed

    Al-Yasiry, Ali Ridha Mustafa; Kiczorowska, Bożena

    2016-01-01

    Recently, increasing interest in natural dietary and therapeutic preparations used as dietary supplements has been observed. One of them is frankincense. This traditional medicine of the East is believed to have anti-inflammatory, expectorant, antiseptic, and even anxiolytic and anti-neurotic effects. The present study aims to verify the reported therapeutic properties of Boswellia resin and describe its chemical composition based on available scientific studies. The main component of frankincense is oil (60%). It contains mono- (13%) and diterpenes (40%) as well as ethyl acetate (21.4%), octyl acetate (13.4%) and methylanisole (7.6%). The highest biological activity among terpenes is characteristic of 11-keto-ß-acetyl-beta-boswellic acid, acetyl-11-keto-ß-boswellic acid and acetyl-α-boswellic acid. Contemporary studies have shown that resin indeed has an analgesic, tranquilising and anti-bacterial effects. From the point of view of therapeutic properties, extracts from Boswellia serrata and Boswellia carterii are reported to be particularly useful. They reduce inflammatory conditions in the course of rheumatism by inhibiting leukocyte elastase and degrading glycosaminoglycans. Boswellia preparations inhibit 5-lipoxygenase and prevent the release of leukotrienes, thus having an anti-inflammatory effect in ulcerative colitis, irritable bowel syndrome, bronchitis and sinusitis. Inhalation and consumption of Boswellia olibanum reduces the risk of asthma. In addition, boswellic acids have an antiproliferative effect on tumours. They inhibit proliferation of tumour cells of the leukaemia and glioblastoma subset. They have an anti-tumour effect since they inhibit topoisomerase I and II-alpha and stimulate programmed cell death (apoptosis). PMID:27117114

  9. Cystic Fibrosis Therapeutics

    PubMed Central

    Ramsey, Bonnie W.

    2013-01-01

    A great deal of excitement and hope has followed the successful trials and US Food and Drug Administration approval of the drug ivacaftor (Kalydeco), the first therapy available that targets the underlying defect that causes cystic fibrosis (CF). Although this drug has currently demonstrated a clinical benefit for a small minority of the CF population, the developmental pathway established by ivacaftor paves the way for other CF transmembrane conductance regulator (CFTR) modulators that may benefit many more patients. In addition to investigating CFTR modulators, researchers are actively developing numerous other innovative CF therapies. In this review, we use the catalog of treatments currently under evaluation with the support of the Cystic Fibrosis Foundation, known as the Cystic Fibrosis Foundation Therapeutics Pipeline, as a platform to discuss the variety of candidate treatments for CF lung disease that promise to improve CF care. Many of these approaches target the individual components of the relentless cycle of airway obstruction, inflammation, and infection characteristic of lung disease in CF, whereas others are aimed directly at the gene defect, or the resulting dysfunctional protein, that instigates this cycle. We discuss how new findings from the laboratory have informed not only the development of novel therapeutics, but also the rationales for their use and the outcomes used to measure their effects. By reviewing the breadth of candidate treatments currently in development, as well as the recent progress in CF therapies reflected by the evolution of the therapeutics pipeline over the past few years, we hope to build upon the optimism and anticipation generated by the recent success of Kalydeco. PMID:23276843

  10. Telomerase and cancer therapeutics.

    PubMed

    Harley, Calvin B

    2008-03-01

    Telomerase is an attractive cancer target as it appears to be required in essentially all tumours for immortalization of a subset of cells, including cancer stem cells. Moreover, differences in telomerase expression, telomere length and cell kinetics between normal and tumour tissues suggest that targeting telomerase would be relatively safe. Clinical trials are ongoing with a potent and specific telomerase inhibitor, GRN163L, and with several versions of telomerase therapeutic vaccines. The prospect of adding telomerase-based therapies to the growing list of new anticancer products is promising, but what are the advantages and limitations of different approaches, and which patients are the most likely to respond? PMID:18256617

  11. [Achievement of therapeutic objectives].

    PubMed

    Mantilla, Teresa

    2014-07-01

    Therapeutic objectives for patients with atherogenic dyslipidemia are achieved by improving patient compliance and adherence. Clinical practice guidelines address the importance of treatment compliance for achieving objectives. The combination of a fixed dose of pravastatin and fenofibrate increases the adherence by simplifying the drug regimen and reducing the number of daily doses. The good tolerance, the cost of the combination and the possibility of adjusting the administration to the patient's lifestyle helps achieve the objectives for these patients with high cardiovascular risk. PMID:25043543

  12. Revitalizing Psychiatric Therapeutics

    PubMed Central

    Hyman, Steven E

    2014-01-01

    Despite high prevalence and enormous unmet medical need, the pharmaceutical industry has recently de-emphasized neuropsychiatric disorders as ‘too difficult' a challenge to warrant major investment. Here I describe major obstacles to drug discovery and development including a lack of new molecular targets, shortcomings of current animal models, and the lack of biomarkers for clinical trials. My major focus, however, is on new technologies and scientific approaches to neuropsychiatric disorders that give promise for revitalizing therapeutics and may thus answer industry's concerns. PMID:24317307

  13. [Is therapeutic deadlock inevitable?].

    PubMed

    Vignat, Jean-Pierre

    2016-01-01

    Many long-term treatments appear to be an expression of therapeutic deadlock. The situation leads to a questioning of the concept of chronicity and the identification of the determining factors of situations which are apparently blocked, marked by the search for solutions taking a back seat to the taking of action. The interaction between patients' mental apparatus and the care apparatus lies at the heart of the question, interpreted from an institutional, collective and individual perspective, supported by the clinical and psychopathological approach, and the return to the prioritisation of the thought. PMID:27389427

  14. The Therapeutic Roller Coaster

    PubMed Central

    CHU, JAMES A.

    1992-01-01

    Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

  15. Therapeutic Endoscopic Ultrasound

    PubMed Central

    Cheriyan, Danny

    2015-01-01

    Endoscopic ultrasound (EUS) technology has evolved dramatically over the past 20 years, from being a supplementary diagnostic aid available only in large medical centers to being a core diagnostic and therapeutic tool that is widely available. Although formal recommendations and practice guidelines have not been developed, there are considerable data supporting the use of EUS for its technical accuracy in diagnosing pancreaticobiliary and gastrointestinal pathology. Endosonography is now routine practice not only for pathologic diagnosis and tumor staging but also for drainage of cystic lesions and celiac plexus neurolysis. In this article, we cover the use of EUS in biliary and pancreatic intervention, ablative therapy, enterostomy, and vascular intervention. PMID:27118942

  16. [Diabetic nephropathy: emerging treatments].

    PubMed

    Gueutin, Victor; Gauthier, Marion; Cazenave, Maud; Izzedine, Hassane

    2014-07-01

    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been management of hyperglycaemia, blood pressure and proteinuria using hypoglycemic agents, ACE inhibitors, and angiotensin receptor blockers. Since 2000, new therapeutic strategies began to emerge targeting the biochemical activity of glucose molecules on the renal tissue. Various substances have been studied with varying degrees of success, ranging from vitamin B to camel's milk. Silymarin reduces urinary excretion of albumin, tumor necrosis factor (TNF)-α, and malondialdehyde in patients with diabetic nephropathy and may be considered as a novel addition to the anti-diabetic nephropathy armamentarium. Although some results are promising, studies on a larger scale are needed to validate the utility of these molecules in the treatment of the DN. PMID:24938412

  17. Emerging small molecule drugs.

    PubMed

    Colin, Sophie; Chinetti-Gbaguidi, Giulia; Kuivenhoven, Jan A; Staels, Bart

    2015-01-01

    Dyslipidaemia is a major risk factor for cardiovascular diseases. Pharmacological lowering of LDL-C levels using statins reduces cardiovascular risk. However, a substantial residual risk persists especially in patients with type 2 diabetes mellitus. Because of the inverse association observed in epidemiological studies of HDL-C with the risk for cardiovascular diseases, novel therapeutic strategies to raise HDL-C levels or improve HDL functionality are developed as complementary therapy for cardiovascular diseases. However, until now most therapies targeting HDL-C levels failed in clinical trials because of side effects or absence of clinical benefits. This chapter will highlight the emerging small molecules currently developed and tested in clinical trials to pharmacologically modulate HDL-C and functionality including new CETP inhibitors (anacetrapib, evacetrapib), novel PPAR agonists (K-877, CER-002, DSP-8658, INT131 and GFT505), LXR agonists (ATI-111, LXR-623, XL-652) and RVX-208. PMID:25523004

  18. Laparoscopic exploration in pediatric surgery emergencies

    PubMed Central

    Drăghici, L; Popescu, M; Liţescu, M

    2010-01-01

    The laparoscopic approach of pediatric surgery emergencies represents a specific preoccupation in hospitals everywhere in the world. Nowadays, when confronted with this pathology, pediatric surgeons are able to apply certain well–defined therapeutic protocols, depending on the technical equipment at their disposal and their laparoscopic expertise and training. We hereby present some of the surgical pediatric emergencies that have been subjected to minimally invasive celioscopic techniques, in the Department of Pediatric Surgery ‘Maria Sklodowska Curie’ Hospital, from August 1999 to July 2007. Out of 83 exploratory laparoscopies, 12 were performed for emergency pathology, other than acute appendicitis (in its various forms, including peritonitis) or acute cholecystitis. However, during the above–mentioned period, the number of therapeutic laparoscopies for emergencies has grown significantly (239 from a total of 663 laparoscopies), reflecting to a large extent the activity of a clinic with an emergency surgery profile. The authors conclude that exploratory laparoscopies in pediatric surgery emergencies are suited for surgical teams with a solid experience in celioscopy and a certain professional maturity, necessary to correctly appreciate the surgical and anesthetic risks involved by each individual case. It is not recommended that inexperienced laparoscopic surgeons embark on the ‘adventure’ of this minimally invasive approach for this type of pathology. Only when the training and learning process is fully and correctly completed, specialists are offered the advantage of continuing a celioscopic exploration by performing a minimally invasive therapeutic procedure, even for a pediatric emergency case. PMID:20302204

  19. Assessment of the Framingham risk factors among ED patients with newly diagnosed atrial fibrillation

    PubMed Central

    Barrett, Tyler W.; Storrow, Alan B.; Jenkins, Cathy A.; Harrell, Frank E.; Amdahl, John; Russ, Stephan; Slovis, Corey M.; Darbar, Dawood

    2010-01-01

    Study Objective Atrial fibrillation (AF) is often first diagnosed in the emergency department (ED) and accounts for nearly 1% of all ED visits. Our objective was to assess the Framingham Heart Study risk score for AF development in ED patients with newly diagnosed AF. Methods We systematically reviewed the electronic medical records of ED patients with newly diagnosed AF between August 2005 and July 2008. We measured the frequency of the Framingham Heart Study predictors and calculated each patient's risk score. Results During the 3-year study period, 914 patients had 1228 ED visits. New AF was diagnosed in 296 (32%) patients. Among these patients, 107 (36%) were female, 127 (43%) had prior ED visits since 2003, 189 (64%) were taking hypertension medications and 170 (57.4%) had previous electrocardiograms with measurable PR intervals. The median PR interval was 166 ms (151 to 180) and 60% of available PR intervals were ≥160 ms. The median (Interquartile range) age, body mass index, and systolic blood pressure were 66 years (53 to 77), 27 (23 to 31), and 134 mm Hg (118 to 151), respectively. Median risk score was 7 (3 to 9) indicating high predicted risk. Heart failure and cardiac murmurs were previously diagnosed in 45 (15%) and 32 (11%) of these patients, respectively. Conclusions The Framingham risk factors for AF are commonly encountered among ED patients with newly diagnosed AF. The ED might provide an opportunity to identify patients at high risk for AF and refer them for primary prevention interventions. PMID:21208770

  20. Shared decision making in the management of children with newly diagnosed immune thrombocytopenia.

    PubMed

    Beck, Carolyn E; Boydell, Katherine M; Stasiulis, Elaine; Blanchette, Victor S; Llewellyn-Thomas, Hilary; Birken, Catherine S; Breakey, Vicky R; Parkin, Patricia C

    2014-10-01

    This study aimed to examine the treatment decision-making process for children hospitalized with newly diagnosed immune thrombocytopenia (ITP). Using focus groups, we studied children with ITP, parents of children with ITP, and health care professionals, inquiring about participants' experience with decision support and decision making in newly diagnosed ITP. Data were examined using thematic analysis. Themes that emerged from children were feelings of "anxiety, fear, and confusion"; the need to "understand information"; and "treatment choice," the experience of which was age dependent. For parents, "anxiety, fear, and confusion" was a dominant theme; "treatment choice" revealed that participants felt directed toward intravenous immune globulin (IVIG) for initial treatment. For health care professionals, "comfort level" highlighted factors contributing to professionals' comfort with offering options; "assumptions" were made about parental desire for participation in shared decision making (SDM) and parental acceptance of treatment options; "providing information" was informative regarding modes of facilitating SDM; and "treatment choice" revealed a discrepancy between current practice (directed toward IVIG) and the ideal of SDM. At our center, families of children with newly diagnosed ITP are not experiencing SDM. Our findings support the implementation of SDM to facilitate patient-centered care for the management of pediatric ITP. PMID:24577546

  1. AMUM LECTURE: Therapeutic ultrasound

    NASA Astrophysics Data System (ADS)

    Crum, Lawrence A.

    2004-01-01

    The use of ultrasound in medicine is now quite commonplace, especially with the recent introduction of small, portable and relatively inexpensive, hand-held diagnostic imaging devices. Moreover, ultrasound has expanded beyond the imaging realm, with methods and applications extending to novel therapeutic and surgical uses. These applications broadly include: tissue ablation, acoustocautery, lipoplasty, site-specific and ultrasound mediated drug activity, extracorporeal lithotripsy, and the enhancement of natural physiological functions such as wound healing and tissue regeneration. A particularly attractive aspect of this technology is that diagnostic and therapeutic systems can be combined to produce totally non-invasive, imageguided therapy. This general lecture will review a number of these exciting new applications of ultrasound and address some of the basic scientific questions and future challenges in developing these methods and technologies for general use in our society. We shall particularly emphasize the use of High Intensity Focused Ultrasound (HIFU) in the treatment of benign and malignant tumors as well as the introduction of acoustic hemostasis, especially in organs which are difficult to treat using conventional medical and surgical techniques.

  2. Winnicott's therapeutic consultations revisited.

    PubMed

    Brafman, A H

    1997-08-01

    Winnicott described in his book 'Therapeutic Consultations' (1971) how a diagnostic assessment of a referred child developed into a fruitful therapeutic intervention when he was able to discover the unconscious fantasy that underlay the child's symptoms. Because these were children who were, essentially, developing normally, he used the word 'knot' to depict the obstacle the child had met. Any conflicts the parents might have were not explored in that context. This work present cases in which child and parents are seen together for the diagnostic assessment. The child's feelings about his world and his difficulties are explored through a variety of techniques including drawings. In the same interview, an analytic enquiry into the parents' history and also their views of the child reveals how the child's fantasies and the parents' past experiences interact and create a mutually reinforcing vicious circle. In other words, the 'knot' involves all of them. If the child's unconscious fantasy can be verbalised and if the parents are able to approach the child in a manner that acknowledges the child's real needs, the 'knot' disappears and normal development can be resumed. PMID:9306188

  3. Engineering therapeutic protein disaggregases.

    PubMed

    Shorter, James

    2016-05-15

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  4. Engineering therapeutic protein disaggregases

    PubMed Central

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  5. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  6. Mechanisms of Plasma Therapeutics

    NASA Astrophysics Data System (ADS)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  7. Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

    PubMed Central

    Kim, Eunhee G.; Kim, Kristine M.

    2015-01-01

    Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris® (anti-CD30-drug conjugate) and Kadcyla® (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed. PMID:26535074

  8. [Diagnosis and treatment of hypertensive emergencies].

    PubMed

    Burnier, M; Waeber, B; Brunner, H R

    1995-11-25

    In hospital as well as in the office, the physician is often confronted with clinical situations in which blood pressure values are very high. In each case, he will have to evaluate rapidly the degree of emergency and the need for immediate antihypertensive therapy. In the last few years, the therapeutic approach to some hypertensive emergencies has changed. The purpose of the present article is to review: 1) the clinical situations where immediate control of blood pressure is necessary, 2) the present therapeutic approaches and 3) the cardiac and cerebral risks linked to an excessive and too rapid fall in blood pressure. PMID:8539574

  9. Editorial: advances in therapeutic glycopeptides.

    PubMed

    Zeng, Wenbin; Chen, Yue-Lei

    2014-01-01

    Glycopeptides, peptides containing sugar β-amino acids, have significant impact on medicinal chemistry research and pharmaceutical industr. In 1956, the discovery of one classic glycopeptide, vancomycin, broke the dawn of a new age for antibacterial research. Employing glycopeptides for the therapeutic purposes used to be regarded as proposals. Owing largely to the recent improvements in separation practices, characterization techniques, synthetic methods, and biological research, these proposals have been transformed into ongoing research projects in many laboratories around the world. Previously known as antibiotics, glycopeptides have been used as chemotherapeutic, antiviral, antitubercular, antifungal, antiproliferative and apoptotic agents. Nowadays they are even considered for the development of HIV and cancer vaccines. While several of them are in clinical trials, it could be expected that in the near future, treatment regimen of such difficult diseases might be reformed accordingly. Many interesting preliminary results are being produced in this emerging area. As witnesses and practitioners in this exciting area, however, we notice that the related communication in public domain is still limited due to the relatively small number of researchers involved. Thus, we feel the necessity to compile a timely issue about the special topic "Advances in Therapeutic Glycopeptides", covering state-of-the-art research papers and expert reviews from this area. We are glad that Protein & Peptide Letters is willing to realize the idea with us. The opening paper of this issue by Dr. Voglmeir and coauthor discusses three types of PNGases in respect of their general properties and applications of the commercially available PNGases in glycopeptide and glycoprotein analysis. Dr. Liu and coauthors describe current techniques such as high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), and mass spectrometry (MS), for the characterization of

  10. Implementation of newly adopted technology in acute care settings: a qualitative analysis of clinical staff

    PubMed Central

    Langhan, Melissa L.; Riera, Antonio; Kurtz, Jordan C.; Schaeffer, Paula; Asnes, Andrea G.

    2015-01-01

    Objective Technologies are not always successfully implemented into practise. We elicited experiences of acute care providers with the introduction of technology and identified barriers and facilitators in the implementation process. Methods A qualitative study using one-on-one interviews among a purposeful sample of 19 physicians and nurses within ten emergency departments and intensive care units was performed. Grounded theory, iterative data analysis and the constant comparative method were used to inductively generate ideas and build theories. Results Five major categories emerged: decision-making factors, the impact on practise, technology's perceived value, facilitators and barriers to implementation. Barriers included negative experiences, age, infrequent use, and access difficulties. A positive outlook, sufficient training, support staff, and user friendliness were facilitators. Conclusions This study describes strategies implicated in the successful implementation of newly adopted technology in acute care settings. Improved implementation methods and evaluation of implementation processes are necessary for successful adoption of new technology. PMID:25367721

  11. Implementation of newly adopted technology in acute care settings: a qualitative analysis of clinical staff.

    PubMed

    Langhan, Melissa L; Riera, Antonio; Kurtz, Jordan C; Schaeffer, Paula; Asnes, Andrea G

    2015-01-01

    Technologies are not always successfully implemented into practice. This study elicited experiences of acute care providers with the introduction of technology and identified barriers and facilitators in the implementation process. A qualitative study using one-on-one interviews among a purposeful sample of 19 physicians and nurses within 10 emergency departments and intensive care units was performed. Grounded theory, iterative data analysis and the constant comparative method were used to inductively generate ideas and build theories. Five major categories emerged: decision-making factors, the impact on practice, technology's perceived value, facilitators and barriers to implementation. Barriers included negative experiences, age, infrequent use and access difficulties. A positive outlook, sufficient training, support staff and user friendliness were facilitators. This study describes strategies implicated in the successful implementation of newly adopted technology in acute care settings. Improved implementation methods and evaluation of implementation processes are necessary for successful adoption of new technology. PMID:25367721

  12. Newly generated neurons at 2 months post-status epilepticus are functionally integrated into neuronal circuitry in mouse hippocampus.

    PubMed

    Hu, Ming; Zhu, Kun; Chen, Xin-Lin; Zhang, Yao-Jie; Zhang, Jian-Shui; Xiao, Xin-Li; Liu, Jian-Xin; Liu, Yong

    2015-11-01

    Emerging evidence has linked chronic temporal lobe epilepsy to dramatically reduced neurogenesis in the dentate gyrus. However, the profile of different components of neurogenesis in the chronically epileptic hippocampus is still unclear, especially the incorporation of newly generated cells. To address the issue, newly generated cells in the sub-granular zone of the dentate gyrus were labeled by the proliferation marker bromodeoxyuridine (BrdU) or retroviral vector expressing green fluorescent protein 2 months after pilocarpine-induced status epilepticus. The newly generated neurons that extended axons to CA3 area or integrated into memory circuits were visualized by cholera toxin B subunit retrograde tracing, and detecting activation of BrdU(+) cells following a recall of spatial memory test at the chronic stage of TLE. We found that the microenvironment was still able to sustain significant neuronal differentiation of newly generated cells at 2 months post-status epilepticus time-point, and newly added neurons into granular cell layer were still able to integrate into neuronal circuitry, both anatomically and functionally. Quantified analyses of BrdU(+) or Ki-67(+) cells demonstrated that there was a reduced proliferation of progenitor cells and diminished survival of newly generated cells in the epileptic hippocampus. Both decreased levels of neurotrophic factors in the surrounding milieu and cell loss in the CA3 area might contribute the decreased production of new cells and their survival following chronic epilepsy. These results suggest that decreased neurogenesis in the chronically epileptic hippocampus 2 months post status epilepticus is not associated with altered integration of newly generated neurons, and that developing strategies to augment hippocampal neurogenesis in chronic epilepsy might be protective. PMID:26384773

  13. [Crohn's disease. Clinical and therapeutical considerations].

    PubMed

    Paşalega, M; Calotă, F; Paraliov, T; Meşină, C; Vîlcea, D; Tomescu, P; Pănuş, A; Tenea, T; Mirea, C; Traşcă, E; Ene, D; Vasile, I

    2005-01-01

    Crohn's disease is a chronic granulomatous inflammatory condition of the intestinal tract of unknown etiology. Most commonly the disease affects the small bowel, the colon and the rectum. The acute and aggressive forms can evolve fast, mimicking an acute surgical illness, requiring surgical intervention in emergency. Surgical therapeutical option, in this condition, must be determined strictly by establishing a correct intraoperative diagnosis, through macroscopic features and histologic evidence. Because it is an incurable disease with variable evolution, marked by recurrence, that involves repeated surgical intervention, the surgical treatment (often resection), must be most conservative from the small bowel. We present 3 cases of surgical interventions with emergency characteristics (bowel obstruction through fitobezoar, colonic tumors obstruction of colon splenic angle, urachal infected tumors). In these cases the diagnosis was established intraoperatively and the surgical intervention was adapted to the particular cases. PMID:16372678

  14. Regression in schizophrenia and its therapeutic value.

    PubMed

    Yazaki, N

    1992-03-01

    Using the regression evaluation scale, 25 schizophrenic patients were classified into three groups of Dissolution/autism (DAUG), Dissolution----attachment (DATG) and Non-regression (NRG). The regression of DAUG was of the type in which autism occurred when destructiveness emerged, while the regression of DATG was of the type in which attachment occurred when destructiveness emerged. This suggests that the regressive phenomena are an actualized form of the approach complex. In order to determine the factors distinguishing these two groups, I investigated psychiatric symptoms, mother-child relationships, premorbid personalities and therapeutic interventions. I believe that these factors form a continuity in which they interrelatedly determine the regressive state. Foremost among them, I stressed the importance of the mother-child relationship. PMID:1353128

  15. Newly Released Inmates Account for 1 in 10 Fatal ODs

    MedlinePlus

    ... fullstory_159858.html Newly Released Inmates Account for 1 in 10 Fatal ODs Many may not realize ... the general population," Persaud added. Not only did one in 10 overdose deaths involve a recently released ...

  16. Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins

    PubMed Central

    Gimber, Niclas; Tadeus, Georgi; Maritzen, Tanja; Schmoranzer, Jan; Haucke, Volker

    2015-01-01

    Neurotransmission relies on the calcium-triggered exocytic fusion of non-peptide neurotransmitter-containing small synaptic vesicles (SVs) with the presynaptic membrane at active zones (AZs) followed by compensatory endocytic retrieval of SV membranes. Here, we study the diffusional fate of newly exocytosed SV proteins in hippocampal neurons by high-resolution time-lapse imaging. Newly exocytosed SV proteins rapidly disperse within the first seconds post fusion until confined within the presynaptic bouton. Rapid diffusional spread and confinement is followed by slow reclustering of SV proteins at the periactive endocytic zone. Confinement within the presynaptic bouton is mediated in part by SV protein association with the clathrin-based endocytic machinery to limit diffusional spread of newly exocytosed SV proteins. These data suggest that diffusion, and axonal escape of newly exocytosed vesicle proteins, are counteracted by the clathrin-based endocytic machinery together with a presynaptic diffusion barrier. PMID:26399746

  17. Diffusional spread and confinement of newly exocytosed synaptic vesicle proteins

    NASA Astrophysics Data System (ADS)

    Gimber, Niclas; Tadeus, Georgi; Maritzen, Tanja; Schmoranzer, Jan; Haucke, Volker

    2015-09-01

    Neurotransmission relies on the calcium-triggered exocytic fusion of non-peptide neurotransmitter-containing small synaptic vesicles (SVs) with the presynaptic membrane at active zones (AZs) followed by compensatory endocytic retrieval of SV membranes. Here, we study the diffusional fate of newly exocytosed SV proteins in hippocampal neurons by high-resolution time-lapse imaging. Newly exocytosed SV proteins rapidly disperse within the first seconds post fusion until confined within the presynaptic bouton. Rapid diffusional spread and confinement is followed by slow reclustering of SV proteins at the periactive endocytic zone. Confinement within the presynaptic bouton is mediated in part by SV protein association with the clathrin-based endocytic machinery to limit diffusional spread of newly exocytosed SV proteins. These data suggest that diffusion, and axonal escape of newly exocytosed vesicle proteins, are counteracted by the clathrin-based endocytic machinery together with a presynaptic diffusion barrier.

  18. Emergency Lighting

    NASA Technical Reports Server (NTRS)

    1977-01-01

    A lighting system originally developed for NASA's Apollo and Skylab manned spacecraft resulted in a industrial spinoff and creation of a whole new company to produce and market the product line. The company is UDEC Corp., Waltham, Mass. UDEC's "Multi-Mode" electronic lighting systems are designed for plant emergency and supplemental use, such as night lighting, "always-on" stairwell lights and illuminated exit signs. Their advantages stem from the qualities demanded for spacecraft installation: extremely high fight output with very low energy drain, compactness, light weight, and high reliability. The Multi-Mode system includes long-life fluorescent lamps operated by electronic circuitry, a sealed battery that needs no maintenance for 10 years, and a solid-state battery charger. A typical emergency installation consists of a master module with battery and an eight watt lamp, together with four remote "Satellight" modules powered by the master's battery. As a night lighting system for maintenance or I security, UDEC fixtures can bypass the battery and 1 operate on normal current at a fraction of the energy 1 demand of conventional night lighting. Industrial customers have realized savings of better than ninety percent with UDEC night lights. UDEC started as a basement industry in 1972 but the company has already sold more than 1,000 lighting systems to building operators.

  19. Direct visualization of identified and newly synthesized proteins in situ

    PubMed Central

    Dieck, Susanne tom; Kochen, Lisa; Hanus, Cyril; Bartnik, Ina; Nassim-Assir, Belquis; Merk, Katrin; Mosler, Thorsten; Garg, Sakshi; Bunse, Stefanie; Tirrell, David A.; Schuman, Erin M.

    2015-01-01

    Protein synthesis is a dynamic process to tune the cellular proteome to internal and external demands. Metabolic labeling approaches identify the general proteomic response but missing is a tool to visualize within cells specific newly synthesized proteins. Here we describe a technique that couples non-canonical amino acid tagging or puromycylation with the proximity-ligation assay to visualize identified newly synthesized proteins and monitor their origin, redistribution and turnover in situ. PMID:25775042

  20. Microfabricated therapeutic actuators

    SciTech Connect

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  1. Microfabricated therapeutic actuators

    DOEpatents

    Lee, A.P.; Northrup, M.A.; Ciarlo, D.R.; Krulevitch, P.A.; Benett, W.J.

    1999-06-15

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use. 8 figs.

  2. Aptamers in Therapeutics

    PubMed Central

    2016-01-01

    Aptamers are single strand DNA or RNA molecules, selected by an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to various advantages of aptamers such as high temperature stability, animal free, cost effective production and its high affinity and selectivity for its target make them attractive alternatives to monoclonal antibody for use in diagnostic and therapeutic purposes. Aptamer has been generated against vesicular endothelial growth factor 165 involved in age related macular degeneracy. Macugen was the first FDA approved aptamer based drug that was commercialized. Later other aptamers were also developed against blood clotting proteins, cancer proteins, antibody E, agents involved in diabetes nephropathy, autoantibodies involved in autoimmune disorders, etc. Aptamers have also been developed against viruses and could work with other antiviral agents in treating infections. PMID:27504277

  3. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  4. Homocystinuria: Therapeutic approach.

    PubMed

    Kumar, Tarun; Sharma, Gurumayum Suraj; Singh, Laishram Rajendrakumar

    2016-07-01

    Homocystinuria is a disorder of sulfur metabolism pathway caused by deficiency of cystathionine β-synthase (CBS). It is characterized by increased accumulation of homocysteine (Hcy) in the cells and plasma. Increased homocysteine results in various vascular and neurological complications. Present strategies to lower cellular and plasma homocysteine levels include vitamin B6 intake, dietary methionine restriction, betaine supplementation, folate and vitamin B12 administration. However, these strategies are inefficient for treatment of homocystinuria. In recent years, advances have been made towards developing new strategies to treat homocystinuria. These mainly include functional restoration to mutant CBS, enhanced clearance of Hcy from the body, prevention of N-homocysteinylation-induced toxicity and inhibition of homocysteine-induced oxidative stress. In this review, we have exclusively discussed the recent advances that have been achieved towards the treatment of homocystinuria. The review is an attempt to help clinicians in developing effective therapeutic strategies and designing novel drugs against homocystinuria. PMID:27059523

  5. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  6. Principles of therapeutics.

    PubMed

    Miller, T R

    1992-12-01

    Topical administration of drugs is the treatment of choice for diseases of the anterior segment. Drug levels attained by this means are usually of short duration, however, necessitating frequent therapy or continuous perfusion if prolonged drug levels are required. A drug-delivery device (collagen shield or contact lens) or subconjunctival injections can be used to augment topical therapy if frequent treatment is not possible. Subconjunctival injections are recommended for drugs that have low solubility and, hence, low corneal penetration. Retrobulbar injections are seldom indicated, except for regional anesthesia. Systemic administration is useful for anti-inflammatory therapy but it may be difficult to establish therapeutic levels of antibiotic agents in the eye because of the blood-ocular barrier. In severe cases, intraocular injection may be required. PMID:1458325

  7. Antioxidant therapeutics: Pandora's box.

    PubMed

    Day, Brian J

    2014-01-01

    Evolution has favored the utilization of dioxygen (O2) in the development of complex multicellular organisms. O2 is actually a toxic mutagenic gas that is highly oxidizing and combustible. It is thought that plants are largely to blame for polluting the earth's atmosphere with O2 owing to the development of photosynthesis by blue-green algae over 2 billion years ago. The rise of the plants and atmospheric O2 levels placed evolutionary stress on organisms to adapt or become extinct. This implies that all the surviving creatures on our planet are mutants that have adapted to the "abnormal biology" of O2. Much of the adaptation to the presence of O2 in biological systems comes from well-coordinated antioxidant and repair systems that focus on converting O2 to its most reduced form, water (H2O), and the repair and replacement of damaged cellular macromolecules. Biological systems have also harnessed O2's reactive properties for energy production, xenobiotic metabolism, and host defense and as a signaling messenger and redox modulator of a number of cell signaling pathways. Many of these systems involve electron transport systems and offer many different mechanisms by which antioxidant therapeutics can alternatively produce an antioxidant effect without directly scavenging oxygen-derived reactive species. It is likely that each agent will have a different set of mechanisms that may change depending on the model of oxidative stress, organ system, or disease state. An important point is that all biological processes of aerobes have coevolved with O2 and this creates a Pandora's box for trying to understand the mechanism(s) of action of antioxidants being developed as therapeutic agents. PMID:23856377

  8. GTI-2040. Lorus Therapeutics.

    PubMed

    Orr, R M

    2001-10-01

    Loris Therapeutics (formerly GeneSense Therapeutics) is developing the antisense oligonucleotide GTI-2040, directed against the R2 component of ribonucleotide reductase, for the potential treatment of cancer [348194]. It is in phase I/II trials [353796] and Lorus had anticipated phase II trials would be initiated in July 2001. By August 2001, GTI-2040 was undergoing a phase II trial as a monotherapy for the potential treatment of renal cell carcinoma, and was about to enter a phase II combination study for this indication with capecitabine (Hoffmann-La Roche). At this time, the company was also planning a phase II trial to study the drug's potential in the treatment of colorectal cancer [418739]. GTI-2040 has been tested in nine different tumor models, including tumors derived from colon, liver, lung, breast, kidney and ovary. Depending on the tumor model, significant inhibition of tumor growth, disease stabilization and dramatic tumor regressions was observed [347683]. Lorus filed an IND to commence phase I/II trials with GTI-2040 in the US in November 1999 [347683], and received approval for the trials in December 1999 [349623]. As of January 2000, these trials had commenced at the University of Chicago Cancer Research Center; it was reported in February 2000 that dosing to date had been well tolerated with no apparent safety concerns [357449]. Lorus has entered into a strategic supply alliance with Proligo to provide the higher volumes of drug product required for the planned multiple phase II trials [385976]. In February 1998, Genesense (now Lorus) received patent WO-09805769. Loris also received a patent (subsequently identified as WO-00047733) from the USPTO in January 2000, entitled 'Antitumor antisense sequences directed against components of ribonucleotide reductase' covering the design and use of unique antisense anticancer drugs, including GTI-2040 and GTI-2501 [353538]. PMID:11890366

  9. Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects

    PubMed Central

    Braun, Gerald S; Horster, Sophia; Wagner, Katrin S; Ihrler, Stephan; Schmid, Holger

    2007-01-01

    Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis. PMID:17308210

  10. Emerging and Re-Emerging Zoonoses of Dogs and Cats

    PubMed Central

    Chomel, Bruno B.

    2014-01-01

    Simple Summary Dogs and cats have been sharing our environment for a long time and as pets they bring major psychological well-being to our modern urbanized society. However, they still can be a source of human infection by various pathogens, including viruses, bacteria, parasites, and fungi. Abstract Since the middle of the 20th century, pets are more frequently considered as “family members” within households. However, cats and dogs still can be a source of human infection by various zoonotic pathogens. Among emerging or re-emerging zoonoses, viral diseases, such as rabies (mainly from dog pet trade or travel abroad), but also feline cowpox and newly recognized noroviruses or rotaviruses or influenza viruses can sicken our pets and be transmitted to humans. Bacterial zoonoses include bacteria transmitted by bites or scratches, such as pasteurellosis or cat scratch disease, leading to severe clinical manifestations in people because of their age or immune status and also because of our closeness, not to say intimacy, with our pets. Cutaneous contamination with methicillin-resistant Staphylococcus aureus, Leptospira spp., and/or aerosolization of bacteria causing tuberculosis or kennel cough are also emerging/re-emerging pathogens that can be transmitted by our pets, as well as gastro-intestinal pathogens such as Salmonella or Campylobacter. Parasitic and fungal pathogens, such as echinococcosis, leishmaniasis, onchocercosis, or sporotrichosis, are also re-emerging or emerging pet related zoonoses. Common sense and good personal and pet hygiene are the key elements to prevent such a risk of zoonotic infection. PMID:26480316

  11. Active Region Emergence and Remote Flares

    NASA Astrophysics Data System (ADS)

    Fu, Yixing; Welsch, Brian T.

    2016-02-01

    We study the effect of new emerging solar active regions on the large-scale magnetic environment of existing regions. We first present a theoretical approach to quantify the "interaction energy" between new and pre-existing regions as the difference between i) the summed magnetic energies of their individual potential fields and ii) the energy of their superposed potential fields. We expect that this interaction energy can, depending upon the relative arrangements of newly emerged and pre-existing magnetic flux, indicate the existence of "topological" free magnetic energy in the global coronal field that is independent of any "internal" free magnetic energy due to coronal electric currents flowing within the newly emerged and pre-existing flux systems. We then examine the interaction energy in two well-studied cases of flux emergence, but find that the predicted energetic perturbation is relatively small compared to energies released in large solar flares. Next, we present an observational study of the influence of the emergence of new active regions on flare statistics in pre-existing active regions, using NOAA's Solar Region Summary and GOES flare databases. As part of an effort to precisely determine the emergence time of active regions in a large event sample, we find that emergence in about half of these regions exhibits a two-stage behavior, with an initial gradual phase followed by a more rapid phase. Regarding flaring, we find that the emergence of new regions is associated with a significant increase in the occurrence rate of X- and M-class flares in pre-existing regions. This effect tends to be more significant when pre-existing and new emerging active regions are closer. Given the relative weakness of the interaction energy, this effect suggests that perturbations in the large-scale magnetic field, such as topology changes invoked in the "breakout" model of coronal mass ejections, might play a significant role in the occurrence of some flares.

  12. Emergent spin

    SciTech Connect

    Creutz, Michael

    2014-03-15

    Quantum mechanics and relativity in the continuum imply the well known spin–statistics connection. However for particles hopping on a lattice, there is no such constraint. If a lattice model yields a relativistic field theory in a continuum limit, this constraint must “emerge” for physical excitations. We discuss a few models where a spin-less fermion hopping on a lattice gives excitations which satisfy the continuum Dirac equation. This includes such well known systems such as graphene and staggered fermions. -- Highlights: •The spin–statistics theorem is not required for particles on a lattice. •Spin emerges dynamically when spinless fermions have a relativistic continuum limit. •Graphene and staggered fermions are examples of this phenomenon. •The phenomenon is intimately tied to chiral symmetry and fermion doubling. •Anomaly cancellation is a crucial feature of any valid lattice fermion action.

  13. [When should the nephrologist be called in the emergency room?].

    PubMed

    Favre, Nathalie; Burnier, Michel; Kissling, Sébastien

    2016-02-24

    Nephrology emergencies are not the most frequent in the emergency room but they often generate some diagnostic and therapeutic problems. Most common renal emergencies are due most often to acute renal failure whatever the cause, electrolytes disturbances, hypertensive crisis and less frequently intoxications or acute decompensation of chronic kidney diseases. The goal of this paper is to review some of these clinical situations both in the diagnostic and therapeutic perspective but essentially to discuss when the nephrologist should be called in the emergency room so that the coordination of care is optimal for the patients. PMID:27039605

  14. Disruption of Helmet Streamers by Current Emergence

    NASA Technical Reports Server (NTRS)

    Guo, W. P.; Wu, S. T.; Tandberg-Hanssen, E.

    1996-01-01

    We have investigated the dynamic response of a coronal helmet streamer to the emergence from below of a current with its magnetic field in a direction opposite to the overlying streamer field. Once the emerging current moves into the closed region of the streamer, a current sheet forms between the emerging field and the streamer field, because the preexisting field and the newly emerging field have opposite polarities. Thus magnetic reconnection will occur at the flanks of the emerged structure where the current density is maximum. If the emerging current is large enough, the energy contained in the current and the reconnection will promptly disrupt the streamer. If the emerging current is small, the streamer will experience a stage of slow evolution. In this stage, slow magnetic reconnection occurring at the flanks of the emerged structure leads to the degeneration of the emerged current to a neutral point. Above this point, a new magnetic bubble will form. The resulting configuration resembles an inverse-polarity prominence. Depending on the initial input energy of the current, the resulting structure will either remain in situ, forming a quasi-static structure, or move upward, forming a coronal transient similar to coronal jets. The numerical method used in this paper can be used to construct helmet streamers containing a detached magnetic structure in their closed field region. The quasi-static solution may serve as a preevent corona for studying coronal mass ejection initiation.

  15. Cancer Stem Cell Plasticity Drives Therapeutic Resistance

    PubMed Central

    Doherty, Mary R.; Smigiel, Jacob M.; Junk, Damian J.; Jackson, Mark W.

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  16. Cancer Stem Cell Plasticity Drives Therapeutic Resistance.

    PubMed

    Doherty, Mary R; Smigiel, Jacob M; Junk, Damian J; Jackson, Mark W

    2016-01-01

    The connection between epithelial-mesenchymal (E-M) plasticity and cancer stem cell (CSC) properties has been paradigm-shifting, linking tumor cell invasion and metastasis with therapeutic recurrence. However, despite their importance, the molecular pathways involved in generating invasive, metastatic, and therapy-resistant CSCs remain poorly understood. The enrichment of cells with a mesenchymal/CSC phenotype following therapy has been interpreted in two different ways. The original interpretation posited that therapy kills non-CSCs while sparing pre-existing CSCs. However, evidence is emerging that suggests non-CSCs can be induced into a transient, drug-tolerant, CSC-like state by chemotherapy. The ability to transition between distinct cell states may be as critical for the survival of tumor cells following therapy as it is for metastatic progression. Therefore, inhibition of the pathways that promote E-M and CSC plasticity may suppress tumor recurrence following chemotherapy. Here, we review the emerging appreciation for how plasticity confers therapeutic resistance and tumor recurrence. PMID:26742077

  17. Emerging Tools for Synthetic Genome Design

    PubMed Central

    Lee, Bo-Rahm; Cho, Suhyung; Song, Yoseb; Kim, Sun Chang; Cho, Byung-Kwan

    2013-01-01

    Synthetic biology is an emerging discipline for designing and synthesizing predictable, measurable, controllable, and transformable biological systems. These newly designed biological systems have great potential for the development of cheaper drugs, green fuels, biodegradable plastics, and targeted cancer therapies over the coming years. Fortunately, our ability to quickly and accurately engineer biological systems that behave predictably has been dramatically expanded by significant advances in DNA-sequencing, DNA-synthesis, and DNA-editing technologies. Here, we review emerging technologies and methodologies in the field of building designed biological systems, and we discuss their future perspectives. PMID:23708771

  18. Strategies for the discovery of therapeutic Aptamers

    PubMed Central

    Yang, Xianbin; Li, Na; Gorenstein, David G.

    2010-01-01

    Importance of the field Therapeutic aptamers are synthetic, structured oligonucleotides that bind to a very broad range of targets with high affinity and specificity. They are an emerging class of targeting ligand that show great promise for treating a number of diseases. A series of aptamers currently in various stages of clinical development highlights the potential of aptamers for therapeutic applications. Area covered in this review This review will cover in vitro selection of oligonucleotide ligands, called aptamers, from a combinatorial library using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process as well as the other known strategies for finding aptamers against various targets. What the reader will gain Readers will gain an understanding of the highly useful strategies for successful aptamer discovery. They may also be able combine two or more of the presented strategies for their aptamer discovery projects. Take home message Although many processes are available for discovering aptamers, it is not trivial to discover an aptamer candidate that is ready to move toward pharmaceutical drug development. It is also apparent that there have been relatively few therapeutic advances and clinical trials undertaken due to the small number of companies that participate in aptamer development. PMID:21359096

  19. Comparison of newly developed anti-bone morphogenetic protein 4 llama-derived antibodies with commercially available BMP4 inhibitors

    PubMed Central

    Calpe, Silvia; Correia, Ana C. P.; Sancho-Serra, Maria del Carmen; Krishnadath, Kausilia K.

    2016-01-01

    ABSTRACT Due to improved understanding of the role of bone morphogenetic protein 4 (BMP4) in an increasing number of diseases, the development of selective inhibitors of BMP4 is an attractive therapeutic option. The currently available BMP4 inhibitors are not suitable as therapeutics because of their low specificity and low effectiveness. Here, we compared newly generated anti-BMP4 llama-derived antibodies (VHHs) with 3 different types of commercially available BMP4 inhibitors, natural antagonists, small molecule BMPR inhibitors and conventional anti-BMP4 monoclonal antibodies. We found that the anti-BMP4 VHHs were as effective as the natural antagonist or small molecule inhibitors, but had higher specificity. We also showed that commercial anti-BMP4 antibodies were inferior in terms of both specificity and effectiveness. These findings might result from the fact that the VHHs C4C4 and C8C8 target a small region within the BMPR1 epitope of BMP4, whereas the commercial antibodies target other areas of the BMP4 molecule. Our results show that the newly developed anti-BMP4 VHHs are promising antibodies with better specificity and effectivity for inhibition of BMP4, making them an attractive tool for research and for therapeutic applications. PMID:26967714

  20. Psychiatric emergencies.

    PubMed

    Cavanaugh, S V

    1986-09-01

    Psychiatric disorders are common in medical inpatient and outpatient populations. As a result, internists commonly are the first to see psychiatric emergencies. As with all medical problems, a good history, including a collateral history from relatives and friends, physical and mental status examination, and appropriate laboratory tests help establish a preliminary diagnosis and treatment plan. Patients with suicidal ideation usually have multiple stressors in the environment and/or a psychiatric disorder (i.e., a major affective disorder, dysthymic disorder, anxiety or panic disorder, psychotic disorder, alcohol or drug abuse, a personality disorder, and/or an adjustment disorder). Of all patients who commit suicide, 70% have a major depressive disorder, schizophrenia, psychotic organic mental disorder, alcoholism, drug abuse, and borderline personality disorder. Patients who are at great risk have minimal supports, a history of previous suicide attempts, a plan with high lethality, hopelessness, psychosis, paranoia, and/or command self-destructive hallucinations. Treatment is directed toward placing the patient in a protected environment and providing psychotropic medication and/or psychotherapy for the underlying psychiatric problem. Other psychiatric emergencies include psychotic and violent patients. Psychotic disorders fall into two categories etiologically: those that have an identifiable organic factor causing the psychosis and those that have an underlying psychiatric disorder. Initially, it is essential to rule out organic pathology that is life-threatening or could cause irreversible brain damage. After such organic causes are ruled out, neuroleptic medication is indicated. If the patient is not agitated or combative, he or she may be placed on oral divided doses of neuroleptics in the antipsychotic range. Patients who are agitated or psychotic need rapid tranquilization with an intramuscular neuroleptic every half hour to 1 hour until the agitation and

  1. Emerging infections of the central nervous system.

    PubMed

    Lyons, Jennifer; McArthur, Justin

    2013-12-01

    Emerging infections affecting the central nervous system often present as encephalitis and can cause substantial morbidity and mortality. Diagnosis requires not only careful history taking, but also the application of newly developed diagnostic tests. These diseases frequently occur in outbreaks stemming from viruses that have mutated from an animal host and gained the ability to infect humans. With globalization, this can translate to the rapid emergence of infectious clusters or the establishment of endemicity in previously naïve locations. Since these infections are often vector borne and effective treatments are almost uniformly lacking, prevention is at least as important as prompt diagnosis and institution of supportive care. In this review, we focus on some of the recent literature addressing emerging and resurging viral encephalitides in the United States and around the world-specifically, West Nile virus, dengue, polio, and cycloviruses. We also discuss new, or "emerging," techniques for the precise and rapid diagnosis of encephalitides. PMID:24136412

  2. Factors and determinants of disease emergence.

    PubMed

    Morse, S S

    2004-08-01

    Emerging infectious diseases can be defined as infections that have newly appeared in a population or are rapidly increasing in incidence or geographic range. Many of these diseases are zoonoses, including such recent examples as avian influenza, severe acute respiratory syndrome, haemolytic uraemic syndrome (a food-borne infection caused by certain strains of Escherichia coli) and probably human immunodeficiency virus/acquired immune deficiency syndrome. Specific factors precipitating the emergence of a disease can often be identified. These include ecological, environmental or demographic factors that place people in increased contact with the natural host for a previously unfamiliar zoonotic agent or that promote the spread of the pathogen. These factors are becoming increasingly prevalent, suggesting that infections will continue to emerge and probably increase. Strategies for dealing with the problem include focusing special attention on situations that promote disease emergence, especially those in which animals and humans come into contact, and implementing effective disease surveillance and control. PMID:15702712

  3. Protein Engineering: A New Frontier for Biological Therapeutics

    PubMed Central

    Tobin, Peter H.; Richards, David H.; Callender, Randolph A.

    2016-01-01

    Protein engineering holds the potential to transform the metabolic drug landscape through the development of smart, stimulus-responsive drug systems. Protein therapeutics are a rapidly expanding segment of Food and Drug Administration approved drugs that will improve clinical outcomes over the long run. Engineering of protein therapeutics is still in its infancy, but recent general advances in protein engineering capabilities are being leveraged to yield improved control over both pharmacokinetics and pharmacodynamics. Stimulus-responsive protein therapeutics are drugs which have been designed to be metabolized under targeted conditions. Protein engineering is being utilized to develop tailored smart therapeutics with biochemical logic. This review focuses on applications of targeted drug neutralization, stimulus-responsive engineered protein prodrugs, and emerging multicomponent smart drug systems (e.g., antibody-drug conjugates, responsive engineered zymogens, prospective biochemical logic smart drug systems, drug buffers, and network medicine applications). PMID:25495737

  4. Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions

    PubMed Central

    Breakefield, Xandra O.; Leonard, Joshua N.

    2015-01-01

    This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury. PMID:25292428

  5. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed. PMID:23097262

  6. Therapeutic applications of extracellular vesicles: clinical promise and open questions.

    PubMed

    György, Bence; Hung, Michelle E; Breakefield, Xandra O; Leonard, Joshua N

    2015-01-01

    This review provides an updated perspective on rapidly proliferating efforts to harness extracellular vesicles (EVs) for therapeutic applications. We summarize current knowledge, emerging strategies, and open questions pertaining to clinical potential and translation. Potentially useful EVs comprise diverse products of various cell types and species. EV components may also be combined with liposomes and nanoparticles to facilitate manufacturing as well as product safety and evaluation. Potential therapeutic cargoes include RNA, proteins, and drugs. Strategic issues considered herein include choice of therapeutic agent, means of loading cargoes into EVs, promotion of EV stability, tissue targeting, and functional delivery of cargo to recipient cells. Some applications may harness natural EV properties, such as immune modulation, regeneration promotion, and pathogen suppression. These properties can be enhanced or customized to enable a wide range of therapeutic applications, including vaccination, improvement of pregnancy outcome, and treatment of autoimmune disease, cancer, and tissue injury. PMID:25292428

  7. High Expression of the Newly Found Long Noncoding RNA Z38 Promotes Cell Proliferation and Oncogenic Activity in Breast Cancer

    PubMed Central

    Deng, Rilin; Liu, Bin; Wang, Yan; Yan, Feng; Hu, Shifan; Wang, Hongcan; Wang, Tingting; Li, Bin; Deng, Xiyun; Xiang, Shuanglin; Yang, Yinke; Zhang, Jian

    2016-01-01

    The aberrant expression of long noncoding RNAs (lncRNAs) has great impacts on cancer origination and progression. In the current study, a newly found lncRNA Z38, which was identified through combining experiments of suppression subtractive hybridization (SSH) and reverse dot-blotting, was found to have high expression in breast cancer. More importantly, inhibiting Z38 expression by gene silencing greatly suppressed breast cancer cell proliferation and tumorigenesis, and treatment with Z38 siRNAs significantly induced cell apoptosis and inhibited tumor growth. In conclusion, the newly found lncRNA Z38, which plays important roles in breast cancer, may act as a candidate biomarker and therapeutic target in carcinomas. PMID:27053956

  8. High Expression of the Newly Found Long Noncoding RNA Z38 Promotes Cell Proliferation and Oncogenic Activity in Breast Cancer.

    PubMed

    Deng, Rilin; Liu, Bin; Wang, Yan; Yan, Feng; Hu, Shifan; Wang, Hongcan; Wang, Tingting; Li, Bin; Deng, Xiyun; Xiang, Shuanglin; Yang, Yinke; Zhang, Jian

    2016-01-01

    The aberrant expression of long noncoding RNAs (lncRNAs) has great impacts on cancer origination and progression. In the current study, a newly found lncRNA Z38, which was identified through combining experiments of suppression subtractive hybridization (SSH) and reverse dot-blotting, was found to have high expression in breast cancer. More importantly, inhibiting Z38 expression by gene silencing greatly suppressed breast cancer cell proliferation and tumorigenesis, and treatment with Z38 siRNAs significantly induced cell apoptosis and inhibited tumor growth. In conclusion, the newly found lncRNA Z38, which plays important roles in breast cancer, may act as a candidate biomarker and therapeutic target in carcinomas. PMID:27053956

  9. Clinical applications of therapeutic phlebotomy

    PubMed Central

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  10. Therapeutic proteins: A to Z.

    PubMed

    Ozgur, Aykut; Tutar, Yusuf

    2013-12-01

    In recent years, therapeutic proteins have become an important growing class of drugs in the pharmaceutics industry. The development of recombinant DNA technology has caused to appreciation of therapeutic value of many proteins and peptides in medicine. Currently, approximately 100 therapeutic proteins obtained approval from Food and Drug Administration (FDA) and they are widely used in the treatment of various diseases such as cancer, diabetes, anemia and infections. This paper will summarize the production processes, pharmaceuticals and physicochemical properties and important classes of therapeutic proteins with their potential use in clinical applications. PMID:24261980

  11. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  12. Emerging technologies

    SciTech Connect

    Hodson, C.O.; Williams, D.

    1996-07-01

    Among the emerging technologies for air, hazardous waste and water come new ways of looking at pollution, in both the figurative and quite literal sense. The use of microbes for remediation and pollution control is a component in many of the technologies in this report and is the focus of environmental research at many university and industry labs. Bacteria are the engines driving one featured emissions control technology: the air biofilter. Biofilters are probably more acceptable to most engineers as a soil remediation technology--such as the innovative method described in the hazardous waste section--rather than as means of cleaning off-gases, but in many cases bugs can perform the function inexpensively. The authors give the basics on this available technology. A more experimental application of microbes is being investigated as a potential quantum leap in heavy metals removal technology: bio-engineered, metal consuming plants. The effort to genetically engineer a green remediation tool is detailed in the hazardous waste section.

  13. Emerging technologies

    SciTech Connect

    Lu, Shin-yee

    1993-03-01

    The mission of the Emerging Technologies thrust area at Lawrence Livermore National Laboratory is to help individuals establish technology areas that have national and commercial impact, and are outside the scope of the existing thrust areas. We continue to encourage innovative ideas that bring quality results to existing programs. We also take as our mission the encouragement of investment in new technology areas that are important to the economic competitiveness of this nation. In fiscal year 1992, we have focused on nine projects, summarized in this report: (1) Tire, Accident, Handling, and Roadway Safety; (2) EXTRANSYT: An Expert System for Advanced Traffic Management; (3) Odin: A High-Power, Underwater, Acoustic Transmitter for Surveillance Applications; (4) Passive Seismic Reservoir Monitoring: Signal Processing Innovations; (5) Paste Extrudable Explosive Aft Charge for Multi-Stage Munitions; (6) A Continuum Model for Reinforced Concrete at High Pressures and Strain Rates: Interim Report; (7) Benchmarking of the Criticality Evaluation Code COG; (8) Fast Algorithm for Large-Scale Consensus DNA Sequence Assembly; and (9) Using Electrical Heating to Enhance the Extraction of Volatile Organic Compounds from Soil.

  14. [Hypercholesterolemia: a therapeutic approach].

    PubMed

    Moráis López, A; Lama More, R A; Dalmau Serra, J

    2009-05-01

    High blood cholesterol levels represent an important cardiovascular risk factor. Hypercholesterolemia is defined as levels of total cholesterol and low-density lipoprotein cholesterol above 95th percentile for age and gender. For the paediatric population, selective screening is recommended in children older than 2 years who are overweight, with a family history of early cardiovascular disease or whose parents have high cholesterol levels. Initial therapeutic approach includes diet therapy, appropriate physical activity and healthy lifestyle changes. Drug treatment should be considered in children from the age of 10 who, after having followed appropriate diet recommendations, still have very high LDL-cholesterol levels or moderately high levels with concomitant risk factors. In case of extremely high LDL-cholesterol levels, drug treatment should be taken into consideration at earlier ages (8 years old). Modest response is usually observed with bile acid-binding resins. Statins can be considered first-choice drugs, once evidence on their efficacy and safety has been shown. PMID:19427823

  15. [Liver metastasis: therapeutic strategy].

    PubMed

    Gennari, L; Doci, R; Bignami, P

    1996-01-01

    The liver is one of the most frequent sites of metastatic growth, in particular from digestive malignancies (DM). The first goal is to reduce the incidence of metastases. Adjuvant systemic chemotherapies have been demonstrated to reduce the recurrence rate and to improve survival in Dukes C colon cancer. Fluorouracil is the pivot of adjuvant treatment modulated by Leucovorin or Levamisol. A short postoperative administration of fluorouracil by intraportal route has been tested, but the results are controversial. Adjuvant treatments for different DM are under investigation. When hepatic metastases are clinically evident, therapeutic decisions depend on several factors: site and nature of primary, extent of hepatic and extrahepatic disease, patient characteristics, efficacy of treatments. A staging system should be adopted to allow a rational approach. In selected cases a locoregional treatment can achieve consistent results. Hepatic Intrarterial Chemotherapy (HIAC) for colorectal metastases achieves objective responses in more than 50% of patients. Survival seems positively affected. When feasible, Ro hepatic resection is the most effective treatment, five-year survival rate being about 30% when metastases are from colorectal cancer. Since the liver is the most frequent site of recurrence after resection, repeat resection have been successfully performed. PMID:9214269

  16. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  17. Leech Therapeutic Applications

    PubMed Central

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  18. Therapeutic Cancer Vaccines.

    PubMed

    Ye, Zhenlong; Li, Zhong; Jin, Huajun; Qian, Qijun

    2016-01-01

    Cancer is one of the major leading death causes of diseases. Prevention and treatment of cancer is an important way to decrease the incidence of tumorigenesis and prolong patients' lives. Subversive achievements on cancer immunotherapy have recently been paid much attention after many failures in basic and clinical researches. Based on deep analysis of genomics and proteomics of tumor antigens, a variety of cancer vaccines targeting tumor antigens have been tested in preclinical and human clinical trials. Many therapeutic cancer vaccines alone or combination with other conventional treatments for cancer obtained spectacular efficacy, indicating the tremendously potential application in clinic. With the illustration of underlying mechanisms of cancer immune regulation, valid, controllable, and persistent cancer vaccines will play important roles in cancer treatment, survival extension and relapse and cancer prevention. This chapter mainly summarizes the recent progresses and developments on cancer vaccine research and clinical application, thus exploring the existing obstacles in cancer vaccine research and promoting the efficacy of cancer vaccine. PMID:27240458

  19. Experimental Therapeutics for Dystonia

    PubMed Central

    Jinnah, H. A.; Hess, Ellen J.

    2008-01-01

    Dystonia is a neurological syndrome characterized by excessive involuntary muscle contractions leading to twisting movements and unnatural postures. It has many different clinical manifestations, and many different causes. More than 3 million people worldwide suffer from dystonia, yet there are few broadly effective treatments. In the past decade, progress in research has advanced our understanding of the pathogenesis of dystonia to a point where drug discovery efforts are now feasible. There are several strategies that can be used to develop novel therapeutics for dystonia. Existing therapies have only modest efficacy, but may be refined and improved to increase benefits while reducing side effects. Identifying rational targets for drug intervention based on the pathogenesis of dystonia is another strategy. The surge in both basic and clinical research discoveries has provided insights at all levels including etiological, physiological and nosological, to enable such a targeted approach. The empirical approach to drug discovery is complementary to the rational approach whereby compounds are identified using a non-mechanistic strategy. [MD1] With the recent development of multiple animal models of dystonia, it is now possible to develop assays and perform drug screens on vast number of compounds. This multifaceted approach to drug discovery in dystonia will likely provide lead compounds that can then be translated for clinical use. PMID:18394563

  20. Therapeutic approaches for shankopathies.

    PubMed

    Wang, Xiaoming; Bey, Alexandra L; Chung, Leeyup; Krystal, Andrew D; Jiang, Yong-Hui

    2014-02-01

    Despite recent advances in understanding the molecular mechanisms of autism spectrum disorders (ASD), the current treatments for these disorders are mostly focused on behavioral and educational approaches. The considerable clinical and molecular heterogeneity of ASD present a significant challenge to the development of an effective treatment targeting underlying molecular defects. Deficiency of SHANK family genes causing ASD represent an exciting opportunity for developing molecular therapies because of strong genetic evidence for SHANK as causative genes in ASD and the availability of a panel of Shank mutant mouse models. In this article, we review the literature suggesting the potential for developing therapies based on molecular characteristics and discuss several exciting themes that are emerging from studying Shank mutant mice at the molecular level and in terms of synaptic function. PMID:23536326

  1. Emergency uroradiology for the nontraumatized patient.

    PubMed

    Elink, M

    1978-04-01

    Emergency uroradiology is warranted in a number of clinical conditions in the nontraumatized patient in order to determine proper therapeutic management. Among such urgent conditions are: severe gross hematuria, severe internal blood loss with possible origin in the urinary tract, acute renal artery obstruction, major extravasation of urine, severe sepsis possibly from the urinary tract, anuria, and obstructive uropathy with superimposed infection. PMID:684204

  2. Secukinumab: a promising therapeutic option in spondyloarthritis.

    PubMed

    Maldonado-Ficco, Hernan; Perez-Alamino, Rodolfo; Maldonado-Cocco, José A

    2016-09-01

    Psoriatic arthritis (PsA) is the second most common chronic inflammatory joint disease. Ankylosing spondylitis (AS) is another less common but equally chronic and disabling spondyloarthritis (SpA). Therapeutic agents for the treatment of these diseases have been somewhat lacking as compared with those available for rheumatoid arthritis, which represents a significant challenge for both the treating physician and the pharmaceutical industry. A promising development for our understanding of the physiopathology of PsA and AS involves new targets to interrupt IL-17 and IL-12/IL-23 pathways. Up to 30-40 % of SpA patients have inadequate or poor response, or are intolerant to anti-TNF therapies. Therefore, there has been a clear unmet medical need in an important group of these patients. As a result, new therapeutic targets have emerged for the treatment of both axial and peripheral SpA. Interleukin 17 (IL-17) is a pro-inflammatory cytokine that is increased in psoriatic lesions as well as in the synovial fluid of patients with PsA and in sites of enthesitis in SpA. IL-23 has been shown to play an important role in the polarization of CD4+ T-cells to become IL-17 producers. Based on these evidences, blockade of the cytokine IL-17 or its receptors was considered to have therapeutic implications for the treatment of psoriasis, as well as PsA and AS.This article presents a thorough review of an IL-17 A blocking agent, its mechanism of action, its clinical efficacy and its therapeutic safety. PMID:27437696

  3. Using spatiotemporal models and distance sampling to map the space use and abundance of newly metamorphosed Western Toads (Anaxyrus boreas)

    USGS Publications Warehouse

    Chelgren, Nathan D.; Samora, Barbara; Adams, Michael J.; McCreary, Brome

    2011-01-01

    High variability in abundance, cryptic coloration, and small body size of newly metamorphosed anurans have limited demographic studies of this life-history stage. We used line-transect distance sampling and Bayesian methods to estimate the abundance and spatial distribution of newly metamorphosed Western Toads (Anaxyrus boreas) in terrestrial habitat surrounding a montane lake in central Washington, USA. We completed 154 line-transect surveys from the commencement of metamorphosis (15 September 2009) to the date of first snow accumulation in fall (1 October 2009), and located 543 newly metamorphosed toads. After accounting for variable detection probability associated with the extent of barren habitats, estimates of total surface abundance ranged from a posterior median of 3,880 (95% credible intervals from 2,235 to 12,600) in the first week of sampling to 12,150 (5,543 to 51,670) during the second week of sampling. Numbers of newly metamorphosed toads dropped quickly with increasing distance from the lakeshore in a pattern that differed over the three weeks of the study and contradicted our original hypotheses. Though we hypothesized that the spatial distribution of toads would initially be concentrated near the lake shore and then spread outward from the lake over time, we observed the opposite. Ninety-five percent of individuals occurred within 20, 16, and 15 m of shore during weeks one, two, and three respectively, probably reflecting continued emergence of newly metamorphosed toads from the lake and mortality or burrow use of dispersed individuals. Numbers of toads were highest near the inlet stream of the lake. Distance sampling may provide a useful method for estimating the surface abundance of newly metamorphosed toads and relating their space use to landscape variables despite uncertain and variable probability of detection. We discuss means of improving the precision of estimates of total abundance.

  4. Making Meaning Together: An Exploratory Study of Therapeutic Conversation between Helping Professionals and Homeless Shelter Residents

    ERIC Educational Resources Information Center

    Walsh, Christine A.; Rutherford, Gayle E.; Sarafincian, Kristina N.; Sellmer, Sabine E. R.

    2010-01-01

    This exploratory study examined the nature of therapeutic conversation between helping professionals and homeless persons as an intervention to optimize health. Meaningful conversation occurred in relationships where there was a sense of connection and the presence of rapport. Emergent facilitators of therapeutic conversation included respectful…

  5. Emergency Contraception.

    PubMed

    Batur, Pelin; Kransdorf, Lisa N; Casey, Petra M

    2016-06-01

    Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner. PMID:27261868

  6. Emergency contraception

    PubMed Central

    Langille, Donald B.; Allen, Michael; Whelan, Anne Marie

    2012-01-01

    Abstract Objective To determine the extent to which Nova Scotian FPs prescribe and provide emergency contraceptive pills (ECPs) and to explore their knowledge of and attitudes toward ECPs. Design Survey of Nova Scotian FPs using a modified Dillman method. Setting All regions of Nova Scotia. Participants Family physicians registered with Dalhousie University’s Division of Continuing Medical Education. Main outcome measures Sex differences in the provision of ECPs and knowledge and attitudes about the ECP Plan B. Results Of 913 eligible FPs, 155 (17.0%) participated in the survey. Respondents resembled the sampling frame closely. Most physicians (64.0%) had prescribed ECPs in the previous year (mean number of prescriptions, 4.92); only 12.9% provided ECPs in advance of need. Knowledge about Plan B was quite good, except for knowledge of the time frame for potential effectiveness; only 29.2% of respondents answered that question correctly. Respondents generally supported nonprescription availability of ECPs, but 25.0% of FPs were concerned that this could lead to less use of more effective methods of contraception, and 39.2% believed that it would encourage repeat use. Younger FPs provided ECPs more often than their older colleagues, while female respondents had better knowledge about Plan B. In multivariate analysis being younger than 40 years was marginally associated with prescribing Plan B and with prescribing any form of ECP. Conclusion Most Nova Scotian FPs provided ECPs and had generally good knowledge about and attitudes toward providing such contraception without prescription. However, FPs were poorly informed about the length of time that Plan B can be effective, which could potentially affect use when patients consult several days after unprotected sex. There were some concerns about nonprescription availability of ECPs, which could have implications for recommending it to patients. Rarely were ECPs prescribed for advance use, which might represent a lost

  7. Advances in the treatment of newly diagnosed glioblastoma.

    PubMed

    Theeler, Brett J; Gilbert, Mark R

    2015-01-01

    Glioblastoma is a refractory malignancy with limited treatment options at tumor recurrence. Only a small proportion of patients survive 2 years or longer with the current standard of care. Gene expression profiling can segregate newly diagnosed patients into groups with different prognoses, and these biomarkers are being incorporated into a new generation of personalized clinical trials. Using the experience from recently completed large scale, multi-faceted, randomized glioblastoma clinical trials, a new clinical trial paradigm is being established to move promising therapies forward into the newly diagnosed treatment setting. Upcoming trials using the immune check-point inhibitors are an example of this changing paradigm and these and other immunotherapies have potential as promising new treatment modalities for newly diagnosed GB patients. PMID:26646075

  8. Targeting Transmission Pathways for Emerging Zoonotic Disease Surveillance and Control.

    PubMed

    Loh, Elizabeth H; Zambrana-Torrelio, Carlos; Olival, Kevin J; Bogich, Tiffany L; Johnson, Christine K; Mazet, Jonna A K; Karesh, William; Daszak, Peter

    2015-07-01

    We used literature searches and a database of all reported emerging infectious diseases (EIDs) to analyze the most important transmission pathways (e.g., vector-borne, aerosol droplet transmitted) for emerging zoonoses. Our results suggest that at the broad scale, the likelihood of transmission occurring through any one pathway is approximately equal. However, the major transmission pathways for zoonoses differ widely according to the specific underlying drivers of EID events (e.g., land-use change, agricultural intensification). These results can be used to develop better targeting of surveillance for, and more effective control of newly emerged zoonoses in regions under different underlying pressures that drive disease emergence. PMID:26186515

  9. Emerging pathogens--the white horse of the apocalypse?

    PubMed

    Malloy, C D; Gallo, R J; Leib, H B; Marr, J S

    1995-01-01

    The concept of emerging microbial disease is discussed both in a historical and contemporary perspective. Major factors contributing to emergence of viral, bacterial, rickettsial, and parasitic diseases over the last 25 years are discussed. Forty agents are listed in a table by year of recognition/emergence, mode of transmission, geographical distribution, and symptom complex. Public health prevention and control measures and long-term public health implications are also summarized. Suggestions are offered on how to retrieve appropriate information on newly emerging pathogens and to obtain authoritative and timely information on surveillance data using electronic mail access. PMID:10186609

  10. Therapeutics in Huntington's Disease.

    PubMed

    Killoran, Annie; Biglan, Kevin M

    2012-02-01

    OPINION STATEMENT: There is no specific treatment for Huntington's disease (HD). Its many symptoms of motor, psychiatric, and cognitive deterioration are managed with symptomatic relief, rehabilitation, and support. The only drug approved by the US Food and Drug Administration (FDA) for the treatment of HD is an antichoreic agent, tetrabenazine, but this drug is used sparingly because of uneasiness regarding its propensity to cause depression and suicidality in this population, which is already at risk for these complications. Neuroleptics are still first-line treatments for chorea accompanied by comorbid depression and/or behavioral or psychotic symptoms, as is often the case. Psychiatric features, which have a significant impact on a patient's professional and personal life, often become the major focus of management. In addition to neuroleptics, commonly used medications include antidepressants, mood stabilizers, anxiolytics, and psychostimulants. In contrast, few treatment options are available for cognitive impairment in HD; this remains an important and largely unmet therapeutic need. HD patients typically lack insight into their disease manifestations, failing to recognize their need for treatment, and possibly even arguing against it. Multipurpose medications are employed advantageously to simplify the medication regimen, so as to facilitate compliance and not overwhelm the patient. For example, haloperidol can be prescribed for a patient with chorea, agitation, and anorexia, rather than targeting each symptom with a different drug. This approach also limits the potential for adverse effects, which can be difficult to distinguish from the features of the disease itself. With HD's complexity, it is best managed with a multidisciplinary approach that includes a movement disorders specialist, a genetic counselor, a mental health professional, a physical therapist, and a social worker for support and coordination of services. As the disease progresses, there

  11. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  12. Bacteriophage Procurement for Therapeutic Purposes.

    PubMed

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  13. Bacteriophage Procurement for Therapeutic Purposes

    PubMed Central

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  14. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

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

    2008-01-01

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

  15. Therapeutic cloning: promises and issues

    PubMed Central

    Kfoury, Charlotte

    2007-01-01

    Advances in biotechnology necessitate both an understanding of scientific principles and ethical implications to be clinically applicable in medicine. In this regard, therapeutic cloning offers significant potential in regenerative medicine by circumventing immunorejection, and in the cure of genetic disorders when used in conjunction with gene therapy. Therapeutic cloning in the context of cell replacement therapy holds a huge potential for de novo organogenesis and the permanent treatment of Parkinson’s disease, Duchenne muscular dystrophy, and diabetes mellitus as shown by in vivo studies. Scientific roadblocks impeding advancement in therapeutic cloning are tumorigenicity, epigenetic reprogramming, mitochondrial heteroplasmy, interspecies pathogen transfer, low oocyte availability. Therapeutic cloning is also often tied to ethical considerations concerning the source, destruction and moral status of IVF embryos based on the argument of potential. Legislative and funding issues are also addressed. Future considerations would include a distinction between therapeutic and reproductive cloning in legislative formulations. PMID:18523539

  16. Metrics for antibody therapeutics development.

    PubMed

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  17. [Emergency contraception].

    PubMed

    Bastianelli, C; Farris, M; Di Miscia, A

    2006-06-01

    A specific formulation has been approved for use in Italy for emergency contraception (EC) in 2000. As expected, marketing of this levonorgestrel (LNG) only formulation has been accompanied by an increased interest and, often, controversies leading to even strong opposition on the part of those ethically opposed to the use of any method that may act after fertilization. At present, several trials on the exact mechanism of action and safety have been conducted, giving good reason for simplifying access, providing it free or over the counter, in several European countries. EC, also known as ''the morning after pill'' or postcoital contraception, is a modality of preventing the establishment of an unwanted pregnancy after unprotected intercourse and thus, probably, of reducing the number of voluntary pregnancy terminations. Two different forms are available: the hormonal and the intrauterine. Hormonal estrogen only EC was first proposed in the 60s and in 1974 Yuzpe following his studies proposed for the first time his combined regimen, that showed better efficacy and lower side effects. More recently, a new regimen, consisting of LNG, administered alone at the dose of 1.5 mg, was introduced and found in clinical trials to be more effective than the Yuzpe regimen, if taken as early as possible, within 72 h, thereby replacing the latter in common use. Mechanism of action of both hormonal preparations used for EC is inhibiting or delaying ovulation, therefore a prefertilization action. No effect has been reported on the process of implantation nor on an ongoing pregnancy. The WHO have developed a third regimen based on the use of the selective progesterone receptor modulator (antiprogestin) Mifepristone and conducted trials with different dosages, reporting similar efficacy and safety compared to LNG. Intrauterine EC was first proposed by Lippes in 1976. It has the advantage of being effective if inserted within 5 days after unprotected intercourse and the disadvantage

  18. Rare emerging malignant skin tumours.

    PubMed

    Rongioletti, F; Ferreli, C; Pinna, A L; Atzori, L

    2015-08-01

    As clinical skills improve and innovative diagnostic techniques become available in the field of dermatology and dermatopathology, new types or additional variants of malignant skin tumors are described. This article reviews the current nomenclature, clinico-pathological features, differential diagnosis, prognostic and therapeutic implications of some new dermato(patho)logical rare emerging skin tumors, including epithelial tumors (squamous cell carcinoma with mucinous metaplasia), adnexal tumors (endocrine mucin-producing sweat gland carcinoma), soft tissue tumors of vascular differentiation (pseudolymphomatous cutaneous angiosarcoma, pseudomyogenic hemangioendothelioma), hematopoietic tumors (blastic plasmacytoid dendritic cell neoplasm) and mixed epithelial/melanocytic tumor (squamomelanocytic tumor). PMID:26086411

  19. Successful Use of Therapeutic Hypothermia in a Pregnant Patient.

    PubMed

    Oguayo, Kevin N; Oyetayo, Ola O; Stewart, David; Costa, Steven M; Jones, Richard O

    2015-08-01

    Out-of-hospital cardiac arrest is a leading cause of death in the United States. Pregnant women are not immune to cardiac arrest, and the treatment of such patients can be difficult. Pregnancy is a relative contraindication to the use of therapeutic hypothermia after cardiac arrest. A 20-year-old woman who was 18 weeks pregnant had an out-of-hospital cardiac arrest. Upon her arrival at the emergency department, she was resuscitated and her circulation returned spontaneously, but her score on the Glasgow Coma Scale was 3. After adequate family discussion of the risks and benefits of therapeutic hypothermia, a decision was made to initiate therapeutic hypothermia per established protocol for 24 hours. The patient was successfully cooled and rewarmed. By the time she was discharged, she had experienced complete neurologic recovery, apart from some short-term memory loss. Subsequently, at 40 weeks, she delivered vaginally a 7-lb 3-oz girl whose Apgar scores were 8 and 9, at 1 and 5 minutes respectively. To our knowledge, this is only the 3rd reported case of a successful outcome following the initiation of therapeutic hypothermia for out-of-hospital cardiac arrest in a pregnant woman. On the basis of this and previous reports of successful outcomes, we recommend that therapeutic hypothermia be considered an option in the management of out-of-hospital cardiac arrest in the pregnant population. To facilitate a successful outcome, a multidisciplinary approach involving cardiology, emergency medicine, obstetrics, and neurology should be used. PMID:26413021

  20. Therapeutic postprostatectomy irradiation.

    PubMed

    Youssef, Emad; Forman, Jeffrey D; Tekyi-Mensah, Samuel; Bolton, Susan; Hart, Kim

    2002-06-01

    involvement, pathological stage, surgical margin, and perineural invasion. Upon multivariate analysis, only preradiation therapy PSA (P < 0.001) and the PSA trend during radiation therapy (P < 0.001) were significant factors. The results of therapeutic radiation for patients with elevated postprostatectomy PSA levels are sufficiently poor; other strategies should be explored as alternatives, including early adjuvant postprostatectomy irradiation or the use of combined hormonal and radiation therapy in the salvage situation. PMID:15046710

  1. Ovarian cancer: emerging molecular-targeted therapies

    PubMed Central

    Sourbier, Carole

    2012-01-01

    With about 22,000 new cases estimated in 2012 in the US and 15,500 related deaths, ovarian cancer is a heterogeneous and aggressive disease. Even though most of patients are sensitive to chemotherapy treatment following surgery, recurring disease is almost always lethal, and only about 30% of the women affected will be cured. Thanks to a better understanding of the molecular mechanisms underlying ovarian cancer malignancy, new therapeutic options with molecular-targeted agents have become available. This review discusses the rationale behind molecular-targeted therapies and examines how newly identified molecular targets may enhance personalized therapies for ovarian cancer patients. PMID:22807625

  2. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines.

    PubMed

    Filho, Edismauro Garcia Freitas; da Silva, Elaine Zayas Marcelino; Zanotto, Camila Ziliotto; Oliver, Constance; Jamur, Maria Célia

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators. PMID:27578923

  3. Cross-Linking Mast Cell Specific Gangliosides Stimulates the Release of Newly Formed Lipid Mediators and Newly Synthesized Cytokines

    PubMed Central

    Zanotto, Camila Ziliotto

    2016-01-01

    Mast cells are immunoregulatory cells that participate in inflammatory processes. Cross-linking mast cell specific GD1b derived gangliosides by mAbAA4 results in partial activation of mast cells without the release of preformed mediators. The present study examines the release of newly formed and newly synthesized mediators following ganglioside cross-linking. Cross-linking the gangliosides with mAbAA4 released the newly formed lipid mediators, prostaglandins D2 and E2, without release of leukotrienes B4 and C4. The effect of cross-linking these gangliosides on the activation of enzymes in the arachidonate cascade was then investigated. Ganglioside cross-linking resulted in phosphorylation of cytosolic phospholipase A2 and increased expression of cyclooxygenase-2. Translocation of 5-lipoxygenase from the cytosol to the nucleus was not induced by ganglioside cross-linking. Cross-linking of GD1b derived gangliosides also resulted in the release of the newly synthesized mediators, interleukin-4, interleukin-6, and TNF-α. The effect of cross-linking the gangliosides on the MAP kinase pathway was then investigated. Cross-linking the gangliosides induced the phosphorylation of ERK1/2, JNK1/2, and p38 as well as activating both NFκB and NFAT in a Syk-dependent manner. Therefore, cross-linking the mast cell specific GD1b derived gangliosides results in the activation of signaling pathways that culminate with the release of newly formed and newly synthesized mediators. PMID:27578923

  4. Therapeutic Approaches in the Stimulation of the Coronary Collateral Circulation

    PubMed Central

    Degen, Achim; Millenaar, Dominic; Schirmer, Stephan H.

    2014-01-01

    Arteriogenesis as a way to restore blood flow after arterial occlusion has been under investigation for the treatment of coronary artery disease (CAD) for decades. Therapeutic approaches so far have included delivery of cytokines and growth factors as well as mechanical stimulation such as external counterpulsation. As knowledge on the mechanisms of arteriogenesis expanded, new therapeutic approaches have emerged. This review summarizes recent attempts to stimulate the growth of the coronary vasculature and discusses their potential in clinical application. This article also delivers an overview of current studies and trials on coronary arteriogenesis. PMID:23721076

  5. Management of Mucositis During Chemotherapy: From Pathophysiology to Pragmatic Therapeutics.

    PubMed

    Van Sebille, Ysabella Z A; Stansborough, Romany; Wardill, Hannah R; Bateman, Emma; Gibson, Rachel J; Keefe, Dorothy M

    2015-11-01

    Chemotherapy-induced mucositis is a common condition caused by the breakdown of the mucosal barrier. Symptoms can include pain, vomiting and diarrhoea, which can often necessitate chemotherapy treatment breaks or dose reductions, thus compromising survival outcomes. Despite the significant impact of mucositis, there are currently limited clinically effective pharmacological therapies for the pathology. New emerging areas of research have been proposed to play key roles in the development of mucositis, providing rationale for potential new therapeutics for the prevention, treatment or management of chemotherapy-induced mucositis. This review aims to address these new areas of research and to comment on the therapeutics arising from them. PMID:26384312

  6. Dilemmas of a Newly Recruited Academic Qualified Professor: A Case

    ERIC Educational Resources Information Center

    Agrawal, Anand

    2015-01-01

    This case describes the situation of a newly recruited academic professor who volunteered to teach a course on Research Methods to first-term MBA students in a practitioner-oriented case method Business School. Research Methods is a unique course due to its relevance not only in business but also across all graduate programs. Instructional and…

  7. Enhancing the Employability of Newly Qualified Nurses: A Pilot Study

    ERIC Educational Resources Information Center

    Dray, Beattie; Burke, Linda; Hurst, Heather M.; Ferguson, Anne; Marks-Maran, Diane

    2011-01-01

    Vocationally based higher education programmes are meant to prepare people for employment in their chosen fields of study. In nursing, historically, employment after qualifying has been almost assured, with sufficient vacancies available for newly qualified nurses. Recently, however, for a number of reasons, primarily related to economic…

  8. Triadic Interaction among Newly Acquainted 2-Year-Olds

    ERIC Educational Resources Information Center

    Ishikawa, Fumiko; Hay, Dale F.

    2006-01-01

    Are children as young as 2 years old able to interact in groups of three? The study applied the family triad model first introduced by Parke, Power, and Gottman (1979) to the case of peer interaction. In Experiment 1, the model was refined for use in studies of peer interaction and applied to an existing dataset of 16 triads of newly acquainted…

  9. 30 CFR 46.6 - Newly hired experienced miner training.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Newly hired experienced miner training. 46.6 Section 46.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING TRAINING AND RETRAINING OF MINERS ENGAGED IN SHELL DREDGING OR EMPLOYED AT SAND, GRAVEL,...

  10. 30 CFR 46.6 - Newly hired experienced miner training.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Newly hired experienced miner training. 46.6 Section 46.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING TRAINING AND RETRAINING OF MINERS ENGAGED IN SHELL DREDGING OR EMPLOYED AT SAND, GRAVEL,...

  11. 30 CFR 46.6 - Newly hired experienced miner training.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Newly hired experienced miner training. 46.6 Section 46.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING TRAINING AND RETRAINING OF MINERS ENGAGED IN SHELL DREDGING OR EMPLOYED AT SAND, GRAVEL,...

  12. 30 CFR 46.6 - Newly hired experienced miner training.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Newly hired experienced miner training. 46.6 Section 46.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING TRAINING AND RETRAINING OF MINERS ENGAGED IN SHELL DREDGING OR EMPLOYED AT SAND, GRAVEL,...

  13. 30 CFR 46.6 - Newly hired experienced miner training.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Newly hired experienced miner training. 46.6 Section 46.6 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR EDUCATION AND TRAINING TRAINING AND RETRAINING OF MINERS ENGAGED IN SHELL DREDGING OR EMPLOYED AT SAND, GRAVEL,...

  14. Newly Generated Liquid Waste Processing Alternatives Study, Volume 1

    SciTech Connect

    Landman, William Henry; Bates, Steven Odum; Bonnema, Bruce Edward; Palmer, Stanley Leland; Podgorney, Anna Kristine; Walsh, Stephanie

    2002-09-01

    This report identifies and evaluates three options for treating newly generated liquid waste at the Idaho Nuclear Technology and Engineering Center of the Idaho National Engineering and Environmental Laboratory. The three options are: (a) treat the waste using processing facilities designed for treating sodium-bearing waste, (b) treat the waste using subcontractor-supplied mobile systems, or (c) treat the waste using a special facility designed and constructed for that purpose. In studying these options, engineers concluded that the best approach is to store the newly generated liquid waste until a sodium-bearing waste treatment facility is available and then to co-process the stored inventory of the newly generated waste with the sodium-bearing waste. After the sodium-bearing waste facility completes its mission, two paths are available. The newly generated liquid waste could be treated using the subcontractor-supplied system or the sodium-bearing waste facility or a portion of it. The final decision depends on the design of the sodium-bearing waste treatment facility, which will be completed in coming years.

  15. Nuclear reaction effects in use of newly recommended quality factor

    NASA Technical Reports Server (NTRS)

    Shinn, Judy L.; Wilson, John W.

    1991-01-01

    The biological risk for energetic ion exposure cannot be reliably estimated exclusive of the target nuclear reaction products produced within the local tissue. A theoretical basis is derived for evaluating target fragment contributions that are evaluated for the newly proposed quality factor.

  16. Impact of weed barriers on newly planted peach trees

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Newly planted (Feb. 2005) ‘Sunracer’ and ‘Sunhome’ nectarine and ‘Tropic Snow’ peach (Prunus persica (L.) Batsch) trees were subjected to conventional and four 'organic' weed control methods. Two of the 'organic' methods used weed barriers of white plastic (WP) or landscape fabric (LF). A third co...

  17. Field Performance of a Newly Developed Upflow Filtration Device

    EPA Science Inventory

    The objective of this research is to examine the removal capacities of a newly developed Upflow filtration device for treatment of stormwater. The device was developed by engineers at the University of Alabama through a Small Business Innovative Research (SBIR) grant from the U....

  18. Creating a Positive School Culture in Newly Opened Schools

    ERIC Educational Resources Information Center

    Holmes, Michael Todd

    2009-01-01

    The purpose of this study was to determine the most effective practices by school administrators when creating school culture in newly opened schools. Using semi-structured interviews, four principals who opened a new school were interviewed individually and in a focus group. The constant comparative method was used to analyze the data. Two themes…

  19. Death Concerns among Individuals Newly Diagnosed with Lung Cancer

    ERIC Educational Resources Information Center

    Lehto, Rebecca; Therrien, Barbara

    2010-01-01

    Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited…

  20. Who Is Doing Well? A Typology of Newly Homeless Adolescents

    ERIC Educational Resources Information Center

    Milburn, Norweeta; Liang, Li-Jung; Lee, Sung-Jae; Rotheram-Borus, Mary Jane; Rosenthal, Doreen; Mallett, Shelley; Lightfoot, Marguerita; Lester, Patricia

    2009-01-01

    There is growing evidence to support developing new typologies for homeless adolescents. Current typologies focus on the risks associated with being homeless, with less consideration of the positive attributes of homeless adolescents. The authors examined both risk and protective factors in a sample of newly homeless adolescents. Using cluster…

  1. Recontextualising Professional Knowledge--Newly Qualified Nurses and Physicians

    ERIC Educational Resources Information Center

    Smeby, Jens-Christian; Vagan, Andre

    2008-01-01

    This article examines the discrepancy between newly qualified nurses' and physicians' assessment of acquired knowledge in education and their assessment of the knowledge demands in occupational practice. Knowledge learned in educational institutions is traditionally conceived as general and decontextualised with great potential for transmission…

  2. Self-Regulation in Newly Arrived International Adoptees

    ERIC Educational Resources Information Center

    Tirella, Linda Grey; Miller, Laurie C.

    2011-01-01

    Many newly arrived international adoptees (IA) have difficulties with eating, sleeping, and self-soothing/self-stimulating (SS) behaviors. However, to date the prevalence of these problems and associated risk factors have not been clearly identified. Therefore, we proposed to evaluate 387 IA for the presence of these self-regulation and behavioral…

  3. Oral Definitions of Newly Learned Words: An Error Analysis

    ERIC Educational Resources Information Center

    Steele, Sara C.

    2012-01-01

    This study examined and compared patterns of errors in the oral definitions of newly learned words. Fifteen 9- to 11-year-old children with language learning disability (LLD) and 15 typically developing age-matched peers inferred the meanings of 20 nonsense words from four novel reading passages. After reading, children provided oral definitions…

  4. Increased gluconeogenesis in youth with newly diagnosed type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The role of increased gluconeogenesis as an important contributor to fasting hyperglycaemia at diabetes onset is not known. We evaluated the contribution of gluconeogenesis and glycogenolysis to fasting hyperglycaemia in newly diagnosed youths with type 2 diabetes following an overnight fast. Basal ...

  5. The Newly Qualified Teacher in the Working Community

    ERIC Educational Resources Information Center

    Nyman, Tarja

    2014-01-01

    Focusing on the working community, this article concentrates on the newly qualified foreign language teachers' (NQT) experiences and on factors that promoted or prevented the development of professional expertise at the outset of their working life. It draws on a qualitative longitudinal study conducted at the University of Jyväskylä,…

  6. Resume Writing in Russia and the Newly Independent States

    ERIC Educational Resources Information Center

    Bowen, Betsy; Sapp, David Alan; Sargsyan, Nelly

    2006-01-01

    This article examines the teaching of resume writing at one university in Russia and several institutions in the Newly Independent States (NIS). The authors explore challenges including variable cultural norms for written versus oral communication, severe financial and material hardship in the educational sector, cultural discomfort with the norms…

  7. 26. View of fully flooded drydock with caisson opened. Newly ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    26. View of fully flooded drydock with caisson opened. Newly arrived submarine is being placed in position. Berthed submarine on right is same as that seen in photo WA-116-25. Camera is pointed S from bulkhead. - Puget Sound Naval Shipyard, Drydock No. 3, Farragut Avenue, Bremerton, Kitsap County, WA

  8. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5090 Emergency airway needle....

  9. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5090 Emergency airway needle....

  10. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5090 Emergency airway needle....

  11. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5090 Emergency airway needle....

  12. 21 CFR 868.5090 - Emergency airway needle.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Emergency airway needle. 868.5090 Section 868.5090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5090 Emergency airway needle....

  13. [Lung sarcoidosis: Clinical features and therapeutic issues].

    PubMed

    Uzunhan, Y; Jeny, F; Crockett, F; Piver, D; Kambouchner, M; Valeyre, D; Nunes, H

    2016-09-01

    Sarcoidosis is a granulomatous disease of unknown cause. This proteiform disease is characterized by an almost constant and often predominant lung involvement. The natural history of disease is difficult to predict at presentation. Diagnosis is based on a compatible clinical and radiological presentation and evidence of non-caseating granulomas. Exclusion of alternative diseases is also required according to clinical presentation. Biopsy samples of superficial lesions should be considered before other sites like per-endoscopic bronchial biopsies or endobronchial ultrasound-guided transbronchial needle aspiration. Therapeutic strategy for lung disease has to take into account the possible spontaneous resolution observed in newly diagnosed patients. Corticosteroids are the first choice when a treatment is decided, which concerns half of patients. Second and third line therapy are based respectively on immunosuppressive drugs and anti-TNFα drugs. Sarcoidosis mortality and morbidity are mainly linked to advanced pulmonary sarcoidosis - lung fibrosis, pulmonary hypertension, bronchial stenosis and chronic pulmonary aspergillosis. "Non anti-inflammatory" treatments have to be considered as well. Clinicians have an essential role in treatment indication, end-point targets and evaluation of response to treatment during follow-up and in finding the best benefice to risk balance. Progress made on pharmacogenetics may offer more personalized treatments for the patients. PMID:26897112

  14. Laboratory markers slightly overestimate retention in HIV care among newly diagnosed individuals.

    PubMed

    Halperin, Jason; Bean, Madelyne C; Richey, Lauren E

    2016-09-01

    Patients who are retained in HIV care have a higher likelihood of viral suppression and increased survival. Lab markers have been used as surrogate markers for clinical visits to estimate retention, but the accuracy of these markers at predicting retention in care has not been validated. A retrospective cohort study was conducted using patients newly diagnosed with HIV in the Emergency Department of Interim Louisiana Public Hospital (ILPH). Retention in care was defined as two clinical visits to an HIV provider separated by at least three months within a one-year period as per the Health Resources and Services Administration (HRSA) definition. Retention by lab markers was defined as two documented labs, either a CD4 count or an HIV viral load, separated by at least three months within the same one-year period. Ninety-nine patients were newly diagnosed with HIV; 36 patients (36%) were retained at 1 year using the HRSA definition and 40 patients (40%) using lab markers. The sensitivity and specificity of using lab markers among the newly diagnosed were 100% and 93.7%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 90% and 100%, respectively. Among the 99 patients, 56 were linked to the HIV clinic associated with our hospital, of which 63% (36) were retained at year 1 using the HRSA definition and 70% (39) using lab markers. The sensitivity and specificity of using lab markers among linked patients were 100% and 85%, respectively. The PPV and NPV were 92% and 100%, respectively. Lab markers slightly overestimate currently accepted definitions of retention. While lab markers may be the easiest way to estimate retention at the population level, further study should be done before lab markers are accepted as the gold standard surrogate measure for retention. PMID:27010972

  15. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future. PMID:18991725

  16. Post-Adoption Depression: Clinical Windows on an Emerging Concept

    ERIC Educational Resources Information Center

    Speilman, Eda

    2011-01-01

    In recent years, the concept of post-adoption depression--with both parallels and differences from postpartum depression--has emerged as a salient descriptor of the experience of a significant minority of newly adoptive parents. This article offers a clinical perspective on post-adoption depression through the stories of several families seen in…

  17. Telementoring in education of laparoscopic surgeons: An emerging technology

    PubMed Central

    Bogen, Etai M; Augestad, Knut M; Patel, Hiten RH; Lindsetmo, Rolv-Ole

    2014-01-01

    Laparoscopy, minimally invasive and minimal access surgery with more surgeons performing these advanced procedures. We highlight in the review several key emerging technologies such as the telementoring and virtual reality simulators, that provide a solid ground for delivering surgical education to rural area and allow young surgeons a safety net and confidence while operating on a newly learned technique. PMID:24944728

  18. Development and novel therapeutics in hepatocellular carcinoma: a review.

    PubMed

    Ingle, Pravinkumar Vishwanath; Samsudin, Sarah Zakiah; Chan, Pei Qi; Ng, Mei Kei; Heng, Li Xuan; Yap, Siu Ching; Chai, Amy Siaw Hui; Wong, Audrey San Ying

    2016-01-01

    This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions. PMID:27042086

  19. Development and novel therapeutics in hepatocellular carcinoma: a review

    PubMed Central

    Ingle, Pravinkumar Vishwanath; Samsudin, Sarah Zakiah; Chan, Pei Qi; Ng, Mei Kei; Heng, Li Xuan; Yap, Siu Ching; Chai, Amy Siaw Hui; Wong, Audrey San Ying

    2016-01-01

    This review summarizes the epidemiological trend, risk factors, prevention strategies such as vaccination, staging, current novel therapeutics, including the drugs under clinical trials, and future therapeutic trends for hepatocellular carcinoma (HCC). As HCC is the third most common cause of cancer-related death worldwide, its overall incidence remains alarmingly high in the developing world and is steadily rising across most of the developed and developing world. Over the past 15 years, the incidence of HCC has more than doubled and it increases with advancing age. Chronic infection with hepatitis B virus is the leading cause of HCC, closely followed by infection with hepatitis C virus. Other factors contributing to the development of HCC include alcohol abuse, tobacco smoking, and metabolic syndrome (including obesity, diabetes, and fatty liver disease). Treatment options have improved in the past few years, particularly with the approval of several molecular-targeted therapies. The researchers are actively pursuing novel therapeutic targets as well as predictive biomarker for treatment of HCC. Advances are being made in understanding the mechanisms underlying HCC, which in turn could lead to novel therapeutics. Nevertheless, there are many emerging agents still under clinical trials and yet to show promising results. Hence, future therapeutic options may include different combination of novel therapeutic interventions. PMID:27042086

  20. Characteristics of Newly Enrolled Members of an Integrated Delivery System after the Affordable Care Act.

    PubMed

    Bayliss, Elizabeth A; Ellis, Jennifer L; Strobel, Mary Jo; Mcquillan, Deanna B; Petsche, Irena B; Barrow, Jennifer C; Beck, Arne

    2015-01-01

    Of 89,289 newly enrolled non-Medicare members, 25.3% completed the Brief Health Questionnaire between 1/1/2014, and 8/31/2014. Of these, 3593 respondents were insured through Medicaid, 9434 through the individual health exchange, and 9521 through primarily commercial plans. Of Medicaid, exchange, and commercial members, 19.5%, 7.1%, and 5.3%, respectively, self-reported fair or poor health; 12.9%, 2.0%, and 3.3% of each group self-reported 2 or more Emergency Department visits during the previous year; and 8.1%, 4.3%, and 4.4% self-reported an inpatient admission during the previous year. PMID:26057681