Chylothorax after left side pneumothorax surgery managed by OK-432 pleurodesis: an effective alternative.

PubMed

Huang, Sheng-Yang; Yeh, Chou-Ming; Chou, Chia-Man; Chen, Hou-Chuan

2014-12-01

Chylothorax, a relatively rare complication of thoracic surgery, mostly occurs on the right side. We present a 16-year-old male who received thoracoscopic surgery for left spontaneous pneumothorax. Chylothorax developed on the postoperative 2(nd) day and resolved after diet control on the 4(th) day. Unfortunately, chylothorax recurred 2 weeks later. Chest drainage and nil per os with total parental nutrition were given but in vain. Thereafter, chemical pleurodesis with OK-432 was performed. Chylothorax resolved on the next day. The relevant literature is reviewed and possible pathogenesis clarified. Copyright © 2014. Published by Elsevier Taiwan.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human.

PubMed

Morgan, Michael M; Christie, MacDonald J

2011-10-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Do Student Learning Styles Translate to Different "Testing Styles"?

ERIC Educational Resources Information Center

Leithner, Anika

2011-01-01

Professors seem to be more aware of different student learning styles than ever before and are utilizing various teaching techniques in order to appeal to different students in their classes. Unfortunately, presenting materials is only one side of the coin, while the other side--assessment--has not received the same amount of attention. After all,…

[Herbal preparations have both effects and side effects. Widespread usage dictates knowledge among physicians].

PubMed

Mattsson, Karin; Nilsson, Inger

2002-12-12

The article gives a clinically oriented overview of the efficacy and safety of Ginkgo biloba, St. John's wort, ginseng, Echinacea, saw palmetto and kava based on American experiences. Clinical data support the efficacy for some of these drugs. None of them is free of adverse effects. Generally speaking, trials of herbal medicinal products have been too few, too small and too short. The lack of long-term studies is especially unfortunate since many of the drugs are used for a long time. The difference between American and Swedish legislation on herbal medicine products is described.

Overview of skin whitening agents with an insight into the illegal cosmetic market in Europe.

PubMed

Desmedt, B; Courselle, P; De Beer, J O; Rogiers, V; Grosber, M; Deconinck, E; De Paepe, K

2016-06-01

Lightening skin tone is an ancient and well-documented practice, and remains common practice among many cultures. Whitening agents such as corticosteroids, tretinoin and hydroquinone are medically applied to effectively lighten the skin tone of hyperpigmented lesions. However, when these agents are used cosmetically, they are associated with a variety of side-effect. Alternative agents, such as arbutin and its derivatives kojic acid and nicotinamide have been subsequently developed for cosmetic purposes. Unfortunately, some cosmetics contain whitening agents that are banned for use in cosmetic products. This article provides an overview of the mode of action and potential side-effects of cosmetic legal and illegal whitening agents, and the pattern of use of these types of products. Finally, an EU analysis of the health problems due to the presence of illegal products on the market is summarized. © 2016 European Academy of Dermatology and Venereology.

Development of universal antidotes to control aptamer activity

PubMed Central

Oney, Sabah; Lam, Ruby T S; Bompiani, Kristin M; Blake, Charlene M; Quick, George; Heidel, Jeremy D; Liu, Joanna Yi-Ching; Mack, Brendan C; Davis, Mark E; Leong, Kam W; Sullenger, Bruce A

2010-01-01

With an ever increasing number of people taking numerous medications, the need to safely administer drugs and limit unintended side effects has never been greater. Antidote control remains the most direct means to counteract acute side effects of drugs, but, unfortunately, it has been challenging and cost prohibitive to generate antidotes for most therapeutic agents. Here we describe the development of a set of antidote molecules that are capable of counteracting the effects of an entire class of therapeutic agents based upon aptamers. These universal antidotes exploit the fact that, when systemically administered, aptamers are the only free extracellular oligonucleotides found in circulation. We show that protein-and polymer-based molecules that capture oligonucleotides can reverse the activity of several aptamers in vitro and counteract aptamer activity in vivo. The availability of universal antidotes to control the activity of any aptamer suggests that aptamers may be a particularly safe class of therapeutics. PMID:19801990

Present and Future: Pharmacologic Treatment of Obesity

PubMed Central

Glandt, Mariela; Raz, Itamar

2011-01-01

Obesity now presents one of the biggest health problems of our times. Diet and exercise are best for both prevention and treatment; unfortunately, both require much discipline and are difficult to maintain. Medications offer a possible adjunct, but their effect is modest, they are limited by side effects, and the weight loss lasts only as long as the drug is being taken, since as soon as treatment is stopped, the weight is regained. Sibutramine, a sympathomimetic medication which was available for long-term treatment, is the most recent of the drugs to be withdrawn from the market due to side effects; in this case it was an increased risk of cardiovascular events. This paper reviews those medications which are available for treatment of obesity, including many of those recently taken off the market. It also discusses some of the newer treatments that are currently being investigated. PMID:21331293

Brazilian keratin hair treatment: a review.

PubMed

Weathersby, Courtney; McMichael, Amy

2013-06-01

Brazilian keratin treatments are widely available products that are used by women all over the world to straighten hair. Marketers of these products claim that the keratin treatments render naturally curly hair more manageable and frizz-free while enhancing color and shine, giving the hair a healthier appearance. Although widely used, there have been virtually no reports of adverse side effects. Unfortunately, many of the products that are applied by salon professionals contain formaldehyde or its derivatives and are being marketed as safe. © 2013 Wiley Periodicals, Inc.

Emerging strategies for lowering serum phosphorous in patients with end-stage renal disease.

PubMed

Ashfaq, Akhtar; Gitman, Michael; Singhal, Pravin C

2006-10-01

Hyperphosphataemia is a major problem in patients with chronic kidney disease as it has been associated with increased morbidity and mortality. Over the last four decades, different modalities have been applied to treat hyperphosphataemia with varying degrees of success. Unfortunately, treatment strategies have led to unforeseen complications. These have prompted the development of new classes of medications with potentially better efficacy and few short-term and long-term side effects. This article reviews the causes, mechanism and management of hyperphosphataemia.

Checkpoint Inhibitor Sensitizes Human Tumor Cells | Center for Cancer Research

Cancer.gov

One unfortunate and detrimental side effect of ionizing radiation as a treatment for cancer is the damage it imparts to normal tissue near the targeted tumor. Technology has improved radiation delivery, minimizing the volume of normal tissue in the radiation field, but has not eliminated it completely. Thus, the identification of drugs that increase the sensitivity of cancer cells to radiation while sparing normal cells would go a long way toward improving patient quality of life and outcome.

Drug safety evaluation of dronedarone in atrial fibrillation.

PubMed

De Ferrari, Gaetano M; Dusi, Veronica

2012-11-01

Dronedarone was developed with the intent of replicating the antiarrhythmic effects of amiodarone, while minimizing its side effects. Side effects reported in eight randomized clinical trials are discussed, comparing dronedarone and placebo (DAFNE, EURIDIS, ADONIS, ERATO, ANDROMEDA, ATHENA, PALLAS, total number of patients treated with dronedarone 5347), or dronedarone and amiodarone (DIONYSOS, total number of patients treated with dronedarone 249). The results of the first trials, including ATHENA, set high expectations by suggesting that dronedarone may decrease the risk of hospitalization (and even cardiovascular mortality) among patients with paroxysmal and persistent atrial fibrillation (AF), and that it could be regarded as an easy-to-use drug that could be prescribed by general practitioners; unfortunately, dronedarone has not met these expectations. Dronedarone may increase mortality and heart failure hospitalization in patients with advanced NYHA class and in patients with permanent AF, preventing its use in these settings. In addition to gastrointestinal side effects that may lead to discontinuation in 5 - 10% of patients, dronedarone may induce very rare but severe liver and lung toxicity. Despite these limitations and its relatively limited antiarrhythmic potency, dronedarone may still be a useful drug for well-selected patients.

Analysis of opioid efficacy, tolerance, addiction and dependence from cell culture to human

PubMed Central

Morgan, Michael M; Christie, MacDonald J

2011-01-01

Opioid agonists are the most effective treatment for pain, but their use is limited by side effects, tolerance and fears of addiction and dependence. A major goal of opioid research is to develop agonists that have high analgesic efficacy and a low profile for side effects, tolerance, addiction and dependence. Unfortunately, there is a serious lack of experimental data comparing the degree to which different opioids produce these effects in humans. In contrast, a wide range of experimental techniques from heterologous expression systems to behaviour assessment in whole animals have been developed to study these problems. The objective of this review is to describe and evaluate these techniques as they are used to study opioid efficacy, tolerance, addiction and dependence. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21434879

Neuropsychiatric manifestation after a stroke: newly developed symptoms or side-effect of drug?

PubMed Central

Tan, Eng Chai; Aziz, Noor Azah; Ahmad, Saharuddin

2012-01-01

A 55-year-old woman presented with sudden onset of left-sided body weakness and numbness, which was diagnosed as multifocal cerebral infarct with right thalamic bleed. She had concurrent hypertension, diabetes mellitus and chronic kidney disease. She suffered from central poststroke pain and reactive depression as poststroke complications, for which amitriptyline was prescribed. Unfortunately, she developed symptoms suggestive of mania and psychosis upon initiation of medications, which resolved upon withdrawal of amitriptyline. Amitriptyline is effective for treatment of poststroke pain and particularly useful in concomitant depression. Unexpectedly, this patient developed new psychopathologies after initiation of this medication. This case highlights the development of new psychopathologies that could be due to the antidepressant, underlying bipolar disorder or a complication of the stroke itself. Primary care providers need to actively enquire regarding neuropsychiatric symptoms because they can adversely affect the patient's quality of life as well as impede rehabilitation efforts. PMID:22907854

Diagnosing the Causes and Severity of One-sided Message Contention

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

Tallent, Nathan R.; Vishnu, Abhinav; van Dam, Hubertus

Two trends suggest network contention for one-sided messages is poised to become a performance problem that concerns application developers: an increased interest in one-sided programming models and a rising ratio of hardware threads to network injection bandwidth. Unfortunately, it is difficult to reason about network contention and one-sided messages because one-sided tasks can either decrease or increase contention. We present effective and portable techniques for diagnosing the causes and severity of one-sided message contention. To detect that a message is affected by contention, we maintain statistics representing instantaneous (non-local) network resource demand. Using lightweight measurement and modeling, we identify themore » portion of a message's latency that is due to contention and whether contention occurs at the initiator or target. We attribute these metrics to program statements in their full static and dynamic context. We characterize contention for an important computational chemistry benchmark on InfiniBand, Cray Aries, and IBM Blue Gene/Q interconnects. We pinpoint the sources of contention, estimate their severity, and show that when message delivery time deviates from an ideal model, there are other messages contending for the same network links. With a small change to the benchmark, we reduce contention up to 50% and improve total runtime as much as 20%.« less

Recurrent ectopic pregnancy in a woman suffering from infertility due to male factor presented with heterotopic pregnancy

PubMed Central

Chaudhari, Hemang D; Gandhi, Viplav S; Banker, Hiral; Suri, Amar

2012-01-01

Heterotopic pregnancy is the simultaneous occurrence of intrauterine and extrauterine pregnancies. A 27-year-old third gravida with history of two ectopic pregnancies, presented with cramping pain in pelvis radiating to left side and bleeding from vagina. Ultrasonographic diagnosis of heterotopic pregnancy was put forward. Unfortunately intrauterine component of heterotopic pregnancy resulted in blighted ovum and linear salpingostomy was done for left-sided tubal pregnancy. PMID:22605872

Novel Formulation Strategy to Improve the Feasibility of Amifostine Administration.

PubMed

Ranganathan, Kavitha; Simon, Eric; Lynn, Jeremy; Snider, Alicia; Zhang, Yu; Nelson, Noah; Donneys, Alexis; Rodriguez, Jose; Buchman, Lauren; Reyna, Dawn; Lipka, Elke; Buchman, Steven R

2018-03-19

Amifostine (AMF), a radioprotectant, is FDA-approved for intravenous administration in cancer patients receiving radiation therapy (XRT). Unfortunately, it remains clinically underutilized due to adverse side effects. The purpose of this study is to define the pharmacokinetic profile of an oral AMF formulation potentially capable of reducing side effects and increasing clinical feasibility. Calvarial osteoblasts were radiated under three conditions: no drug, AMF, and WR-1065 (active metabolite). Osteogenic potential of cells was measured using alkaline phosphatase staining. Next, rats were given AMF intravenously or directly into the jejunum, and pharmacokinetic profiles were evaluated. Finally, rats were given AMF orally or subcutaneously, and blood samples were analyzed for pharmacokinetics. WR-1065 preserved osteogenic potential of calvarial osteoblasts after XRT to a greater degree than AMF. Direct jejunal AMF administration incurred a systemic bioavailability of 61.5%. Subcutaneously administrated AMF yielded higher systemic levels, a more rapid peak exposure (0.438 vs. 0.875 h), and greater total systemic exposure of WR-1065 (116,756 vs. 16,874 ng*hr/ml) compared to orally administered AMF. Orally administered AMF achieves a similar systemic bioavailability and decreased peak plasma level of WR-1065 compared to intravenously administered AMF, suggesting oral AMF formulations maintain radioprotective efficacy without causing onerous side effects, and are clinically feasible.

Marijuana-based drugs: innovative therapeutics or designer drugs of abuse?

PubMed

Seely, Kathryn A; Prather, Paul L; James, Laura P; Moran, Jeffery H

2011-02-01

The principal psychoactive component of marijuana, Δ(9)-tetrahydrocannabinol (THC), activates CB1 cannabinoid receptors (CB1Rs). Unfortunately, pharmacological research into the design of effective THC analogs has been hampered by psychiatric side effects. THC-based drug design of a less academic nature, however, has led to the marketing of "synthetic marijuana," labeled as K2 or "Spice," among other terms, which elicits psychotropic actions via CB1R activation. Because of structural dissimilarity to THC, the active ingredients of K2/Spice preparations are widely unregulated. The K2/Spice "phenomenon" provides a context for considering whether marijuana-based drugs will truly provide innovative therapeutics or merely perpetuate drug abuse.

Calcium channel modulation as a target in chronic pain control

PubMed Central

Montagut‐Bordas, Carlota; Dickenson, Anthony H

2017-01-01

Neuropathic pain remains poorly treated for large numbers of patients, and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt™) was developed and approved as a first‐in‐class synthetic version of ω‐conotoxin MVIIA, a peptide blocker of Cav2.2 channels. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide have restricted its use to exceptional circumstances. Ziconotide exhibits no state or use‐dependent block of Cav2.2 channels; activation state‐dependent blockers were hypothesized to circumvent the side effects of state‐independent blockers by selectively targeting high‐frequency firing of nociceptive neurones in chronic pain states, thus alleviating aberrant pain but not affecting normal sensory transduction. Unfortunately, numerous drugs, including state‐dependent calcium channel blockers, have displayed efficacy in preclinical models but have subsequently been disappointing in clinical trials. In recent years, it has become more widely acknowledged that trans‐aetiological sensory profiles exist amongst chronic pain patients and may indicate similar underlying mechanisms and drug sensitivities. Heterogeneity amongst patients, a reliance on stimulus‐evoked endpoints in preclinical studies and a failure to utilize translatable endpoints, all are likely to have contributed to negative clinical trial results. We provide an overview of how electrophysiological and operant‐based assays provide insight into sensory and affective aspects of pain in animal models and how these may relate to chronic pain patients in order to improve the bench‐to‐bedside translation of calcium channel modulators. Linked Articles This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc PMID:28320042

β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia

PubMed Central

Bohn, Laura M.

2016-01-01

Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843

Psoriasis and Microbiota: A Systematic Review.

PubMed

Benhadou, Farida; Mintoff, Dillon; Schnebert, Benjamin; Thio, Hok Bing

2018-06-02

Recent advances have highlighted the crucial role of microbiota in the pathophysiology of chronic inflammatory diseases as well as its impact on the efficacy of therapeutic agents. Psoriasis is a chronic, multifactorial inflammatory skin disorder, which has a microbiota distinct from healthy, unaffected skin. Through an extensive review of the literature, we aim to discuss the skin and gut microbiota and redefine their role in the pathogenesis of psoriasis. Unfortunately, the direct link between the skin microbiota and the pathogenesis of psoriasis remains to be clearly established. Apart from improving the course of psoriasis, selective modulation of the microbiota may increase the efficacy of medical treatments as well as attenuate their side effects.

Designing biologic selectivity for inflammatory bowel disease – role of vedolizumab

PubMed Central

Krupka, Niklas; Baumgart, Daniel C

2015-01-01

Crohn’s disease and ulcerative colitis are two chronic inflammatory bowel conditions. Current approved biologic therapies are limited to blocking tumor necrosis factor alpha. Unfortunately, some patients are primary nonresponders, experiencing a loss of response, intolerance, or side effects. This defines an unmet need for novel therapeutic strategies. The rapid recruitment and inappropriate retention of leukocytes is a hallmark of chronic inflammation and a potentially promising therapeutic target. Here we discuss the clinical trial results of vedolizumab (anti-α4β7, LDP-02, MLN-02, and MLN0002) and its impact on future management of inflammatory bowel disease. PMID:25552903

A Case of Chronic Total Occlusion of the Left Anterior Descending Artery Successfully Treated with Side Branch Technique Using the Soutenir CV

PubMed Central

Niizeki, Takeshi; Ikeno, Eiichiro; Kubota, Isao

2017-01-01

Patient: Male, 54 Final Diagnosis: Old myocardial infarction Symptoms: Lower extremity swelling • respiratory distress Medication: — Clinical Procedure: Success Specialty: Cardiology Objective: Unusual setting of medical care Background: Success rates for treatment of chronic total occlusion (CTO) have dramatically improved in recent years with the development of new CTO guidewires and development of new techniques such as the retrograde approach. In the antegrade approach, a guidewire is occasionally passed through a side branch despite successful wire crossing of the CTO lesion. In order to pass a wire through the main artery, there are a few side branch techniques such as a reverse wire technique. Case Report: A 54-year-old man with symptoms of heart failure was admitted to our hospital. Coronary angiography showed CTO of the proximal left anterior descending artery. Percutaneous coronary intervention with an antegrade approach was started. We succeeded in passing the wire through a side branch but not the main artery. Unfortunately, a reverse wire technique failed in this case. Next, the wire passed through a side branch was exchanged with the Soutenir CV, and a retrograde approach was started. The wire crossing from retrograde was entwined around the Soutenir CV. After that, the retrograde wire was snared and guided to the antegrade guiding catheter, which resulted in successful wiring into the main artery easily. Conclusions: The side branch technique using the Soutenir CV may be an effective strategy in some cases. PMID:28082733

Translational strategies for therapeutic development in nicotine addiction: rethinking the conventional bench to bedside approach.

PubMed

Le Foll, Bernard; Pushparaj, Abhiram; Pryslawsky, Yaroslaw; Forget, Benoit; Vemuri, Kiran; Makriyannis, Alexandros; Trigo, Jose M

2014-07-03

Tobacco produces an impressive burden of disease resulting in premature death in half of users. Despite effective smoking cessation medications (nicotine replacement therapies, bupropion and varenicline), there is a very high rate of relapse following quit attempts. The use of efficient strategies for the development of novel treatments is a necessity. A 'bench to bedside strategy' was initially used to develop cannabinoid CB1 receptor antagonists for the treatment of nicotine addiction. Unfortunately, after being tested on experimental animals, what seemed to be an interesting approach for the treatment of nicotine addiction resulted in serious unwanted side effects when tested in humans. Current research is focusing again on pre-clinical models in an effort to eliminate unwanted side effects while preserving the initially observed efficacy. A 'bed side to bench strategy' was used to study the role of the insula (part of the frontal cortex) in nicotine addiction. This line of research started based on clinical observations that patients suffering stroke-induced lesions to the insula showed a greater likelihood to report immediate smoking cessation without craving or relapse. Subsequently, animal models of addiction are used to explore the role of insula in addiction. Due to the inherent limitations existing in clinical versus preclinical studies, the possibility of close interaction between both models seems to be critical for the successful development of novel therapeutic strategies for nicotine dependence. © 2013.

Teaching Argumentation by Using Facebook Groups

ERIC Educational Resources Information Center

Delen, Ibrahim

2017-01-01

Today argumentation is widely emphasized in the policy documents in Europe, and the US. Once we look at the literature in the last two decades, many studies noted students' challenges in this process. On the other side of the coin, we see in-service teachers with problems to support this process. Unfortunately, very few studies focused on this…

Can "Success" Become a "Curse"? "A View of Its Darker Side"

ERIC Educational Resources Information Center

Burch, Barbara; Cangemi, Joseph P.; Allen, Greg

2017-01-01

This article is about success, its positive aspects and, unfortunately, its negative aspects. Since most individuals are motivated to seek success from early on, what happens when an individual becomes quite successful and then believes he/she is more deserving of it? Such individuals often develop an overblown self-belief system, suggesting a…

How to Pay for Your One-to-One Program

ERIC Educational Resources Information Center

Kiker, Rich

2011-01-01

These days, school district budgets are getting hit on both sides: State budgets are facing drastic cuts across the United States at the same time that many schools are dealing with rising insurance premiums and retirement fund payouts. It's no wonder that technology is often an early casualty in district fiscal planning. Unfortunately, in this…

Anti-Diabetic Potential of Noni: The Yin and the Yang.

PubMed

Nerurkar, Pratibha V; Hwang, Phoebe W; Saksa, Erik

2015-09-25

Escalating trends of chronic diseases such as type-2 diabetes (T2D) have sparked a renewed interest in complementary and alternative medicine, including herbal products. Morinda citrifolia (noni) has been used for centuries by Pacific Islanders to treat various ailments. Commercial noni fruit juice has been marketed as a dietary supplement since 1996. In 2003, the European Commission approved Tahitian noni juice as a novel food by the Health and Consumer Protection Directorate General. Among noni's several health benefits, others and we have demonstrated the anti-diabetic effects of fermented noni fruit juice in animal models. Unfortunately, noni's exciting journey from Polynesian medicine to the research bench does not reach its final destination of successful clinical outcomes when translated into commercial products. Noni products are perceived to be safe due to their "natural" origin. However, inadequate evidence regarding bioactive compounds, molecular targets, mechanism of action, pharmacokinetics, long-term safety, effective dosages, and/or unanticipated side effects are major roadblocks to successful translation "from bench side to bedside". In this review we summarize the anti-diabetic potential of noni, differences between traditional and modern use of noni, along with beneficial clinical studies of noni products and challenges in clinical translation of noni's health benefits.

Use of lipid-lowering medicinal herbs during pregnancy: A systematic review on safety and dosage

PubMed Central

Rouhi-Boroujeni, Hojjat; Heidarian, Esfandiar; Rouhi-Boroujeni, Hamid; Khoddami, Minasadat; Gharipour, Mojgan; Rafieian-Kopaei, Mahmoud

2017-01-01

BACKGROUND Hyperlipidemia is one of the important diseases in pregnancy that causes fetal abnormalities during pregnancy and after the birth. Unfortunately, the usual anti-fat drugs are associated with high morbidity in fetus and due to people's inclination towards taking herbs, it is required to identify side effects of medicinal herbs in pregnancy. The aim of this study was to present hypolipidemic herbs that would not any complications for mother and fetus. METHODS In this review article, the major electronic databases such as EBSCO, Central Register of Controlled Trials (CENTRAL), China Network Knowledge Infrastructure (CNKI), Cochrane, Google scholar, MEDLINE, SciVerse, Scopus, and Web of Science were searched using the key words “herbal” and “hyperlipidemia”, “herbal” and “pregnancy” matched by MeSH from their respective inceptions till September, 2016. Total of 1723 publications (145 review articles, 855 original research articles, and 723 abstracts) about the effect of herbals on hyperlipidemia and 682 publications (200 abstracts, 423 original research articles, and 59 review articles) about the effect of herbals in pregnancy were retrieved. At the end, a list of medicinal plants effective on hyperlipidemia alongside their effects on pregnancy was developed. Finally, the plants effective on hyperlipidemia and safe during pregnancy were determined and their dosage, complications, mechanism of action, and side effects were reported. RESULTS A total of 110 effective herbs on hyperlipidemia were identified and complications of 95 plants in pregnancy were studied. At last, among the 55 selected plants effective on hyperlipidemia and examined for pregnancy, we reported 12 herbs with their dosage and special considerations that can be used to treat hyperlipidemia during pregnancy. CONCLUSION Some medicinal plants can be used to treat hyperlipidemia during pregnancy without any significant side effects both on mother or fetus. PMID:29147122

Concurrent Chagas’ disease and borderline disseminated cutaneous leishmaniasis: The role of amiodarone as an antitrypanosomatidae drug

PubMed Central

Paniz-Mondolfi, Alberto E; Pérez-Álvarez, Alexandra M; Reyes-Jaimes, Oscar; Socorro, Gustavo; Zerpa, Olga; Slova, Denisa; Concepción, Juan L

2008-01-01

The occurrence of mixed infections of Trypanosoma cruzi and Leishmania spp. is becoming a common feature in Central and South America due to overlapping endemic areas. Unfortunately, the possibilities for treating flagellated kinetoplastid infections are still very limited and most of the available drugs exhibit severe side effects. Although the development of new drugs for Leishmania has markedly improved in the last years, the tendency is still to employ antimonial compounds. On the other hand, treatment for Chagas’ disease is only available for the acute phase with no effective therapeutical options for chronic stage disease. The following case report substantiates the recently discovered effect of amiodarone as a nonconventional antiparasitic drug, particularly against Leishmania, breaching a new perspective in the therapeutic management of these important infectious parasitic diseases. PMID:18827865

[Leiomyoma of the bladder causing the destruction of a kidney].

PubMed

Kehila, Mehdi; Mekni, Karima; Abouda, Hassine Saber; Chtourou, Maher; Zeghal, Dorra; Chanoufi, Mohamed Badis

2016-01-01

Leiomyoma of the bladder is a rare benign tumor deemed to have a good prognosis after surgical treatment. This is unfortunately not always true. We report the case of a 33 year-old patient who consulted for lumbar pain on right side. Exploration of patient revealed bladder floor solid tumor with non-functioning right kidney and left urinary tract dilation. Cystoscopy objectified solid tumor of the right perimeatal bladder. Tumor biopsies were performed together with the insertion of a left double J stent. Anatomo-pathologic study showed leiomyoma of the bladder. The patient underwent laparoscopic myomectomy. The postoperative course was uneventful. Pathological effect and sequelae was complete distruction of kidney.

Medical management of heavy menstrual bleeding

PubMed Central

Maybin, Jacqueline A; Critchley, Hilary OD

2016-01-01

Women with benign heavy menstrual bleeding have the choice of a number of medical treatment options to reduce their blood loss and improve quality of life. The role of the clinician is to provide information to facilitate women in making an appropriate choice. Unfortunately, many options can be associated with hormonal side effects, prevention of fertility and lack of efficacy, leading to discontinuation and progression to surgical interventions. Herein, we discuss the various options currently available to women, including antifibrinolytics, nonsteroidal anti-inflammatory preparations, oral contraceptive pills and oral, injectable and intrauterine progestogens. In addition, we describe the more novel option of selective progesterone receptor modulators and their current benefits and limitations. PMID:26695687

High-fluence 1064-nm Q-Switched Nd:YAG laser: Safe and effective treatment of café-au-lait macules in Asian patients.

PubMed

Baek, Jin Ok; Park, Il-Joong; Lee, Kyung Real; Ryu, Ha Ryeong; Kim, Jeongsoo; Lee, Seulki; Kim, Yu Ri; Hur, Hoon

2018-06-01

Café-au-lait macules (CALMs) are benign cutaneous hyperpigmentary disorders. Usually, laser therapies for cosmetic concerns result in more severe side effects in the people of Asian descent than that of Caucasians. Unfortunately, there is no gold standard for the laser treatment of CALMs in skin of people of Asian descent. To investigate the efficacy and safety of a high-fluence 1064-nm Q-switched neodymium-doped yttrium aluminum garnet (Nd:YAG) laser treatment of CALMs in Asian patients. The medical records of 35 Korean patients (age range: 1 to 40 years old, mean age: 18.5 years) diagnosed with isolated CALMs were reviewed retrospectively. The patients were treated with a 1064-nm Q-switched Nd:YAG laser. The parameters were a spot size of 7 mm, a fluence of 2.2-2.4 J/cm 2 with a slow single sliding-stacking pass, and a pulse rate of 10 Hz with a 1-week interval for 20-50 sessions. At the week of the final treatment, all treated CALMs showed considerable pigmentation removal without any permanent side effects, such as scaring, mottled hypopigmentation and postinflammatory hyperpigmentation (PIH). All treated CALMs showed more than 50% clinical improvement. No recurrence was observed in any of the patients after 12 months of follow-up. A high-fluence 1064-nm Q-switched Nd:YAG laser treatment of CALMs in Asian patients is a safe and effective method without side effects and recurrence. © 2018 Wiley Periodicals, Inc.

Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.

PubMed

Arriola Apelo, Sebastian I; Neuman, Joshua C; Baar, Emma L; Syed, Faizan A; Cummings, Nicole E; Brar, Harpreet K; Pumper, Cassidy P; Kimple, Michelle E; Lamming, Dudley W

2016-02-01

Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA-approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effective management of low back pain: it’s time to accept the evidence

PubMed Central

Manga, Pran; Angus, Douglas E; Swan, William R

1993-01-01

Low back pain is a ubiquitous and economically costly problem. Unfortunately, the clinical management of low back pain is not yet well understood. Chiropractic management of back pain, long the black sheep of back care, has undergone a transition and is now a more respected and understood alternative to conservative medical care, itself under increased scrutiny due to unsatisfactory outcomes and unacceptable iatrogenic side effects. The substantial amount of clinical and related research on the effectiveness of manipulation for low back pain is summarized here from a larger study, divided into randomized control trials, case-control trials, meta-analyses and descriptive studies. The chiropractic management of low back pain is found to be a more effective way of dealing with this medical, social and economic problem. It is suggested that greater utilization of chiropractors be encouraged such that the “right people are doing the right things at the right time”.

Calcium channel modulation as a target in chronic pain control.

PubMed

Patel, Ryan; Montagut-Bordas, Carlota; Dickenson, Anthony H

2018-06-01

Neuropathic pain remains poorly treated for large numbers of patients, and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (Prialt™) was developed and approved as a first-in-class synthetic version of ω-conotoxin MVIIA, a peptide blocker of Ca v 2.2 channels. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide have restricted its use to exceptional circumstances. Ziconotide exhibits no state or use-dependent block of Ca v 2.2 channels; activation state-dependent blockers were hypothesized to circumvent the side effects of state-independent blockers by selectively targeting high-frequency firing of nociceptive neurones in chronic pain states, thus alleviating aberrant pain but not affecting normal sensory transduction. Unfortunately, numerous drugs, including state-dependent calcium channel blockers, have displayed efficacy in preclinical models but have subsequently been disappointing in clinical trials. In recent years, it has become more widely acknowledged that trans-aetiological sensory profiles exist amongst chronic pain patients and may indicate similar underlying mechanisms and drug sensitivities. Heterogeneity amongst patients, a reliance on stimulus-evoked endpoints in preclinical studies and a failure to utilize translatable endpoints, all are likely to have contributed to negative clinical trial results. We provide an overview of how electrophysiological and operant-based assays provide insight into sensory and affective aspects of pain in animal models and how these may relate to chronic pain patients in order to improve the bench-to-bedside translation of calcium channel modulators. This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc. © 2017 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Magnesium enhances opioid-induced analgesia - What we have learnt in the past decades?

PubMed

Bujalska-Zadrożny, Magdalena; Tatarkiewicz, Jan; Kulik, Kamila; Filip, Małgorzata; Naruszewicz, Marek

2017-03-01

Opioids are increasingly used in alleviating pain, including cancer-related pain and postoperative pain. Unfortunately, the development of tolerance, the resistance of neuropathic pain on opioid analgesia or other undesirable effects may limit their utility. In order to reduce opioid doses, and thereby to avoid the risk of side effects and sudden deaths due to overdosing, attempts have been made to introduce co-analgesics. Due to an increasing amount of data concerning a potential enhance of opioid analgesia by the physiological antagonist of N-methyl-d-aspartate receptors, magnesium ions (Mg 2+ ), a concomitant use of such a combination seems to be interesting from a clinical point of view. Therefore, the aim of this review is to provide an analysis of existing preclinical and clinical studies in the context of the benefits of using this combination in clinical practice. A potential mechanism of magnesium - opioid interaction is also suggested. The potential influence of Mg on opioid adverse/side effects as well as conclusions on the safety of combined administration of magnesium and opioid drugs were also summarized. Data from animal studies indicate that magnesium increases opioid analgesia in chronic (e.g., neuropathic, inflammatory) as well as acute pain. In clinical trials, most authors confirmed that magnesium reduces opioid consumption and alleviates postoperative pain scores while not increasing the risk of side effects after opioids. However, more clinical studies are needed concerning an influence of Mg on opioid activity in other difficult to treat types of pain, especially neuropathic and inflammatory. Copyright © 2016 Elsevier B.V. All rights reserved.

Biopolymers Containing Unnatural Amino Acids

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

Schultz, Peter

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

Biopolymers Containing Unnatural Building Blocks

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

Schultz, Peter G.

2013-06-30

Although the main chain structure of polymers has a profound effect on their materials properties, the side groups can also have dramatic effects on their properties including conductivity, liquid crystallinity, hydrophobicity, elasticity and biodegradability. Unfortunately control over the side chain structure of polymers remains a challenge – it is difficult to control the sequence of chain elongation when mixtures of monomers are polymerized, and postpolymerization side chain modification is made difficult by polymer effects on side chain reactivity. In contrast, the mRNA templated synthesis of polypeptides on the ribosome affords absolute control over the primary sequence of the twenty aminomore » acid monomers. Moreover, the length of the biopolymer is precisely controlled as are sites of crosslinking. However, whereas synthetic polymers can be synthesized from monomers with a wide range of chemically defined structures, ribosomal biosynthesis is largely limited to the 20 canonical amino acids. For many applications in material sciences, additional building blocks would be desirable, for example, amino acids containing metallocene, photoactive, and halogenated side chains. To overcome this natural constraint we have developed a method that allows unnatural amino acids, beyond the common twenty, to be genetically encoded in response to nonsense or frameshift codons in bacteria, yeast and mammalian cells with high fidelity and good yields. Here we have developed methods that allow identical or distinct noncanonical amino acids to be incorporated at multiple sites in a polypeptide chain, potentially leading to a new class of templated biopolymers. We have also developed improved methods for genetically encoding unnatural amino acids. In addition, we have genetically encoded new amino acids with novel physical and chemical properties that allow selective modification of proteins with synthetic agents. Finally, we have evolved new metal-ion binding sites in proteins using a novel metal-ion binding amino acid, which may facilitate our ability to generate new protein based sensors and catalysts.« less

Effect of Molecular Rotation on Charge Transport Phenomena

NASA Astrophysics Data System (ADS)

Garg, O. P.; Lamba, Vijay Kr; Kaushik, D. K.

2015-12-01

The study of electron transport properties of molecular systems could be explained on the basis of the Landauer formalism. Unfortunately, due to the complexity of the experimental setup, most of these measurements have no control over the details of the electrode geometry, rotation of molecules, variation in angle of contacts, effect of fano resonances associated with side groups attached to rigid backbones, which results in a spectrum of IV-characteristics. Theoretical models can therefore help to understand and helps to develop new applications such as molecular sensors, etc. Thus we used simulation methods that generate the required structural ensemble, which is then analyzed with Green’s function methods to characterize the electronic transport properties. In present work we had discussed applications of this approach to understand the conductance in molecular system in the direction of controlling electron transport through molecules and studied the effect of rotation of sandwiched molecule.

Small RNA Enhances Antitumor T-cell Therapy | Center for Cancer Research

Cancer.gov

Adoptive T-cell transfer is an effective form of anticancer immunotherapy in which patients receive infusions of cytotoxic T cells that seek out and destroy targeted cancer cells. This type of therapy is usually preceded by a lymphodepleting chemotherapy regimen and combined with high doses of the cytokine interleukin-2 (IL-2) to eliminate immunosuppressive and other immune cells and to enhance the survival and activity of the transplanted cells. Unfortunately, these high-intensity treatments often lead to severe side effects, such as a prolonged reduction of white blood cells, an increased risk of clotting events, or an accumulation of fluid in the tissues, which limit the pool of patients healthy enough to receive the treatment and can result in prolonged hospitalization and higher health care costs. New approaches that are less toxic but equally effective could allow for more widespread use of adoptive T-cell transfer.

Antennas.

DTIC Science & Technology

1982-03-03

drum of a particular diameter [3]. The supply drum was braked in doing this in order to create the necessary stretching force. The rewinding was done...Solar .4 and Lunar disc . Unfortunately, the accuracy of this method is low, and side lobes are practically impossible to measure. Preliminary trueing of...component). This recording of the Sun contains radiation from a group of spots on the right half (of the recording) of the Solar disc . Since the

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

PubMed Central

2014-01-01

Background Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. Methods These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. Results These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Conclusions Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments. PMID:25081580

Dexamethasone-induced catatonia in a patient with multiple myeloma.

PubMed

Vanstechelman, Sylvie; Vantilborgh, Anna; Lemmens, Gilbert

2016-12-01

Catatonia is a complex neuropsychiatric syndrome, caused by different underlying metabolic, neurologic, psychiatric and toxic conditions. Although catatonia is often associated with psychiatric disorders such as schizophrenia or depression, in about 20 to 39% of the patients a somatic illness is found. Unfortunately, this diagnosis is often missed although catatonia is characterized by a specific symptom complex. We report a case of acute catatonia with psychotic features in a patient with multiple myeloma (MM), caused by systemic use of dexamethasone. Physicians should be aware of possible psychiatric side effects when prescribing high doses of dexamethasone. Further, MM patients on corticosteroids should be closely monitored for mild psychological and/or psychiatric symptoms since they may be predictive for the onset of catatonia.

Corticosteroids in brain cancer patients: benefits and pitfalls

PubMed Central

Dietrich, Jörg; Rao, Krithika; Pastorino, Sandra; Kesari, Santosh

2011-01-01

Glucocorticoids have been used for decades in the treatment of brain tumor patients and belong to the most powerful class of agents in reducing tumor-associated edema and minimizing side effects and the risk of encephalopathy in patients undergoing radiation therapy. Unfortunately, corticosteroids are associated with numerous and well-characterized adverse effects, constituting a major challenge in patients requiring long-term application of corticosteroids. Novel anti-angiogenic agents, such as bevacizumab (Avastin®), which have been increasingly used in cancer patients, are associated with significant steroid-sparing effects, allowing neuro-oncologists to reduce the overall use of corticosteroids in patients with progressive malignant brain tumors. Recent experimental studies have revealed novel insights into the mechanisms and effects of corticosteroids in cancer patients, including modulation of tumor biology, angiogenesis and steroid-associated neurotoxicity. This article summarizes current concepts of using corticosteroids in brain cancer patients and highlights potential pitfalls in their effects on both tumor and neural progenitor cells. PMID:21666852

The Manned Penetrating Bomber: Time to Reconsider

DTIC Science & Technology

2016-06-01

choice: spend billions on nuclear weapons we no longer need or fund programs that educate our children and help find cures to deadly diseases. The...security of our nation’s future will be ensured by investing in education not nuclear annihilation…We need to stop pouring billions into the nuclear...event.61 Unfortunately, the president’s reaction to the launch received negative reviews from the general public. On a comical side note, the whole

Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma

PubMed Central

Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

2017-01-01

Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC. PMID:28322221

Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma.

PubMed

Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

2017-03-21

Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC.

Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

PubMed Central

Laube, Markus; Kniess, Torsten; Pietzsch, Jens

2016-01-01

Radiation therapy (RT) evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2) are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents. PMID:27104573

Hot topics in parenteral nutrition. A review of the use of glutamine supplementation in the nutritional support of patients undergoing bone-marrow transplantation and traditional cancer therapy.

PubMed

Crowther, Mark

2009-08-01

The relationship between glutamine and malignancy can be traced back to the 1950s and the requirement for glutamine for malignant-cell growth in culture. Later studies demonstrated an association between the rate of proliferation of the malignant cells and glutamine usage. The excessive use of glutamine by malignant cells was seen as an opportunity for the development of a treatment using glutamine analogues, but unfortunately excessive toxicity was observed during clinical studies. In animal models glutamine supplementation, initially thought to increase tumour growth, actually causes tumour regression as a result of improved immune clearance of the tumour and appears to reduce the severity of the side effects of chemo- and radiotherapy. This finding led to human studies in both traditional cancer therapy and bone-marrow transplantation, which are reviewed here. Unfortunately, the majority of the studies performed are small and have poor methodological reporting. There is clinical heterogeneity in terms of routes of administration, dosing schedules, chemotherapy regimens and diseases. Studies of glutamine in non-bone-marrow transplantation chemo- and/or radiotherapy treatment suggest a possible trend towards reductions in objective mucositis but no effect on subjective symptoms. There is no evidence for its effect on other clinical outcomes. For bone-marrow transplantation there appears to be some benefit from oral glutamine in reducing mucositis and graft v. host disease, while intravenous glutamine may reduce infections but at the expense of an increased relapse rate. Good-quality studies are required in this area.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation.

PubMed

Lunsford, Keri E; Bodzin, Adam S; Reino, Diego C; Wang, Hanlin L; Busuttil, Ronald W

2016-12-07

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, however, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Exercise in the Prevention and Treatment of Breast Cancer: What Clinicians Need to Tell Their Patients.

PubMed

Kraschnewski, Jennifer L; Schmitz, Kathryn H

In 2016, nearly a quarter-million women were diagnosed with invasive breast cancer, the second deadliest cancer type. Lifestyle behaviors are well-established risk factors for both the development of, and negative outcomes from, breast cancer. New findings demonstrate that engaging in even minimal amounts of exercise is protective against breast cancer. Further, numerous studies have identified the role of exercise in the treatment of breast cancer and improvement in treatment side effects, quality of life, and overall survival. Unfortunately, few patients are physically active due to multiple barriers. Physicians may be helpful in engaging patients in being more active. Further research is necessary to identify programs and approaches to help patients both with, and at-risk for, breast cancer to engage in exercise.

Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky.

PubMed

Skalicka-Woźniak, Krystyna; Georgiev, Milen I; Orhan, Ilkay Erdogan

2017-10-01

The popularity of herbal medicines and dietary supplements is increasing all over the world due to the many side-effects assigned to synthetic drugs. Herbal remedies should be considered as safe, with no side-effects, but unfortunately, even if they are labelled as natural, large numbers of adulterants, not only with toxic heavy metals but also with undeclared synthetic substances, have been detected up to date. In this review, the most frequent instances of adulteration of herbal medicines and dietary supplements acting as sexual enhancers and slimming products are thoroughly discussed. The great success of synthetic phosphodiesterase type-5 (PDE-5) inhibitory drugs like sildenafil, vardenafil and tadalafil, used for the treatment of erectile dysfunction has made them, as well as their unapproved analogues, popular as adulterants in herbal dietary supplements. The second group among blockbuster products are herbal preparations for slimming purpose, as obesity and gaining weight are major problems worldwide. Here, sibutramine hydrochloride monohydrate, an anti-obesity drug which inhibits serotonergic and noradrenergic reuptake, seems to be the most common adulterant. Together with large numbers of its analogues, thyroid hormones, anorexigens, diuretics, stimulants, and laxative agents are also detected in most of tested diet supplements. Copyright © 2016 Elsevier Ltd. All rights reserved.

Is There A Role For Lifestyle Interventions In Obsessive-Compulsive And Related Disorders?

PubMed

Fontenelle, Leonardo F; Quintas, Julliana N; Yücel, Murat

2018-01-04

Many of the currently available treatments for obsessive-compulsive and related disorders (OCRDs) such as pharmacotherapy augmentation strategies, partial hospitalization programs, deep brain stimulation, and neurosurgery are efficacious for individuals suffering from more severe forms of these conditions. Unfortunately, the application of these treatments in milder forms of illness and subclinical samples, which affect a substantial portion of the population, is not justifiable by their costs (e.g. cognitive-behavioral therapy) and/or potential for side effects (serotonin-reuptake inhibitors associated sexual side effects). As such, there is an urgent need to develop simple yet effective treatments, such as modifiable lifestyle interventions, that can be employed on a broader scale. Here, we review the current state of evidence that supports or refutes the efficacy of lifestyle approaches for OCRDs. We focus on dimensions of lifestyle that are deemed important for cardiovascular diseases; namely, physical activity, stress, sleep, diet and eating behaviors, alcohol consumption, and smoking. Despite the relative scarcity of well-designed randomized controlled trials targeting unhealthy life styles in OCRDs, we found meditation-based therapies and interventions focusing on eliminating sedentarism to be promising approaches. In the future, these strategies may represent valid alternative for subjects with subthreshold symptoms or at risk for OCRDs or other "compulsive" disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development and characterization of targeted poly(NIPAm) nanoparticles for delivery of anti-inflammatory peptides in peripheral artery disease and osteoarthritis

NASA Astrophysics Data System (ADS)

McMasters, James F.

Inflammation is the underlying cause of several severe diseases including cardiovascular disease and osteoarthritis. Peripheral artery disease (PAD) is characterized by atherosclerotic occlusions within the peripheral vasculature. Current treatment for severe PAD involves mechanical widening of the artery via percutaneous transluminal angioplasty. Unfortunately, deployment of the balloon damages the endothelial layer, exposing the underlying collagenous matrix. Circulating platelets can bind to this collagen and become activated, releasing proinflammatory cytokines that promote proliferation of local smooth muscle cells. These proliferating cells eventually reocclude the vessel, resulting in restenosis and necessitating the need for a second procedure to reopen the vessel. Current treatments for moderate osteoarthritis include local injection of anti-inflammatory compounds such as glucocorticoids. Unfortunately, prolonged treatment carries with it significant side effects including osteoporosis, and cardiovascular complications. Our lab has developed an anti-inflammatory cell-penetrating peptide that inhibits mitogen-activated protein kinase activated protein kinase 2 (MK2). MK2 is implicated in the inflammatory cascade of atherosclerosis and osteoarthritis, making it a potentially effective strategy for reducing inflammation in both disease states. Unfortunately, these peptides are untargeted and quickly degraded in the presence of serum proteases, making the development of an effective delivery system of paramount importance. The overall goal of the research presented here is to detail the development of a poly(N-isopropylacrylamide) nanoparticle that is able to effectively load and release anti-inflammatory peptides for the treatment of these inflammatory diseases. In this dissertation, I will discuss the development of a collagen-binding nanoparticle that is able to inhibit platelet binding following angioplasty, thereby halting the initial inflammatory cascade. Additionally, these particles demonstrate the ability to reduce inflammation by through the loading and release of MK2-inhibiting cell-penetrating peptides. Additionally, I will cover the development of a hollow nanoparticle system that is designed to load increased quantities of these anti-inflammatory peptides for the treatment of osteoarthritis. This particle demonstrated increased macrophage uptake and prolonged drug release, resulting in a progressive inhibition of osteoarthritic inflammation over 8 days. The results presented here advance our understanding of these nanoparticle platforms, and suggest that they may serve at effective platforms for the treatment of restenosis following angioplasty, as well as osteoarthritis.

Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS

DTIC Science & Technology

2008-05-01

Unfortunately, among the methylation status of the AP2, CYCLIN D, ECAD , GSTP, and SSOCS genes, either as individual genes, or in combinations, no...0.61 to 4.10) 1.00 (referent) 0.35 ECAD M UM 0 100 3 97 GSTP M UM 40 60 24 76 2.02 (0.72 to 5.64) 1.00...Missing data: 1.4% for AP2, CYCLIN D, ECAD , GSTP; 4.2% for SSOCS; 2.8% for nuclear grade. §M=methylated; UM=unmethylated; +Two-sided

Archambault wearing LES in the FD on STS-117 Space Shuttle Atlantis

NASA Image and Video Library

2007-06-21

S117-E-09438 (21 June 2007) --- Attired in his launch and entry garment, astronaut Lee Archambault, STS-117 pilot, appears all ready for re-entry and landing of the Space Shuttle Atlantis, as he signals thumbs-up from the pilot's station on the starboard side of the shuttle's flight deck. Unfortunately, the weather in Florida was not ready, and the crew had to wait until the following day to land. They ultimately landed in California.

Flexible organic light-emitting diodes with enhanced light out-coupling efficiency fabricated on a double-sided nanotextured substrate.

PubMed

Luo, Yu; Wang, Chunhui; Wang, Li; Ding, Yucheng; Li, Long; Wei, Bin; Zhang, Jianhua

2014-07-09

High-efficiency organic light-emitting diodes (OLEDs) have generated tremendous research interest. One of the exciting possibilities of OLEDs is the use of flexible plastic substrates, which unfortunately have a mismatching refractive index compared with the conventional ITO anode and the air. To unlock the light loss on flexible plastic, we report a high-efficiency flexible OLED directly fabricated on a double-sided nanotextured polycarbonate substrate by thermal nanoimprint lithography. The template for the nanoimprint process is a replicate from a silica arrayed with nanopillars and fabricated by ICP etching through a SiO2 colloidal spheres mask. It has been shown that with the internal quasi-periodical scattering gratings the efficiency enhancement can reach 50% for a green light OLED, and with an external antireflection structure, the normal transmittance is increased from 89% to 94% for paraboloid-like pillars. The OLED directly fabricated on the double-sided nanotextured polycarbonate substrate has reached an enhancing factor of ∼2.8 for the current efficiency.

Side-locked headaches: an algorithm-based approach.

PubMed

Prakash, Sanjay; Rathore, Chaturbhuj

2016-12-01

The differential diagnosis of strictly unilateral hemicranial pain includes a large number of primary and secondary headaches and cranial neuropathies. It may arise from both intracranial and extracranial structures such as cranium, neck, vessels, eyes, ears, nose, sinuses, teeth, mouth, and the other facial or cervical structure. Available data suggest that about two-third patients with side-locked headache visiting neurology or headache clinics have primary headaches. Other one-third will have either secondary headaches or neuralgias. Many of these hemicranial pain syndromes have overlapping presentations. Primary headache disorders may spread to involve the face and / or neck. Even various intracranial and extracranial pathologies may have similar overlapping presentations. Patients may present to a variety of clinicians, including headache experts, dentists, otolaryngologists, ophthalmologist, psychiatrists, and physiotherapists. Unfortunately, there is not uniform approach for such patients and diagnostic ambiguity is frequently encountered in clinical practice.Herein, we review the differential diagnoses of side-locked headaches and provide an algorithm based approach for patients presenting with side-locked headaches. Side-locked headache is itself a red flag. So, the first priority should be to rule out secondary headaches. A comprehensive history and thorough examinations will help one to formulate an algorithm to rule out or confirm secondary side-locked headaches. The diagnoses of most secondary side-locked headaches are largely investigations dependent. Therefore, each suspected secondary headache should be subjected for appropriate investigations or referral. The diagnostic approach of primary side-locked headache starts once one rule out all the possible secondary headaches. We have discussed an algorithmic approach for both secondary and primary side-locked headaches.

Opioids Resistance in Chronic Pain Management

PubMed Central

Morrone, Luigi A.; Scuteri, Damiana; Rombolà, Laura; Mizoguchi, Hirokazu; Bagetta, Giacinto

2017-01-01

Abstract: Chronic pain management represents a serious healthcare problem worldwide. Chronic pain affects approximately 20% of the adult European population and is more frequent in women and older people. Unfortunately, its management in the community remains generally unsatisfactory and rarely under the control of currently available analgesics. Opioids have been used as analgesics for a long history and are among the most used drugs; however, while there is no debate over their short term use for pain management, limited evidence supports their efficacy of long-term treatment for chronic non-cancer pain. Therapy with opioids is hampered by inter-individual variability and serious side effects and some opioids often result ineffective in the treatment of chronic pain and their use is controversial. Accordingly, for a better control of chronic pain a deeper knowledge of the molecular mechanisms underlying resistance to opiates is mandatory. PMID:28503117

Ultra-Low Doses of Naltrexone Enhance the Antiallodynic Effect of Pregabalin or Gabapentin in Neuropathic Rats.

PubMed

Pineda-Farias, Jorge B; Caram-Salas, Nadia L; Salinas-Abarca, Ana B; Ocampo, Jorge; Granados-Soto, Vinicio

2017-12-01

Preclinical Research Treatment of neuropathic pain is an area of largely unmet medical need. Pregabalin and gabapentin are anticonvulsants widely used for the treatment of neuropathic pain. Unfortunately, these drugs are only effective in 50-60% of the treated patients. In addition, both drugs have substantial side effects. Several studies have reported that ultralow doses of opioid receptor antagonists can induce analgesia and enhance the analgesic effect of opioids in rodents and humans. The objective of the present study was to assess the antiallodynic synergistic interaction between gabapentinoids and naltrexone in rats. Oral administration of pregabalin (ED 50  = 2.79 ± 0.16 mg/kg) or gabapentin (ED 50  = 21.04 ± 2.87 mg/kg) as well as intrathecal naltrexone (ED 50  = 0.11 ± 0.02 ng) reduced in a dose-dependent manner tactile allodynia in rats. Maximal antiallodynic effects (∼100%) were reached with 30 mg/kg of pregabalin, 300 mg/kg of gabapentin or 0.5 ng of naltrexone. Co-administration of pregabalin or gabapentin and naltrexone in a fixed-dose ratio (1:1) remarkably reduced spinal nerve ligation-induced tactile allodynia showing a synergistic interaction. The data indicate that combinations of pregabalin or gabapentin and ultra-low doses of naltrexone are able to reduce tactile allodynia in neuropathic rats with lower doses that those used when drugs are given individually and with an improved side effects profile. Drug Dev Res 78 : 371-380, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Pharmacological Effects of Active Components of Chinese Herbal Medicine in the Treatment of Alzheimer's Disease: A Review.

PubMed

Wang, Zhi-Yong; Liu, Jian-Gang; Li, Hao; Yang, Hui-Ming

2016-01-01

Alzheimer's disease (AD), the most common neurodegenerative disorder associated with dementia, not only severely decreases the quality of life for its victims, but also brings a heavy economic burden to the family and society. Unfortunately, few chemical drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far, and combined with their significant side-effects, there is therefore an urgent need for new strategies to be developed for AD treatment. Traditional Chinese Medicine has accumulated many experiences in the treatment of dementia during thousands of years of practice; modern pharmacological studies have confirmed the therapeutic effects of many active components derived from Chinese herbal medicines (CHM). Ginsenoside Rg1, extracted from Radix Ginseng, exerts a [Formula: see text]-secretase inhibitor effect so as to decrease A[Formula: see text] aggregation. It can also inhibit the apoptosis of neuron cells. Tanshinone IIA, extracted from Radix Salviae miltiorrhizae, and baicalin, extracted from Radix Scutellariae[Formula: see text] can inhibit the oxidative stress injury in neuronal cells. Icariin, extracted from Epimedium brevicornum, can decrease A[Formula: see text] levels and the hyperphosphorylation of tau protein, and can also inhibit oxidative stress and apoptosis. Huperzine A, extracted from Huperzia serrata, exerts a cholinesterase inhibitor effect. Evodiamine, extracted from Fructus Evodiae, and curcumin, extracted from Rhizoma Curcumae Longae, exert anti-inflammatory actions. Curcumin can act on A[Formula: see text] and tau too. Due to the advantages of multi-target effects and fewer side effects, Chinese medicine is more appropriate for long-term use. In this present review, the pharmacological effects of commonly used active components derived from Chinese herbal medicines in the treatment of AD are discussed.

Side-by-side ANFIS as a useful tool for estimating correlated thermophysical properties

NASA Astrophysics Data System (ADS)

Grieu, Stéphane; Faugeroux, Olivier; Traoré, Adama; Claudet, Bernard; Bodnar, Jean-Luc

2015-12-01

In the present paper, an artificial intelligence-based approach dealing with the estimation of correlated thermophysical properties is designed and evaluated. This new and "intelligent" approach makes use of photothermal responses obtained when homogeneous materials are subjected to a light flux. Commonly, gradient-based algorithms are used as parameter estimation techniques. Unfortunately, such algorithms show instabilities leading to non-convergence in case of correlated properties to be estimated from a rebuilt impulse response. So, the main objective of the present work was to simultaneously estimate both the thermal diffusivity and conductivity of homogeneous materials, from front-face or rear-face photothermal responses to pseudo random binary signals. To this end, we used side-by-side neuro-fuzzy systems (adaptive network-based fuzzy inference systems) trained with a hybrid algorithm. We focused on the impact on generalization of both the examples used during training and the fuzzification process. In addition, computation time was a key point to consider. That is why the developed algorithm is computationally tractable and allows both the thermal diffusivity and conductivity of homogeneous materials to be simultaneously estimated with very good accuracy (the generalization error ranges between 4.6% and 6.2%).

Inhibition of PKCδ reduces cisplatin-induced nephrotoxicity without blocking chemotherapeutic efficacy in mouse models of cancer

PubMed Central

Pabla, Navjotsingh; Dong, Guie; Jiang, Man; Huang, Shuang; Kumar, M. Vijay; Messing, Robert O.; Dong, Zheng

2011-01-01

Cisplatin is a widely used cancer therapy drug that unfortunately has major side effects in normal tissues, notably nephrotoxicity in kidneys. Despite intensive research, the mechanism of cisplatin-induced nephrotoxicity remains unclear, and renoprotective approaches during cisplatin-based chemotherapy are lacking. Here we have identified PKCδ as a critical regulator of cisplatin nephrotoxicity, which can be effectively targeted for renoprotection during chemotherapy. We showed that early during cisplatin nephrotoxicity, Src interacted with, phosphorylated, and activated PKCδ in mouse kidney lysates. After activation, PKCδ regulated MAPKs, but not p53, to induce renal cell apoptosis. Thus, inhibition of PKCδ pharmacologically or genetically attenuated kidney cell apoptosis and tissue damage, preserving renal function during cisplatin treatment. Conversely, inhibition of PKCδ enhanced cisplatin-induced cell death in multiple cancer cell lines and, remarkably, enhanced the chemotherapeutic effects of cisplatin in several xenograft and syngeneic mouse tumor models while protecting kidneys from nephrotoxicity. Together these results demonstrate a role of PKCδ in cisplatin nephrotoxicity and support targeting PKCδ as an effective strategy for renoprotection during cisplatin-based cancer therapy. PMID:21633170

Herbal medicine for sports: a review.

PubMed

Sellami, Maha; Slimeni, Olfa; Pokrywka, Andrzej; Kuvačić, Goran; D Hayes, Lawrence; Milic, Mirjana; Padulo, Johnny

2018-01-01

The use of herbal medicinal products and supplements has increased during last decades. At present, some herbs are used to enhance muscle strength and body mass. Emergent evidence suggests that the health benefits from plants are attributed to their bioactive compounds such as Polyphenols, Terpenoids, and Alkaloids which have several physiological effects on the human body. At times, manufacturers launch numerous products with banned ingredient inside with inappropriate amounts or fake supplement inducing harmful side effect. Unfortunately up to date, there is no guarantee that herbal supplements are safe for anyone to use and it has not helped to clear the confusion surrounding the herbal use in sport field especially. Hence, the purpose of this review is to provide guidance on the efficacy and side effect of most used plants in sport. We have identified plants according to the following categories: Ginseng, alkaloids, and other purported herbal ergogenics such as Tribulus Terrestris , Cordyceps Sinensis. We found that most herbal supplement effects are likely due to activation of the central nervous system via stimulation of catecholamines. Ginseng was used as an endurance performance enhancer, while alkaloids supplementation resulted in improvements in sprint and cycling intense exercises. Despite it is prohibited, small amount of ephedrine was usually used in combination with caffeine to enhance muscle strength in trained individuals. Some other alkaloids such as green tea extracts have been used to improve body mass and composition in athletes. Other herb (i.e. Rhodiola, Astragalus) help relieve muscle and joint pain, but results about their effects on exercise performance are missing.

Recent advances in discovery and development of natural products as source for anti-Parkinson's disease lead compounds.

PubMed

Zhang, Hongjia; Bai, Lan; He, Jun; Zhong, Lei; Duan, Xingmei; Ouyang, Liang; Zhu, Yuxuan; Wang, Ting; Zhang, Yiwen; Shi, Jianyou

2017-12-01

Parkinson's disease (PD) is a common chronic degenerative disease of the central nervous system. Although the cause remains unknown, several pathological processes and central factors such as oxidative stress, mitochondrial injury, inflammatory reactions, abnormal deposition of α-synuclein, and cell apoptosis have been reported. Currently, anti-PD drugs are classified into two major groups: drugs that affect dopaminergic neurons and anti-cholinergic drugs. Unfortunately, the existing conventional strategies against PD are with numerous side effects, and cannot fundamentally improve the degenerative process of dopaminergic neurons. Therefore, novel therapeutic approaches which have a novel structure, high efficiency, and fewer side effects are needed. For many years, natural products have provided an efficient resource for the discovery of potential therapeutic agents. Among them, many natural products possess anti-PD properties as a result of not only their wellrecognized anti-oxidative and anti-inflammatory activities but also their inhibitory roles regarding protein misfolding and the regulatory effects of PD related pathways. Indeed, with the steady improvement in the technologies for the isolation and purification of natural products and the in-depth studies on the pathogenic mechanisms of PD, many monomer components of natural products that have anti-PD effects have been gradually discovered. In this article, we reviewed the research status of 37 natural products that have been discovered to have significant anti-PD effects as well as their mode of action. Overall, this review may guide the design of novel therapeutic drugs in PD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Endocannabinoids in Body Weight Control.

PubMed

Horn, Henrike; Böhme, Beatrice; Dietrich, Laura; Koch, Marco

2018-05-30

Maintenance of body weight is fundamental to maintain one's health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing. Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis. Initially, blocking of eCB signaling by first generation cannabinoid type 1 receptor (CB1) inverse agonists such as rimonabant revealed body weight-reducing effects in laboratory animals and men. Unfortunately, rimonabant also induced severe psychiatric side effects. At this point, it became clear that future cannabinoid research has to decipher more precisely the underlying central and peripheral mechanisms behind eCB-driven control of feeding behavior and whole body energy metabolism. Here, we will summarize the most recent advances in understanding how central eCBs interfere with circuits in the brain that control food intake and energy expenditure. Next, we will focus on how peripheral eCBs affect food digestion, nutrient transformation and energy expenditure by interfering with signaling cascades in the gastrointestinal tract, liver, pancreas, fat depots and endocrine glands. To finally outline the safe future potential of cannabinoids as medicines, our overall goal is to address the molecular, cellular and pharmacological logic behind central and peripheral eCB-mediated body weight control, and to figure out how these precise mechanistic insights are currently transferred into the development of next generation cannabinoid medicines displaying clearly improved safety profiles, such as significantly reduced side effects.

Harsh medicine. [retail wheeling experiment in Michigan and side effects

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

Studness, C.M.

1993-07-15

Retailing wheeling's harmful side-effects may surface in a Michigan experiment. In the final analysis, the debate over retail wheeling is about whether there will be direct price competition in the electric power industry. Retail wheeling would extend to the electric power market the same freedom of choice among customers that is present elsewhere in the economy. It would provide a mechanism through which competition could enforce an efficient allocation of resources. It also undoubtedly would eliminate most of the huge discrepancies that exist between so many neighboring service areas. It is unlikely that permitting retail wheeling would actually result inmore » much wheeling or loss of load. Utilities will no doubt meet the threat of the loss of load by cutting rates to hold their customers. Hence, the primary effect would be on the pricing of electricity, not the wheeling of power. The retail wheeling experiment under consideration in Michigan can become an important step toward making the utility industry more efficient for the nation and more equitable for ratepayers. Unfortunately, it also is potentially unfair to the utilities involved. A retail wheeling experiment in one state is likely to put those utilities at risk for competitive attack, but is unlikely to give those utilities the countervailing power to use retail wheeling elsewhere to market their power. Fairness and economic efficiency require that retail wheeling exist everywhere, and that is is accessible to utilities as well as non-utilities.« less

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration

PubMed Central

Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V.; Glick, Stanley D.; Ron, Dorit

2013-01-01

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action. PMID:21040239

The current state of drug discovery and a potential role for NMR metabolomics.

PubMed

Powers, Robert

2014-07-24

The pharmaceutical industry has significantly contributed to improving human health. Drugs have been attributed to both increasing life expectancy and decreasing health care costs. Unfortunately, there has been a recent decline in the creativity and productivity of the pharmaceutical industry. This is a complex issue with many contributing factors resulting from the numerous mergers, increase in out-sourcing, and the heavy dependency on high-throughput screening (HTS). While a simple solution to such a complex problem is unrealistic and highly unlikely, the inclusion of metabolomics as a routine component of the drug discovery process may provide some solutions to these problems. Specifically, as the binding affinity of a chemical lead is evolved during the iterative structure-based drug design process, metabolomics can provide feedback on the selectivity and the in vivo mechanism of action. Similarly, metabolomics can be used to evaluate and validate HTS leads. In effect, metabolomics can be used to eliminate compounds with potential efficacy and side effect problems while prioritizing well-behaved leads with druglike characteristics.

Cell Culture Models and Pharmacological Perspective for the Study of Breast Cancer Markers

PubMed Central

Tovar, Cristian Layton

2013-01-01

Among the most prevalent neoplasias, breast cancer shows an astonishing tendency. Unfortunately this cancer has a high mortality worldwide, requiring sustained management of all actors involved in public health in order to get an early diagnosis and treatment. The methods associated with conventional cytogenetics and molecular cell culture, besides early detection of gene expression patterns associated with cancer susceptibility, have contributed to identify inherited genes and metabolic disorders related to obesity, which are also involved in breast cancer. In any case, a broad study of the above mentioned factors can give a predictive value to support the design of public health models to determine cancer risk in order to decrease the mortality from this disease. (1) Cell cultures offers a wide range of scientific approach for the study of breast cancer, including the analysis of biological function of several compounds in search of increasingly effective treatments with fewer side effects against this malignancy. (2) PMID:27683438

Laparoscopic totally extraperitoneal repair of inguinal hernia using two-hand approach--a gold standard alternative to open repair.

PubMed

Rajapandian, S; Senthilnathan, P; Gupta, Atul; Gupta, Pinak Das; Praveenraj, P; Vaitheeswaran, V; Palanivelu, C

2010-10-01

As laparoscopy gained popularity, minimal invasive approach was also applied for hernia surgery. Unfortunately the initial efforts were disappointing due to high early recurrence rate. Experience led to refinement of technique, with acceptable recurrence rates. This combined with the advantages of minimal invasive surgery resulted in a gradual rise in worldwide acceptance of this technique. Our preferred approach for inguinal hernia repair is laparoscopic totally extraperitoneal (TEP); only in complicated hernias (sliding or incarcerated inguinal hernias) we use the transabdominal preperitoneal repair (TAPP) technique. Records of all patients who underwent TEP repair for inguinal hernia at our centre in last 15 years were retrospectively analysed. We have done 8659 hernias in 7023 patients by TEP approach. We have developed minor modifications for the TEP repair over the years. Out of total 8659 hernias 5262 was right sided and 3397 left sided. Of these, 5387 hernias were unilateral and the remainder were bilateral; 324 cases of recurrent hernias following open repair underwent TEP. Most of the patients were males with a mean age of 46 years. Indirect hernias were most common, followed by direct hernias. Right-sided hernias were more common than left-sided hernias. In 39 cases conversion to TAPP was needed. There were intra-operative problems in 250 patients (3.56%).Postoperative complications were seen in 192 patients (2.73%), majority of which were minor complications. There was no mortality. Recurrence rate was 0.39%. The TEP technique is comfortable and highly effective. Our port placement maintains triangular orientation that is considered vital to the ergonomics of laparoscopy. Nearly 98-99% of inguinal hernias can be treated by TEP approach with excellent results.

Current STEREO Status on the Far Side of the Sun

NASA Astrophysics Data System (ADS)

Thompson, William T.; Gurman, Joseph; Ossing, Daniel; Luhmann, Janet; Curtis, David; Schroeder, Peter; Mewaldt, Richard; Davis, Andrew; Wortman, Kristin; Russell, Christopher; Galvin, Antoinette; Kistler, Lynn; Ellis, Lorna; Howard, Russell; Vourlidas, Angelos; Rich, Nathan; Hutting, Lynn; Maksimovic, Milan; Bale, Stuart D.; Goetz, Keith

2015-04-01

The current positions of the two STEREO spacecraft on the opposite side of the Sun from Earth (superior solar conjunction) has forced some significant changes in the spacecraft and instrument operations. No communications are possible when the spacecraft is within 2 degrees of the Sun, requiring that the spacecraft be put into safe mode until communications can be restored. Unfortunately, communications were lost with the STEREO Behind spacecraft on October 1, 2014, during testing for superior solar conjunction operations. We will discuss what is known about the causes of loss of contact, the steps being taken to try to recover the Behind spacecraft, and what has been done to prevent a similar occurrence on STEREO Ahead.We will also discuss the effect of being on the far side of the Sun on the science operations of STEREO Ahead. Starting on August 20, 2014, the telemetry rate from the STEREO Ahead spacecraft has been tremendously reduced due to the need to keep the temperature of the feed horn on the high gain antenna below acceptable limits. However, the amount of telemetry that can be brought down has been highly reduced. Even so, significant science is still possible from STEREO's unique position on the solar far side. We will discuss the science and space weather products that are, or will be, available from each STEREO instrument, when those products will be available, and how they will be used. Some data, including the regular space weather beacon products, are brought down for an average of a few hours each day during the daily real-time passes, while the in situ and radio beacon data are being stored on the onboard recorder to provide a continuous 24-hour coverage for eventual downlink once the spacecraft is back to normal operations.

Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.

PubMed

Luca, Giovanni; Calvitti, Mario; Mancuso, Francesca; Falabella, Giulia; Arato, Iva; Bellucci, Catia; List, Edward O; Bellezza, Enrico; Angeli, Giovanni; Lilli, Cinzia; Bodo, Maria; Becchetti, Ennio; Kopchick, John J; Cameron, Don F; Baroni, Tiziano; Calafiore, Riccardo

2013-01-10

Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth. Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain. In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome. These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans. Copyright © 2012 Elsevier B.V. All rights reserved.

Protein Side-Chain Resonance Assignment and NOE Assignment Using RDC-Defined Backbones without TOCSY Data3

PubMed Central

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

2011-01-01

One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA have backbone RMSD 0.8 – 1.5 Å from the reference structures determined by traditional NMR approaches. PMID:21706248

The effect of coenzyme Q10 in statin myopathy.

PubMed

Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

2012-01-01

Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (p<0.0001), muscle weakness by 44.4% (p<0.0001). The CQ10 levels were increased by more than 194% (from 0,903 μg/ml to 2.66 μg/ml; p<0.0001). After a six-month administration of coenzyme Q10, muscle pain and sensitivity statistically significantly decreased.

Iron deficiency: new insights into diagnosis and treatment.

PubMed

Camaschella, Clara

2015-01-01

Iron deficiency and iron deficiency anemia are common conditions worldwide affecting especially children and young women. In developing countries, iron deficiency is caused by poor iron intake and/or parasitic infection, whereas vegetarian dietary choices, poor iron absorption, and chronic blood loss are common causes in high-income countries. Erythropoiesis stimulating agents can result in functional iron deficiency for erythropoiesis even when stores are iron-replete. Diagnosis of iron deficiency is straightforward, except when it occurs in the context of inflammatory disorders. Oral iron salts correct absolute iron deficiency in most patients, because low hepcidin levels facilitate iron absorption. Unfortunately frequent side effects limit oral iron efficacy. Intravenous iron is increasingly utilized, because currently available preparations allow rapid normalization of total body iron even with a single infusion and are effective also in functional iron deficiency and in iron deficiency associated with inflammatory disorders. The evidence is accumulating that these preparations are safe and effective. However, long-term safety issues of high doses of iron need to be further explored. © 2015 by The American Society of Hematology. All rights reserved.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

PubMed

Nagano, Nobuo; Tsutsui, Takaaki

2016-06-01

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

The effect of immunodeficiency on the evolution of virulence: an experimental test with the rodent malaria Plasmodium chabaudi.

PubMed

Barclay, Victoria C; Kennedy, David A; Weaver, Veronika C; Sim, Derek; Lloyd-Smith, James O; Read, Andrew F

2014-08-01

Host immunity plays an important role in the evolution of pathogen virulence and disease emergence. There is increasing theoretical and empirical evidence that enhanced immunity through vaccination may have the unfortunate side effect of selecting for more virulent parasites, but the effect of host immune suppression on pathogen evolution is less clear. Here, we use serial passage experiments in mice to test how immune-suppressed hosts may alter pathogen virulence evolution. We passaged Plasmodium chabaudi through CD4(+) T cell-depleted or control mice every 7 days for 20 weeks and then measured virulence differences during infection of immunologically normal mice. We found that those parasites that had been selected through CD4(+) T cell-depleted mice were more virulent than parasites selected through control mice. Virulence increases during serial passage are believed to be caused by pathogen adaptation to the passage host. These data suggest that immune-suppressed hosts could provide a within-host environment that lowers the barrier to parasite adaptation and promotes the evolution of virulence.

Genetics of antipsychotic-induced weight gain: update and current perspectives.

PubMed

Kao, Amy C C; Müller, Daniel J

2013-12-01

Antipsychotic medications are used to effectively treat various symptoms for different psychiatric conditions. Unfortunately, antipsychotic-induced weight gain (AIWG) is a common side effect that frequently results in obesity and secondary medical conditions. Twin and sibling studies have indicated that genetic factors are likely to be highly involved in AIWG. Over recent years, there has been considerable progress in this area, with several consistently replicated findings, as well as the identification of new genes and implicated pathways. Here, we will review the most recent genetic studies related to AIWG using the Medline database (PubMed) and Google Scholar. Among the steadiest findings associated with AIWG are serotonin 2C receptors (HTR2C) and leptin promoter gene variants, with more recent studies implicating MTHFR and, in particular, MC4R genes. Additional support was reported for the HRH1, BDNF, NPY, CNR1, GHRL, FTO and AMPK genes. Notably, some of the reported variants appear to have relatively large effect sizes. These findings have provided insights into the mechanisms involved in AIWG and will help to develop predictive genetic tests in the near future.

[Photodynamic therapy of dysplasias and early carcinomas in Barrett esophagus with a diode laser system--a pilot study].

PubMed

Zöpf, T; Rosenbaum, A; Apel, D; Jakobs, R; Arnold, J C; Riemann, J F

2001-04-15

Photodynamic therapy (PDT) of dysplasia and early cancer of the esophagus could show good results in the potential of ablation. Unfortunately, the existing expensive and temperamental dye laser systems foiled a broad clinical use. In this pilot study, we investigated the feasibility of an inexpensive and maintenance-free diode laser system for PDT of dysplasia and early cancer in Barrett's esophagus. Eight patients with Barrett's esophagus and/or early cancer were treated. As light source we used a diode laser system with a maximum power output of 2 W and a wavelength of 633 +/- 3 nm. One patient was treated initially with Photosan-3, seven patients received 5-aminolevulinic acid. In all patients we could achieve reduction in length and/or histologically proven downgrading. In three quarters of the patients, complete eradication of adenocarcinoma could be attained. Columnar-lined metaplastic epithelium could also be completely eradicated. PDT using a diode laser system is comparably effective in Barrett's esophagus/early cancer as PDT with dye laser systems. PDT is a gentle and effective technique with little side effects.

Design strategies and applications of circulating cell-mediated drug delivery systems.

PubMed

Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

2015-01-01

Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

Three-dimensional CT might be a potential evaluation modality in correction of asymmetrical masseter muscle hypertrophy by botulinum toxin injection.

PubMed

No, Yeon A; Ahn, Byeong Heon; Kim, Beom Joon; Kim, Myeung Nam; Hong, Chang Kwon

2016-01-01

For correction of this asymmetrical hypertrophy, botulinum toxin type A (BTxA) injection is one of convenient treatment modalities. Unfortunately, physical examination of masseter muscle is not enough to estimate the exact volume of muscle hypertrophy difference. Two Koreans, male and female, of bilateral masseter hypertrophy with asymmetricity were evaluated. BTxA (NABOTA(®), Daewoong, Co. Ltd., Seoul, Korea) was injected at master muscle site with total 50 U (25 U at each side) and volume change was evaluated with three-dimensional (3D) CT image analysis. Maximum reduction of masseter hypertrophy was recognized at 2-month follow-up and reduced muscle size started to restore after 3 months. Mean reduction of masseter muscle volume was 36% compared with baseline. More hypertrophied side of masseter muscle presented 42% of volume reduction at 2-month follow-up but less hypertrophied side of masseter muscle showed 30% of volume shrinkage. In conclusion, 3D CT image analysis might be the exact evaluation tool for correction of asymmetrical masseter hypertrophy by botulinum toxin injection.

RSQRT: AN HEURISTIC FOR ESTIMATING THE NUMBER OF CLUSTERS TO REPORT.

PubMed

Carlis, John; Bruso, Kelsey

2012-03-01

Clustering can be a valuable tool for analyzing large datasets, such as in e-commerce applications. Anyone who clusters must choose how many item clusters, K, to report. Unfortunately, one must guess at K or some related parameter. Elsewhere we introduced a strongly-supported heuristic, RSQRT, which predicts K as a function of the attribute or item count, depending on attribute scales. We conducted a second analysis where we sought confirmation of the heuristic, analyzing data sets from theUCImachine learning benchmark repository. For the 25 studies where sufficient detail was available, we again found strong support. Also, in a side-by-side comparison of 28 studies, RSQRT best-predicted K and the Bayesian information criterion (BIC) predicted K are the same. RSQRT has a lower cost of O(log log n) versus O(n(2)) for BIC, and is more widely applicable. Using RSQRT prospectively could be much better than merely guessing.

RSQRT: AN HEURISTIC FOR ESTIMATING THE NUMBER OF CLUSTERS TO REPORT

PubMed Central

Bruso, Kelsey

2012-01-01

Clustering can be a valuable tool for analyzing large datasets, such as in e-commerce applications. Anyone who clusters must choose how many item clusters, K, to report. Unfortunately, one must guess at K or some related parameter. Elsewhere we introduced a strongly-supported heuristic, RSQRT, which predicts K as a function of the attribute or item count, depending on attribute scales. We conducted a second analysis where we sought confirmation of the heuristic, analyzing data sets from theUCImachine learning benchmark repository. For the 25 studies where sufficient detail was available, we again found strong support. Also, in a side-by-side comparison of 28 studies, RSQRT best-predicted K and the Bayesian information criterion (BIC) predicted K are the same. RSQRT has a lower cost of O(log log n) versus O(n2) for BIC, and is more widely applicable. Using RSQRT prospectively could be much better than merely guessing. PMID:22773923

The Rapalogue, CCI-779, improves salivary gland function following radiation.

PubMed

Morgan-Bathke, Maria; Harris, Zoey I; Arnett, Deborah G; Klein, Rob R; Burd, Randy; Ann, David K; Limesand, Kirsten H

2014-01-01

The standard of care for head and neck cancer typically includes surgical resection of the tumor followed by targeted head and neck radiation. However depending on tumor location and stage, some cases may not require surgical resection while others may be treated with chemoradiation. Unfortunately, these radiation treatments cause chronic negative side effects for patients. These side effects are associated with damage to surrounding normal salivary gland tissue and include xerostomia, changes in taste and malnutrition. The underlying mechanisms of chronic radiation-induced salivary gland dysfunction are unknown, however, in rodent models persistently elevated proliferation is correlated with reduced stimulated salivary flow. The rapalogue, CCI-779, has been used in other cell systems to induce autophagy and reduce proliferation, therefore the aim of this study was to determine if CCI-779 could be utilized to ameliorate chronic radiation-induced salivary gland dysfunction. Four to six week old Atg5f/f; Aqp5-Cre, Atg5+/+; Aqp5-Cre and FVB mice were treated with targeted head and neck radiation. FVB mice were treated with CCI-779, chloroquine, or DMSO post-radiation. Stimulated salivary flow rates were determined and parotid and submandibular salivary gland tissues were collected for analyses. Mice with a defect in autophagy, via a conditional knockout of Atg5 in the salivary glands, display increased compensatory proliferation in the acinar cell compartment and hypertrophy at 24-72 hours following radiation. FVB mice treated with post-therapy CCI-779 have significant improvements in salivary gland physiology as determined by stimulated salivary flow rates, proliferation indices and amylase production and secretion. Consequently, post-radiation use of CCI-779 allows for improvement of salivary gland function and reestablishment of glandular homeostasis. As CCI-779 is already FDA approved for other uses, it could have a secondary use to alleviate the chronic side effects in head and neck cancer patients who have completed anti-tumor therapy.

Noribogaine, but not 18-MC, exhibits similar actions as ibogaine on GDNF expression and ethanol self-administration.

PubMed

Carnicella, Sebastien; He, Dao-Yao; Yowell, Quinn V; Glick, Stanley D; Ron, Dorit

2010-10-01

Ibogaine is a naturally occurring alkaloid that has been reported to decrease various adverse phenotypes associated with exposure to drugs of abuse and alcohol in human and rodent models. Unfortunately, ibogaine cannot be used as a medication to treat addiction because of severe side effects. Previously, we reported that the desirable actions of ibogaine to reduce self-administration of, and relapse to, alcohol consumption are mediated via the upregulation of the expression of the glial cell line-derived neurotrophic factor (GDNF) in the midbrain ventral tegmental area (VTA), and the consequent activation of the GDNF pathway. The ibogaine metabolite, noribogaine, and a synthetic derivative of ibogaine, 18-Methoxycoronaridine (18-MC), possess a similar anti-addictive profile as ibogaine in rodent models, but without some of its adverse side effects. Here, we determined whether noribogaine and/or 18-MC, like ibogaine, increase GDNF expression, and whether their site of action to reduce alcohol consumption is the VTA. We used SH-SY5Y cells as a cell culture model and found that noribogaine, like ibogaine, but not 18-MC, induces a robust increase in GDNF mRNA levels. Next, we tested the effect of intra-VTA infusion of noribogaine and 18-MC on rat operant alcohol self-administration and found that noribogaine, but not 18-MC, in the VTA decreases responding for alcohol. Together, our results suggest that noribogaine and 18-MC have different mechanisms and sites of action. © 2010 The Authors, Addiction Biology © 2010 Society for the Study of Addiction.

Sofosbuvir and ABT-450: terminator of hepatitis C virus?

PubMed

Zeng, Qing-Lei; Zhang, Ji-Yuan; Zhang, Zheng; Wang, Li-Feng; Wang, Fu-Sheng

2013-06-07

Combination therapy with peginterferon (pegIFN)-α and ribavirin (RBV) has been the standard of care (SOC) for chronic hepatitis C. Unfortunately, not all patients can achieve a sustained virologic response (SVR) with this regimen. SVR rates are approximately 80% in patients with hepatitis C virus (HCV) genotype 2, 3, 5 and 6 and 40%-50% in patients with genotype 1 and 4. Therefore, strategies to improve SVR rates have been an important issue for clinical physicians. Several direct acting antiviral agents (DAAs) have significantly higher SVR rates when combined with pegIFN-α and RBV than pegIFN-α and RBV alone. Treatments containing DAAs have several advantages over the previous SOC, including higher specificity and efficacy, shorter treatment durations, fewer side effects, and oral administration. Based on these advantages, treatment with pegIFN-α and RBV plus telaprevir or boceprevir has become the current SOC for patients with genotype 1 HCV infection. However, many patients are either not eligible for therapy or decline treatment due to coexisting relative or absolute contraindications as well as an inability to tolerate the hematological side effects and adverse events caused by the new SOC. These factors have contributed to the advent of pegIFN-α-free regimens. The newest therapeutic regimens containing sofosbuvir and ABT-450 have shown promising results. In this review, we summarize the development of anti-HCV agents and the clinical efficacy of sofosbuvir and ABT-450-based therapies as well as the potential for future HCV studies.

Inhibition of Nuclear Factor κB Activation and Cyclooxygenase-2 Expression by Aqueous Extracts of Hispanic Medicinal Herbs

PubMed Central

Gonzales, Amanda M.; Hunsaker, Lucy A.; Franco, Carolina R.; Royer, Robert E.; Vander Jagt, David L.; Vander Jagt, Dorothy J.

2010-01-01

Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) are a primary choice of therapy for diseases with a chronic inflammatory component. Unfortunately, long-term NSAID therapy is often accompanied by severe side effects, including cardiovascular and gastrointestinal complications. Because of this, there is critical need for identification of new and safer treatments for chronic inflammation to circumvent these side effects. Inflammatory diseases have been successfully remedied with natural herbs by many cultures. To better understand the potential of natural herbs in treating chronic inflammation and to identify their mechanism of action, we have evaluated the anti-inflammatory activities of 20 medicinal herbs commonly used in the Hispanic culture. We have established a standardized method for preparing aqueous extracts (teas) from the selected medicinal herbs and screened for inhibition of tumor necrosis factor-α-induced activation of nuclear factor κB (NF-κB), which is the central signaling pathway of the inflammatory response. A number of herbal teas were identified that exhibited significant anti-inflammatory activity. In particular, tea from the herb commonly called laurel was found to be an especially potent inhibitor of NF-κB-dependent cyclooxygenase-2 gene expression and prostaglandin E2 production in cultured murine macrophages. These findings indicate that laurel tea extract contains potent anti-inflammatory compounds that function by inhibiting the major signal transduction pathway responsible for inducing an inflammatory event. Based on these results, laurel may represent a new, safe therapeutic agent for managing chronic inflammation. PMID:20482259

Formulation and clinical evaluation of topical dosage forms of Indian Penny Wort, walnut and turmeric in eczema.

PubMed

Khiljee, Sonia; Rehman, Nisarur; Khiljee, Tanzila; Loebenberg, Raimar; Ahmad, Rao Saeed

2015-11-01

Eczema is characterized by itching, lichenification, scaling, oedema and erythema. Current management strategies include corticosteroids, which are limited due to side effects. Many herbal remedies are used traditionally but unfortunately have not been validated in controlled clinical trials. Three popular traditional treatments of eczema include Indian pennywort, Walnut and Turmeric. In this study three topical formulations (micro emulsion, gel and ointment) were prepared from extracts of Indian pennywort, Walnut and Turmeric. These formulations were monitored for stability for a period of three months. Controlled clinical trials were conducted on 360 eczema patients. Clinical parameters observed were degree of erythema, oedema, scaling, itching and lichenification. Effects of each formulation on these clinical parameters were compared with placebo formulations. Micro emulsion formulations in all cases proved to be more effective in reducing semi quantitative scores of erythema and oedema. Itching was relieved more by gel formulation. The ointment showed more efficacy towards scaling and lichenification. Comparison of the effects of placebo and the specific formulations was performed by chi-square statistics and found to be highly significant. In summary it is concluded that all the formulations could be used as promising source for treatment of eczema.

Proton pump inhibitors induce a caspase-independent antitumor effect against human multiple myeloma.

PubMed

Canitano, Andrea; Iessi, Elisabetta; Spugnini, Enrico Pierluigi; Federici, Cristina; Fais, Stefano

2016-07-01

Multiple Myeloma (MM) is the second most common hematological malignancy and is responsive to a limited number of drugs. Unfortunately, to date, despite the introduction of novel drugs, no relevant increase in survival rates has been obtained. Proton pump inhibitors (PPIs) have been shown to have significant antitumor action as single agents as well as in combination with chemotherapy. This study investigates the potential anti-tumor effectiveness of two PPIs, Lansoprazole and Omeprazole, against human MM cells. We found that Lansoprazole exerts straightforward efficacy against myeloma cells, even at suboptimal concentrations (50 µM), while Omeprazole has limited cytotoxic action. The Lansoprazole anti-MM effect was mostly mediated by a caspase-independent apoptotic-like cytotoxicity, with only a secondary anti-proliferative action. This study provides clear evidence supporting the use of Lansoprazole in the strive against MM with an efficacy proven much higher than current therapeutical approaches and without reported side effects. It is however conceivable that, consistent with the results obtained in other human tumors, Lansoprazole may well be combined with existing anti-myeloma therapies with the aim to improve the low level of efficacy of the current strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease: Clinical Evidence and Possible Mechanisms

PubMed Central

Scuteri, Damiana; Morrone, Luigi Antonio; Rombolà, Laura; Avato, Pina Rosa; Corasaniti, Maria Tiziana; Sakurada, Shinobu; Sakurada, Tsukasa

2017-01-01

The treatment of agitation and aggression, typical Behavioural and Psychological Symptoms of Dementia (BPSDs) of Alzheimer's Disease (AD), is one of the most complicated aspects of handling patients suffering from dementia. Currently, the management of these symptoms often associated with an increased pain perception, which notably reduces the patients' quality of life (QoL), relies on the employment of antipsychotic drugs. Unfortunately, the use of these pharmacological agents has some limits: in the long term, they do not result in being equally effective as in the first weeks of treatment and they present important side effects. Therefore, there is growing interest, supported by clinical evidence, in aromatherapy for the control of agitation, aggression, and psychotic symptoms. Some molecular mechanisms have been proposed to explain the behavioural effects of essential oils, as the whole phytocomplex or the single components, but important basic research effort is still needed. For this reason, rigorous preclinical studies are necessary in order to understand the pharmacological basis of aromatherapy in the treatment of BPSDs and to widen the cluster of effective essential oils in pharmacotherapeutic practice. PMID:28465709

[Successful treatment of Candida meningitis with miconazole].

PubMed

Fukui, S; Tabata, H; Hayashi, H; Matsushima, Y

1990-09-01

This paper presents a case of successful treatment of candida meningitis with miconazole. A 55-year-old woman was admitted due to high fever, vomiting and urinary incontinence on November 11, 1986. Four months prior to this episode, she had been treated for a ruptured aneurysm with neck-clipping and V-P shunt for NPH. Candida albicans was cultured from her CSF. The shunt system was immediately removed and an Ommaya's reservoir was installed for external drainage and intrathecal administrations. Combination therapy (amphotericin B and flucytosine) was initiated. However, it was discontinued after ten days because of high fever and chills after intrathecal injection of amphotericin B. Treatment with miconazole intrathecally (10-90 mg/week, total 565 mg) and intravenously (200-1200 mg/day, total 70.4 g) was begun on November 23. Clinical and CSF findings were improved soon. No side effect of miconazole was observed. After V-P shunt revision, she was discharged without neurological deficit on March 12, 1987. Reports of mycosis in central nervous system are recently increasing, especially for candidosis. Cryptococcosis is noted frequently as an opportunistic infection of AIDS. The administration of amphotericin B and flucytosine has been the main therapy for mycotic meningitis. Unfortunately, however, Amphotericin B has many toxic effects, including renal dysfunction, and flucytosine can induce the emergent resistance. Miconazole has been used to successfully treat cryptococcosis, aspergillosis or coccidiosis, and was effective in our case of candida meningitis. Few side effects have been reported with its use. The intrathecal injection of miconazole is recommended for meningitis, because the drug is taken up minimally into CSF space after intravenous administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved astigmatic focus error detection method

NASA Technical Reports Server (NTRS)

Bernacki, Bruce E.

1992-01-01

All easy-to-implement focus- and track-error detection methods presently used in magneto-optical (MO) disk drives using pre-grooved media suffer from a side effect known as feedthrough. Feedthrough is the unwanted focus error signal (FES) produced when the optical head is seeking a new track, and light refracted from the pre-grooved disk produces an erroneous FES. Some focus and track-error detection methods are more resistant to feedthrough, but tend to be complicated and/or difficult to keep in alignment as a result of environmental insults. The astigmatic focus/push-pull tracking method is an elegant, easy-to-align focus- and track-error detection method. Unfortunately, it is also highly susceptible to feedthrough when astigmatism is present, with the worst effects caused by astigmatism oriented such that the tangential and sagittal foci are at 45 deg to the track direction. This disclosure outlines a method to nearly completely eliminate the worst-case form of feedthrough due to astigmatism oriented 45 deg to the track direction. Feedthrough due to other primary aberrations is not improved, but performance is identical to the unimproved astigmatic method.

New approaches to the management of schizophrenia: focus on aberrant hippocampal drive of dopamine pathways

PubMed Central

Perez, Stephanie M; Lodge, Daniel J

2014-01-01

Schizophrenia is a disease affecting up to 1% of the population. Current therapies are based on the efficacy of chlorpromazine, discovered over 50 years ago. These drugs block dopamine D2-like receptors and are effective at primarily treating positive symptoms in a subset of patients. Unfortunately, current therapies are far from adequate, and novel treatments require a better understanding of disease pathophysiology. Here we review the dopamine, gamma-aminobutyric acid (GABA), and glutamate hypotheses of schizophrenia and describe a pathway whereby a loss of inhibitory signaling in ventral regions of the hippocampus actually drives a dopamine hyperfunction. Moreover, we discuss novel therapeutic approaches aimed at attenuating ventral hippocampal activity in a preclinical model of schizophrenia, namely the MAM GD17 rat. Specifically, pharmacological (allosteric modulators of the α5 GABAA receptor), neurosurgical (deep brain stimulation), and cell-based (GABAergic precursor transplants) therapies are discussed. By better understanding the underlying circuit level dysfunctions in schizophrenia, novel treatments can be advanced that may provide better efficacy and a superior side effect profile to conventional antipsychotic medications. PMID:25061280

Predictions of wing and pylon forces caused by propeller installation

NASA Technical Reports Server (NTRS)

Martinez, Rudolph

1987-01-01

Replacement of current turbojets by high-efficiency unducted propfans could have the unfortunate side effect of increasing cabin noise, essentially because unsteady-aerodynamic mechanisms are likely to be introduced whereby some of the energy saved may be lost again, to the production of propeller noise and to wing/pylon vibrations coupling to the cabin as a sounding board. The present study estimates theoretically associated harmonic aerodynamic forces for two candidate configurations: a pusher propeller which chops through the mean wake of the pylon supporting it, and in the process generates a blade-rate force driving the structure, and a tractor wing-mounted propeller, whose trailing rotating wake induces an unsteady downwash field generating unsteady wing airloads. Reported predictions of such propfan aerodynamic sources of structure-borne sound, or vibration, could be the basis for devising means for their mechanical isolation, and thus for the effective interruption of the structural noise path into the cabin. Both mechanisms are analyzed taking advantage of the high subsonic Mach number and high reduced frequency of the interaction between the impinging flow and the affected aerodynamic element.

New approaches to the management of schizophrenia: focus on aberrant hippocampal drive of dopamine pathways.

PubMed

Perez, Stephanie M; Lodge, Daniel J

2014-01-01

Schizophrenia is a disease affecting up to 1% of the population. Current therapies are based on the efficacy of chlorpromazine, discovered over 50 years ago. These drugs block dopamine D2-like receptors and are effective at primarily treating positive symptoms in a subset of patients. Unfortunately, current therapies are far from adequate, and novel treatments require a better understanding of disease pathophysiology. Here we review the dopamine, gamma-aminobutyric acid (GABA), and glutamate hypotheses of schizophrenia and describe a pathway whereby a loss of inhibitory signaling in ventral regions of the hippocampus actually drives a dopamine hyperfunction. Moreover, we discuss novel therapeutic approaches aimed at attenuating ventral hippocampal activity in a preclinical model of schizophrenia, namely the MAM GD17 rat. Specifically, pharmacological (allosteric modulators of the α5 GABAA receptor), neurosurgical (deep brain stimulation), and cell-based (GABAergic precursor transplants) therapies are discussed. By better understanding the underlying circuit level dysfunctions in schizophrenia, novel treatments can be advanced that may provide better efficacy and a superior side effect profile to conventional antipsychotic medications.

Combination therapy of apatinib with icotinib for primary acquired icotinib resistance in patients with advanced pulmonary adenocarcinoma with EGFR mutation.

PubMed

Xia, Pinghui; Cao, Jinlin; Lv, Xiayi; Wang, Luming; Lv, Wang; Hu, Jian

2018-05-01

Multi-targeted agents represent the next generation of targeted therapies for solid tumors, and patients with acquired resistance to EGFR-tyrosine kinase inhibitors (TKIs) may also benefit from their combination with TKI therapy. Third-generation targeted drugs, such as osimertinib, are very expensive, thus a more economical solution is required. The aim of this study was to explore the use of apatinib combined with icotinib therapy for primary acquired resistance to icotinib in three patients with advanced pulmonary adenocarcinoma with EGFR mutations. We achieved favorable oncologic outcomes in all three patients, with progression-free survival of four to six months. Unfortunately, the patients ultimately had to cease combination therapy because of intolerable adverse effects of hand and foot syndrome and oral ulcers. Combination therapy of apatinib with icotinib for primary acquired resistance to icotinib may be an option for patients with advanced pulmonary adenocarcinoma with EGFR mutations, but physicians must also be aware of the side effects caused by such therapy. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

The Current State of Drug Discovery and a Potential Role for NMR Metabolomics

PubMed Central

2015-01-01

The pharmaceutical industry has significantly contributed to improving human health. Drugs have been attributed to both increasing life expectancy and decreasing health care costs. Unfortunately, there has been a recent decline in the creativity and productivity of the pharmaceutical industry. This is a complex issue with many contributing factors resulting from the numerous mergers, increase in out-sourcing, and the heavy dependency on high-throughput screening (HTS). While a simple solution to such a complex problem is unrealistic and highly unlikely, the inclusion of metabolomics as a routine component of the drug discovery process may provide some solutions to these problems. Specifically, as the binding affinity of a chemical lead is evolved during the iterative structure-based drug design process, metabolomics can provide feedback on the selectivity and the in vivo mechanism of action. Similarly, metabolomics can be used to evaluate and validate HTS leads. In effect, metabolomics can be used to eliminate compounds with potential efficacy and side effect problems while prioritizing well-behaved leads with druglike characteristics. PMID:24588729

Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

PubMed Central

Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

2011-01-01

An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function. PMID:21315756

Alzheimer's disease and age-related memory decline (preclinical).

PubMed

Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

2011-08-01

An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function. Copyright © 2011 Elsevier Inc. All rights reserved.

Precision or Personalized Medicine for Cancer Chemotherapy: Is there a Role for Herbal Medicine.

PubMed

Wang, Zhijun; Liu, Xuefeng; Ho, Rebecca Lucinda Ka Yan; Lam, Christopher Wai Kei; Chow, Moses Sing Sum

2016-07-07

Although over 100 chemotherapeutic agents are currently available for the treatment of cancer patients, the overall long term clinical benefit is disappointing due to the lack of effectiveness or severe side effects from these agents. In order to improve the therapeutic outcome, a new approach called precision medicine or personalized medicine has been proposed and initiated by the U.S. National Institutes of Health. However, the limited availability of effective medications and the high cost are still the major barriers for many cancer patients. Thus alternative approaches such as herbal medicines could be a feasible and less costly option. Unfortunately, scientific evidence for the efficacy of a majority of herbal medicines is still lacking and their development to meet FDA approval or other regulatory agencies is a big challenge. However, herbal medicines may be able to play an important role in precision medicine or personalized medicine. This review will focus on the existing and future technologies that could speed the development of herbal products for treatment of resistant cancer in individual patients. Specifically, it will concentrate on reviewing the phenotypic (activity based) rather than genotypic (mechanism based) approach to develop herbal medicine useful for personalized cancer chemotherapy.

Multi-Market Impacts of Market-Based Recycling Initiatives.

PubMed

Fisher, Linda R

1999-09-01

In 1995 the average tipping fee in the state of New York was $70/ton, with some landfills charging as high as $100. 1 In New Jersey, fees reached prices as high as $165/ton. 2 With budget crises occurring at all levels of government, economists, environmental scientists, policy-makers, and others are scrambling to find alternatives to waste disposal. Recycling as a solution has risen to the forefront, most likely because it both saves landfill space and may use fewer resources than virgin material processing. At every level of government, policies are being set that encourage recycling. Unfortunately, some of these programs may be resulting in unintended and undesirable side effects. To understand these effects, a broader view of the many factors involved in materials use, waste generation, and disposal is necessary. Within this paper, the broader view is considered, including a discussion of the externalities that exist in the markets affected by waste and an analysis of the effects on all alternatives to recycling, including composting and reuse. Through use of mathematical optimization, this paper shows that a recycling subsidy, or the more complicated tax/subsidy scheme, does not necessarily provide greater environmental benefits compared with disposal taxes.

Pharmacogenetics: A strategy for personalized medicine for autoimmune diseases.

PubMed

Tavakolpour, S; Darvishi, M; Ghasemiadl, M

2018-03-01

For many years, a considerable number of patients with autoimmune diseases (ADs) have suffered from a lack of drug response and drug-related toxicity. Despite the emergence of new therapeutic options such as biological agents, patients continue to struggle with these problems. Unfortunately, new challenges, including the paradoxical effects of biological drugs, have complicated the situation. In recent decades, efforts have been made to predict drug response as well as drug-related side effects. Thanks to the many advances in genetics, evaluation of markers to predict drug response/toxicity before the initiation of treatment may be an avenue toward personalizing treatments. Implementing pharmacogenetics and pharmacogenomics in the clinic could improve clinical care; however, obstacles remain to effective personalized medicine for ADs. The present study attempted to clarify the concept of pharmacogenetics/pharmacogenomics for ADs. After an overview on the pathogenesis of the most common types of treatments, this paper focuses on pharmacogenetic studies related to the selected ADs. Bridging the gap between pharmacogenetics and personalized medicine is also discussed. Moreover, the advantages, disadvantages and recommendations related to making personalized medicine practical for ADs have been addressed. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Enhanced photo(geno)toxicity of demethylated chlorpromazine metabolites

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

Palumbo, Fabrizio

Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound. In this case, the metabolites selected for the study are demethylchlorpromazine (DMCPZ), didemethylchlorpromazine (DDMCPZ) and chlorpromazine sulfoxide (CPZSO). The demethylated CPZ metabolites DMCPZ and DDMCPZ maintain identical chromophore tomore » the parent drug. In this work, it has been found that the nature of the aminoalkyl side chain modulates the hydrophobicity and the photochemical properties (for instance, the excited state lifetimes), but it does not change the photoreactivity pattern, which is characterized by reductive photodehalogenation, triggered by homolytic carbon-chlorine bond cleavage with formation of highly reactive aryl radical intermediates. Accordingly, these metabolites are phototoxic to cells, as revealed by the 3T3 NRU assay; their photo-irritation factors are even higher than that of CPZ. The same trend is observed in photogenotoxicity studies, both with isolated and with cellular DNA, where DMCPZ and DDMCPZ are more active than CPZ itself. In summary, side-chain demethylation of CPZ, as a consequence of Phase I biotransformation, does not result a photodetoxification. Instead, it leads to metabolites that exhibit in an even enhanced photo(geno)toxicity. - Highlights: • Demethylated CPZ metabolites are phototoxic to cells, as revealed by the NRU assay. • Single cell electrophoresis (Comet Assay) confirms the photodamage to cellular DNA. • DNA single strand breaks formation is observed on agarose gel electrophoresis. • Photochemical and EPR studies support generation of aryl radicals by C-Cl cleavage. • The aminoalkyl side chain of metabolites modulates the photo(geno)toxic potential.« less

Women's experiences in the armed conflict situation in Sudan.

PubMed

1999-01-01

The negative impact of war is apparent at various levels of the Sudanese society. Economic, social, and political instability is occurring on a large scale and the most vulnerable groups are women and children. This report aimed to document women's human rights violations in the ongoing armed conflict situation in Sudan, with the emphasis on rape; investigate the forms of violence against women in a situation of armed conflict; present testimonies of women survivors; and use the document for advocacy. A total of 20 testimonies were obtained, which clearly indicated that rape is a systematic practice in areas of conflict regardless of whether the Sudanese People's Liberation Army, the Khartoum government, or bandit groups that take advantage of the chaos, have attacked civilians. In view of this, regional agencies should show more seriousness in finding solutions for the war, and perpetrators of rape should be brought to justice so as to change the perception of rape as an unfortunate but inevitable side effect of war.

On-chip plasmon-induced transparency based on plasmonic coupled nanocavities

PubMed Central

Zhu, Yu; Hu, Xiaoyong; Yang, Hong; Gong, Qihuang

2014-01-01

On-chip plasmon-induced transparency offers the possibility of realization of ultrahigh-speed information processing chips. Unfortunately, little experimental progress has been made to date because it is difficult to obtain on-chip plasmon-induced transparency using only a single meta-molecule in plasmonic circuits. Here, we report a simple and efficient strategy to realize on-chip plasmon-induced transparency in a nanoscale U-shaped plasmonic waveguide side-coupled nanocavity pair. High tunability in the transparency window is achieved by covering the pair with different organic polymer layers. It is possible to realize ultrafast all-optical tunability based on pump light-induced refractive index change of a graphene cover layer. Compared with previous reports, the overall feature size of the plasmonic nanostructure is reduced by more than three orders of magnitude, while ultrahigh tunability of the transparency window is maintained. This work also provides a superior platform for the study of the various physical effects and phenomena of nonlinear optics and quantum optics. PMID:24435059

On-chip plasmon-induced transparency based on plasmonic coupled nanocavities.

PubMed

Zhu, Yu; Hu, Xiaoyong; Yang, Hong; Gong, Qihuang

2014-01-17

On-chip plasmon-induced transparency offers the possibility of realization of ultrahigh-speed information processing chips. Unfortunately, little experimental progress has been made to date because it is difficult to obtain on-chip plasmon-induced transparency using only a single meta-molecule in plasmonic circuits. Here, we report a simple and efficient strategy to realize on-chip plasmon-induced transparency in a nanoscale U-shaped plasmonic waveguide side-coupled nanocavity pair. High tunability in the transparency window is achieved by covering the pair with different organic polymer layers. It is possible to realize ultrafast all-optical tunability based on pump light-induced refractive index change of a graphene cover layer. Compared with previous reports, the overall feature size of the plasmonic nanostructure is reduced by more than three orders of magnitude, while ultrahigh tunability of the transparency window is maintained. This work also provides a superior platform for the study of the various physical effects and phenomena of nonlinear optics and quantum optics.

[Networking and integrated disease management. Advantages and disadvantages from the medical point of view].

PubMed

Hänsch, H; Fleck, E

2005-07-01

At the moment the terms "networking", "cost reduction" and "integrated disease management" are frequently discussed in all branches of the German health care system. Unfortunately there are different interpretations of these terms. "Integrated disease management" in the meaning of communication between clinical and outpatient health care has al ready existed for years now. Traditional ways of communication lead to information loss. Losing information is a reason for low cost effectiveness and a prolonged healing process directly harming the patient. A computer network may prevent information loss and may in crease the performance of data transfer. Different sides have al ready started networking, and it is now necessary to bundle the interests. This necessity has been recognized by the German legislative. To lead this project to success it is important to know and to fulfil some medical criteria. Defining and describing these conditions is the topic of this paper. Our special intent is to show that digital technique is necessary to improve cooperation among physicians.

Developing better mouse models to study cisplatin-induced kidney injury.

PubMed

Sharp, Cierra N; Siskind, Leah J

2017-10-01

Cisplatin is a potent chemotherapeutic used for the treatment of many types of cancer. However, its dose-limiting side effect is nephrotoxicity leading to acute kidney injury (AKI). Patients who develop AKI have an increased risk of mortality and are more likely to develop chronic kidney disease (CKD). Unfortunately, there are no therapeutic interventions for the treatment of AKI. It has been suggested that the lack of therapies is due in part to the fact that the established mouse model used to study cisplatin-induced AKI does not recapitulate the cisplatin dosing regimen patients receive. In recent years, work has been done to develop more clinically relevant models of cisplatin-induced kidney injury, with much work focusing on incorporation of multiple low doses of cisplatin administered over a period of weeks. These models can be used to recapitulate the development of CKD after AKI and, by doing so, increase the likelihood of identifying novel therapeutic targets for the treatment of cisplatin-induced kidney injury. Copyright © 2017 the American Physiological Society.

Complementary p- and n-type polymer doping for ambient stable graphene inverter.

PubMed

Yun, Je Moon; Park, Seokhan; Hwang, Young Hwan; Lee, Eui-Sup; Maiti, Uday; Moon, Hanul; Kim, Bo-Hyun; Bae, Byeong-Soo; Kim, Yong-Hyun; Kim, Sang Ouk

2014-01-28

Graphene offers great promise to complement the inherent limitations of silicon electronics. To date, considerable research efforts have been devoted to complementary p- and n-type doping of graphene as a fundamental requirement for graphene-based electronics. Unfortunately, previous efforts suffer from undesired defect formation, poor controllability of doping level, and subtle environmental sensitivity. Here we present that graphene can be complementary p- and n-doped by simple polymer coating with different dipolar characteristics. Significantly, spontaneous vertical ordering of dipolar pyridine side groups of poly(4-vinylpyridine) at graphene surface can stabilize n-type doping at room-temperature ambient condition. The dipole field also enhances and balances the charge mobility by screening the impurity charge effect from the bottom substrate. We successfully demonstrate ambient stable inverters by integrating p- and n-type graphene transistors, which demonstrated clear voltage inversion with a gain of 0.17 at a 3.3 V input voltage. This straightforward polymer doping offers diverse opportunities for graphene-based electronics, including logic circuits, particularly in mechanically flexible form.

[Medically compromised patients in the dental office: demographics and progress in health care].

PubMed

Al-Nawas, B; Grötz, K A

2011-09-01

Due to changing demographics in our society, there are an increasing number of patients with risk factors presenting for dental care. Unfortunately valid screening instruments to identify these patients are lacking. Especially in elderly patients, there is often an association between the high number of prescribed medications and oral symptoms. Using supportive therapy in oncology (e.g., radio(chemo)therapy) as an example, the role of modern dentistry and its interaction with general medicine is illustrated. Modern substances, e.g., antiangiogenetics, with still unknown side effects represent challenging new developments in the field of oral medicine. Even with some examples of positive representation of patients with risk factors in the health systems, e.g., § 28 SGB V, it is clear that the pressure on the costs in the health systems leads to an undertreatment of patients with risk factors. Only by adapting dental and postgraduate training with respect to these aspects, together with better financial reimbursement of the additional efforts, will this trend be overcome.

Effect of medium composition and light on root and rhinacanthin formation in Rhinacanthus nasutus cultures.

PubMed

Panichayupakaranant, P; Meerungrueang, W

2010-11-01

Rhinacanthus nasutus (L.) Kurz (Acanthaceae) has long been used in Thai traditional medicine for treatment of tinea versicolor, ringworm, pruritic rash, and abscess. The active constituents are known as a group of naphthoquinone esters, rhinacanthins. This work focused on establishment of R. nasutus root cultures and determination of rhinacanthin production. Induction of R. nasutus root formation was accomplished on solid Gamborg's B5 (B5) medium, supplied with 0.1 mg/L indole-3-butyric acid (IBA) and 20 g/L sucrose. The effects of explants (whole leaf explants and four-side excised leaf explants), light and medium composition on root and rhinacanthin formation were investigated. The root formation from the whole leaf explants was 10 times higher than that from the four-side excised leaf explants. In addition, light possessed an inhibitory effect on the root and rhinacanthin formation of R. nasutus. Medium manipulation found that Murashige and Skoog (MS) medium supplied with 3 mg/L IBA and 30 g/L sucrose was the most suitable for induction of the root formation. Unfortunately, the obtained root cultures produced only rhinacanthin-C in very low amount, 0.026 mg/g dry weight (DW), when they were transferred into the same MS liquid medium. With semisolid medium (4 g/L agar) of the same MS composition, however, the root cultures appeared to produce higher content of rhinacanthin-C, -D and -N (3.45, 0.07 and 0.07 mg/g DW, respectively). Our finding suggests that culturing in semisolid medium is capable of improving of rhinacanthin production in R. nasutus root cultures.

Testicular tissue cryopreservation in prepubertal male children: an analysis of parental decision-making.

PubMed

Ginsberg, Jill P; Li, Yimei; Carlson, Claire A; Gracia, Clarisa R; Hobbie, Wendy L; Miller, Victoria A; Mulhall, John; Shnorhavorian, Margarett; Brinster, Ralph L; Kolon, Thomas F

2014-09-01

Infertility is an unfortunate treatment-related consequence for some pediatric malignancies as well as some non-malignant conditions treated with stem cell transplant. Unlike pubertal males, prepubertal males cannot produce semen for cryopreservation. This manuscript reports on the acceptability and safety of a multi-institutional protocol for offering testicular tissue cryopreservation to families of prepubertal male children at highest risk for infertility. Data on decision influences, decision-making control, and emotional state when considering this option are described. Prepubertal males facing gonadotoxic therapy were offered testicular cryopreservation. Post-biopsy, patients were followed for acute side effects. In addition, parents and patients were asked to complete questionnaires, whether or not they chose to cryopreserve tissue. Seventy-four prepubertal male children were approached. Fifty-seven families (77%) consented to the testicular biopsy; 48 of 57 underwent the procedure. There was one post-operative side effect. Parents who agreed to testicular cryopreservation and those that did not felt in control of this decision. Parents who consented to the biopsy and refusers were not deterred by the experimental nature of the protocol. An important decision-making influence was the risk of the biopsy. Biopsy and cryopreservation of testicular tissue from prepubertal male children was performed successfully and safely at three institutions. Parents faced with this option at diagnosis can make an informed decision and weigh carefully the risks and benefits. Although asked to make a decision soon after they were given a difficult diagnosis, parents uniformly felt in control of this decision. © 2014 Wiley Periodicals, Inc.

Non-invasive high-intensity focused ultrasound for UV-induced hyperpigmentation in Fitzpatrick skin types III and IV: a prospective, randomized, controlled, evaluator-blinded trial.

PubMed

Vachiramon, Vasanop; Jurairattanaporn, Natthachat; Harnchoowong, Sarawin; Chayavichitsilp, Pamela

2018-02-01

Skin hyperpigmentation is a frequently encountered problem, particularly in darker skin types. Unfortunately, standard treatments for this condition have shown disappointing results. High-intensity focused ultrasound (HIFU) is commonly indicated for skin laxity, but recently was used to treat UV-induced hyperpigmentation in animal models. This study is aimed to evaluate the efficacy and safety of high-intensity focused ultrasound for UVB-induced hyperpigmentation in human subjects. A randomized, evaluator-blinded pilot study was conducted on 20 subjects. Each subject was induced three hyperpigmentary spots by local broadband UVB. After 2 weeks, each spot was randomly allocated to control, low-energy, and high-energy HIFU. Subjects were instructed to follow up weekly for a duration of 1 month. Lightness index measurements, mean improvement scores, subjects' satisfaction, pain scores, and side effects were evaluated. All 20 subjects completed the study. Fourteen subjects had Fitzpatrick (FPT) skin type III and six subjects had FPT skin type IV. Twelve subjects showed greater improvement at control sites while eight subjects showed greater improvement at HIFU-treated sites. In FPT skin type III, HIFU appeared to be inferior to control in both lightness index and mean improvement scores, but in FPT skin type IV, HIFU had greater lightness index improvement and higher improvement scores than control. Side effects were more frequent in high-energy-treated areas. Focused ultrasound may be offered in some patients with hyperpigmentary conditions. More research is needed to determine proper energy settings for optimal outcome.

Self-Delivery Nanoparticles of Amphiphilic Methotrexate-Gemcitabine Prodrug for Synergistic Combination Chemotherapy via Effect of Deoxyribonucleotide Pools.

PubMed

Wang, Yao; Huang, Ping; Hu, Minxi; Huang, Wei; Zhu, Xinyuan; Yan, Deyue

2016-11-16

The distinct and complementary biochemical mechanisms of folic acid analog methotrexate (MTX) and cytidine analog gemcitabine (GEM) make their synergistic combination effective. Unfortunately, such a combination faces severe pharmacokinetic problems and several transportation barriers. To overcome these problems, a new strategy of amphiphilic small molecule prodrug (ASMP) is developed to improve their synergistic combination effect. The ASMP was prepared by the amidation of the hydrophilic GEM with the hydrophobic MTX at a fixed ratio. Owing to its inherent amphiphilicity, the MTX-GEM ASMP self-assembled into stable nanoparticles (ASMP-NPs) with high drug loading capacity (100%), in which the MTX and GEM could self-deliver without any carriers and release synchronously in cancer cells. In vitro studies showed that the MTX-GEM ASMP-NPs could greatly improve the synergistic combination effects by the reason of arresting more S phase of the cell cycle and reducing levels of deoxythymidine triphosphate (dTTP), deoxyadenosine triphosphate (dATP), and deoxycytidine triphosphate (dCTP). The stronger synergistic effects caused the higher cell cytotoxicity and apoptotic ratio, and circumvented the multidrug resistance (MDR) of tumor cells. Additionally, MTX-GEM ASMP-NPs could achieve the same anticancer effect with the greatly reduced dosage compared with the free drugs according to the dose-reduction index (DRI) values of MTX and GEM in MTX-GEM ASMP-NPs, which may be beneficial for reducing the side effects.

Berberine diminishes side population and down-regulates stem cell-associated genes in the pancreatic cancer cell lines PANC-1 and MIA PaCa-2.

PubMed

Park, S H; Sung, J H; Chung, N

2014-09-01

Cancer stem cells play an important role in metastasis and the relapse of drug resistant cancers. Side-population (SP) cells are capable of effluxing Hoechst 33342 dye and are referred to as cancer stem cells. We investigated the effect of berberine on pancreatic cancer stem cells of PANC-1 and MIA PaCa-2. For both cell lines, the proportions of SP cells in the presence of berberine were investigated and compared to the proportions in the presence of gemcitabine, a standard pancreatic anti-cancer drug. The proportions of SP cells in the PANC-1 and MIA PaCa-2 cell lines were about 9 and <0.1%, respectively. After berberine and gemcitabine treatments, the SP cell proportion of PANC-1 decreased to 5.7 ± 2.0 and 6.8 ± 0.8%, respectively, which compares to the control proportion of (9.7 ± 1.7). After berberine and gemcitabine treatment of PANC-1, of the four stem cell-associated genes (SOX2, POU5F1, NANOG, and NOTCH1), all but NOTCH1 were down-regulated. Unfortunately, the effect of berberine and gemcitabine treatments on MIA PaCa-2 SP cells could not be clearly observed because SP cells represented only a very small proportion of MIA PaCa-2 cells. However, SOX2, POU5F1, and NANOG genes were shown to be effectively down-regulated in the MIA PaCa-2 cell line as a whole. Taken together, these results indicate that berberine is as effective at targeting pancreatic cancer cell lines as gemcitabine. Therefore, we believe that POU5F1, SOX2, and NANOG can serve as potential markers, and berberine may be an effective anti-cancer agent when targeting human pancreatic cancer cells and/or their cancer stem cells.

Application of ELJ to create and maintain side channels in a dynamic gravel bed river

NASA Astrophysics Data System (ADS)

Crabbe, E.; Crowe Curran, J.; Ockelford, A.

2017-12-01

Braided and anastomosing rivers create and maintain a large amount of side channel habitat. Unfortunately, many rivers that were once multi-channel rivers have been constrained to single thread channels as a consequence of land use changes that occurred in the 19th and 20th centuries or earlier. An increasingly common management goal today is the re-creation of self-maintaining side and tributary habitat through as natural means as possible. This work examines the geomorphic history of one such channel and the success of recent rehabilitation efforts. Our case study comes from the South Fork Nooksack River in the Cascades Range in Washington State. The Nooksack River is a gravel and sand bed channel with a snowmelt dominated hydrograph. Engineered log jams (ELJ) have been employed to direct flow into side and chute channels with the larger goals of increasing overall channel complexity and salmon spawning opportunities. ELJs have been constructed on the channel since the 2000s, and the ELJs in the study reaches range in age up to 10 years. The size and design of individual jams within the reach vary, enabling a comparison between jam types. ELJs are evaluated for their ability to maintain gravel bar locations and open tributary channels through the snowmelt season over the reach scale. Additional goals of trapping wood onto the jams and existing bars, stabilizing channel banks, and allowing for the growth of bar vegetation are also examined.

Cellular and physiological effects of medium-chain triglycerides.

PubMed

Wanten, Geert J; Naber, Anton H

2004-10-01

From a nutritional standpoint, saturated triglycerides with a medium (6 to 12) carbon chain length (MCT) have traditionally been regarded as biologically inert substances, merely serving as a source of fuel calories that is relatively easily accessible for metabolic breakdown compared with long chain triglycerides (LCT). This quality of MCT has been shown to offer both benefits and risks depending on the clinical situation, with potential positive effects on protein metabolism in some studies on one side, and an increased risk for ketogenesis and metabolic acidosis on the other. At another level, studies regarding lipid effects of MCT on the immune system, as with LCT, so far have yielded equivocal results, although there is a recent experimental evidence to suggest that MCT possess immune modulating properties and should in fact be regarded as bioactive mediators. Most of this information comes from studies where effects of MCT have been compared with those of LCT in lipid emulsions, as part of parenteral (intravenous) nutrition formulations. Unfortunately, the relevance of these observations for clinical practice remains largely unclear because adequately powered trials that clearly point out the position of MCT in relation to structurally different lipids have not been performed. In the present paper we review the experimental and clinical evidence for cellular and physiological effects of nutritional MCT. In addition, studies describing possible mechanisms behind the observed effects of MCT will be discussed.

Potential therapeutic effects of mTOR inhibition in atherosclerosis

PubMed Central

Kurdi, Ammar; De Meyer, Guido R. Y.

2015-01-01

Despite significant improvement in the management of atherosclerosis, this slowly progressing disease continues to affect countless patients around the world. Recently, the mechanistic target of rapamycin (mTOR) has been identified as a pre‐eminent factor in the development of atherosclerosis. mTOR is a constitutively active kinase found in two different multiprotein complexes, mTORC1 and mTORC2. Pharmacological interventions with a class of macrolide immunosuppressive drugs, called rapalogs, have shown undeniable evidence of the value of mTORC1 inhibition to prevent the development of atherosclerotic plaques in several animal models. Rapalog‐eluting stents have also shown extraordinary results in humans, even though the exact mechanism for this anti‐atherosclerotic effect remains elusive. Unfortunately, rapalogs are known to trigger diverse undesirable effects owing to mTORC1 resistance or mTORC2 inhibition. These adverse effects include dyslipidaemia and insulin resistance, both known triggers of atherosclerosis. Several strategies, such as combination therapy with statins and metformin, have been suggested to oppose rapalog‐mediated adverse effects. Statins and metformin are known to inhibit mTORC1 indirectly via 5' adenosine monophosphate‐activated protein kinase (AMPK) activation and may hold the key to exploit the full potential of mTORC1 inhibition in the treatment of atherosclerosis. Intermittent regimens and dose reduction have also been proposed to improve rapalog's mTORC1 selectivity, thereby reducing mTORC2‐related side effects. PMID:26551391

Recent progress on curcumin-based therapeutics: a patent review (2012-2016). Part II: curcumin derivatives in cancer and neurodegeneration.

PubMed

Di Martino, Rita Maria Concetta; Bisi, Alessandra; Rampa, Angela; Gobbi, Silvia; Belluti, Federica

2017-08-01

Curcumin, the main bioactive compound found in the rhizome of Curcuma longa L., is considered a 'privileged structure', due to its ability to modulate different signaling pathways involved in the pathogenesis of several diseases. Unfortunately, its poor pharmacodynamic and pharmacokinetic properties, mainly related to chemical instability, low solubility and rapid metabolism, greatly reduce its therapeutic potential. In the last years a number of derivatives were developed and patented, aimed both at improving its multifaceted biological profile and overcoming its undesired effects. Areas covered: This review summarizes the patent literature of the last five years dealing with synthetic curcumin-related compounds in cancer and neurodegeneration, properly designed in order to avoid the so-called 'dark side of curcumin', and to take advantage of the beneficial properties of this molecule, worth to be further exploited to obtain effective therapeutics. Expert opinion: Due to the synergistic binding to several networked targets, curcumin turned out to be suitable for polypharmacological approaches, and its 'privileged structure' could also provide the key scaffold to develop novel multipotent drugs useful for treating multifactiorial pathologic conditions such as cancer and neurodegeneration.

Recent progress in doxorubicin-induced cardiotoxicity and protective potential of natural products.

PubMed

Yu, Jie; Wang, Changxi; Kong, Qi; Wu, Xiaxia; Lu, Jin-Jian; Chen, Xiuping

2018-02-01

As an anthracycline antibiotic, doxorubicin (DOX) is one of the most potent and widely used chemotherapeutic agents for various types of solid tumors. Unfortunately, clinical application of this drug results in severe side effects of cardiotoxicity. We aim to review the research focused on elimination or reduction of DOX cardiotoxicity without affecting its anticancer efficacy by natural products. This study is based on pertinent papers that were retrieved by a selective search using relevant keywords in PubMed and ScienceDirect. The literature mainly focusing on natural products and herb extracts with therapeutic efficacies against experimental models both in vitro and in vivo was identified. Current evidence revealed that multiple molecules and signaling pathways, such as oxidative stress, iron metabolism, and inflammation, are associated with DOX-induced cardiotoxicity. Based on these knowledge, various strategies were proposed, and thousands of compounds were screened. A number of natural products and herb extracts demonstrated potency in limiting DOX cardiotoxicity toward cultured cells and experimental animal models. Though a panel of natural products and herb extracts demonstrate protective effects on DOX-induced cardiotoxicity in cells and animal models, their therapeutic potentials for clinical needs further investigation. Copyright © 2018 Elsevier GmbH. All rights reserved.

Preclinical activity of melflufen (J1) in ovarian cancer.

PubMed

Carlier, Charlotte; Strese, Sara; Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P; Gullbo, Joachim

2016-09-13

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Preclinical activity of melflufen (J1) in ovarian cancer

PubMed Central

Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P.; Gullbo, Joachim

2016-01-01

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration. PMID:27528037

Developing a New Computer-Aided Clinical Decision Support System for Prediction of Successful Postcardioversion Patients with Persistent Atrial Fibrillation.

PubMed

Sterling, Mark; Huang, David T; Ghoraani, Behnaz

2015-01-01

We propose a new algorithm to predict the outcome of direct-current electric (DCE) cardioversion for atrial fibrillation (AF) patients. AF is the most common cardiac arrhythmia and DCE cardioversion is a noninvasive treatment to end AF and return the patient to sinus rhythm (SR). Unfortunately, there is a high risk of AF recurrence in persistent AF patients; hence clinically it is important to predict the DCE outcome in order to avoid the procedure's side effects. This study develops a feature extraction and classification framework to predict AF recurrence patients from the underlying structure of atrial activity (AA). A multiresolution signal decomposition technique, based on matching pursuit (MP), was used to project the AA over a dictionary of wavelets. Seven novel features were derived from the decompositions and were employed in a quadratic discrimination analysis classification to predict the success of post-DCE cardioversion in 40 patients with persistent AF. The proposed algorithm achieved 100% sensitivity and 95% specificity, indicating that the proposed computational approach captures detailed structural information about the underlying AA and could provide reliable information for effective management of AF.

Adjuvant Endocrine Therapy in Breast Cancer: Evolving Paradigms in Premenopausal Women.

PubMed

Rossi, Lorenzo; Pagani, Olivia

2017-05-01

In the last few years, new adjuvant endocrine treatment options have become available in young women with early breast cancer, such as the addition of ovarian function suppression to tamoxifen or aromatase inhibitors. Treatment duration has been also adapted in the latest guidelines based on the individual risk of recurrence. The oncologist is therefore challenged to precisely assess the risk of recurrence according to currently available predictive and prognostic factors in order to offer the most appropriate therapeutic option to the individual patient, considering also potential side effects, quality of life, pregnancy planning and patients' preferences. The adjuvant treatment planning should always be discussed and agreed in a multidisciplinary context. Tamoxifen remains the standard of care in low-risk patients or in case of intolerance to combined treatment with pharmacological ovarian function suppression or aromatase inhibitors. Combination treatment is indicated in intermediate high-risk disease. The patient should always be considered an active partner in the treatment decision process, to improve treatment motivation and adherence. Finally, the therapeutic choice should take into account drug availability and pharmacoeconomic issues, which unfortunately may prevent, in many low-income countries, the provision of such effective treatments.

Mini-implant-borne Pendulum B appliance for maxillary molar distalisation: design and clinical procedure.

PubMed

Wilmes, Benedict; Katyal, Vandana; Drescher, Dieter

2014-11-01

A treatment objective of upper molar distalisation may often be required during the correction of a malocclusion. Distalisation is not only indicated for the management of Class II patients, but also for Class III surgery patients who require decompensation in the upper arch if upper incisor retrusion is needed. Unfortunately, most conventional intra-oral devices for non-compliance maxillary molar distalisation experience anchorage loss. A Pendulum type of appliance and a mini-implant-borne distalisation mechanism have been designed which can be inserted at chair-side, without a prior laboratory procedure and immediately after mini-implant placement. For re-activation purposes, a distal screw may be added to the Pendulum B appliance.

3D printing technology used in severe hip deformity.

PubMed

Wang, Shanshan; Wang, Li; Liu, Yan; Ren, Yongfang; Jiang, Li; Li, Yan; Zhou, Hao; Chen, Jie; Jia, Wenxiao; Li, Hui

2017-09-01

This study was designed to assess the use of a 3D printing technique in total hip arthroplasty (THA) for severe hip deformities, where new and improved approaches are needed. THAs were performed from January 2015 to December 2016. Bioprosthesis artificial hip joints were used in both conventional and 3D printing hip arthroplasties. A total of 74 patients (57 cases undergoing conventional hip replacements and 17 undergoing 3D printing hip replacements) were followed-up for an average of 24 months. The average age of the patients was 62.7 years. Clinical data between the patients treated with different approaches were compared. Results showed that the time to postoperative weight bearing and the Harris scores of the patients in the 3D printing group were better than those for patients in the conventional hip replacement group. Unfortunately, the postoperative infection and loosening rates were higher in the 3D printing group. However, there were no significant differences in femoral neck anteversion, neck shaft, acetabular or sharp angles between ipsilateral and contralateral sides in the 3D printing group (P>0.05). The femoral neck anteversion angle was significantly different between the two sides in the conventional hip replacement group (P<0.05). Based on these results, we suggest that the 3D printing approach provides a better short-term curative effect that is more consistent with the physiological structure and anatomical characteristics of the patient, and we anticipate that its use will help improve the lives of many patients.

Calibration of Swarm accelerometer data by GPS positioning and linear temperature correction

NASA Astrophysics Data System (ADS)

Bezděk, Aleš; Sebera, Josef; Klokočník, Jaroslav

2018-07-01

Swarm, a mission of the European Space Agency, consists of three satellites orbiting the Earth since November 2013. In addition to the instrumentation aimed at fulfilling the mission's main goal, which is the observation of Earth's magnetic field, each satellite carries a geodetic quality GPS receiver and an accelerometer. Initially put in a 500-km altitude, all Swarm spacecraft slowly decay due to the action of atmospheric drag. Atmospheric particles and radiation forces impinge on the satellite's surface and thus create the main part of the nongravitational force, which together with satellite-induced thrusts can be measured by space accelerometers. Unfortunately, the Swarm accelerometer data are heavily disturbed by the varying onboard temperature. We calibrate the accelerometer data against a calibration standard derived from observed GPS positions, while making use of the models to represent the forces of gravity origin. We show that this procedure can be extended to incorporate the temperature signal. The obtained calibrated accelerations are validated in several different ways; namely by (i) physically modelled nongravitational forces, by (ii) intercomparison of calibrated accelerometer data from two Swarm satellites flying side-by-side, and by (iii) good agreement of our calibrated signals with those released by ESA, obtained via a different approach for reducing temperature effects. Finally, the presented method is applied to the Swarm C accelerometer data set covering almost two years (July 2014-April 2016), which ESA recently released to scientific users.

Evaluation of a BED-SIDE platelet function assay: performance and clinical utility.

PubMed

Lau, Wei C; Walker, C Ty; Obilby, David; Wash, Mark M; Carville, David G M; Guyer, Kirk E; Bates, Eric R

2002-01-01

Platelets have a pivotal role in the initial defense against insult to the vasculature and are also recognized of critical importance in the acute care settings of percutaneous coronary intervention and cardiopulmonary bypass. In these environments both platelet count and function may be markedly compromised. Unfortunately, current assays to evaluate the parameters of platelet count and function are of limited utility for bed-side testing. Moreover, it is suggested that there may be significant inter patient variation in response to antiplatelet therapy that may be exacerbated by other agents (e.g. heparin) that are routinely administered during cardiac intervention. Here we describe a practical, rapid and user-friendly whole blood platelet function assay that has been developed for use in bed-side settings. Platelet agonists were formulated with an anticoagulant and lyophilized in blood collection tubes standardised to receive a l mL fresh whole blood sample. In the presence of an agonist, platelets are activated and interact (aggregate). Using traditional cell counting principles, non-aggregated platelets are counted whereas aggregated platelets are not. The percentage (%) of functional platelets in reference to a baseline tube may then be determined. Results are available within four minutes. Platelet aggregation in whole blood demonstrated good correlation with turbidometric aggregometry for both ADP (r=0.91) and collagen (r=0.88). Moreover, in clinical settings where antiplatelet agents were administered, this rapid, bed-side, platelet function assay demonstrated utility in monitoring patient response to these therapies. This novel bed-side assay of platelet function is extremely suitable for the clinical environment with a rapid turn-around time. In addition, it provides a full haematology profile, including platelet count, and should permit enhancement of transfusion and interventional decisions.

[The use of psychotropic drugs during breast-feeding].

PubMed

Filip, Maria; Kuśmierek, Maciej; Orzechowska, Agata; Błaszczyk, Justyna; Zajączkowska, Marlena; Gałecki, Piotr

2015-07-01

Breast milk is the best source of nutrients and provides much better protection than immune modified milk. In the United States around 500 000 cases of mental disorders affecting pregnant women are diagnosed each year. It is estimated that approximately 1/3 of these women need psychotropic drugs in a period of breast-feeding. Despite the serious consequences of depression and its well-known effect on a newborn, the women are still reluctant to begin pharmacological treatment. The fear of side effects unfortunately still plays an important role in making such a decision. It has been proved that all psychiatric drugs can transfer into breast milk, but their levels are very low or even negligible for the newborn. Most laboratory tests do not reveal an adequate sensitivity to detect these low concentrations. One have to remember that in case of any disturbing symptoms which may result from the use of these drugs, the only procedure is to discontinue breastfeeding immediately. The knowledge of these effects of particular groups of psychotropic drugs in breast-feeding mothers is essential for every practitioner. This knowledge should also be available not only to psychiatrists, but gynecologists and pediatricians as well. For this reason, it seems to be reasonable to summarize the results of previously published studies dealing with the topic. © 2015 MEDPRESS.

Nanotechnology-Based Detection and Targeted Therapy in Cancer: Nano-Bio Paradigms and Applications

PubMed Central

Mousa, Shaker A.; Bharali, Dhruba J.

2011-01-01

The application of nanotechnology to biomedicine, particularly in cancer diagnosis and treatment, promises to have a profound impact on healthcare. The exploitation of the unique properties of nano-sized particles for cancer therapeutics is most popularly known as nanomedicine. The goals of this review are to discuss the current state of nanomedicine in the field of cancer detection and the subsequent application of nanotechnology to treatment. Current cancer detection methods rely on the patient contacting their provider when they feel ill, or relying on non-specific screening methods, which unfortunately often result in cancers being detected only after it is too late for effective treatment. Cancer treatment paradigms mainly rely on whole body treatment with chemotherapy agents, exposing the patient to medications that non-specifically kill rapidly dividing cells, leading to debilitating side effects. In addition, the use of toxic organic solvents/excipients can hamper the further effectiveness of the anticancer drug. Nanomedicine has the potential to increase the specificity of treatment of cancer cells while leaving healthy cells intact through the use of novel nanoparticles. This review discusses the use of nanoparticles such as quantum dots, nanoshells, nanocrystals, nanocells, and dendrimers for the detection and treatment of cancer. Future directions and perspectives of this cutting-edge technology are also discussed. PMID:24212938

Molecular targets of dietary phytochemicals for possible prevention and therapy of uterine fibroids: Focus on fibrosis.

PubMed

Islam, Md Soriful; Akhtar, Most Mauluda; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina

2017-11-22

Uterine fibroids (myomas or leiomyomas) are common benign tumors of reproductive aged women. Fibroids are clinically apparent in 20-50% of women, and cause abnormal uterine bleeding, abdominal pain and discomfort, pregnancy complications and infertility. Unfortunately, limited numbers of medical treatment are available but no effective preventive strategies exist. Moreover, the benefits of medical treatments are tempered by lack of efficacy or serious adverse side effects. Fibrosis has recently been recognized as a key pathological event in leiomyoma development and growth. It is defined by the excessive deposition of extracellular matrix (ECM). ECM plays important role in making bulk structure of leiomyoma, and ECM-rich rigid structure is believed to be a cause of abnormal bleeding and pelvic pain/pressure. Dietary phytochemicals are known to regulate fibrotic process in different biological systems, and being considered as potential tool to manage human health. At present, very few dietary phytochemicals have been studied in uterine leiomyoma, and they are mostly known for their antiproliferative effects. Therefore, in this review, our aim was to introduce some dietary phytochemicals that could target fibrotic processes in leiomyoma. Thus, this review could serve as useful resource to develop antifibrotic drugs for possible prevention and treatment of uterine fibroids.

Latent Presentation of Decompression Sickness After Altitude Chamber Training in an Active Duty Flier.

PubMed

Gentry, James; Rango, Juan; Zhang, Jianzhong; Biedermann, Shane

2017-04-01

Decompression sickness (DCS) is a potential danger and risk for both divers and aircrew alike. DCS is also a potential side effect of altitude (hypobaric) chamber training as well and can present long after training occurs. Literature review shows that altitude chamber induced DCS has approximately a 0.25% incidence. A 32-yr-old, active duty military member developed symptoms of DCS 3 h after his hypobaric chamber training. Unfortunately, he did not seek treatment for DCS until 48 h after the exposure. His initial treatment included ground level oxygen therapy for 30 min at 12 L of oxygen per minute using a nonrebreathing mask. He achieved complete symptom resolution and was returned to duty. However, 12 d after his initial Flight Medicine evaluation, the patient returned complaining of a right temporal headache, multijoint pains, and fatigue. He was treated in the hyperbaric chamber and had complete resolution of symptoms. He was returned to flying status and 5 mo later denied any return of symptoms. Hypobaric chamber familiarity training is a requirement for all military aircrew personnel to allow them assess their ability to identify symptoms of hypoxia. This training method is not only costly to maintain, but it also places aircrew and chamber technicians at risk for potential long-term side effects from failed recompression treatment of DCS. We are presenting a case of recurrent DCS symptoms 12 d after initial ground level oxygen therapy.Gentry J, Rango J, Zhang J, Biedermann S. Latent presentation of decompression sickness after altitude chamber training in an active duty flier. Aerosp Med Hum Perform. 2017; 88(4):427-430.

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study

PubMed Central

Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

2015-01-01

Parkinson’s disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD. PMID:25565772

Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson's disease: a pharmacoinformatics study.

PubMed

Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

2015-01-01

Parkinson's disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD.

[What's new in pediatric dermatology?

PubMed

Léauté-Labrèze, C

2016-12-01

The association of a birth defect and a segmental hemangioma is well established, a consensus concerning evaluation and monitoring of infants with PHACE or LUMBAR syndromes has been published. The efficacy of propranolol in infantile hemangioma is proven; however there were still unresolved issues concerning the safety in children; after 8 years of use on thousands of children safety data collection did not show any unexpected side effects. Topical treatment of infantile hemangiomas with beta-blockers, such as timolol, is very popular, but recent publications revealed a significant systemic absorption that could be responsible for severe side effects, such as bradycardia, in low birthweight infants. As a consequence, this therapeutic option should be considered with caution. In the last 2 years mTOR inhibitors have been tested in low-flow vascular malformations with varying success, but progress remains to be done in the treatment of vascular abnormalities. Today, genetics has led to advances in the understanding of the pathophysiology and in the future targeted therapies could probably be feasible. Skin barrier deficiency is responsible for the development of allergic phenomena in atopic patients, since it has been shown that sensibilisation, even to food, could probably be induced by skin contact. Unfortunately, the topical treatment with crisaborole, a phosphodiesterase 4 inhibitor, does not look like a revolution in children atopic dermatitis, its efficacy seems equivalent to emollient application. In the field of infectious diseases, changes in viral outbreaks are the most reported. Furthermore epidemic Zika virus, enteroviruses are responsible for expanded dermatological manifestations and also severe meningoencephalitis. Paraviral character of various eruptions, such as gloves and socks syndrome or eruptive pseudoangiomatosis is challenged. © 2016 Elsevier Masson SAS. Tous droits réservés.

DF-1, A Nontoxic Carbon Fullerene Based Antioxidant, is Effective as a Biomedical Countermeasure Against Radiation

NASA Technical Reports Server (NTRS)

Theriot, Corey A.; Casey, Rachael; Conyers, Jodie; Wu, Honglu

2010-01-01

A long-term goal of radiation research is the mitigation of inherent risks of radiation exposure. Thus the study and development of safe agents, whether biomedical or dietary, that act as effective radioprotectors is an important step in accomplishing this long-term goal. Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatigability. For example, nausea and emesis occur in most patients treated with WR-2721 (Amifostine), requiring the use of effective antiemetics, with hypotension being the dose-limiting side effect in patients treated. Clearly, the need for a radioprotector that is both effective and safe still exists. Development of biocompatible nano-materials for radioprotection is a promising emerging technology that could be exploited to address the need to minimize biological effects when exposure is unavoidable. Testing free radical scavenging nanoparticles for potential use in radioprotection is exciting and highly relevant. Initial investigations presented here demonstrate the ability of a particular functionalized carbon fullerene nanoparticle, (DF-1), to act as an effective radioprotector. DF-1 was first identified as the most promising candidate in a screen of several functionalized carbon fullerenes based on lack of toxicity and antioxidant therapeutic potential against oxidative injuries (i.e. organ reperfusion and ionizing radiation). Subsequently, DF-1 has been shown to reduce chromosome aberration yield and cell death, as well as overall ROS levels in human lymphocytes and fibroblasts after exposure to gamma radiation and energetic protons while demonstrating no associated toxicity. The dose-reducing factor of DF-1 at LD50 is nearly 2.0 for gamma radiation. In addition, DF-1 treatment also significantly prevented cell cycle arrest after exposure. Finally, DF-1 markedly attenuated COX2 upregulation in cell culture after irradiation thus preventing an inflammatory response to irradiation. Taken together, these results suggest that DF-1 provides potent protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, inflammation and cell death.

Driving and diabetes mellitus in the Gulf Cooperation Council countries: Call for action.

PubMed

Hassoun, Ahmed A K; Abdella, Nabila; Arouj, Monira Al; Awadi, Fatehya Al; Futaisi, Abdullah Al; Lamki, Mohammed Al; Madani, Abdulrazzaq Al; Saber, Feryal Al; Nakhi, Abdallah Ben; Beshyah, Salem A; El-Ali, Samer; Fiad, Tarek M; Hussein, Wiam I; Kaddaha, Ghaida; Ksseiry, Iyad; Morcos, Bassem; Saadi, Hussein

2015-10-01

The aim of the present article is to increase awareness concerning safe driving for patients with diabetes in the Gulf Cooperation Council (GCC) countries and to provide recommendations concerning the management of these patients. The cognitive, motor, and sensory skills required for driving can be adversely affected by diabetes as well as the side effects of anti-diabetic medications, particularly hypoglycemia. The prevalence of diabetes in the GCC countries is among the highest in the world. As the number of diabetic drivers in these countries continues to increase, the number at risk of having a motor vehicle accident is also expected to increase. We reviewed the available literature concerning driving and diabetes, particularly in relation to the current situation in the GGC countries. Unfortunately, very little published information is available addressing this issue in the GCC countries. Most of the GCC countries lack legislation on driving and diabetes. We have proposed recommendations to help diabetic drivers in the GCC countries as well as to provide guidance to health care professionals managing these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The role of the thymus in allogeneic hematopoietic stem cell transplantation.

PubMed

Krenger, Werner; Holländer, Georg A

2010-07-19

Allogeneic haematopoietic stem cell transplantation (HSCT) is used to treat an increasing number of congenital and acquired disorders of the haematopoietic system. Even though cytoreductive conditioning regimens vary in intensity, all clinically used protocols invariably cause side effects that compromise transiently or long-term the response of the natural and the adaptive immune systems. However, in the context of the reconstruction of immunity, the generation of naïve T cells constitutes a slow process, and requires a functionally competent thymus. Unfortunately, regular thymic function is frequently suppressed by transplant-related toxicities. Most notably, graft-versus-host disease (GVHD) causes a state of posttransplantation immune deficiency. Here we discuss preclinical allogeneic HSCT models and clinical observations that have contributed to a detailed understanding of the cellular and molecular mechanisms responsible for the thymic dysfunction caused by acute GVHD. An in-depth knowledge of the mechanisms that control regular thymopoiesis and, conversely, affect thymus function is expected to provide the factual basis for the design of innovative therapies to recover T-cell numbers and function following allogeneic HSCT.

Germline stem cells: Towards the regeneration of spermatogenesis

PubMed Central

Valli, Hanna; Phillips, Bart T.; Shetty, Gunapala; Byrne, James A.; Clark, Amander T.; Meistrich, Marvin L.; Orwig, Kyle E.

2013-01-01

Improved therapies for cancer and other conditions have resulted in a growing population of long-term survivors. Infertility is an unfortunate side effect of some cancer therapies that impacts the quality of life of survivors who are in their reproductive or pre-reproductive years. Some of these patients have the opportunity to preserve their fertility using standard technologies that include sperm, egg or embryo banking, followed by in vitro fertilization and/or embryo transfer. However, these options are not available to all patients, especially the prepubertal patients who are not yet producing mature gametes. For these patients, there are several stem cell technologies in the research pipeline that may give rise to new fertility options and allow infertile patients to have their own biological children. We will review the role of stem cells in normal spermatogenesis as well as experimental stem cell based techniques that may have potential to generate or regenerate spermatogenesis and sperm. We will present these technologies in the context of the fertility preservation paradigm, but we anticipate that they will have broad implications for the assisted reproduction field. PMID:24314923

Nonsurgical management of hypertrophic scars: evidence-based therapies, standard practices, and emerging methods.

PubMed

Atiyeh, Bishara S

2007-01-01

Hypertrophic scars, resulting from alterations in the normal processes of cutaneous wound healing, are characterized by proliferation of dermal tissue with excessive deposition of fibroblast-derived extracellular matrix proteins, especially collagen, over long periods, and by persistent inflammation and fibrosis. Hypertrophic scars are among the most common and frustrating problems after injury. As current aesthetic surgical techniques become more standardized and results more predictable, a fine scar may be the demarcating line between acceptable and unacceptable aesthetic results. However, hypertrophic scars remain notoriously difficult to eradicate because of the high recurrence rates and the incidence of side effects associated with available treatment methods. This review explores the various treatment methods for hypertrophic scarring described in the literature including evidence-based therapies, standard practices, and emerging methods, attempting to distinguish those with clearly proven efficiency from anecdotal reports about therapies of doubtful benefits while trying to differentiate between prophylactic measures and actual treatment methods. Unfortunately, the distinction between hypertrophic scar treatments and keloid treatments is not obvious in most reports, making it difficult to assess the efficacy of hypertrophic scar treatment.

Reply to comment by Rainer Facius et al. on "U.S. Government shutdown degrades aviation radiation monitoring during solar radiation storm"

NASA Astrophysics Data System (ADS)

Tobiska, W. Kent; Gersey, Brad; Wilkins, Richard; Mertens, Chris; Atwell, William; Bailey, Justin

2014-05-01

The premise of this comment perpetuates an unfortunate trend among some radiation researchers to minimize potential risks to human tissue from low-radiation sources. In fact, this discussion on the risk uncertainties of low-dose radiation further illustrates the need for more measurements and a program of active monitoring, especially when solar eruptive events can substantially elevate the radiation environment. This debate also highlights the context of a bigger problem; i.e., how do we as professionals act with due diligence to take the immense body of knowledge of space weather radiation effects on human tissue and distil it into ideas that regulatory agencies can use to maximize the safety of a population at risk. The focus of our article on radiation risks due to solar energetic particle events starts with our best assessment of risks and is based on the body of scientific knowledge while, at the same time, erring on the side of public safety. The uncertainty inherent in our assessment is accepted and described with this same philosophy in mind.

Exact intervals and tests for median when one sample value possibly an outliner

NASA Technical Reports Server (NTRS)

Keller, G. J.; Walsh, J. E.

1973-01-01

Available are independent observations (continuous data) that are believed to be a random sample. Desired are distribution-free confidence intervals and significance tests for the population median. However, there is the possibility that either the smallest or the largest observation is an outlier. Then, use of a procedure for rejection of an outlying observation might seem appropriate. Such a procedure would consider that two alternative situations are possible and would select one of them. Either (1) the n observations are truly a random sample, or (2) an outlier exists and its removal leaves a random sample of size n-1. For either situation, confidence intervals and tests are desired for the median of the population yielding the random sample. Unfortunately, satisfactory rejection procedures of a distribution-free nature do not seem to be available. Moreover, all rejection procedures impose undesirable conditional effects on the observations, and also, can select the wrong one of the two above situations. It is found that two-sided intervals and tests based on two symmetrically located order statistics (not the largest and smallest) of the n observations have this property.

Femtosecond-laser assisted cell reprogramming

NASA Astrophysics Data System (ADS)

Breunig, Hans Georg; Uchugonova, Aisada; Batista, Ana; König, Karsten

2017-02-01

Femtosecond-laser pulses can assist to transfect cells by creating transient holes in the cell membrane, thus making them temporarily permeable for extraneous genetic material. This procedure offers the advantage of being completely "virus free" since no viruses are used for the delivery and integration of gene factors into the host genome and, thereby, avoiding serious side effects which so far prevent clinical application. Unfortunately, focusing of the laser radiation onto individual cell membranes is quite elaborate and time consuming. Regarding these obstacles, we briefly review two optical setups for fast, efficient and high throughput laser-assisted cell transfection based on femtosecond laser pulse excitation. The first setup aims at assisting the transfection of adherent cells. It comprises of a modified laser-scanning microscope with beamshaping optics as well as home-made software to automate the detection, targeting and laser-irradiation process. The second setup aims at laser-assisted transfection of non-adherent cells in suspension which move in a continuous flow through the laser focus region. The setup allows to address a large number of cells, however, with much lower transfection efficiency than the individual-cell targeting approach.

Remotely accessible laboratory for MEMS testing

NASA Astrophysics Data System (ADS)

Sivakumar, Ganapathy; Mulsow, Matthew; Melinger, Aaron; Lacouture, Shelby; Dallas, Tim E.

2010-02-01

We report on the construction of a remotely accessible and interactive laboratory for testing microdevices (aka: MicroElectroMechancial Systems - MEMS). Enabling expanded utilization of microdevices for research, commercial, and educational purposes is very important for driving the creation of future MEMS devices and applications. Unfortunately, the relatively high costs associated with MEMS devices and testing infrastructure makes widespread access to the world of MEMS difficult. The creation of a virtual lab to control and actuate MEMS devices over the internet helps spread knowledge to a larger audience. A host laboratory has been established that contains a digital microscope, microdevices, controllers, and computers that can be logged into through the internet. The overall layout of the tele-operated MEMS laboratory system can be divided into two major parts: the server side and the client side. The server-side is present at Texas Tech University, and hosts a server machine that runs the Linux operating system and is used for interfacing the MEMS lab with the outside world via internet. The controls from the clients are transferred to the lab side through the server interface. The server interacts with the electronics required to drive the MEMS devices using a range of National Instruments hardware and LabView Virtual Instruments. An optical microscope (100 ×) with a CCD video camera is used to capture images of the operating MEMS. The server broadcasts the live video stream over the internet to the clients through the website. When the button is pressed on the website, the MEMS device responds and the video stream shows the movement in close to real time.

A Proposed Collaboration Against Big Tobacco: Common Ground Between the Vaping and Public Health Community in the United States.

PubMed

Wagener, Theodore L; Meier, Ellen; Tackett, Alayna P; Matheny, James D; Pechacek, Terry F

2016-05-01

An unfortunate conflict is underway between the public health community and the vaping community over e-cigarettes' harmfulness or lack thereof. This conflict is made worse by an information vacuum that is being filled by vocal members on both sides of the debate; a perceived lack of credibility of public health officials by those in the vaping community; the tobacco industry's recent involvement in e-cigarettes; and the constant evolution of different styles and types of e-cigarettes. This conflict is avoidable; common ground exists. If both groups rally around what is in their own and the public's best interest-the end of combustible tobacco--all will benefit significantly. If not, the result may be missed opportunities, misguided alliances, and--ultimately-poorer public health. This study brings light to the contentious debate between the vaping and public health communities. It addresses how both sides are responsible for bringing misleading information to the public and vocal leaders on both sides are unknowingly intensifying and polarizing the debate-likely at the expense of public health. It also describes how this conflict is avoidable, and provides a starting point for potential positions of common ground against Big Tobacco. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reforming the politics of animal research.

PubMed

Levin, Lisa Hara; Reppy, William A

2015-07-01

An unfortunate tension exists between the biomedical research and animal welfare/rights communities. We believe that despite the mistrust between these groups, there are individuals on both sides of the controversy who seek to better understand the other. We recommend an update of institutional policies that will better inform the public about the use of non-human animals in biomedical research and improve a dialogue on such use between concerned individuals who either support or oppose non-human animal-based biomedical research. Such interactions may well determine the longevity of using non-human animals as experimental subjects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Motivating Company Personnel by Applying the Semi-self-organized Teams Principle

NASA Astrophysics Data System (ADS)

Kumlander, Deniss

The only way nowadays to improve stability of software development process in the global rapidly evolving world is to be innovative and involve professionals into projects motivating them using both material and non material factors. In this paper self-organized teams are discussed. Unfortunately not all kind of organizations can benefit directly from agile method including applying self-organized teams. The paper proposes semi-self-organized teams presenting it as a new and promising motivating factor allowing deriving many positive sides of been self-organized and partly agile and been compliant to less strict conditions for following this innovating process. The semi-self organized teams are reliable at least in the short-term perspective and are simple to organize and support.

Remote Sensing the Vertical Profile of Cloud Droplet Effective Radius, Thermodynamic Phase, and Temperature

NASA Technical Reports Server (NTRS)

Martins, J. V.; Marshak, A.; Remer, L. A.; Rosenfeld, D.; Kaufman, Y. J.; Fernandez-Borda, R.; Koren, I.; Correia, A. L.; Zubko, V.; Artaxo, P.

2011-01-01

Cloud-aerosol interaction is a key issue in the climate system, affecting the water cycle, the weather, and the total energy balance including the spatial and temporal distribution of latent heat release. Information on the vertical distribution of cloud droplet microphysics and thermodynamic phase as a function of temperature or height, can be correlated with details of the aerosol field to provide insight on how these particles are affecting cloud properties and their consequences to cloud lifetime, precipitation, water cycle, and general energy balance. Unfortunately, today's experimental methods still lack the observational tools that can characterize the true evolution of the cloud microphysical, spatial and temporal structure in the cloud droplet scale, and then link these characteristics to environmental factors and properties of the cloud condensation nuclei. Here we propose and demonstrate a new experimental approach (the cloud scanner instrument) that provides the microphysical information missed in current experiments and remote sensing options. Cloud scanner measurements can be performed from aircraft, ground, or satellite by scanning the side of the clouds from the base to the top, providing us with the unique opportunity of obtaining snapshots of the cloud droplet microphysical and thermodynamic states as a function of height and brightness temperature in clouds at several development stages. The brightness temperature profile of the cloud side can be directly associated with the thermodynamic phase of the droplets to provide information on the glaciation temperature as a function of different ambient conditions, aerosol concentration, and type. An aircraft prototype of the cloud scanner was built and flew in a field campaign in Brazil.

Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance

PubMed Central

Suwanarusk, Rossarin; Russell, Bruce; Ong, Alice; Sriprawat, Kanlaya; Chu, Cindy S.; PyaePhyo, Aung; Malleret, Benoit; Nosten, François; Renia, Laurent

2015-01-01

Objectives Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai–Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. Methods To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. Results P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7–4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6–2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. Conclusions Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria. PMID:25150147

Computational protein design: a review

NASA Astrophysics Data System (ADS)

Coluzza, Ivan

2017-04-01

Proteins are one of the most versatile modular assembling systems in nature. Experimentally, more than 110 000 protein structures have been identified and more are deposited every day in the Protein Data Bank. Such an enormous structural variety is to a first approximation controlled by the sequence of amino acids along the peptide chain of each protein. Understanding how the structural and functional properties of the target can be encoded in this sequence is the main objective of protein design. Unfortunately, rational protein design remains one of the major challenges across the disciplines of biology, physics and chemistry. The implications of solving this problem are enormous and branch into materials science, drug design, evolution and even cryptography. For instance, in the field of drug design an effective computational method to design protein-based ligands for biological targets such as viruses, bacteria or tumour cells, could give a significant boost to the development of new therapies with reduced side effects. In materials science, self-assembly is a highly desired property and soon artificial proteins could represent a new class of designable self-assembling materials. The scope of this review is to describe the state of the art in computational protein design methods and give the reader an outline of what developments could be expected in the near future.

Structural Basis of Resistance to Anti-Cytochrome bc1 Complex Inhibitors: Implication for Drug Improvement

PubMed Central

Esser, Lothar; Yu, Chang-An; Xia, Di

2016-01-01

The emergence of drug resistance has devastating economic and social consequences, a testimonial of which is the rise and fall of inhibitors against the respiratory component cytochrome bc1 complex, a time tested and highly effective target for disease control. Unfortunately, the mechanism of resistance is a multivariate problem, including primarily mutations in the gene of the cytochrome b subunit but also activation of alternative pathways of ubiquinol oxidation and pharmacokinetic effects. There is a considerable interest in designing new bc1 inhibitors with novel modes of binding and lower propensity to induce the development of resistance. The accumulation of crystallographic data of bc1 complexes with and without inhibitors bound provides the structural basis for rational drug design. In particular, the cytochrome b subunit offers two distinct active sites that can be targeted for inhibition - the quinol oxidation site and the quinone reduction site. This review brings together available structural information of inhibited bc1 by various quinol oxidation- and reduction-site inhibitors, the inhibitor binding modes, conformational changes upon inhibitor binding of side chains in the active site and large scale domain movements of the iron-sulfur protein subunit. Structural data analysis provides a clear understanding of where and why existing inhibitors fail and points towards promising alternatives. PMID:23688079

Do you see what I see? The difference between dog and human visual perception may affect the outcome of experiments.

PubMed

Pongrácz, Péter; Ujvári, Vera; Faragó, Tamás; Miklósi, Ádám; Péter, András

2017-07-01

The visual sense of dogs is in many aspects different than that of humans. Unfortunately, authors do not explicitly take into consideration dog-human differences in visual perception when designing their experiments. With an image manipulation program we altered stationary images, according to the present knowledge about dog-vision. Besides the effect of dogs' dichromatic vision, the software shows the effect of the lower visual acuity and brightness discrimination, too. Fifty adult humans were tested with pictures showing a female experimenter pointing, gazing or glancing to the left or right side. Half of the pictures were shown after they were altered to a setting that approximated dog vision. Participants had difficulty to find out the direction of glancing when the pictures were in dog-vision mode. Glances in dog-vision setting were followed less correctly and with a slower response time than other cues. Our results are the first that show the visual performance of humans under circumstances that model how dogs' weaker vision would affect their responses in an ethological experiment. We urge researchers to take into consideration the differences between perceptual abilities of dogs and humans, by developing visual stimuli that fit more appropriately to dogs' visual capabilities. Copyright © 2017 Elsevier B.V. All rights reserved.

Secondary effects of glyphosate on plants

USDA-ARS?s Scientific Manuscript database

Glyphosate is a unique herbicide with interesting secondary effects. Unfortunately, some have assumed that the secondary effects that occur in glyphosate-susceptible plants treated with glyphosate, such as altered mineral nutrition, reduced phenolic compound production and pathogen resistance, also ...

Resveratrol for breast cancer prevention and therapy: Preclinical evidence and molecular mechanisms.

PubMed

Sinha, Dona; Sarkar, Nivedita; Biswas, Jaydip; Bishayee, Anupam

2016-10-01

Globally, breast cancer is the most frequently diagnosed cancer among women. The major unresolved problems with metastatic breast cancer is recurrence after receiving objective response to chemotherapy, drug-induced side effects of first line chemotherapy and delayed response to second line of treatment. Unfortunately, very few options are available as third line treatment. It is clear that under such circumstances there is an urgent need for new and effective drugs. Phytochemicals are among the most promising chemopreventive treatment options for the management of cancer. Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a non-flavonoid polyphenol present in several dietary sources, including grapes, berries, soy beans, pomegranate and peanuts, has been shown to possess a wide range of health benefits through its effect on a plethora of molecular targets.The present review encompasses the role of resveratrol and its natural/synthetic analogue in the light of their efficacy against tumor cell proliferation, metastasis, epigenetic alterations and for induction of apoptosis as well as sensitization toward chemotherapeutic drugs in various in vitro and in vivo models of breast cancer. The roles of resveratrol as a phytoestrogen, an aromatase inhibitor and in stem cell therapy as well as adjuvent treatment are also discussed. This review explores the full potential of resveratrol in breast cancer prevention and treatment with current limitations, challenges and future directions of research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Energetic, Structural, and Antimicrobial Analyses of [beta]-Lactam Side Chain Recognition by [beta]-Lactamases

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

Caselli, E.; Powers, R.A.; Blaszczak, L.C.

2010-03-05

Penicillins and cephalosporins are among the most widely used and successful antibiotics. The emergence of resistance to these {beta}-lactams, most often through bacterial expression of {beta}-lactamases, threatens public health. To understand how {beta}-lactamases recognize their substrates, it would be helpful to know their binding energies. Unfortunately, these have been difficult to measure because {beta}-lactams form covalent adducts with {beta}-lactamases. This has complicated functional analyses and inhibitor design. To investigate the contribution to interaction energy of the key amide (R1) side chain of {beta}-lactam antibiotics, eight acylglycineboronic acids that bear the side chains of characteristic penicillins and cephalosporins, as well asmore » four other analogs, were synthesized. These transition-state analogs form reversible adducts with serine {beta}-lactamases. Therefore, binding energies can be calculated directly from K{sub i} values. The K{sub i} values measured span four orders of magnitude against the Group I {beta}-lactamase AmpC and three orders of magnitude against the Group II {beta}-lactamase TEM-1. The acylglycineboronic acids have K{sub i} values as low as 20 nM against AmpC and as low as 390 nM against TEM-1. The inhibitors showed little activity against serine proteases, such as chymotrypsin. R1 side chains characteristic of {beta}-lactam inhibitors did not have better affinity for AmpC than did side chains characteristic of {beta}-lactam substrates. Two of the inhibitors reversed the resistance of pathogenic bacteria to {beta}-lactams in cell culture. Structures of two inhibitors in their complexes with AmpC were determined by X-ray crystallography to 1.90 {angstrom} and 1.75 {angstrom} resolution; these structures suggest interactions that are important to the affinity of the inhibitors. Acylglycineboronic acids allow us to begin to dissect interaction energies between {beta}-lactam side chains and {beta}-lactamases. Surprisingly, there is little correlation between the affinity contributed by R1 side chains and their occurrence in {beta}-lactam inhibitors or {beta}-lactam substrates of serine {beta}-lactamases. Nevertheless, presented in acylglycineboronic acids, these side chains can lead to inhibitors with high affinities and specificities. The structures of their complexes with AmpC give a molecular context to their affinities and may guide the design of anti-resistance compounds in this series.« less

Preparation and mounting of adult Drosophila structures in Canada balsam.

PubMed

Stern, David L; Sucena, Elio

2012-03-01

The Drosophila cuticle carries a rich array of morphological details. Thus, cuticle examination has had a central role in the history of genetics. To prepare fine "museum-quality," permanent slides, it is best to mount specimens in Canada Balsam. It is difficult to give precise recipes for Canada Balsam, because every user seems to prefer a slightly different viscosity. Dilute solutions spread easily and do not dry too rapidly while mounting specimens. The disadvantage is that there is actually less Balsam in a "drop" of the solution, and when dried, it can contract from the sides of the coverslip, sometimes disturbing the specimen. Unfortunately, there is no substitute for experience when using Canada Balsam. This protocol describes a procedure for mounting adult cuticles in Canada Balsam.

Scaling Up Decision Theoretic Planning to Planetary Rover Problems

NASA Technical Reports Server (NTRS)

Meuleau, Nicolas; Dearden, Richard; Washington, Rich

2004-01-01

Because of communication limits, planetary rovers must operate autonomously during consequent durations. The ability to plan under uncertainty is one of the main components of autonomy. Previous approaches to planning under uncertainty in NASA applications are not able to address the challenges of future missions, because of several apparent limits. On another side, decision theory provides a solid principle framework for reasoning about uncertainty and rewards. Unfortunately, there are several obstacles to a direct application of decision-theoretic techniques to the rover domain. This paper focuses on the issues of structure and concurrency, and continuous state variables. We describes two techniques currently under development that address specifically these issues and allow scaling-up decision theoretic solution techniques to planetary rover planning problems involving a small number of goals.

Hybrid semiconductor fiber lasers for telecommunications

NASA Astrophysics Data System (ADS)

Khalili, Alireza

2006-12-01

Highly stable edge emitting semiconductor lasers are of utmost importance in most telecommunications applications where high-speed data transmission sets strict limits on the purity of the laser signal. Unfortunately, most edge emitting semiconductor lasers, unlike gaseous or solid-state laser sources, operate with many closely spaced axial modes, which accounts for the observed instability and large spikes in the output spectrum of such lasers. Consequently, in most telecom applications distributed feedback (DFB) or distributed Bragg reflector (DBR) techniques are used to ensure stability and single-frequency operation, further adding to the cost and complexity of such lasers. Additionally, coupling of the highly elliptical output beam of these lasers to singlemode fibers complicates the packaging procedure and sub-micron alignment of various optical components is often necessary. Utilizing the evanescent coupling between a semiconductor antiresonant reflecting optical waveguide (ARROW) and a side polished fiber, this thesis presents an alternative side-coupled laser module that eliminates the need for the cumbersome multi-component alignment processes of conventional laser packages, and creates an inherent mode selection mechanism that guarantees singlemode radiation into the fiber without any gratings. We have been able to demonstrate the first side-coupled fiber semiconductor laser in this technology, coupling more than 3mW of power at 850nm directly into a 5/125mum singlemode fiber. This mixed-cavity architecture yields a high thermal stability (˜0.06nm/°C), and negligible spectral spikes are observed. Theoretical background and simulation results, as well as several supplementary materials are also presented to further rationalize the experimental data. A side-coupled light-emitter and pre-amplifier are also proposed and discussed. We also study different architectures for attaining higher efficiency, higher output power, and wavelength tunability in such lasers. Finally, we discuss possible venues for integration of these side-coupled devices in a telecommunication system. Approved for publication.

The design of a wireless batteryless biflash installation with high power LEDs

NASA Astrophysics Data System (ADS)

Cappelle, J.; De Geest, W.; Hanselaer, P.

2011-05-01

Adding flashlights at crosswalks may make these weak traffic points safer. Unfortunately plugging in traffic lights into the electrical grid is expensive and complex. This paper reports about the energetic, the electronic and the optical design and building of a wireless and batteryless biflash installation in the framework of a flemish SME supporting program. The energy is supplied by a small solar panel and is buffered by supercapacitors instead of batteries. This has the advantage of being maintenance free: the number of charge-discharge cycles is almost unlimited because there is no chemical reaction involved in the storage mechanism. On the other hand the limited energy storage capacity of supercapacitors requires a new approach for the system design. Based on the EN-12352 standard for warning light devices, all design choices were filled in to be as energy efficient as possible. The duty cycle and the light output of the high power led flashlights are minimized. The components for the electronic circuits for the led driver, the control and the RF communication are selected based on their energy consumption and power management techniques are implemented. A lot of energy is saved by making the biflash system active. The leds are only flashing on demand or at preprogrammed moments. A biflash installation is typically installed at both sides of a crosswalk. A call at one of the sides should result in flashing at both sides. To maintain the drag and drop principle, a wireless RF communication system is designed.

Oral adverse effects due to the use of Nevirapine.

PubMed

Moura, Mariela Dutra Gontijo; Senna, Maria Inês Barreiros; Madureira, Davidson Fróis; Fonseca, Linaena Merícy Silva; Mesquita, Ricardo Alves

2008-01-01

The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.

Long lifetime generation IV image intensifiers with unfilmed microchannel plate

NASA Astrophysics Data System (ADS)

Estrera, Joseph P.; Bender, Edward J.; Giordana, A.; Glesener, John W.; Iosue, Mike J.; Lin, P. P.; Sinor, Timothy W.

2000-11-01

Current Generation II Gallium Arsenide (GaAs) image intensifier tube technology requires that the tube microchannel plate (MCP) component have a thin dielectric coating on the side facing the tube's photocathode component. This protective coating substantially reduces the release from the MCP of ions and neutral species, particularly when the image intensifier is operated. The prevention of MCP outgassing is necessary in order ot prevent the poisoning of the Cs:O surface on the GaAs photocathode. Many authors have experimented with omitting the MCP coating. Such experiments have consistently led to an intensifier with a significantly reduced lifetime, due to contamination of the Cs:O layer on the photocathode. Unfortunately the MCP film acts as a scattering cneter to electron transport within the intensifier and effectively reduces the photoelectron detection efficiency. Substantial enhancement of the image intensifier operating parameters is the motivation for the removal of the MCP film. Removal of the MCP film promises to simplify MCP fabrication and enhance the intensifier parameters related to Electro-Optical performance and image quality. This paper presents results showing for the first time that it is possible to fabricate a long lifetime image intensifier with a single unfilmed MCP and achieve improved imaging and performance characteristics.

Herbal Medicine in the United States: Review of Efficacy, Safety, and Regulation

PubMed Central

2008-01-01

Introduction Herbal products have gained increasing popularity in the last decade, and are now used by approximately 20% of the population. Herbal products are complex mixtures of organic chemicals that may come from any raw or processed part of a plant, including leaves, stems, flowers, roots, and seeds. Under the current law, herbs are defined as dietary supplements, and manufacturers can therefore produce, sell, and market herbs without first demonstrating safety and efficacy, as is required for pharmaceutical drugs. Although herbs are often perceived as “natural” and therefore safe, many different side effects have been reported owing to active ingredients, contaminants, or interactions with drugs. Results Unfortunately, there is limited scientific evidence to establish the safety and efficacy of most herbal products. Of the top 10 herbs, 5 (ginkgo, garlic, St. John’s wort, soy, and kava) have scientific evidence suggesting efficacy, but concerns over safety and a consideration of other medical therapies may temper the decision to use these products. Conclusions Herbal products are not likely to become an important alternative to standard medical therapies unless there are changes to the regulation, standardization, and funding for research of these products. PMID:18415652

Psychiatric Adverse Effects of Rimonobant in Adults with Prader-Willi syndrome

PubMed Central

Motaghedi, Roja; Lipman, Elizabeth G; Hogg, Jeannette E.; Christos, Paul J.; Vogiatzi, Maria G.; Angulo, Moris A.

2010-01-01

Background Prader Willi syndrome (PWS) without strict environmental modifications can lead to obesity associated with significant morbidity and mortality. In addition to increased appetite, these individuals have decreased energy expenditure with lower insulin like growth factor 1 (IGF-1), which contributes to adiposity. No effective treatment is available for this condition. Endocannabinoid receptor CB1 antagonist, rimonobant, has been effective for treatment of obesity in adult subjects. Rimonabant promotes weight loss by multiple proposed mechanisms, including decreased appetite and lipogenesis, and increased energy expenditure. Therefore, we conducted this pilot study to evaluate the effect of rimonabant on body weight and composition of adults with PWS. Method This was a double blind placebo controlled study. Body weight, total fat mass, fasting ghrelin, leptin, IGF1 and insulin like growth factor binding protein (IGFBP3) were collected at baseline, and after 90 and 180 days of treatment with placebo or 20 mg of rimonabant. Results Due to psychiatric adverse effects, 50% of subjects in the rimonabant group withdrew, and the study was terminated early (N=10) for safety concerns. There was a trend for weight loss, lower fat mass and higher IGF1 level at the end of study in this group. Leptin followed the fat mass and decreased with rimonabant treatment. Conclusion Rimonabant administration may be efficacious for weight loss in adults with PWS; unfortunately it is associated with an unacceptably high risk of psychiatric side effects. Future CB1 antagonists will need a better psychiatric profile before considered in the treatment of obesity in this genetic condition. PMID:20965292

Effectiveness of opioids in the treatment of chronic non-cancer pain.

PubMed

Trescot, Andrea M; Glaser, Scott E; Hansen, Hans; Benyamin, Ramsin; Patel, Samir; Manchikanti, Laxmaiah

2008-03-01

For thousands of years, opioids have been used to treat pain, and they continue to be one of the most commonly prescribed medications for pain. It is estimated that 90% of patients presenting to pain centers and receiving treatment in such facilities are on opioids. Opioids can be considered broad-spectrum analgesics that act at multiple points along the pain pathway. Unfortunately, opioids also have the potential for great harm, with multiple side effects and potential complications, some of which are lethal. They are also uniquely addictive, which can lead to misuse and diversion. We reviewed the relevant English literature and did thorough manual searches of the bibliographies of known primary and review articles. We utilized pain relief as the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, improvement in work status, and evidence of addiction. Short-term use and improvement was defined as less than 6 months and long-term relief was defined as 6 months or longer. The 3 systematic reviews evaluating long-term effectiveness of opioids for chronic non-cancer pain provided unclear and weak evidence. The results of this review showed that many patients in the included studies were dissatisfied with adverse events or insufficient pain relief from opioids and withdrew from the studies. For patients able to continue on opioids, evidence was weak suggesting that their pain scores were lower than before therapy and that this relief could be maintained long-term (> 6 months). There was also weak evidence that long-term opioid therapy with morphine and transdermal fentanyl not only decreases pain but also improves functioning. Limited evidence was available for the most commonly used opioids, oxycodone and hydrocodone. Evidence for the ability to drive on chronic opioid therapy was moderate without major side effects or complications. It is concluded that, for long-term opioid therapy of 6 months or longer in managing chronic non-cancer pain, with improvement in function and reduction in pain, there is weak evidence for morphine and transdermal fentanyl. However, there is limited or lack of evidence for all other controlled substances, including the most commonly used drugs, oxycodone and hydrocodone.

Leveraging graph topology and semantic context for pharmacovigilance through twitter-streams.

PubMed

Eshleman, Ryan; Singh, Rahul

2016-10-06

Adverse drug events (ADEs) constitute one of the leading causes of post-therapeutic death and their identification constitutes an important challenge of modern precision medicine. Unfortunately, the onset and effects of ADEs are often underreported complicating timely intervention. At over 500 million posts per day, Twitter is a commonly used social media platform. The ubiquity of day-to-day personal information exchange on Twitter makes it a promising target for data mining for ADE identification and intervention. Three technical challenges are central to this problem: (1) identification of salient medical keywords in (noisy) tweets, (2) mapping drug-effect relationships, and (3) classification of such relationships as adverse or non-adverse. We use a bipartite graph-theoretic representation called a drug-effect graph (DEG) for modeling drug and side effect relationships by representing the drugs and side effects as vertices. We construct individual DEGs on two data sources. The first DEG is constructed from the drug-effect relationships found in FDA package inserts as recorded in the SIDER database. The second DEG is constructed by mining the history of Twitter users. We use dictionary-based information extraction to identify medically-relevant concepts in tweets. Drugs, along with co-occurring symptoms are connected with edges weighted by temporal distance and frequency. Finally, information from the SIDER DEG is integrate with the Twitter DEG and edges are classified as either adverse or non-adverse using supervised machine learning. We examine both graph-theoretic and semantic features for the classification task. The proposed approach can identify adverse drug effects with high accuracy with precision exceeding 85 % and F1 exceeding 81 %. When compared with leading methods at the state-of-the-art, which employ un-enriched graph-theoretic analysis alone, our method leads to improvements ranging between 5 and 8 % in terms of the aforementioned measures. Additionally, we employ our method to discover several ADEs which, though present in medical literature and Twitter-streams, are not represented in the SIDER databases. We present a DEG integration model as a powerful formalism for the analysis of drug-effect relationships that is general enough to accommodate diverse data sources, yet rigorous enough to provide a strong mechanism for ADE identification.

Advances in the Metrology of Absolute Value Assignments to Isotopic Reference Materials: Consequences from the Avogadro Project

NASA Astrophysics Data System (ADS)

Vocke, Robert; Rabb, Savelas

2015-04-01

All isotope amount ratios (hereafter referred to as isotope ratios) produced and measured on any mass spectrometer are biased. This unfortunate situation results mainly from the physical processes in the source area where ions are produced. Because the ionized atoms in poly-isotopic elements have different masses, such processes are typically mass dependent and lead to what is commonly referred to as mass fractionation (for thermal ionization and electron impact sources) and mass bias (for inductively coupled plasma sources.) This biasing process produces a measured isotope ratio that is either larger or smaller than the "true" ratio in the sample. This has led to the development of numerous fractionation "laws" that seek to correct for these effects, many of which are not based on the physical processes giving rise to the biases. The search for tighter and reproducible precisions has led to two isotope ratio measurement systems that exist side-by-side. One still seeks to measure "absolute" isotope ratios while the other utilizes an artifact based measurement system called a delta-scale. The common element between these two measurement systems is the utilization of isotope reference materials (iRMs). These iRMs are used to validate a fractionation "law" in the former case and function as a scale anchor in the latter. Many value assignments of iRMs are based on "best measurements" by the original groups producing the reference material, a not entirely satisfactory approach. Other iRMs, with absolute isotope ratio values, have been produced by calibrated measurements following the Atomic Weight approach (AW) pioneered by NBS nearly 50 years ago. Unfortunately, the AW is not capable of calibrating the new generation of iRMs to sufficient precision. So how do we get iRMs with isotope ratios of sufficient precision and without bias? Such a focus is not to denigrate the extremely precise delta-scale measurements presently being made on non-traditional and tradition stable isotope systems. But even absolute isotope ratio measurements have an important role to play in delta-scale schemes. Highly precise and unbiased measurements of the artifact anchor for any scale facilitates the replacement of that scale's anchor once the initial supply of the iRM is exhausted. Absolute isotope ratio measurements of artifacts at the positive and negative extremes of a delta-scale will allow the appropriate assignment of delta-values to these normalizing iRMs, thereby minimizing any scale contractions or expansions to either side of the anchor artifact. And finally, absolute values for critical iRMs with also allow delta-scale results to be used in other scientific disciplines that employ other units of measure. Precise absolute isotope ratios of Si has been one of the consequences of the Avogadro Project (an international effort to replace the original kilogram artifact with a natural constant, the Planck constant.) We will present the results of applying such measurements to the principal iRMs for the Si isotope system (SRM 990, Big Batch and Diatomite) and its consequences for their delta-Si29 and delta-Si30 values.

No blank slates: Pre-existing schemas about pharmaceuticals predict memory for side effects.

PubMed

Heller, Monika K; Chapman, Sarah C E; Horne, Rob

2017-04-01

Attribution of symptoms as medication side effects is informed by pre-existing beliefs about medicines and perceptions of personal sensitivity to their effects (pharmaceutical schemas). We tested whether (1) pharmaceutical schemas were associated with memory (recall/recognition) for side effect information (2) memory explained the attribution of a common unrelated symptom as a side effect. In this analogue study participants saw the patient leaflet of a fictitious asthma drug listing eight side effects. We measured recall and recognition memory for side effects and used a vignette to test whether participants attributed an unlisted common symptom (headache) as a side effect. Participants who perceived pharmaceuticals as more harmful in general recalled fewer side effects correctly (r Correct Recall  = -.273), were less able to differentiate between listed and unlisted side effects (r Recognition Sensitivity  = -.256) and were more likely to attribute the unlisted headache symptom as a side effect (r side effect attribution  = .381, ps < .01). The effect of harm beliefs on side effect attribution was partially mediated by correct recall of side effects. Pharmaceutical schemas are associated with memory for side effect information. Memory may explain part of the association between pharmaceutical schemas and the attribution of unrelated symptoms as side effects.

[Single-dose palliative radiotherapy in inoperable non-small-cell lung carcinoma].

PubMed

Scolaro, T; Bacigalupo, A; Giudici, S; Guenzi, M; Vitale, V

1995-12-01

The treatment of choice for advanced inoperable non-small cell lung cancer (NSCLC) is radiation therapy. Palliative radiotherapy schedules vary considerably in different centers, but a 30-Gy dose given in ten fractions over two weeks is a typical standard schedule. Our study was aimed at investigating whether a shorter course of only one 10-Gy fraction allows good palliation in the treatment of inoperable NSCLC patients whose main symptoms are related to an intrathoracic lesion. Patients of both sexes and any age, untreated with radiotherapy, with inoperable and histologically or cytologically proved NSCLC were examined. Seventeen patients, too advanced for radical "curative" radiotherapy and whose main symptoms were related to primary intrathoracic lesions, entered the study even though they had metastases. On admission, 76% (13/17) of patients had cough 76% (13/17) dyspnea, 70.7% (12/17) chest pain and 23.6% (4/17) hemoptysis. They received a single dose of 10 Gy, delivered with an 18-Mv linear accelerator via anteroposteriorly opposing portals without spinal cord shielding. Treatment volume usually included the macroscopically detected lesion identified with a CT simulator. Palliation of symptoms was achieved in high rates of patients: 46% for cough, 69% for dyspnea, 83% for pain and 75% for hemoptysis. These results were obtained within one month of treatment. Unfortunately, palliation of symptoms did not last long, decreasing to 42% within two months of the end of treatment and to 32% at three months. Four patients were retreated, one patient three months and three patients two months after the end of radiotherapy. Ten Gy to the target volume were administered as retreatment with spinal cord shielding. Side-effects were mild: nausea in 3 patients (17%), vomiting in one patient (5%) and grade-II dysphagia in two patients were observed and classified according to WHO criteria. Pain increased 24 hours after radiotherapy in five patients. We can conclude that single dose radiotherapy yields good, but short, palliation of symptoms with acceptable side-effects.

Protein folding, misfolding and aggregation: The importance of two-electron stabilizing interactions

PubMed Central

2017-01-01

Proteins associated with neurodegenerative diseases are highly pleiomorphic and may adopt an all-α-helical fold in one environment, assemble into all-β-sheet or collapse into a coil in another, and rapidly polymerize in yet another one via divergent aggregation pathways that yield broad diversity of aggregates’ morphology. A thorough understanding of this behaviour may be necessary to develop a treatment for Alzheimer’s and related disorders. Unfortunately, our present comprehension of folding and misfolding is limited for want of a physicochemical theory of protein secondary and tertiary structure. Here we demonstrate that electronic configuration and hyperconjugation of the peptide amide bonds ought to be taken into account to advance such a theory. To capture the effect of polarization of peptide linkages on conformational and H-bonding propensity of the polypeptide backbone, we introduce a function of shielding tensors of the Cα atoms. Carrying no information about side chain-side chain interactions, this function nonetheless identifies basic features of the secondary and tertiary structure, establishes sequence correlates of the metamorphic and pH-driven equilibria, relates binding affinities and folding rate constants to secondary structure preferences, and manifests common patterns of backbone density distribution in amyloidogenic regions of Alzheimer’s amyloid β and tau, Parkinson’s α-synuclein and prions. Based on those findings, a split-intein like mechanism of molecular recognition is proposed to underlie dimerization of Aβ, tau, αS and PrPC, and divergent pathways for subsequent association of dimers are outlined; a related mechanism is proposed to underlie formation of PrPSc fibrils. The model does account for: (i) structural features of paranuclei, off-pathway oligomers, non-fibrillar aggregates and fibrils; (ii) effects of incubation conditions, point mutations, isoform lengths, small-molecule assembly modulators and chirality of solid-liquid interface on the rate and morphology of aggregation; (iii) fibril-surface catalysis of secondary nucleation; and (iv) self-propagation of infectious strains of mammalian prions. PMID:28922400

Effect of Similarity-Based Guided Discovery Learning on Conceptual Performance

ERIC Educational Resources Information Center

Mandrin, Pierre-A; Preckel, Daniel

2009-01-01

Analogies are known to foster concept learning, whereas discovery learning is effective for transfer. By combining discovery learning and analogies or similarities of concepts, attractive new arrangements emerge, but do they maintain both concept and transfer effects? Unfortunately, there is a lack of data confirming such combined effectiveness.…

Thermal conductivity of the sideledge in aluminium electrolysis cells: Experiments and numerical modelling

NASA Astrophysics Data System (ADS)

Gheribi, Aïmen E.; Poncsák, Sándor; Guérard, Sébastien; Bilodeau, Jean-François; Kiss, László; Chartrand, Patrice

2017-03-01

During aluminium electrolysis, a ledge of frozen electrolytes is generally formed, attached to the sides of the cells. This ledge acts as a protective layer, preventing erosion and chemical attacks of both the electrolyte melt and the liquid aluminium on the side wall materials. The control of the sideledge thickness is thus essential in ensuring a reasonable lifetime for the cells. The key property for modelling and predicting the sideledge thickness as a function of temperature and electrolyte composition is the thermal conductivity. Unfortunately, almost no data is available on the thermal conductivity of the sideledge. The aim of this work is to alleviate this lack of data. For seven different samples of sideledge microstructures, recovered from post-mortem industrial electrolysis cells, the thermal diffusivity, the density, and the phase compositions were measured in the temperature range of 423 K to 873 K. The thermal diffusivity was measured with a laser flash technique and the average phase compositions by X-ray diffraction analysis. The thermal conductivity of the sideledge is deduced from the present experimental thermal diffusivity and density, and the thermodynamically assessed heat capacity. In addition to the present experimental work, a theoretical model for the prediction of the effective thermal transport properties of the sideledge microstructure is also proposed. The proposed model considers an equivalent microstructure and depends on phase fractions, porosity, and temperature. The strength of the model lies in the fact that only a few key physical properties are required for its parametrization and they can be predicted with a good accuracy via first principles calculations. It is shown that the theoretical predictions are in a good agreement with the present experimental measurements.

Mast cells and IgE in defense against venoms: Possible "good side" of allergy?

PubMed

Galli, Stephen J; Starkl, Philipp; Marichal, Thomas; Tsai, Mindy

2016-01-01

Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

The clinical impact of serrated colorectal polyps

PubMed Central

O’Connell, Brendon M; Crockett, Seth D

2017-01-01

Serrated polyps (SPs) of the colorectum pose a novel challenge to practicing gastroenterologists. Previously thought benign and unimportant, there is now compelling evidence that SPs are responsible for a significant percentage of incident colorectal cancer worldwide. In contrast to conventional adenomas, which tend to be slow growing and polypoid, SPs have unique features that undermine current screening and surveillance practices. For example, sessile serrated polyps (SSPs) are flat, predominately right-sided, and thought to have the potential for rapid growth. Moreover, SSPs are subject to wide variations in endoscopic detection and pathologic interpretation. Unfortunately, little is known about the natural history of SPs, and current guidelines are based largely on expert opinion. In this review, we outline the current taxonomy, epidemiology, and management of SPs with an emphasis on the clinical and public health impact of these lesions. PMID:28260946

Electron Transfer Dissociation with Supplemental Activation to Differentiate Aspartic and Isoaspartic Residues in Doubly Charged Peptide Cations

PubMed Central

Chan, Wai Yi Kelly; Chan, T. W. Dominic; O’Connor, Peter B.

2011-01-01

Electron-transfer dissociation (ETD) with supplemental activation of the doubly charged deamidated tryptic digested peptide ions allows differentiation of isoaspartic acid and aspartic acid residues using c + 57 or z• − 57 peaks. The diagnostic peak clearly localizes and characterizes the isoaspartic acid residue. Supplemental activation in ETD of the doubly charged peptide ions involves resonant excitation of the charge reduced precursor radical cations and leads to further dissociation, including extra backbone cleavages and secondary fragmentation. Supplemental activation is essential to obtain a high quality ETD spectrum (especially for doubly charged peptide ions) with sequence information. Unfortunately, the low-resolution of the ion trap mass spectrometer makes detection of the diagnostic peak for the aspartic acid residue difficult due to interference with side-chain loss from arginine and glutamic acid residues. PMID:20304674

The in vitro effects of some pesticides on carbonic anhydrase activity of Oncorhynchus mykiss and Cyprinus carpio carpio fish.

PubMed

Doğan, Serap

2006-05-20

Systemic carbonic anhydrase (CA) inhibitors are among the most powerful agents to lower intraocular pressure. Unfortunately, their use is frequently accompanied by undesired side effects. Some are due to the relatively large amounts of drug that have to be systematically administered to inhibit the CA in the ciliary processes. The aim of the present work was to study in vitro effects of some pesticides on CA enzyme obtained from blood of fish, which play a key role in salt- and osmoregulation and acid-base balance in the fish, Oncorhynchus mykiss and Cyprinus carpio carpio living in freshwaters, and compared with CA inhibitors. CA activities were significantly inhibited by pesticides and inhibitors. I(50) values of O. mykiss CA enzyme inhibited by lambda-cyhalothrin, deltametrin, diozinon, dorzolamide and brinzolamide were 6.05 x 10(-4), 1.48 x 10(-5), 6.84 x 10(-3), 3.82 x 10(-5) and 1.80 x 10(-6) mol/l, and that for C. c. carpio 6.86 x 10(-4), 4.70 x 10(-4), 3.92 x 10(-3), 8.34 x 10(-6) and 1.42 x 10(-6) mol/l, respectively. The pesticides used in this study inhibited the CA activity from different fish species to various degrees. It was found that the most effective inhibitor of CA enzyme within pesticides used was detrametrin. These findings observed in vitro could be useful in the understanding of the toxic effects that pesticides elicit on aquatic organisms in vivo.

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells.

PubMed

Han, Yangyang; Huang, Weiwei; Liu, Jiakuan; Liu, Dandan; Cui, Yangyan; Huang, Ruimin; Yan, Jun; Lei, Ming

2017-01-01

Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine ( Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro , and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC.

Triptolide Inhibits the AR Signaling Pathway to Suppress the Proliferation of Enzalutamide Resistant Prostate Cancer Cells

PubMed Central

Han, Yangyang; Huang, Weiwei; Liu, Jiakuan; Liu, Dandan; Cui, Yangyan; Huang, Ruimin; Yan, Jun; Lei, Ming

2017-01-01

Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown. In this study, we found that TPL at low dose inhibits the transactivation activity of both full-length and truncated AR without changing their protein levels. Interestingly, TPL inhibits phosphorylation of AR and its CRPC-associated variant AR-V7 at Ser515 through XPB/CDK7. As a result, TPL suppresses the binding of AR to promoter regions in AR target genes along with reduced TFIIH and RNA Pol II recruitment. Moreover, TPL at low dose reduces the viability of prostate cancer cells expressing AR or AR-Vs. Low-dose TPL also shows a synergistic effect with enzalutamide to inhibit CRPC cell survival in vitro, and enhances the anti-cancer effect of enzalutamide on CRPC xenografts with minimal side effects. Taken together, our data demonstrate that TPL targets the transactivation activity of both full-length and truncated ARs. Our results also suggest that TPL is a potential drug for CRPC, and can be used in combination with enzalutamide to treat CRPC. PMID:28638477

Antidotes for poisoning by alcohols that form toxic metabolites.

PubMed

McMartin, Kenneth; Jacobsen, Dag; Hovda, Knut Erik

2016-03-01

The alcohols, methanol, ethylene glycol and diethylene glycol, have many features in common, the most important of which is the fact that the compounds themselves are relatively non-toxic but are metabolized, initially by alcohol dehydrogenase, to various toxic intermediates. These compounds are readily available worldwide in commercial products as well as in homemade alcoholic beverages, both of which lead to most of the poisoning cases, from either unintentional or intentional ingestion. Although relatively infrequent in overall occurrence, poisonings by metabolically-toxic alcohols do unfortunately occur in outbreaks and can result in severe morbidity and mortality. These poisonings have traditionally been treated with ethanol since it competes for the active site of alcohol dehydrogenase and decreases the formation of toxic metabolites. Although ethanol can be effective in these poisonings, there are substantial practical problems with its use and so fomepizole, a potent competitive inhibitor of alcohol dehydrogenase, was developed for a hopefully better treatment for metabolically-toxic alcohol poisonings. Fomepizole has few side effects and is easy to use in practice and it may obviate the need for haemodialysis in some, but not all, patients. Hence, fomepizole has largely replaced ethanol as the toxic alcohol antidote in many countries. Nevertheless, ethanol remains an important alternative because access to fomepizole can be limited, the cost may appear excessive, or the physician may prefer ethanol due to experience. © 2015 The British Pharmacological Society.

Combining drug-loaded nanobubbles and Extracorporeal Shock Waves for difficult-to-treat cancers.

PubMed

Cavalli, Roberta; Marano, Francesca; Argenziano, Monica; Varese, Alessandra; Frairia, Roberto; Catalano, Maria Graziella

2017-10-18

Despite the general great improvement in cancer therapy, to date, some aggressive tumors are still without an efficient therapy. Therefore, accurate delivery of anti-cancer drugs is a very important goal in order to obtain a successful therapy and reduce systemic side effects. Nanobubbles (NBs) are spherical core/shell vesicles filled by a gas with sizes in the nanometer order of magnitude. They have gained an increasing attention for drug delivery, because they can be versatile multifunctional carriers for the targeted release of gases, drugs and genes. Particularly, NBs can carry loaded drugs to the tumor site through the blood stream, taking advantage of the enhanced permeability and retention effect, due to the defective vascular architecture of the tumor (Fang et al. 2011). Unfortunately, vessel leakage, the absence of a functional lymphatic system and an increased extracellular matrix frictional resistance may limit drug delivery (Azzi et al. 2013, Carmeliet and Jain 2011). To overcome this problem, a better drug release to cancer tissues can be obtained by combining physical triggers (e.g. ultrasounds, US) with NBs (Gao et al. 2008, Collis et al. 2010, Cavalli et al. 2012, Cavalli et al. 2016, Argenziano et al. 2017). Indeed, US causes bubble cavitation resulting in cell sonoporation and allowing the extravasation of molecules (Collis et al. 2010). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance.

PubMed

Suwanarusk, Rossarin; Russell, Bruce; Ong, Alice; Sriprawat, Kanlaya; Chu, Cindy S; PyaePhyo, Aung; Malleret, Benoit; Nosten, François; Renia, Laurent

2015-01-01

Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Does increased gender equality lead to a convergence of health outcomes for men and women? A study of Swedish municipalities.

PubMed

Backhans, Mona C; Lundberg, Michael; Månsdotter, Anna

2007-05-01

This study examines associations between indicators of gender equality and public health. We compare Swedish municipalities on nine indicators in both the private and public sphere, and an additive index, and study the correlations with indicators of morbidity and mortality. The hypothesis that a higher level of gender equality is associated with a convergence of health outcomes (life expectancy, sickness absence) between men and women was supported for equality of part-time employment, managerial positions and economic resources for morbidity, and for temporary parental leave for mortality. Our main finding is that gender equality was generally correlated with poorer health for both men and women. Our conclusions are tentative due to the methodological uncertainties. However, the results suggest an unfortunate trade-off between gender equality as we know it and public health. Sweden may have reached a critical point where further one-sided expansion by women into traditionally male roles, spheres and activities will not lead to positive health effects unless men also significantly alter their behaviour. Negative effects of this unfinished equality might be found both for women, who have become more burdened, and men, who as a group have lost many of their old privileges. We propose that this contention be confronted and discussed by policymakers, researchers and others. Further studies are also needed to corroborate or dispute these findings.

A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

PubMed

Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

2017-12-14

Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

Drug side effect extraction from clinical narratives of psychiatry and psychology patients

PubMed Central

Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

2011-01-01

Objective To extract physician-asserted drug side effects from electronic medical record clinical narratives. Materials and methods Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. Results The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. Discussion The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Conclusion Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert. PMID:21946242

What matters when judging intentionality-moral content or normative status? Testing the rational scientist model of the side-effect.

PubMed

Papadopoulos, C; Hayes, B K

2018-06-01

Previous work has demonstrated a "side-effect effect," such that intentionality is more likely to be attributed to agents who bring about negatively valenced as opposed to positively valenced side effects. The rational-scientist model explains this by suggesting that norm-violating side effects are more informative for inferring intentionality than norm-conforming side effects. In the present study we reexamined this account, addressing limitations of previous empirical tests (e.g., Uttich & Lombrozo, Cognition 116: 87-100, 2010). Side-effect valence and norm status were manipulated factorially, enabling an examination of the impact of norm status on intentionality judgments in both positively and negatively valenced side effects. Additionally, the impact of side-effect norm status on the perceived valences of side effects and agents was examined. Effects of norm status were found for both positive and negative side effects. Violation of an ostensibly neutral norm led to negative perceptions of the side effect. However, a norm status effect on intentionality judgments persisted when these effects were controlled. These results support the view that the side-effect effect is the result of the rational use of social-cognitive evidence.

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study

PubMed Central

Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Aim Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. Methods We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Results Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. Conclusion This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers. PMID:29016607

Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study.

PubMed

Pearce, Alison; Haas, Marion; Viney, Rosalie; Pearson, Sallie-Anne; Haywood, Philip; Brown, Chris; Ward, Robyn

2017-01-01

Chemotherapy side effects are often reported in clinical trials; however, there is little evidence about their incidence in routine clinical care. The objective of this study was to describe the frequency and severity of patient-reported chemotherapy side effects in routine care across treatment centres in Australia. We conducted a prospective cohort study of individuals with breast, lung or colorectal cancer undergoing chemotherapy. Side effects were identified by patient self-report. The frequency, prevalence and incidence rates of side effects were calculated by cancer type and grade, and cumulative incidence curves for each side effect computed. Frequencies of side effects were compared between demographic subgroups using chi-squared statistics. Side effect data were available for 449 eligible individuals, who had a median follow-up of 5.64 months. 86% of participants reported at least one side effect during the study period and 27% reported a grade IV side effect, most commonly fatigue or dyspnoea. Fatigue was the most common side effect overall (85%), followed by diarrhoea (74%) and constipation (74%). Prevalence and incidence rates were similar across side effects and cancer types. Age was the only demographic factor associated with the incidence of side effects, with older people less likely to report side effects. This research has produced the first Australian estimates of self-reported incidence of chemotherapy side effects in routine clinical care. Chemotherapy side effects in routine care are common, continue throughout chemotherapy and can be serious. This work confirms the importance of observational data in providing clinical practice-relevant information to decision-makers.

Side effects associated with anti-HIV drugs.

PubMed

Highleyman, L

1998-04-01

Many side effects are associated with the use of anti-HIV drugs, impacting the development of drug resistance and the quality of life for HIV-patients. Concern about side effects is a primary factor in deterring people from beginning HIV therapy. Frequency and severity of side effects vary greatly, but they are frequently more common and severe in people who are taking a new drug or who have advanced HIV disease. Information on side effects comes largely from clinical trials; however, many side effects are not discovered until the drug has been approved and used by larger numbers of people. Side effects vary from serious toxicities that require stopping treatment to uncomfortable or annoying side effects that interfere with daily life. A table categorizes the four major side effects (nausea, fever, skin rash, and fatigue) and divides them into grades that describe their intensity. A chart lists the side effects associated with specific anti-HIV drugs. Suggestions for managing side effects are included.

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

PubMed Central

Mavroudi, Maria; Zarogoulidis, Paul; Porpodis, Konstantinos; Kioumis, Ioannis; Lampaki, Sofia; Yarmus, Lonny; Malecki, Raf; Zarogoulidis, Konstantinos; Malecki, Marek

2014-01-01

Introduction Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The statistics speak for themselves with the grim reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem cells’ guided gene therapy. Review of therapeutic strategies in preclinical and clinical trials Stem cells have the unique potential for self renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells only. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we discuss various strategies to safeguard stem cell guided gene therapy against iatrogenic cancerogenesis. Perspectives Defining cancer biomarkers to facilitate early diagnosis, elucidating cancer genomics and proteomics with modern tools of next generation sequencing, and analyzing patients’ gene expression profiles provide essential data to elucidate molecular dynamics of cancer and to consider them for crafting pharmacogenomics-based personalized therapies. Streamlining of these data into genetic engineering of stem cells facilitates their use as the vectors delivering therapeutic genes into specific cancer cells. In this realm, stem cells guided gene therapy becomes a promising new frontier in personalized and targeted therapy of cancer. PMID:24860662

Side Effect Perceptions and Their Impact on Treatment Decisions in Women.

PubMed

Waters, Erika A; Pachur, Thorsten; Colditz, Graham A

2017-04-01

Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women ( N = 149) aged 40 to 74 years were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected 4 measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principal components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. The PCA revealed 4 components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all 4 measures. Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice.

Side Effect Perceptions and their Impact on Treatment Decisions in Women

PubMed Central

Waters, Erika A.; Pachur, Thorsten; Colditz, Graham A.

2016-01-01

Background Side effects prompt some patients to forego otherwise-beneficial therapies. This study explored which characteristics make side effects particularly aversive. Methods We used a psychometric approach, originating from research on risk perception, to identify the factors (or components) underlying side effect perceptions. Women (N=149) aged 40–74 were recruited from a patient registry to complete an online experiment. Participants were presented with hypothetical scenarios in which an effective and necessary medication conferred a small risk of a single side effect (e.g., nausea, dizziness). They rated a broad range of side effects on several characteristics (e.g., embarrassing, treatable). In addition, we collected four measures of aversiveness for each side effect: choosing to take the medication, willingness to pay to avoid the side effect (WTP), negative affective attitude associated with the side effect, and how each side effect ranks among others in terms of undesirability. A principle-components analysis (PCA) was used to identify the components underlying side effect perceptions. Then, for each aversiveness measure separately, regression analyses were used to determine which components predicted differences in aversiveness among the side effects. Results The PCA revealed four components underlying side effect perceptions: affective challenge (e.g., frightening), social challenge (e.g., disfiguring), physical challenge (e.g., painful), and familiarity (e.g., common). Side effects perceived as affectively and physically challenging elicited the highest levels of aversiveness across all four measures. Conclusions Understanding what side effect characteristics are most aversive may inform interventions to improve medical decisions and facilitate the translation of novel biomedical therapies into clinical practice. PMID:27216581

An assessment of The Effects of Elevation and Aspect on Deposition of Airborne Pollution and Water Quality in an Alpine Critical Zone: San Juan Mountains, Colorado, USA

NASA Astrophysics Data System (ADS)

Price, A.; Giardino, J. R.; Marcantonio, F.

2015-12-01

The alpine critical zone is affected by various inputs, storages, pathways, and outputs. Unfortunately, many of these processes distribute the pollutants beyond the immediate area and into the surrounding biological and anthropogenic communities. Years of mining and improper disposal of the tailings and acid-mine drainage have degraded the quality of surface water within the San Juan Mountains. However, mining may not be the only factor significantly affecting the surface water quality in this high-elevation environment. As a high elevation system, this area is a fragile ecosystem with inputs ranging from local mining to atmospheric transport and deposition. Studies from around the world have shown atmospheric transport and deposition affect high-elevation systems. Thus, a significant question arises: does elevation or aspect affect the volume and rate of atmospheric deposition of pollutants? We assume atmospheric deposition occurs on the slopes in addition to in streams, lakes, and ponds. Deposition on slopes can be transported to nearby surface waters and increase the impact of the atmospheric pollutants along with residence time. Atmospheric deposition data were collected for aluminum, iron, manganese, nitrate, phosphate, and sulfate. Water chemistry data were collected for the same constituents as the atmospheric deposition with the addition of temperature, dissolved oxygen, pH, and specific conductance. Deposition samples were collected on a five-day sampling regime during two summers. Water quality samples were collected in-stream adjacent to the deposition-ample collectors. Collection sites were located on opposite sides of Red Mountain at five equal elevations providing two different aspects. The north side is drained by Red Mountain Creek and the south side is drained by Mineral Creek. Differences in atmospheric deposition and water quality at different elevations and aspects suggest there is a relationship between aspect and elevation on atmospheric pollution deposition. It is suggested that degradation of water quality in the San Juan Mountains is affected by atmospheric deposition along with the damage sustained from local mining activities. These results facilitate a better understanding of this high-elevation critical-zone system.

In tepid defense of population health: physicians and antibiotic resistance.

PubMed

Saver, Richard S

2008-01-01

Antibiotic resistance menaces the population as a dire public health threat and costly social problem. Recent proposals to combat antibiotic resistance focus to a large degree on supply side approaches. Suggestions include tinkering with patent rights so that pharmaceutical companies have greater incentives to discover novel antibiotics as well as to resist overselling their newer drugs already on market. This Article argues that a primarily supply side emphasis unfortunately detracts attention from physicians' important demand side influences. Physicians have a vital and unavoidably necessary role to play in ensuring socially optimal access to antibiotics. Dismayingly, physicians' management of the antibiotic supply has been poor and their defense of population health tepid at best. Acting as a prudent steward of the antibiotic supply often seems to be at odds with a physician's commonly understood fiduciary duties, ethical obligations, and professional norms, all of which traditionally emphasize the individual health paradigm as opposed to population health responsibilities. Meanwhile, physicians face limited incentives for antibiotic conservation from other sources, such as malpractice liability, regulatory standards, and reimbursement systems. While multifaceted efforts are needed to combat antibiotic resistance effectively, physician gatekeeping behavior should become a priority area of focus. This Article considers how health law and policy tools could favorably change the incentives physicians face for antibiotic conservation. A clear lesson from the managed care reform battles of the recent past is that interventions, to have the best chance of success, need to respect physician interest in clinical autonomy and individualized medicine even if, somewhat paradoxically, vigorously promoting population health perspectives. Also, physicians' legal and ethical obligations need to be reconceptualized in the antibiotic context in order to better support gatekeeping in defense of population health. The principal recommendation is for increased use of financial incentives to reward physicians for compliance with recommended guidelines on antibiotic prescribing. Although not a panacea, greater experimentation with financial incentives can provide a much needed jump-start to physician interest in antibiotic conservation and likely best address physicians' legitimate clinical autonomy concerns.

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

PubMed

Sawant, Ruta V; Beatty, Collin R; Sansgiry, Sujit S

2016-10-25

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.

A Markov Random Field Framework for Protein Side-Chain Resonance Assignment

NASA Astrophysics Data System (ADS)

Zeng, Jianyang; Zhou, Pei; Donald, Bruce Randall

Nuclear magnetic resonance (NMR) spectroscopy plays a critical role in structural genomics, and serves as a primary tool for determining protein structures, dynamics and interactions in physiologically-relevant solution conditions. The current speed of protein structure determination via NMR is limited by the lengthy time required in resonance assignment, which maps spectral peaks to specific atoms and residues in the primary sequence. Although numerous algorithms have been developed to address the backbone resonance assignment problem [68,2,10,37,14,64,1,31,60], little work has been done to automate side-chain resonance assignment [43, 48, 5]. Most previous attempts in assigning side-chain resonances depend on a set of NMR experiments that record through-bond interactions with side-chain protons for each residue. Unfortunately, these NMR experiments have low sensitivity and limited performance on large proteins, which makes it difficult to obtain enough side-chain resonance assignments. On the other hand, it is essential to obtain almost all of the side-chain resonance assignments as a prerequisite for high-resolution structure determination. To overcome this deficiency, we present a novel side-chain resonance assignment algorithm based on alternative NMR experiments measuring through-space interactions between protons in the protein, which also provide crucial distance restraints and are normally required in high-resolution structure determination. We cast the side-chain resonance assignment problem into a Markov Random Field (MRF) framework, and extend and apply combinatorial protein design algorithms to compute the optimal solution that best interprets the NMR data. Our MRF framework captures the contact map information of the protein derived from NMR spectra, and exploits the structural information available from the backbone conformations determined by orientational restraints and a set of discretized side-chain conformations (i.e., rotamers). A Hausdorff-based computation is employed in the scoring function to evaluate the probability of side-chain resonance assignments to generate the observed NMR spectra. The complexity of the assignment problem is first reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is used to find a set of optimal side-chain resonance assignments that best fit the NMR data. We have tested our algorithm on NMR data for five proteins, including the FF Domain 2 of human transcription elongation factor CA150 (FF2), the B1 domain of Protein G (GB1), human ubiquitin, the ubiquitin-binding zinc finger domain of the human Y-family DNA polymerase Eta (pol η UBZ), and the human Set2-Rpb1 interacting domain (hSRI). Our algorithm assigns resonances for more than 90% of the protons in the proteins, and achieves about 80% correct side-chain resonance assignments. The final structures computed using distance restraints resulting from the set of assigned side-chain resonances have backbone RMSD 0.5 - 1.4 Å and all-heavy-atom RMSD 1.0 - 2.2 Å from the reference structures that were determined by X-ray crystallography or traditional NMR approaches. These results demonstrate that our algorithm can be successfully applied to automate side-chain resonance assignment and high-quality protein structure determination. Since our algorithm does not require any specific NMR experiments for measuring the through-bond interactions with side-chain protons, it can save a significant amount of both experimental cost and spectrometer time, and hence accelerate the NMR structure determination process.

76 FR 57642 - TRICARE: Unfortunate Sequelae From Noncovered Services in a Military Treatment Facility

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... TRICARE: Unfortunate Sequelae From Noncovered Services in a Military Treatment Facility AGENCY: Office of... treatment of complications (unfortunate sequelae) resulting from a noncovered incident of treatment provided in a Military Treatment Facility (MTF), when the initial noncovered service has been authorized by...

Google Search Mastery Basics

ERIC Educational Resources Information Center

Hill, Paul; MacArthur, Stacey; Read, Nick

2014-01-01

Effective Internet search skills are essential with the continually increasing amount of information available on the Web. Extension personnel are required to find information to answer client questions and to conduct research on programs. Unfortunately, many lack the skills necessary to effectively navigate the Internet and locate needed…

Health Related Quality of Life in Patients with Side-Effects after Antimuscarinic Treatment for Overactive Bladder.

PubMed

Kim, Aram; Lee, Kyu-Sung; Jung, Rangrhee; Na, Selee; Kim, Joon-Chul; Kim, Hyeong Gon; Choo, Myung-Soo

2017-09-01

Drug therapy is the mainstay of treatment for overactive bladder (OAB), but antimuscarinic agents possess side-effects. These side-effects decrease the patients' quality of life. We therefore assessed the impact of side-effects on health-related quality of life (HR-QoL) through an analysis of EQ-5D questionnaire. This study was designed to investigate the patients' satisfaction by quality weight of health status as affected by the side-effects of OAB medications. Patients who had OAB symptoms lasting longer than 3 months and have experienced side-effects after any antimuscarinic treatments filled in the EQ-5D questionnaire. The enrolled patients had two EQ-5D questionnaires for two different health statuses, i.e., presence or absence of side-effects. Quality weight was calculated using the ED-5D health status score with Korean tariff. One hundred patients were enrolled and completed the HR-QoL questionnaire. The most prevalent side-effect was dry mouth (61%) and 28% patients had dry mouth and constipation concurrently. Most of the patients with side-effects tried to endure and overcome these side-effects (79%), but 10% desired a change in medication, and 6% stopped medication altogether. The quality weight of EQ-5D without side-effects was 0.863, while the quality weight with side-effects was 0.666 (P < 0.001). The VAS score was 79 in patient without side-effects and 57 in those with side-effects, supporting the results of quality weight assessment. Overactive bladder patients may enjoy a better quality of life if side-effects associated with antimuscarinic therapy are fewer. © 2016 John Wiley & Sons Australia, Ltd.

The Effects of Group Coaching on the Homework Problems Experienced by Secondary Students with and without Disabilities

ERIC Educational Resources Information Center

Merriman, Donald; Codding, Robin S.; Tryon, Georgiana Shick; Minami, Takuya

2016-01-01

Research on the effectiveness of homework provides ample evidence that homework has a positive effect on learning, particularly for secondary students. Unfortunately, the rate of consistent homework completion for students, with and without disabilities, is low. This study used a between-groups design to examine the differential effectiveness of…

Explanations for side effect aversion in preventive medical treatment decisions

PubMed Central

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen

2008-01-01

Objective Many laypeople demonstrate excessive sensitivity to negative side effects of medical treatments, which may lead them to refuse beneficial therapies. This Internet-based experiment investigated three possible explanations for such “side effect aversion.” One was derived from mental accounting, one examined the mere presence of a side effect, and one focused on computational difficulties. Design Participants (N = 5,379) were presented with a hypothetical cancer preventive treatment situation that was or was not accompanied by one or two small side effects. The side effects were either beneficial or harmful. In all conditions the net absolute risk reduction associated with the treatment was 15%. Main Outcome Measures Participants indicated their willingness to accept treatment and their perceptions of the treatment’s effects on their overall cancer risk. Results Data were consistent only with the “mere presence” explanation of side effect aversion, the idea that side effects act as a strong negative cue that directly affects treatment appraisal. The number of negative side effects did not influence treatment willingness. Conclusion Side effect aversion is a challenge to informed decision making. Specific mechanisms that produce side effect aversion should be identified. PMID:19290712

Cognition through a Social Network: The Propagation of Induced Forgetting and Practice Effects

ERIC Educational Resources Information Center

Coman, Alin; Hirst, William

2012-01-01

Although a burgeoning literature has shown that practice effects and socially shared retrieval-induced forgetting can reshape the memories of speakers and listeners involved in a conversation, it has generally failed to examine whether such effects can propagate through a sequence of conversational interactions. This lacuna is unfortunate, since…

Learning Problems Reported by College Students: Are They Using Learning Strategies?

ERIC Educational Resources Information Center

Rachal, K. Chris; Daigle, Sherri; Rachal, Windy S.

2007-01-01

As teachers of higher education, we expect students to enter college with some understanding of what it means to be an effective learner and the ability to apply effective learning strategies. Unfortunately, many students do not develop effective learning strategies unless they receive explicit instruction and the opportunity to apply these…

Children and TV Violence

MedlinePlus

... powerful influence in developing value systems and shaping behavior. Unfortunately, much of today's television programming is violent. Hundreds of studies of the effects of TV violence on children and teenagers have found that children may: become " ...

Subjective Report of Side Effects of Prescribed and Nonprescribed Psychostimulant Use in Young Adults.

PubMed

Smith, Tess E; Martel, Michelle M; DeSantis, Alan D

2017-03-21

Side effects of prescribed and nonprescribed psychostimulant use are understudied. The study examined side effects of prescribed and nonprescribed psychostimulant use in a college sample with attention to possible gender differences. 2716 undergraduates (1448 male) between the ages of 17 and 57 years (M = 19.43 years, SD = 1.7 years) completed an online survey that included questions about the subjective side effects of prescribed and nonprescribed psychostimulant use. Results suggested that prescribed users more frequently reported side effects, compared to nonprescribed users. For prescribed users, females more frequently reported appetite, somatic, and anxiety-related side effects compared to males. For nonprescribed users, while females reported more somatic and anxiety-related side effects, males more frequently reported loss of sex drive and sweating as side effects. Conclusions/Importance: These findings suggest prescribed users of psychostimulants more frequently report side effects with prominent gender differences in line with gender roles.

Sexual side effects associated with conventional and atypical antipsychotics.

PubMed

Compton, M T; Miller, A H

2001-01-01

The sexual side effects of psychotropic medications are becoming increasingly recognized in clinical psychiatry. The magnitude of the problem of sexual side effects associated with antipsychotic medications has yet to be fully elucidated, but a multitude of references in the literature demonstrate the importance of these side effects in both men and women. All currently used antipsychotic medications are associated with sexual side effects of various types. Although each antipsychotic medication may have a specific side effect profile determined by its various receptor affinities and by the degree to which it elevates serum prolactin, there is currently no evidence that specific side effects can be predicted. Sexual side effects can be categorized according to the phase of the sexual response cycle with which they interfere. Suggestions for clinical evaluation and treatment options are provided, including risk factor modification, dose reduction, switching agents, and addition of other agents. Sexual side effects associated with conventional and atypical antipsychotic medications represent an underestimated and understudied set of side effects that may diminish a patient's quality of life and lead to treatment noncompliance. Clinicians prescribing antipsychotic medications should be familiar with the classification, evaluation, and treatment of these side effects.

Identifying Effective Characteristics for Teaching in Urban and Suburban Settings

ERIC Educational Resources Information Center

Jones, Shawn Cecil

2017-01-01

Classroom size, curriculum, and student attendance are all important factors that affect student outcomes, but these factors cannot compare to the classroom teacher's influence on student academic performance. Unfortunately, highly qualified teachers are not equally effective in different school settings. Findings associated with highly effective…

Identifying Characteristics for Effective Teaching in Urban and Suburban Settings.

ERIC Educational Resources Information Center

Jones, Shawn Cecil

2017-01-01

Classroom size, curriculum, and student attendance are all important factors that affect student outcomes, but these factors cannot compare to the classroom teacher's influence on student academic performance. Unfortunately, highly qualified teachers are not equally effective in different school settings. Findings associated with highly effective…

EFFECTS OF NUTRIENT PRE-EXPOSURE ON ATRAZINE TOXICITY TO VALLISNERIA AMERICANA MICHX. (WILD CELERY)

EPA Science Inventory

The importance of aquatic plants as a valued component of coastal environments is receiving increased attention in the public policy and scientific community. Unfortunately, the fact remains that the effects of anthropogenic contaminants on both emergent (marsh) and submerged aq...

Effects of calcium magnesium acetate, a road deicer, on the lentic environment in interior Alaska, interim report

DOT National Transportation Integrated Search

1985-03-01

The application of chloride deicing salts to roadways has increased dramatically in recent years due to public demand for safer winter driving conditions. Unfortunately, these salts create adverse effects such as corrosion of vehicles and bridge stru...

The stress and underground environment

NASA Astrophysics Data System (ADS)

Chama, A.

2009-04-01

Currently,the program of prevention in occupational health needs mainly to identify occupational hazards and strategy of their prevention.Among these risks,the stress represents an important psycho-social hazard in mental health,which unfortunately does not spare no occupation.My Paper attempts to highlight and to develop this hazard in its different aspects even its regulatory side in underground environment as occupational environment.In the interest of better prevention ,we consider "the information" about the impact of stress as the second prevention efficient and no expensive to speleologists,hygienists and workers in the underground areas. In this occasion of this event in Vienna,we also highlight the scientific works on the stress of the famous viennese physician and endocrinologist Doctor Hans Selye (1907-1982),nicknamed "the father of stress" and note on relation between biological rhythms in this underground area and psychological troubles (temporal isolation) (Jurgen Aschoff’s works and experiences out-of time).

Scedosporium apiospermum causing brain abscess in a renal allograft recipient.

PubMed

Sharma, Amit; Singh, Divya

2015-11-01

Scedosporium apiospermum is the asexual form of a rare fungus Pseudallescheria boydii that is usually present in the soil, sewage and dirty water. In immunocompromised patients, it is a rare infection involving multiple organs. We present a case of renal allograft recipient who developed fever two weeks post renal transplant. He was initially found to have dengue fever. After five days, he became drowsy and developed right-sided hemiparesis. Magnetic resonance imaging of the brain revealed multiple irregular masses with associated edema consistent with fungal brain abscesses. Left parietal abscess was drained and he was started on voriconazole. His cyclosporine was stopped. Drained pus revealed fungal hyphae on potassium hydroxide stain and Scedosporium apiospermum on culture. Unfortunately, the patient died after five days. Scedosporium infections should be kept as a possibility in transplant recipients with disseminated infections, especially with a brain abscess. Despite antifungal therapy and surgical drainage, mortality rates are high.

A restricted Steiner tree problem is solved by Geometric Method II

NASA Astrophysics Data System (ADS)

Lin, Dazhi; Zhang, Youlin; Lu, Xiaoxu

2013-03-01

The minimum Steiner tree problem has wide application background, such as transportation system, communication network, pipeline design and VISL, etc. It is unfortunately that the computational complexity of the problem is NP-hard. People are common to find some special problems to consider. In this paper, we first put forward a restricted Steiner tree problem, which the fixed vertices are in the same side of one line L and we find a vertex on L such the length of the tree is minimal. By the definition and the complexity of the Steiner tree problem, we know that the complexity of this problem is also Np-complete. In the part one, we have considered there are two fixed vertices to find the restricted Steiner tree problem. Naturally, we consider there are three fixed vertices to find the restricted Steiner tree problem. And we also use the geometric method to solve such the problem.

Guest Editorial Image Quality

NASA Astrophysics Data System (ADS)

Cheatham, Patrick S.

1982-02-01

The term image quality can, unfortunately, apply to anything from a public relations firm's discussion to a comparison between corner drugstores' film processing. If we narrow the discussion to optical systems, we clarify the problem somewhat, but only slightly. We are still faced with a multitude of image quality measures all different, and all couched in different terminology. Optical designers speak of MTF values, digital processors talk about summations of before and after image differences, pattern recognition engineers allude to correlation values, and radar imagers use side-lobe response values measured in decibels. Further complexity is introduced by terms such as information content, bandwidth, Strehl ratios, and, of course, limiting resolution. The problem is to compare these different yardsticks and try to establish some concrete ideas about evaluation of a final image. We need to establish the image attributes which are the most important to perception of the image in question and then begin to apply the different system parameters to those attributes.

Compensating for the effects of site and equipment variation on delphinid species identification from their echolocation clicks.

PubMed

Roch, Marie A; Stinner-Sloan, Johanna; Baumann-Pickering, Simone; Wiggins, Sean M

2015-01-01

A concern for applications of machine learning techniques to bioacoustics is whether or not classifiers learn the categories for which they were trained. Unfortunately, information such as characteristics of specific recording equipment or noise environments can also be learned. This question is examined in the context of identifying delphinid species by their echolocation clicks. To reduce the ambiguity between species classification performance and other confounding factors, species whose clicks can be readily distinguished were used in this study: Pacific white-sided and Risso's dolphins. A subset of data from autonomous acoustic recorders located at seven sites in the Southern California Bight collected between 2006 and 2012 was selected. Cepstral-based features were extracted for each echolocation click and Gaussian mixture models were used to classify groups of 100 clicks. One hundred Monte-Carlo three-fold experiments were conducted to examine classification performance where fold composition was determined by acoustic encounter, recorder characteristics, or recording site. The error rate increased from 6.1% when grouped by acoustic encounter to 18.1%, 46.2%, and 33.2% for grouping by equipment, equipment category, and site, respectively. A noise compensation technique reduced error for these grouping schemes to 2.7%, 4.4%, 6.7%, and 11.4%, respectively, a reduction in error rate of 56%-86%.

Measurement of Quality of Life VI. Quality-Adjusted Life Years (QALY) is an Unfortunate Use of the Quality-of-Life Concept

PubMed Central

Ventegodt, Soren; Merrick, Joav; Andersen, Niels Jorgen

2003-01-01

The QALY (quality-adjusted life years) attempts to incorporate the dimension of quality of life into the evaluation by adjusting life years by a quality factor. In practice, this is based on discussing with people the progression of a number of hypothetical illnesses and their ensuing side effects. From this information, the person assesses how each state of health described compares with a theoretical maximum state of health. For example, 1 day with a certain condition might the equivalent of living only 0.5 days in good health.We believe that QALY value only represents a superficial impression of a person's quality of life. In short, the QALY does not express what it means for a person to live a life at reduced quality. We believe that if the patients were optimally informed and allowed to decide for themselves, they would more often reject high-tech expensive biomedical treatments that only serve to prolong life and do not increase its quality. The problem of priorities may then turn out to be far more simple and also more ethical: the focus will be on the quality of life, not on QALY, and the question of the meaning of life and death will achieve greater openness and respect. PMID:14570991

Drug delivery strategies for Alzheimer's disease treatment.

PubMed

Di Stefano, Antonio; Iannitelli, Antonio; Laserra, Sara; Sozio, Piera

2011-05-01

Current Alzheimer's disease (AD) therapy is based on the administration of the drugs donepezil, galantamine, rivastigmine and memantine. Until disease-modifying therapies become available, further research is needed to develop new drug delivery strategies to ensure ease of administration and treatment persistence. In addition to the conventional oral formulations, a variety of drug delivery strategies applied to the treatment of AD are reviewed in this paper, with a focus on strategies leading to simplified dosage regimens and to providing new pharmacological tools. Alternatives include extended release, orally disintegrating or sublingual formulations, intranasal or short- and long-acting intramuscular or transdermal forms, and nanotechnology-based delivery systems. The advent of new research on molecular mechanisms of AD pathogenesis has outlined new strategies for therapeutic intervention; these include the stimulation of α-secretase cleavage, the inhibition of γ-secretase activity, the use of non-steroidal anti-inflammatory drugs, neuroprotection based on antioxidant therapy, the use of estrogens, NO synthetase inhibitors, and natural agents such as polyphenols. Unfortunately, these compounds might not help patients with end stage AD, but might hopefully slow or stop the disease process in its early stage. Nanotechnologies may prove to be a promising contribution in future AD drug delivery strategies, in particular drug carrier nano- or microsystems, which can limit the side effects of anti-Alzheimer drugs.

Epilepsy as a Network Disorder (2): What can we learn from other network disorders such as dementia and schizophrenia, and what are the implications for translational research?

PubMed

Scharfman, Helen E; Kanner, Andres M; Friedman, Alon; Blümcke, Ingmar; Crocker, Candice E; Cendes, Fernando; Diaz-Arrastia, Ramon; Förstl, Hans; Fenton, André A; Grace, Anthony A; Palop, Jorge; Morrison, Jason; Nehlig, Astrid; Prasad, Asuri; Wilcox, Karen S; Jette, Nathalie; Pohlmann-Eden, Bernd

2018-01-01

There is common agreement that many disorders of the central nervous system are 'complex', that is, there are many potential factors that influence the development of the disease, underlying mechanisms, and successful treatment. Most of these disorders, unfortunately, have no cure at the present time, and therapeutic strategies often have debilitating side effects. Interestingly, some of the 'complexities' of one disorder are found in another, and the similarities are often network defects. It seems likely that more discussions of these commonalities could advance our understanding and, therefore, have clinical implications or translational impact. With this in mind, the Fourth International Halifax Epilepsy Conference and Retreat was held as described in the prior paper, and this companion paper focuses on the second half of the meeting. Leaders in various subspecialties of epilepsy research were asked to address aging and dementia or psychosis in people with epilepsy (PWE). Commonalities between autism, depression, aging and dementia, psychosis, and epilepsy were the focus of the presentations and discussion. In the last session, additional experts commented on new conceptualization of translational epilepsy research efforts. Here, the presentations are reviewed, and salient points are highlighted. Copyright © 2017 Elsevier Inc. All rights reserved.

Assessing elemental mercury vapor exposure from cultural and religious practices.

PubMed

Riley, D M; Newby, C A; Leal-Almeraz, T O; Thomas, V M

2001-08-01

Use of elemental mercury in certain cultural and religious practices can cause high exposures to mercury vapor. Uses include sprinkling mercury on the floor of a home or car, burning it in a candle, and mixing it with perfume. Some uses can produce indoor air mercury concentrations one or two orders of magnitude above occupational exposure limits. Exposures resulting from other uses, such as infrequent use of a small bead of mercury, could be well below currently recognized risk levels. Metallic mercury is available at almost all of the 15 botanicas visited in New York, New Jersey, and Pennsylvania, but botanica personnel often deny having mercury for sale when approached by outsiders to these religious and cultural traditions. Actions by public health authorities have driven the mercury trade underground in some locations. Interviews indicate that mercury users are aware that mercury is hazardous, but are not aware of the inhalation exposure risk. We argue against a crackdown by health authorities because it could drive the practices further underground, because high-risk practices may be rare, and because uninformed government intervention could have unfortunate political and civic side effects for some Caribbean and Latin American immigrant groups. We recommend an outreach and education program involving religious and community leaders, botanica personnel, and other mercury users.

Assessing elemental mercury vapor exposure from cultural and religious practices.

PubMed Central

Riley, D M; Newby, C A; Leal-Almeraz, T O; Thomas, V M

2001-01-01

Use of elemental mercury in certain cultural and religious practices can cause high exposures to mercury vapor. Uses include sprinkling mercury on the floor of a home or car, burning it in a candle, and mixing it with perfume. Some uses can produce indoor air mercury concentrations one or two orders of magnitude above occupational exposure limits. Exposures resulting from other uses, such as infrequent use of a small bead of mercury, could be well below currently recognized risk levels. Metallic mercury is available at almost all of the 15 botanicas visited in New York, New Jersey, and Pennsylvania, but botanica personnel often deny having mercury for sale when approached by outsiders to these religious and cultural traditions. Actions by public health authorities have driven the mercury trade underground in some locations. Interviews indicate that mercury users are aware that mercury is hazardous, but are not aware of the inhalation exposure risk. We argue against a crackdown by health authorities because it could drive the practices further underground, because high-risk practices may be rare, and because uninformed government intervention could have unfortunate political and civic side effects for some Caribbean and Latin American immigrant groups. We recommend an outreach and education program involving religious and community leaders, botanica personnel, and other mercury users. PMID:11564612

Management of diabetes mellitus in individuals with chronic kidney disease: therapeutic perspectives and glycemic control

PubMed Central

Betônico, Carolina C R; Titan, Silvia M O; Correa-Giannella, Maria Lúcia C; Nery, Márcia; Queiroz, Márcia

2016-01-01

The purpose of this study was to evaluate the therapeutic options for diabetes treatment and their potential side effects, in addition to analyzing the risks and benefits of tight glycemic control in patients with diabetic kidney disease. For this review, a search was performed using several pre-defined keyword combinations and their equivalents: “diabetes kidney disease” and “renal failure” in combination with “diabetes treatment” and “oral antidiabetic drugs” or “oral hypoglycemic agents.” The search was performed in PubMed, Endocrine Abstracts and the Cochrane Library from January 1980 up to January 2015. Diabetes treatment in patients with diabetic kidney disease is challenging, in part because of progression of renal failure-related changes in insulin signaling, glucose transport and metabolism, favoring both hyperglycemic peaks and hypoglycemia. Additionally, the decline in renal function impairs the clearance and metabolism of antidiabetic agents and insulin, frequently requiring reassessment of prescriptions. The management of hyperglycemia in patients with diabetic kidney disease is even more difficult, requiring adjustment of antidiabetic agents and insulin doses. The health team responsible for the follow-up of these patients should be vigilant and prepared to make such changes; however, unfortunately, there are few guidelines addressing the nuances of the management of this specific population. PMID:26872083

Infrared and Skin: Friend or Foe

PubMed Central

Barolet, Daniel; Christiaens, François; Hamblin, Michael R

2016-01-01

In the last decade, it has been proposed that the sun's IR-A wavelengths might be deleterious to human skin and that sunscreens, in addition to their desired effect to protect against UV-B and UV-A, should also protect against IR-A (and perhaps even visible light). Several studies showed that NIR may damage skin collagen content via an increase in MMP-1 activity in the same manner as is known for UVR. Unfortunately, the artificial NIR light sources used in such studies were not representative of the solar irradiance. Yet, little has been said about the other side of the coin. This article will focus on key information suggesting that IR-A may be more beneficial than deleterious when the skin is exposed to the appropriate irradiance/dose of IR-A radiation similar to daily sun exposure received by people in real life. IR-A might even precondition the skin – a process called photoprevention - from an evolutionary standpoint since exposure to early morning IR-A wavelengths in sunlight may ready the skin for the coming mid-day deleterious UVR. Consequently IR-A appears to be the solution, not the problem. It does more good than bad for the skin. It is essentially a question of intensity and how we can learn from the sun. PMID:26745730

Genetic modification to induce CXCR2 overexpression in mesenchymal stem cells enhances treatment benefits in radiation-induced oral mucositis.

PubMed

Shen, Zongshan; Wang, Jiancheng; Huang, Qiting; Shi, Yue; Wei, Zhewei; Zhang, Xiaoran; Qiu, Yuan; Zhang, Min; Wang, Yi; Qin, Wei; Huang, Shuheng; Huang, Yinong; Liu, Xin; Xia, Kai; Zhang, Xinchun; Lin, Zhengmei

2018-02-14

Radiation-induced oral mucositis affects patient quality of life and reduces tolerance to cancer therapy. Unfortunately, traditional treatments are insufficient for the treatment of mucositis and might elicit severe side effects. Due to their immunomodulatory and anti-inflammatory properties, the transplantation of mesenchymal stem cells (MSCs) is a potential therapeutic strategy for mucositis. However, systemically infused MSCs rarely reach inflamed sites, impacting their clinical efficacy. Previous studies have demonstrated that chemokine axes play an important role in MSC targeting. By systematically evaluating the expression patterns of chemokines in radiation/chemical-induced oral mucositis, we found that CXCL2 was highly expressed, whereas cultured MSCs negligibly express the CXCL2 receptor CXCR2. Thus, we explored the potential therapeutic benefits of the transplantation of CXCR 2 -overexpressing MSCs (MSCs CXCR2 ) for mucositis treatment. Indeed, MSCs CXCR2 exhibited enhanced targeting ability to the inflamed mucosa in radiation/chemical-induced oral mucositis mouse models. Furthermore, we found that MSC CXCR2 transplantation accelerated ulcer healing by suppressing the production of pro-inflammatory chemokines and radiogenic reactive oxygen species (ROS). Altogether, these findings indicate that CXCR2 overexpression in MSCs accelerates ulcer healing, providing new insights into cell-based therapy for radiation/chemical-induced oral mucositis.

Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds

PubMed Central

Rahman, Mona N.; Vukomanovic, Dragic; Vlahakis, Jason Z.; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

2013-01-01

The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. PMID:23097500

Poverty reduction and Millennium Development Goals: recognizing population, health, and environment linkages in rural Madagascar.

PubMed

Gaffikin, Lynne; Ashley, Jeffrey; Blumenthal, Paul D

2007-10-23

The Millennium Development Goals (MDGs), committed to by all 191 United Nations member states, are rooted in the concept of sustainable development. Although 2007 (midway) reports indicated that programs are under way, unfortunately many countries are unlikely to reach their goals by 2015 due to high levels of poverty. Madagascar is one such example, although some gains are being made. Attempts of this island nation to achieve its MDGs, expressed most recently in the form of a Madagascar Action Plan, are notable in their emphasis on (1) conserving the country's natural resource base, (2) the effect of demographic trends on development, and (3) the importance of health as a prerequisite for development. Leadership in the country's struggle for economic growth comes from the president of the Republic, in part, through his "Madagascar Naturally" vision as well as his commitment to universal access to family planning, among other health and development interventions. However, for resource-limited countries, such as Madagascar, to get or stay "on track" to achieving the MDGs will require support from many sides. "Madagascar cannot do it alone and should not do it alone." This position is inherent in the eighth MDG: "Develop a global partnership for development." Apparently, it takes a village after all - a global one.

Ultrasound image guidance of cardiac interventions

NASA Astrophysics Data System (ADS)

Peters, Terry M.; Pace, Danielle F.; Lang, Pencilla; Guiraudon, Gérard M.; Jones, Douglas L.; Linte, Cristian A.

2011-03-01

Surgical procedures often have the unfortunate side-effect of causing the patient significant trauma while accessing the target site. Indeed, in some cases the trauma inflicted on the patient during access to the target greatly exceeds that caused by performing the therapy. Heart disease has traditionally been treated surgically using open chest techniques with the patient being placed "on pump" - i.e. their circulation being maintained by a cardio-pulmonary bypass or "heart-lung" machine. Recently, techniques have been developed for performing minimally invasive interventions on the heart, obviating the formerly invasive procedures. These new approaches rely on pre-operative images, combined with real-time images acquired during the procedure. Our approach is to register intra-operative images to the patient, and use a navigation system that combines intra-operative ultrasound with virtual models of instrumentation that has been introduced into the chamber through the heart wall. This paper illustrates the problems associated with traditional ultrasound guidance, and reviews the state of the art in real-time 3D cardiac ultrasound technology. In addition, it discusses the implementation of an image-guided intervention platform that integrates real-time ultrasound with a virtual reality environment, bringing together the pre-operative anatomy derived from MRI or CT, representations of tracked instrumentation inside the heart chamber, and the intra-operatively acquired ultrasound images.

T Cells that Recognize HPV Protein Can Target Virus-Infected Cells | Center for Cancer Research

Cancer.gov

Adoptive T-cell transfer (ACT) is a promising form of cancer immunotherapy. Treating patients with T cells isolated from a tumor and subsequently expanded in the lab can cause the complete regression of some melanomas and cervical cancers, but the treatment is currently restricted to a few cancer types. An approach that may be applied to a wider array of cancers involves modifying peripheral blood T cells with chimeric antigen receptors or T-cell receptors (TCR) that target specific tumor antigens. Unfortunately, epithelial cancers, which are the vast majority of cancers diagnosed, have proven difficult to treat this way because most identified antigens are shared with healthy tissues and targeting them leads to toxic side effects. However, cancers caused by persistent human papillomavirus (HPV) infection, including cervical, head and neck, anal, vaginal, vulvar, and penile cancers, may be particularly amenable to the latter form of ACT since the E6 and E7 viral proteins are essential for cancer formation but are not produced in normal tissues. To test this idea, Christian Hinrichs, M.D., and his colleagues examined tumor infiltrating lymphocytes (TILs) from a patient who experienced a prolonged disease-free period after her second surgical removal of metastatic anal cancer in the hopes of identifying a TCR against one of the HPV oncoproteins.

Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature.

PubMed

Amjad, Waseem; Qureshi, Waqas; Farooq, Ali; Sohail, Umair; Khatoon, Salma; Pervaiz, Sarah; Narra, Pratyusha; Hasan, Syeda M; Ali, Farman; Ullah, Aman; Guttmann, Steven

2017-09-03

Antiarrhythmic drugs are commonly prescribed cardiac drugs. Due to their receptor mimicry with several of the gastrointestinal tract receptors, they can frequently lead to gastrointestinal side effects. These side effects are the most common reasons for discontinuation of these drugs by the patients. Knowledge of these side effects is important for clinicians that manage antiarrhythmic drugs. This review focuses on the gastrointestinal side effects of these drugs and provides a detailed up-to-date literature review of the side effects of these drugs. The review provides case reports reported in the literature as well as possible mechanisms that lead to gastrointestinal side effects.

Memory for Medication Side Effects in Younger and Older Adults: The Role of Subjective and Objective Importance

PubMed Central

Friedman, Michael C.; McGillivray, Shannon; Murayama, Kou; Castel, Alan D.

2014-01-01

Older adults often experience memory impairments, but can sometimes use selective processing and schematic support to remember important information. The current experiments investigate to what degree younger and healthy older adults remember medication side effects that were subjectively or objectively important to remember. Participants studied a list of common side effects, and rated how negative these effects were if they were to experience them, and were then given a free recall test. In Experiment 1, the severity of the side effects ranged from mild (e.g., itching) to severe (e.g., stroke), and in Experiment 2, certain side effects were indicated as critical to remember (i.e., “contact your doctor if you experience this”). There were no age differences in terms of free recall of the side effects, and older adults remembered more severe side effects relative to mild effects. However, older adults were less likely to recognize critical side effects on a later recognition test, relative to younger adults. The findings suggest that older adults can selectively remember medication side effects, but have difficulty identifying familiar but potentially critical side effects, and this has implications for monitoring medication use in older age. PMID:25331278

Direct Behavioral Consultation in Head Start to Increase Teacher Use of Praise and Effective Instruction Delivery

ERIC Educational Resources Information Center

Dufrene, Brad A.; Parker, Kizzy; Menousek, Kathryn; Zhou, Qi; Harpole, Lauren Lestremau; Olmi, D. Joe

2012-01-01

Chronic disruptive behaviors during early childhood are associated with many poor developmental outcomes including, but not limited to, school dropout and conduct disorder during adolescence. Much is known regarding effective intervention procedures for disruptive classroom behaviors by preschool children. Unfortunately, evidence-based…

An integrated approach to detecting and monitoring chemicals of biological concern in Great Lakes ecosystems

EPA Science Inventory

Chemical monitoring strategies are most effective for those chemicals whose hazards are well understood and for which sensitive and cost effective analytical methods are available. Unfortunately, such chemicals represent a minor fraction of those that may currently occur in the e...

Implementing Parent Management Training in the Context of Poverty.

ERIC Educational Resources Information Center

Eamon, Mary Keegan; Venkataraman, Meenakshi

2003-01-01

Parent management training (PMT) is a well-investigated, effective, and preferred treatment for children's externalizing behaviors and related disorders. This article explores why, unfortunately, PMT is not as effective for children living in poor families, who disproportionately exhibit the behaviors that PMT is designed to correct. (Contains 40…

Continuous Improvement in Online Education: Documenting Teaching Effectiveness in the Online Environment through Observations

ERIC Educational Resources Information Center

Purcell, Jennifer W.; Scott, Heather I.; Mixson-Brookshire, Deborah

2017-01-01

Teaching observations are commonly used among educators to document and improve teaching effectiveness. Unfortunately, the necessary protocols and supporting infrastructure are not consistently available for faculty who teach online. This paper presents a brief literature review and reflective narratives of educators representing online education…

A Review of Psychotherapy Outcome Research: Considerations for School-Based Mental Health Providers

ERIC Educational Resources Information Center

Zirkelback, Emily A.; Reese, Robert J.

2010-01-01

Evaluating psychotherapeutic outcome is an important endeavor given psychology's focus on identifying effective treatments. There is ample evidence to suggest that psychotherapy interventions for children and adolescents are effective. Unfortunately, the child and adolescent psychotherapy outcome literature lags behind the adult-focused outcome…

“So far it’s been choosing which side effects I want or I can deal with”: A grounded theory of HIV treatment side effects among people living with HIV

PubMed Central

Holmes, Dave

2016-01-01

Despite the availability of new antiretroviral drugs and the simplification of treatment options, side effects continue to affect people living with HIV. In this paper, we present the findings of a grounded theory study designed to gain a critical understanding of the experience of side effects. Three main categories emerged from the data: the side effects, the experience, and the connections. The first category suggests that we need to change how we think about side effects in order to take into account the context in which they are experienced as well as the types and nature of side effects. The second category puts forward the idea that the experience of side effects is composed of three interrelated processes: becoming with, living with, and dealing with. Finally, the third category points to new connections that are formed with people, things and systems in the presence of side effects. PMID:27867446

Randomized trial - oxybutynin for treatment of persistent plantar hyperhidrosis in women after sympathectomy

PubMed Central

da Silva Costa, Altair; Leão, Luiz Eduardo Villaça; Succi, José Ernesto; Perfeito, Joao Aléssio Juliano; Filho, Adauto Castelo; Rymkiewicz, Erika; Filho, Marco Aurelio Marchetti

2014-01-01

OBJECTIVE: Hyperhidrosis is a common disease, and thoracoscopic sympathectomy improves its symptoms in up to 95% of cases. Unfortunately, after surgery, plantar hyperhidrosis may remain in 50% of patients, and compensatory sweating may be observed in 70%. This clinical scenario remains a challenge. Our objective was to evaluate the effectiveness of oxybutynin in the treatment of persistent plantar hyperhidrosis and compensatory sweating and its effects on quality of life in women after thoracoscopic sympathectomy. METHOD: We conducted a prospective, randomized study to compare the effects of oxybutynin at 10 mg daily and placebo in women with persistent plantar hyperhidrosis. The assessment was performed using a quality-of-life questionnaire for hyperhidrosis and sweating measurement with a device for quantifying transepidermal water loss. Clinicaltrials.gov: NCT01328015. RESULTS: Sixteen patients were included in each group (placebo and oxybutynin). There were no significant differences between the groups prior to treatment. After oxybutynin treatment, there was a decrease in symptoms and clinical improvement based on the quality-of-life questionnaire (before treatment, 40.4 vs. after treatment, 17.5; p = 0.001). The placebo group showed modest improvement (p = 0.09). The outcomes of the transepidermal water loss measurements in the placebo group showed no differences (p = 0.95), whereas the oxybutynin group revealed a significant decrease (p = 0.001). The most common side effect was dry mouth (100% in the oxybutynin group vs. 43.8% in the placebo group; p = 0.001). CONCLUSION: Oxybutynin was effective in the treatment of persistent plantar hyperhidrosis, resulting in a better quality of life in women who had undergone thoracoscopic sympathectomy. PMID:24519200

Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses.

PubMed

Broux, B; De Clercq, D; Decloedt, A; Vera, L; Devreese, M; Gehring, R; Croubels, S; van Loon, G

2018-05-01

Arrhythmias in horses may require long-term anti-arrhythmic therapy. Unfortunately, oral anti-arrhythmic drugs for use in horses are currently scarce. In human patients and small animals, sotalol, a β-blocker with class III anti-arrhythmic properties, is often used for long-term treatment. To determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted horses, as well as the effects on electro- and echocardiographic measurements, right atrial and ventricular monophasic action potential (MAP) and effective refractory period (ERP). Placebo controlled, double-blinded experiment. Six healthy, unfasted Warmblood horses were given either 0, 2, 3 or 4 mg/kg bodyweight (bwt) sotalol orally (PO) twice daily (bid) for 9 days in a randomised cross-over design. Echocardiography and surface electrocardiography were performed and plasma concentrations of sotalol and right atrial and right ventricular MAPs and ERPs were determined at steady-state conditions. Statistical analysis was performed using a repeated measures univariate analysis with post hoc Bonferroni corrections. Calculated mean steady-state plasma concentrations determined by nonlinear mixed-effect modelling were 287 (range 234-339), 409 (359-458) and 543 (439-646) ng/mL for 2, 3 and 4 mg/kg bwt sotalol PO bid respectively. Sotalol significantly increased the QT interval and ERPs, but, despite increasing plasma concentrations, higher dosages did not result in a progressive increase in QT interval or ERPs. Echocardiographic and other electrocardiographic measurements did not change significantly. MAP durations at 90% repolarisation were not significantly different during sotalol treatment. Besides transient local sweating, no side effects were noted. Study size and ad libitum feeding of hay. Sotalol at a dose of 2, 3 and 4 mg/kg bwt PO bid increases the QT interval and ERP and might be a useful drug for long-term anti-arrhythmic therapy in horses. © 2017 EVJ Ltd.

Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD.

PubMed

Lee, James; Grizenko, Natalie; Bhat, Venkataramana; Sengupta, Sarojini; Polotskaia, Anna; Joober, Ridha

2011-04-21

The desired (therapeutic) and undesired (side) effects of methylphenidate might have underlying correlations. The aim of this study was to explore the strength and the possible sources of these correlations. One hundred and fifty-seven children with ADHD (6-12 years) were administered placebo and methylphenidate (0.5 mg/kg in a divided b.i.d. dose), each for a one-week period, in a double-blind, crossover trial. Therapeutic response was assessed using the Conners' Global Index for parents (CGI-Parents) and teachers (CGI-Teachers), while side effects were assessed using the Barkley Side Effects Rating Scale (SERS). The side effect profile as assessed by the SERS was similar to that of previous studies with insomnia, decreased appetite, and headaches showing significant treatment effects (p < 0.005). These "somatic/physical" side effects did not correlate with CGI-Parents or CGI-Teachers. However, the side effects of "irritability", "proneness to crying", and "anxiousness" showed significant relationships with CGI-Parents. These "mood/anxiety" side effects showed no significant correlations with the CGI-Teachers. The greater "mood/anxiety" side effects on methylphenidate and placebo, the less the parents observe improvement of their children while treated with methylphenidate. This suggests that the correlations between "mood/anxiety" side effects and poor response to treatment may be driven by observer effects rather than biological commonalities between therapeutic and side effects of methylphenidate.

Influence of framing on medical decision making

PubMed Central

Gong, Jingjing; Zhang, Yan; Feng, Jun; Huang, Yonghua; Wei, Yazhou; Zhang, Weiwei

2013-01-01

Numerous studies have demonstrated the robustness of the framing effect in a variety of contexts, especially in medical decision making. Unfortunately, research is still inconsistent as to how so many variables impact framing effects in medical decision making. Additionally, much attention should be paid to the framing effect not only in hypothetical scenarios but also in clinical experience. PMID:27034630

Influence of framing on medical decision making.

PubMed

Gong, Jingjing; Zhang, Yan; Feng, Jun; Huang, Yonghua; Wei, Yazhou; Zhang, Weiwei

2013-01-01

Numerous studies have demonstrated the robustness of the framing effect in a variety of contexts, especially in medical decision making. Unfortunately, research is still inconsistent as to how so many variables impact framing effects in medical decision making. Additionally, much attention should be paid to the framing effect not only in hypothetical scenarios but also in clinical experience.

Side Effects

Cancer.gov

Side effects are problems that occur when cancer treatment affects healthy tissues or organs. Learn about side effects caused by cancer treatment. Know what signs and symptoms to call your doctor about. Learn about treatments for side effects.

Nuclear Winter Revisited: can it Make a Difference This Time?

NASA Astrophysics Data System (ADS)

Schneider, S.

2006-12-01

Some 23 years ago, in the middle of a Cold War and the threat of a strategic nuclear weapons exchange between NATO and the Warsaw Pact nations, atmospheric scientists pointed out that the well-anticipated side effects of a large-scale nuclear war ozone depletion, radioactive contamination and some climatic effects had massively underestimated the more likely implications: massive fires, severe dimming and cooling beneath circulating smoke clouds, disruption to agriculture in non-combatant nations, severe loss of imports of food to already-food-deficient regions and major alterations to atmospheric circulation. While the specific consequences were dependent on both scenarios of weapons use and injections and removals of smoke and dust and other chemicals into the atmosphere, it was clear that this would be despite passionately argued uncertainties a large major additional effect. As further investigations of smoke removal, patchy transport, etc., were pursued, the basic concerns remained, but the magnitude calculated with one-dimensional models diminished creating an unfortunate media debate over nuclear winter vs. nuclear autumn. Of course, one can't grow summer crops in any autumn natural or nuclear but that concern often got lost in the contentious political debate. Of course, it was pointed out that anyone who required knowing the additional environmental consequences of a major nuclear exchange to be finally deterred was already so far from the reality of the direct effects of the blasts that they might never see the concerns. But for non-combatants, it was a major awakening of their inability to escape severe consequences of the troubles of others, even if they were bystanders in the east-west conflicts. Two decades later, things have radically changed: the prospect of a massive strategic nuclear exchange is greatly diminished good news but the possibility of limited regional exchanges or terrorist incidents is widely believed to have greatly increased bad news. Therefore, the re- examination in this AGU session of the entire subject of environmental and social after-effects of any nuclear weapons use is, unfortunately, once again timely. Hopefully it will convince anyone not already convinced based on conventional damages from nuclear weapons use of the urgent need to abate proliferation and monitor and control access to and potential capabilities of those who might contemplate using such weapons for some Strangelove-like strategic or ideological objective. The extent to which a scientific re-examination of the broader horrendous implications of any scale of use of nuclear weapons will deter those contemplating their use is questionable. However, it seems likely such research would increase the resolve of the large number of countries and institutions already pressing to prevent nuclear weapons use.

Side Effects of HIV Medicines: HIV and Lactic Acidosis

MedlinePlus

... Drugs Clinical Trials Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact ... and Immunizations What is a Drug Interaction? Side Effects of HIV Medicines HIV Medicines and Side Effects ...

Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats.

PubMed

Suttorp, Christiaan M; Xie, Rui; Lundvig, Ditte M S; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C; Wagener, Frank A D T G

2016-01-01

Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.

Orthodontic Forces Induce the Cytoprotective Enzyme Heme Oxygenase-1 in Rats

PubMed Central

Suttorp, Christiaan M.; Xie, Rui; Lundvig, Ditte M. S.; Kuijpers-Jagtman, Anne Marie; Uijttenboogaart, Jasper Tom; Van Rheden, René; Maltha, Jaap C.; Wagener, Frank A. D. T. G.

2016-01-01

Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, “fast” and “slow” tooth movers during orthodontic treatment. PMID:27486402

Framing effects on expectations, decisions, and side effects experienced: the case of influenza immunization.

PubMed

O'Connor, A M; Pennie, R A; Dales, R E

1996-11-01

To examine the effects of using positive or negative frames to describe influenza vaccine benefits and side effects on patients' expectations, decisions, decisional conflict, and reported side effects. 292 previously unimmunized patients with chronic respiratory or cardiac disease were randomly assigned to receive benefit/risk information that was framed: (1) positively as the percentage who remain free of influenza and have no vaccine side effects, or (2) negatively as the percentage who acquire influenza and have vaccine side effects. Questionnaires elicited expectations, decisions, and decisional conflict. Vaccines were telephoned 3 days later for a self-report of local and systemic side effects and work absenteeism. Both groups had similar immunization rates and decisional conflict scores. The positive frame group had lower and more realistic expectations of vaccine side effects, fewer systemic side effects, and less work absenteeism (p < 0.05). In contrast to previous studies of health care workers, framing did not influence patients' decisions, possibly due to the patients' awareness of their higher risk of influenza complications and greater desire to follow recommendations. The common practice of using negative frames when describing probabilities of side effects may need to be reexamined, considering its deleterious influence on self-reported side effects and work absenteeism.

Side Effects of Leukotriene Receptor Antagonists in Asthmatic Children.

PubMed

Erdem, Semiha Bahceci; Nacaroglu, Hikmet Tekin; Unsal Karkiner, Canan Sule; Gunay, Ilker; Can, Demet

2015-10-01

Leukotriene receptor antagonists (LTRAs) are drugs which have been widely used more than ten years. As the use of LTRAs increases, our knowledge with respect to their side effects increases as well. The objective of our study was to evaluat the observed side effects of LTRAs used in patients with astma. 1024 patients treated only with LTRAs owing to asthma or early wheezing were included in the study for a five-year period. The observed side effects of LTRAs in these patients were retrospectively investigated. The side effects were divided into two parts as psychiatric and non-psychiatric. Among the 1024 cases included in the study, 67.5% of the patients out of 41 with side effects were male, 32.5% were female and the average age was 6.5 years. The rate of patients with asthma was 63.41% and 36.58% of the patients had early wheezing. It was determined that sex, age and diagnosis (early wheezing or asthma) of the patients were ineffective in the emergence of side effects. The average period for the emergence of side effects was the first month. It was observed that hyperactivity was the most frequently observed psychiatric side effect and that abdominal pain was the non-psychiatric side effect. The side effects of LTRAs were common in children. Therefore, patients must be informed at the beginning of the treatment and they must be evaluated at certain intervals.

Potential for Intrathecal Baclofen in Treatment of Essential Tremor.

PubMed

Hamad, Mousa; Holland, Ryan; Kamal, Naveed; Luceri, Robert; Mammis, Antonios

2017-09-01

Essential tremor (ET) is the most common movement disorder of adults, affecting an estimated 7 million Americans. Symptoms of ET range from slightly noticeable to debilitating, with 1 cohort study finding 15% of patients were forced into early retirement. Additionally, depression has also been correlated with the severity of disability of ET. Treatment options include propranolol and primidone. Current treatment options are not very effective, with more than half (56.3%) of patients discontinuing medications because of no changes in symptoms. Unfortunately, there is a relative void and controversy in the literature explaining ET pathophysiology; however, the gamma-aminobutyric acid (GABA) hypothesis is the strongest. We conducted a PubMed search on 30 September 2015 with no time constraints using the search terms "essential tremor" and "baclofen," which resulted in a total of 5 articles. Neurohistopathologic studies have demonstrated decreased GABA-A and GABA-B receptors in the cerebellar cortex of ET patients. GABA, the major inhibitory neurotransmitter in the central nervous system, is proposed to have an inhibitory effect on pacemaker output activity of the cerebello-thalamo-cortical pathway, with lower receptors resulting in decreased inhibition of baseline tremors. Tariq et al showed delayed onset and intensity of tremor with oral administration of R-baclofen in a mouse model of ET. With a better side-effect profile and success in a physiologically related condition, we propose more clinical trials and research be carried out on intrathecal baclofen as a potential treatment option, especially drug refractory ET, so as to increase the quality of life of this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs

PubMed Central

Jacques, Vincent; Czarnik, Anthony W.; Judge, Thomas M.; Van der Ploeg, Lex H. T.; DeWitt, Sheila H.

2015-01-01

Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using “deuterium-enabled chiral switching” (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (−)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics. PMID:25775521

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

PubMed Central

Yu, Xuemei; Sainz, Bruno; Petukhov, Pavel A.

2012-01-01

With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC50]/50% effective concentration [EC50]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments. PMID:22948883

Peptide YY: a potential therapy for obesity.

PubMed

Renshaw, D; Batterham, R L

2005-03-01

Obesity now represents a modern epidemic in western society with major health and economic consequences. Unfortunately, previous pharmacological approaches to the treatment of obesity have been associated with life-threatening side effects and limited efficacy. Over recent years there has been a marked increase in our understanding of the physiological mechanisms that regulate body weight and how these are perturbed in obesity. One therapeutic strategy is to develop drugs which both mimic and enhance the body's own satiety signals. The gut hormone peptide tyrosine tyrosine (PYY), which is released postprandially from the gastrointestinal tract, has recently been shown to be a physiological regulator of food intake. Peripheral administration of PYY reduces feeding in rodents via a mechanism which requires the Y2 receptor and is thought to primarily involve modulation of the hypothalamic arcuate nucleus (ARC) circuitry. In humans a single 90-minute infusion of PYY has been shown to markedly reduce subsequent 24-hour caloric intake in lean, normal-weight and obese subjects. Moreover, obese subjects have been found to have low levels of fasting and postprandial PYY suggesting a role for this hormone in the pathogenesis of obesity. Although studies examining the effects of chronic peripheral administration of PYY to humans are awaited, the results from continuous infusion studies in a number of obese rodent models are encouraging with reductions in food intake, body weight and adiposity observed. Potential therapeutic manipulations based on the PYY system include development of Y2 agonists, exogenously administration of PYY or increased endogenous release from the gastrointestinal tract.

Drug development against sleeping sickness: old wine in new bottles?

PubMed

Stein, J; Mogk, S; Mudogo, C N; Sommer, B P; Scholze, M; Meiwes, A; Huber, M; Gray, A; Duszenko, M

2014-01-01

Atoxyl, the first medicinal drug against human African trypanosomiasis (HAT), also known as sleeping sickness, was applied more than 100 years ago. Ever since, the search for more effective, more specific and less toxic drugs continued, leading to a set of compounds currently in use against this devastating disease. Unfortunately, none of these medicines fulfill modern pharmaceutical requirements and may be considered as therapeutic ultima ratio due to the many, often severe side effects. Starting with a historic overview on drug development against HAT, we present a selection of trypanosome specific pathways and enzymes considered as highly potent druggable targets. In addition, we describe cellular mechanisms the parasite uses for differentiation and cell density regulation and present our considerations how interference with these steps, elementary for life cycle progression and infection, may lead to new aspects of drug development. Finally we refer to our recent work about CNS infection that offers novel insights in how trypanosomes hide in an immune privileged area to establish a chronic state of the disease, thereby considering new ways for drug application. Depressingly, HAT specific drug development has failed over the last 30 years to produce better suited medicine. However, unraveling of parasite-specific pathways and cellular behavior together with the ability to produce high resolution structures of essential parasite proteins by X-ray crystallography, leads us to the optimistic view that development of an ultimate drug to eradicate sleeping sickness from the globe might just be around the corner.

Design and preliminary testing of a handheld antagonistic SMA actuator for cancellation of human tremor

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan

2009-03-01

Essential Tremor is a debilitating disorder that in the US alone is estimated to affect up to ten million people. Unfortunately current treatments (i.e. drug therapy and surgical procedures), are limited in effectiveness and often pose a risk of adverse side-effects. In response to this problem, this paper describes an active cancellation device based on a hand-held Shape Memory Alloy (SMA) actuated stabilization platform. The assistive device is designed to hold and stabilize various objects (e.g. eating utensils, tools, pointing implements, etc.) by sensing the user's tremor and moving the object in an opposite direction using SMA actuators configured in biologically inspired antagonistic pairs. To aid in the design, performance prediction and control of the device, a device model is described that accounts for the device kinematics, SMA thermo-mechanics, and the heat transfer resulting from electrical heating and convective cooling. The system of differential equations in this device model coupled with the controller gain can be utilized to design the operation given a frequency range and power requirement. To demonstrate this, a prototype was built and experimentally tested under external disturbances in the range of 1-5 Hz, resulting in amplitude reduction of up to 80%. The extent of cancellation measured for both single-frequencies and actual human tremor disturbances demonstrate the promise of this approach as a broadly used assistive device for the multitudes afflicted by tremor.

A Comparison of Sexual Side Effects of Antidepressants With and Without Naltrexone.

PubMed

Thapa, Mona; Petrakis, Ismene; Ralevski, Elizabeth

2017-01-01

The aim of the study was to compare the rate of sexual side effects of the selective serotonin reuptake inhibitor paroxetine versus the tricyclic antidepressant desipramine and to examine the effect of co-prescription of naltrexone on sexual side effects among participants in a randomized clinical trial. This was a secondary analysis (N = 88) of veterans who participated in a 12-week trial. All veterans were randomized into one of four treatment groups: (a) desipramine/naltrexone, (b) desipramine/placebo, (c) paroxetine/naltrexone, and (d) paroxetine/placebo. The main outcome measure was the frequency of sexual side effects consisting of "decreased sex drive" and/or "impotence" reported by veterans at each weekly visit. Approximately 61% of the veterans reported sexual side effects at least once during the trial, and 26.4% reported sexual side effects throughout the study. There were no significant differences in the frequency of sexual side effects among the four treatment groups. The results were similar when the comparison was made between the two antidepressant groups. There were no significant differences in the reporting of sexual side effects between those receiving desipramine and paroxetine. Also, the comparison between naltrexone and placebo did not alter the results. This is the first study to compare frequency of sexual side effect reporting between paroxetine and desipramine. We found no statistically significant differences in sexual side effect reporting between the two antidepressants. Also, the addition of naltrexone did not show any beneficial effect on the sexual side effect profile.

Efficacy of herbal shampoo base on native plant against head lice (Pediculus humanus capitis De Geer, Pediculidae: Phthiraptera) in vitro and in vivo in Thailand.

PubMed

Soonwera, Mayura

2014-09-01

Head lice infestation (or pediculosis) is an important public health problem in Thailand, especially in children between the ages 5 and 11 years. Head lice resistance is increasing, chemical pediculicides have lost their efficacy, and, therefore, alternative pediculicides such as herbal shampoos have been proposed to treat head lice infestation. Thus, the present study investigated the efficacy of three herbal shampoos based on native plants in Thailand (Acorus calamus Linn., Phyllanthus emblica Linn., and Zanthoxylum limonella Alston) against head lice and compared them with carbaryl shampoo (Hafif shampoo, 0.6% w/v carbaryl), malathion shampoo (A-Lice shampoo, 1.0% w/v malathion), and commercial shampoos (Babi Mild Natural' N Mild and Johnson's baby shampoo) in order to assess their in vitro and in vivo efficacy. For in vitro study, doses of 0.12 and 0.25 ml/cm(2) of each herbal shampoo were applied to filter paper, then 10 head lice were place on the filter paper. The mortalities of head lice were recorded at 5, 15, 30, and 60 min. The results revealed that all herbal shampoo were more effective on pediculicidal activity than chemical and commercial shampoos with 100% mortality at 15 min; LT₅₀ values ranged from 0.25 to 1.90 min. Meanwhile, chemical shampoos caused 20-80% mortality, and LT₅₀ values ranged from 6.50 to 85.43 min. On the other side, commercial shampoos showed 4.0% mortality. The most effective pediculicide was Z. limonella shampoo, followed by A. calamus shampoo, P. emblica shampoo, carbaryl shampoo, malathion shampoo, and commercial shampoo, respectively. In vivo results showed that all herbal shampoos were also more effective for head lice treatment than chemical and commercial shampoos with 94.67-97.68% of cure rate after the first treatment; the second treatment, 7 days later, revealed that the cure rate was 100%. Meanwhile, chemical shampoo showed 71.67-93.0% of cure rate and, unfortunately, commercial shampoos were nontoxic to head lice and showed 0% of cure rate after the first and the second treatments. Our data showed that three herbal shampoos of native plants in Thailand in this study are suitable to be used as pediculicides for Thai children since it is safe for children and there is no side-effect after application.

How does the side-effect information in patient information leaflets influence peoples' side-effect expectations? A cross-sectional national survey of 18- to 65-year-olds in England.

PubMed

Webster, Rebecca K; Weinman, John; Rubin, G James

2017-12-01

To establish how the terms recommended by the European Commission to describe side-effect risk in patient information leaflets (PILs) influences expectations of side-effects and to identify factors associated with these side-effect expectations. A cross-sectional online survey was carried out by a market research company. Data were collected in England between 18th March and 1st April 2016. A total of 1003 adults aged between 18 and 65. Self-reported expectation that the described side-effects would affect participants if they took the medicine, measured on a likelihood scale from 1 (very unlikely) to 5 (very likely). Participants formed high expectations of side-effects for "very common" and "common" side-effects, with 51.9% and 45.0% of participants rating these as "very likely" or "likely" to happen to them, respectively. This fell to 8.1% for "uncommon," 5.8% for "rare" and 4.1% for "very rare." For each descriptor, higher expectations of side-effects were more associated with women or being from an ethnic minority, or having less education, a household illness, high perceived sensitivity to medicines or negative beliefs about medicines. The current use of verbal descriptors to communicate side-effect risk in PILs leads to high side-effect expectations. These expectations could contribute to nocebo-induced medication side-effects experienced by patients. Additional work is required to identify ways to improve the way risk information is conveyed in PILs. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

Side Effects to Antidepressant Treatment in Patients With Depression and Comorbid Panic Disorder.

PubMed

Shankman, Stewart A; Gorka, Stephanie M; Katz, Andrea C; Klein, Daniel N; Markowitz, John C; Arnow, Bruce A; Manber, Rachel; Rothbaum, Barbara O; Thase, Michael E; Schatzberg, Alan F; Keller, Martin B; Trivedi, Madhukar H; Kocsis, James H

2017-04-01

Side effects to antidepressant medication can affect the efficacy of treatment, but few predictors foretell who experiences side effects and which side effects they experience. This secondary data analysis examined whether depressed patients with comorbid panic disorder were more likely to experience side effects than those without panic disorder. The study also examined whether greater burden of side effects predicted a poorer treatment course for patients with panic disorder than those without panic disorder. To examine the specificity of these effects, analyses also examined 2 other anxiety disorders-social phobia and generalized anxiety disorder (GAD). Between 2002 and 2006, a large sample (N = 808) of chronically depressed individuals (assessed using the Structured Clinical Interview for DSM-IV-TR Axis I Disorders [SCID-IV]) received antidepressants according to a predetermined algorithm for 12 weeks. Every 2 weeks, depressive symptoms (per the Hamilton Depression Rating Scale) and side effects (specific side effects as well as several indicators of side effect burden) were assessed. Lifetime diagnosis of panic disorder (assessed using the SCID-IV) at baseline was associated with higher likelihood of gastrointestinal (OR = 1.6 [95% CI, 1.0-2.6]), cardiac (OR = 1.8 [95% CI, 1.1-3.1]), neurologic (OR = 2.6 [95% CI, 1.6-4.2]), and genitourinary side effects (OR = 3.0 [95% CI, 1.7-5.3]) during treatment. Increases in side effect frequency, intensity, and impairment over time were more strongly associated with increases in depressive symptoms for patients with panic disorder compared to those without panic disorder. Neither social phobia nor GAD was associated with these effects. Potentially due to heighte​ned interoceptive awareness of changes in their body, chronically depressed individuals with panic disorder may be at greater risk than those without panic disorder for antidepressant side effects and to experience a worsening of depressive symptoms as a result of these side effects over time. ClinicalTrials.gov identifier: NCT00057551​. © Copyright 2017 Physicians Postgraduate Press, Inc.

The Relationship between Teacher Satisfaction and Frequency of Interaction with Site Administration

ERIC Educational Resources Information Center

Schwartz, Adam G.

2012-01-01

The primary determinant of student achievement is the quality of the classroom teacher. Some teachers are naturally talented, but the majority of teachers become effective through classroom experience. Unfortunately, the teaching profession experiences a high rate of turnover; many teachers leave before reaching the peak of their effectiveness. If…

Effectiveness of "Essentials for College Math" as a High School Transitional Course

ERIC Educational Resources Information Center

Riggleman, Jennifer S.

2017-01-01

Statistics on the number of students who leave high school underprepared for postsecondary education, and have to take remedial coursework upon entrance to college vary, but, unfortunately, for at least the last 10 years, these statistics have remained high. This study examined the effectiveness of one transitional high school math curriculum…

Organizing Your Parents for Effective Advocacy

ERIC Educational Resources Information Center

Elpus, Kenneth

2008-01-01

In today's world of restrictive school budgets and increasing property taxes, it is an unfortunate reality that many school districts will be faced with a budget crunch crisis that unenlightened school boards may try to solve by cutting or eliminating funds for music. At the crisis stage, it is often only the effective advocacy of an organized…

How to find nothing.

PubMed

Hemenway, David

2009-09-01

Hypothesis testing can be misused and misinterpreted in various ways. Limitations in the research design, for example, can make it almost impossible to reject the null hypothesis that a policy has no effect. This article discusses two examples of such experimental designs and analyses, in which, unfortunately, the researchers touted their null results as strong evidence of no effect.

Application of an integrated strategy for monitoring of contaminants, including endocrine active chemicals, in Great Lakes Areas of Concern

EPA Science Inventory

Chemical monitoring strategies are most effective for those chemicals whose hazards are well understood and for which sensitive and cost effective analytical methods are available. Unfortunately, such chemicals represent a minor fraction of those that may currently occur in the e...

Retention and Rewards: Promoting Career Advancement for Effective Leaders. [Federal Policy Platform Series. Brief 5

ERIC Educational Resources Information Center

New Leaders, 2014

2014-01-01

Principals are the leverage point for education reforms and the primary drivers of school improvement. A critical part of maintaining a corps of effective principals is rewarding and retaining the best school leaders. Unfortunately, few systems systematically identify principals that make important contributions to student learning or celebrate…

Increasing Teachers' Use of Behavior-Specific Praise Using a Multitiered System for Professional Development

ERIC Educational Resources Information Center

Gage, Nicholas A.; MacSuga-Gage, Ashley S.; Crews, Emily

2017-01-01

Successful instruction is contingent upon effective classroom management. Unfortunately, not all teachers are effective classroom managers and many require in-service professional development (PD) to increase their use of evidence-based classroom management skills. Although PD models have been developed and evaluated, many are resource-intensive.…

Medications and Side Effects

MedlinePlus

... to fully work. You might feel some side effects of your medication before your feel the benefits – ... as sleepiness, anxiety or headache) is a side effect or a symptom of your illness. Many side ...

Cancer Treatment for Women: Possible Sexual Side Effects

MedlinePlus

... the clitoris. These play a major part in sexual arousal in women. Removing the vulva and the clitoris ... www.cancer.org/treatment/treatments-and-side-effects/physical-side-effects/fertility-and-sexual-side-effects/sexuality-for-women-with-cancer.html. ...

"There is a chain of connections": using syndemics theory to understand HIV treatment side effects.

PubMed

Gagnon, Marilou

2018-03-12

Side effects are central to the experience of living longer with HIV but rarely have they been studied alone. Unlike other aspects of that experience, like quality of life, treatment adherence, chronicity, episodic disability, aging, health, and viral load suppression, side effects have not benefited from the same level of empirical and theoretical engagement from qualitative researchers. In this paper, we draw on syndemics theory and 50 qualitative interviews to better understand the experience of HIV treatment side effects. Two main categories were identified in the data: side effects as a product and side effects as a risk factor. The first category suggests that side effects are not just the product of taking antiretroviral drugs. They are also the product of particular conditions and tend to cluster with other health problems. The second category puts forward the idea that side effects can act as a syndemic risk factor by exposing PLWH to a greater risk of developing health problems and creating conditions in which psychosocial issues are more likely to emerge. The paper concludes by calling for more research on the complex nature of side effects and for the development of comprehensive approaches for the assessment and management of side effects.

Patient-provider communication and hormonal therapy side effects in breast cancer survivors.

PubMed

Lin, Jenny J; Chao, Jennifer; Bickell, Nina A; Wisnivesky, Juan P

2017-09-01

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

The fundamental unit of pain is the cell.

PubMed

Reichling, David B; Green, Paul G; Levine, Jon D

2013-12-01

The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of "pain molecules," as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain.

A new strategy to mitigate the initial capacity loss of lithium ion batteries

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

Su, Xin; Lin, Chikai; Wang, Xiaoping

2016-08-01

Hard carbon (non-graphitizable) and related materials, like tin, tin oxide, silicon, and silicon oxide, have a high theoretical lithium delivery capacity (>550 mAh/g depending on their structural and chemical properties) but unfortunately they also exhibit a large initial capacity loss (ICL) that overrides the true reversible capacity in a full cell. Overcoming the large ICL of hard carbon in a full-cell lithium-ion battery (LIB) necessitates a new strategy wherein a sacrificial lithium source additive, such as, Li5FeO4 (LFO), is inserted on the cathode side. Full batteries using hard carbon coupled with LFO-LiCoO2 (LCO) are currently under development at our laboratory.more » We find that the reversible capacity of a cathode containing LFO can be increased by 14%. Furthermore, the cycle performance of full cells with LFO additive is improved from <90% to >95%. We show that the LFO additive not only can address the irreversible capacity loss of the anode, but can also provide the additional lithium ion source required to mitigate the lithium loss caused by side reactions. In addition, we have explored the possibility to achieve higher capacity with hard carbon, whereby the energy density of full cells can be increased from ca. 300 Wh/kg to >400 Wh/kg.« less

Statistical Study of Interplanetary Coronal Mass Ejections with Strong Magnetic Fields

NASA Astrophysics Data System (ADS)

Murphy, Matthew E.

Coronal Mass Ejections (CMEs) with strong magnetic fields (B ) are typically associated with significant Solar Energetic Particle (SEP) events, high solar wind speed and solar flare events. Successful prediction of the arrival time of a CME at Earth is required to maximize the time available for satellite, infrastructure, and space travel programs to take protective action against the coming flux of high-energy particles. It is known that the magnetic field strength of a CME is linked to the strength of a geomagnetic storm on Earth. Unfortunately, the correlations between strong magnetic field CMEs from the entire sun (especially from the far side or non-Earth facing side of the sun) to SEP and flare events, solar source regions and other relevant solar variables are not well known. New correlation studies using an artificial intelligence engine (Eureqa) were performed to study CME events with magnetic field strength readings over 30 nanoteslas (nT) from January 2010 to October 17, 2014. This thesis presents the results of this study, validates Eureqa to obtain previously published results, and presents previously unknown functional relationships between solar source magnetic field data, CME initial speed and the CME magnetic field. These new results enable the development of more accurate CME magnetic field predictions and should help scientists develop better forecasts thereby helping to prevent damage to humanity's space and Earth assets.

ASSESSING THE EFFECTIVENESS OF RESTORATION TECHNOLOGIES

EPA Science Inventory

Numerous stream and riparian restoration projects are being undertaken across the nation at a variety of scales and for disparate reasons. Unfortunately, there are very few studies associated with these restoration efforts which provide a consistent and practical methodology to e...

Side effect burden of antipsychotic drugs in real life - Impact of gender and polypharmacy.

PubMed

Iversen, Trude Seselie Jahr; Steen, Nils Eiel; Dieset, Ingrid; Hope, Sigrun; Mørch, Ragni; Gardsjord, Erlend Strand; Jørgensen, Kjetil Nordbø; Melle, Ingrid; Andreassen, Ole A; Molden, Espen; Jönsson, Erik G

2018-03-02

Antipsychotic-associated side effects are well known and represent a significant treatment challenge. Still, few large studies have investigated the overall side effect burden of antipsychotics in real-life settings. To describe the occurrence of side effects and perceived burden of antipsychotics in a large naturalistic sample, taking polypharmacy and patient characteristics into account. Patients (n=1087) with psychotic disorders were assessed for side effects using the Udvalg for Kliniske Undersøgelser (UKU) side effect rating scale in addition to assessment of clinical and pharmacological data. Statistical analyses were performed controlling for possible confounding factors. Use of antipsychotics showed significant associations to neurologic and sexual symptoms, sedation and weight gain, and >75% of antipsychotics-users reported side effects. More side effects were observed in patients using several antipsychotics (p=0.002), with increasing total dose (p=0.021) and with antipsychotics in combinations with other psychotropic drugs. Patients and investigators evaluated the side effect burden differently, particularly related to severity, gender and antipsychotics dose. Twice as many females described side effect burden as severe (p=0.004). Patients with psychotic disorders have a high occurrence of symptoms associated with use of antipsychotics, and polypharmacy and female gender are seemingly risk factors for reporting a severe side effect burden. Due to the cross-sectional design evaluation of causality is tentative, and these findings should be further investigated in prospective studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The Glasgow antipsychotic side-effects scale for clozapine in inpatients and outpatients with schizophrenia or schizoaffective disorder.

PubMed

Ignjatović Ristić, Dragana; Cohen, Dan; Obradović, Andrea; Nikić-Đuričić, Katarina; Drašković, Marija; Hinić, Darko

2018-02-01

The inconsistency in clinician and patient ratings of clozapine-induced side effects underscore the need to supplement clinician-based estimates of side effects with patient-reported ones. The main aims of the study are validation of the Glasgow antipsychotic side-effects scale for clozapine (GASS-C) in Serbian inpatients/outpatients with schizophrenia or schizo-affective disorder and recommendations for its future use, based on common and rare clozapine-associated side-effects. The GASS-C was administered to 95 outpatients/inpatients diagnosed with schizophrenia, schizoaffective, or chronic psychotic disorder. The scale showed good overall reliability, with an internal consistency coefficient of α = 0.84, an average retest coefficient of rho = 0.76, and a Spearman-Brown coefficient of validity of 0.81. Side effects were absent or mild in 64.2% of the patients, moderate in 31.6%, severe in 4.2%; 14% of the subjects considered their symptoms distressing. The most commonly reported side-effects were drowsiness, thirst, frequent urination, and dry mouth. Women reported more side effects than men, and patients not in a relationship reported significantly fewer side effects than patients in a relationship. Results indicate a weak positive correlation (rho = 0.231; p = .025) between severity of side effects and clozapine dose. The GASS-C showed good psychometric characteristics in clinical population of patients on clozapine. In future studies, clozapine serum concentrations should be measured when using the GASS-C to monitor side effects.

Learning to experience side effects after antidepressant intake - Results from a randomized, controlled, double-blind study.

PubMed

Rheker, Julia; Winkler, Alexander; Doering, Bettina K; Rief, Winfried

2017-02-01

Side effects play a key role in patients' failure to take antidepressants. There is evidence that verbal suggestions and informed consent elicit expectations that can in turn trigger the occurrence of side effects. Prior experience or learning mechanisms are also assumed to contribute to the development of side effects, although their role has not been thoroughly investigated. In this study, we examined whether an antidepressant's side effects can be learned via Pavlovian conditioning. Participants (n = 39) were randomly allocated to one of two groups and were exposed to a classical conditioning procedure. During acquisition, 19 participants received amitriptyline and 20 participants received a placebo pill. Pills were taken for four nights together with a novel-tasting drink. After a washout phase, both groups received a placebo pill together with the novel-tasting drink (evocation). Side effects were assessed via the Generic Assessment of Side Effects Scale prior to acquisition (baseline), after acquisition, and after evocation. A score of antidepressant-specific side effects was calculated. Participants taking amitriptyline reported significantly more antidepressant-specific side effects after acquisition compared to both baseline and the placebo group. After evocation, participants who underwent the conditioning procedure with amitriptyline reported significantly more antidepressant-specific side effects than those who never received amitriptyline, even though both groups received a placebo. Our results indicate that antidepressant side effects can be learned using a conditioning paradigm and evoked via a placebo pill when applied with the same contextual factors as the verum.

The association of HIV/AIDS treatment side effects with health status, work productivity, and resource use.

PubMed

daCosta DiBonaventura, Marco; Gupta, Shaloo; Cho, Michelle; Mrus, Joseph

2012-01-01

Due to stable incidence and improved survival rates, there are an increasing number of patients living with HIV/AIDS in the USA. Although highly effective, current antiretroviral therapies are associated with a variety of side effects. The role side effects play on health outcomes has not been fully examined. The current study assessed the association of medication side effects with (1) self-assessed health status; (2) work productivity and activity impairment; and (3) healthcare resource utilization. Data were from a cross-sectional patient-reported survey fielded in the USA using a dual methodology of Internet and paper questionnaires. A total of 953 patients living with HIV/AIDS who were currently taking a medication for their condition were included in the analyses. The most frequent side effects reported by patients were fatigue (70.72%), diarrhea (62.96%), insomnia (58.97%), dizziness (52.78%), neuropathy (52.68%), joint pain (52.36%), nausea (51.63%), and abdominal pain (50.37%). The presence of each side effect was associated with reduced self-assessed health status, increased productivity loss, increased activity impairment, and increased healthcare resource use. Controlling for CD4 cell counts in regression modeling did little to diminish the impact of side effects. Although not all side effects were associated with all outcomes, every side effect was associated with worse health status, some measure of increased work productivity loss, and/or some measure of increased healthcare resource use. Patients are living longer with HIV and, therefore, spending a greater length of time on treatment. The results of the current study suggest that many of these patients are experiencing a wide array of side effects from these therapies. These side effects have demonstrated a profound association with self-assessed health, work productivity, and healthcare resource use. Improved management of these side effects or development of treatments with a better side effect profile may have a substantial humanistic and economic benefit.

Decreasing the Burden of Side Effects Through Positive Message Framing: an Experimental Proof-of-Concept Study.

PubMed

Wilhelm, Marcel; Rief, Winfried; Doering, Bettina K

2018-05-21

Informing patients about treatment side effects increases the occurrence and intensity of side effects. Since the obligatory informed consent procedure in drug treatments requires transparency and nocebo research suggests that the informed consent of a drug leads to an increased occurrence of the mentioned side effects, the aim of this proof of concept study was to determine the effect of two different framings of informed consent on the occurrence, intensity, and perceived threat of side effects. Healthy male participants (n = 80) were randomized to one of two framing groups. The positive framing group was informed that the common side effect dizziness was a sign that the drug had started to work, while the neutral framing group was told that dizziness is an unpleasant but well-known side effect. Side effects were measured after the administration of metoprolol, an antihypertensive agent. Post hoc moderator analyses investigated the effect of pre-existing negative beliefs about the general harm of medication on the framing manipulation. Metoprolol-specific drug-attributed side effects were rated significantly less threatening in the positive framing group. The between-group effect size (Cohen's d) was small (d = 0.38, p = 0.049). Exploratory post hoc moderator analyses suggest that participants who believed that medication is a source of harmful effects benefited from positive framing, compared to neutral framing of drug-attributed side effects. Positive framing was partially effective in decreasing specific side effect measures, particularly among participants with a tendency to believe that medicine is harmful. Informed consent procedures should therefore be personalized, focusing on patients with negative treatment beliefs.

Combined use of alcohol and energy drinks: Dose relationship with self-reported physiological stimulation and sedation side effects.

PubMed

Droste, Nicolas; Peacock, Amy; Bruno, Raimondo; Pennay, Amy; Zinkiewicz, Lucy; Lubman, Dan I; Miller, Peter

2017-08-01

Negative physiological stimulation and sedation side effects are experienced by a significant proportion of consumers who consume alcohol mixed with energy drinks (AmED). Few studies have compared the frequency of side effects between sessions of AmED and sessions of alcohol only within-subject, and none have explored a dose relationship. Explore the occurrence of self-reported physiological stimulant and sedative side effects between sessions of AmED and alcohol only, and at varying ED dosage levels within AmED sessions. A convenience sample of 2953 residents of New South Wales, Australia completed an online survey. N=731 AmED users reported daily caffeine intake, typical alcohol and AmED consumption, and past 12-month experience of physiological stimulation and sedation side effects during AmED and alcohol only sessions. Within-subject analyses compared occurrence of side effects between session types. Hierarchical binary logistic regression analyses explored the association of ED dose during AmED sessions with the experience of physiological side effects. There were greater odds of most stimulant side effects, and lower odds of sedation side effects, during AmED sessions compared to alcohol only sessions. Compared to one ED, consumption of three or more EDs was significantly associated with the majority of both stimulant and alcohol intoxication side effects after controlling for demographics and consumption covariates. AmED is associated with perceived changes in physiological stimulant and sedation side effects of alcohol. Experience of side effects is positively associated with ED dosage. Future research should account for varying ED dosage, and reflect real world consumption levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reading Instruction with Gifted and Talented Readers: A Series of Unfortunate Events or a Sequence of Auspicious Results?

ERIC Educational Resources Information Center

Wood, Patricia F.

2008-01-01

The enigmatic author Lemony Snicket is quick to establish from the start that happy events are not to be expected in his collection, "A Series of Unfortunate Events." Every happy event in the lives of the three clever and charming Baudelaire children is countered with an even more unfortunate one, events rife with misery, misfortune, and despair.…

Extracorporeal shock waves: perspectives in malignant tumor treatment.

PubMed

Frairia, R; Berta, L; Catalano, M G

2016-01-01

Progress in basic research led to the design of new generations of anticancer drugs with some notable achievements. Over the years, more and more powerful drugs have been developed with the purpose of increasing the rate of response to therapy. As molecular power of chemotherapeutic agents increased, unfortunately also toxicity and undesired side-effects increased. The search for new therapeutic strategies to be used in the management of cancer is one of the more promising strategies to reduce chemotherapy toxicity. Extracorporeal Shock Waves (ESW), widely used for the treatment of urolithiasis, have been reported to cause modifications of cell growth both in vitro and in vivo. They exert an agonist cytotoxic effect with several chemotherapeutic agents, such as cisplatin, doxorubicin, bleomycin, paclitaxel. Moreover, as it has been reported that their main mechanism of action is an increase in cell membrane permeability, ESW are also used to deliver oligonucleotides and other small particles to cells. Recently, it was found that certain dye compounds, in particular porphyrins, can achieve a cytopathogenic effect when the disease site is subjected to ultrasound irradiation. This technique is referred to as sonodynamic therapy. Based on the new knowledge regarding the interaction between ultrasound with bulk liquid, several studies have shown a synergic effect of ESW and porphyrins in vitro, thus opening a new perspective in sonodynamic therapy, able to overcome some drawbacks encountered during conventional anticancer drug treatment. Finally, current advances in bioengineering encouraged the application of nano-scale technologies to medicine. Nanobubbles, composed of an external shell and a gas core, can deliver chemotropic drugs and porfirins, to target tumour tissues in response to physical triggers, and ESW features make them an ideal alternative to ultrasound in combination with drug-loaded nanobubbles in delivery strategies.

Effects of realistic force feedback in a robotic assisted minimally invasive surgery system.

PubMed

Moradi Dalvand, Mohsen; Shirinzadeh, Bijan; Nahavandi, Saeid; Smith, Julian

2014-06-01

Robotic assisted minimally invasive surgery systems not only have the advantages of traditional laparoscopic procedures but also restore the surgeon's hand-eye coordination and improve the surgeon's precision by filtering hand tremors. Unfortunately, these benefits have come at the expense of the surgeon's ability to feel. Several research efforts have already attempted to restore this feature and study the effects of force feedback in robotic systems. The proposed methods and studies have some shortcomings. The main focus of this research is to overcome some of these limitations and to study the effects of force feedback in palpation in a more realistic fashion. A parallel robot assisted minimally invasive surgery system (PRAMiSS) with force feedback capabilities was employed to study the effects of realistic force feedback in palpation of artificial tissue samples. PRAMiSS is capable of actually measuring the tip/tissue interaction forces directly from the surgery site. Four sets of experiments using only vision feedback, only force feedback, simultaneous force and vision feedback and direct manipulation were conducted to evaluate the role of sensory feedback from sideways tip/tissue interaction forces with a scale factor of 100% in characterising tissues of varying stiffness. Twenty human subjects were involved in the experiments for at least 1440 trials. Friedman and Wilcoxon signed-rank tests were employed to statistically analyse the experimental results. Providing realistic force feedback in robotic assisted surgery systems improves the quality of tissue characterization procedures. Force feedback capability also increases the certainty of characterizing soft tissues compared with direct palpation using the lateral sides of index fingers. The force feedback capability can improve the quality of palpation and characterization of soft tissues of varying stiffness by restoring sense of touch in robotic assisted minimally invasive surgery operations.

Treatment factors affecting longitudinal quality of life in new onset pediatric epilepsy.

PubMed

Modi, Avani C; Ingerski, Lisa M; Rausch, Joseph R; Glauser, Tracy A

2011-05-01

Recognizing the importance of patient-reported outcomes, this longitudinal, prospective study examined: Changes in health-related quality of life (HRQOL) over seven months following antiepileptic drug (AED) initiation and the relationship of seizures, AED side-effects, and AED type to HRQOL. Parents of 124 children with newly diagnosed epilepsy completed measures of HRQOL and side-effects at each clinic visit. Treatment information was also collected. HRQOL remained stable over time; however, seizures and AED side-effects significantly affected multiple HRQOL domains. Higher seizure activity was associated with decreased Physical HRQOL. Side-effects were negatively associated with all HRQOL domains. Children taking carbamazepine who experienced higher side-effects early in therapy demonstrated declining emotional functioning compared to children experiencing no/some side-effects. AED side-effects, AED type, and seizure frequency were associated with longitudinal HRQOL in children with newly-diagnosed epilepsy. Routine assessment of AED side-effects and HRQOL may be useful for clinical decision making.

Management Options for Biochemically Recurrent Prostate Cancer.

PubMed

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

2017-05-01

Prostate cancer is the most common solid tumor malignancy in men worldwide. Treatment with surgery and radiation can be curative in organ-confined disease. Unfortunately, about one third of men develop biochemically recurrent disease based only on rising prostate-specific antigen (PSA) in the absence of visible disease on conventional imaging. For these patients with biochemical recurrent prostate cancer, there is no uniform guideline for subsequent management. Based on available data, it seems prudent that biochemical recurrent prostate cancer should initially be evaluated for salvage radiation or prostatectomy, with curative intent. In selected cases, high-intensity focused ultrasound and cryotherapy may be considered in patients that meet very narrow criteria as defined by non-randomized trials. If salvage options are not practical or unsuccessful, androgen deprivation therapy (ADT) is a standard option for disease control. While some patients prefer ADT to manage the disease immediately, others defer treatment because of the associated toxicity. In the absence of definitive randomized data, patients may be followed using PSA doubling time as a trigger to initiate ADT. Based on retrospective data, a PSA doubling time of less than 3-6 months has been associated with near-term development of metastasis and thus could be used signal to initiate ADT. Once treatment is begun, patients and their providers can choose between an intermittent and continuous ADT strategy. The intermittent approach may limit side effects but in patients with metastatic disease studies could not exclude a 20% greater risk of death. In men with biochemical recurrence, large studies have shown that intermittent therapy is non-inferior to continuous therapy, thus making this a reasonable option. Since biochemically recurrent prostate cancer is defined by technological limitations of radiographic detection, as new imaging (i.e., PSMA) strategies are developed, it may alter how the disease is monitored and perhaps managed. Furthermore, patients have no symptoms related to their disease and thus many prefer options that minimize toxicity. For this reason, herbal agents and immunotherapy are under investigation as potential alternatives to ADT and its accompanying side effects. New therapeutic options combined with improved imaging to evaluate the disease may markedly change how biochemically recurrent prostate cancer is managed in the future.

[Treatment side effects and compliance in patients with depression].

PubMed

Petrova, N N; Kucher, E O

2012-01-01

The impact of treatment side-effects on the compliance was studied in 85 depressive patients with different mental disorders - recurrent depressive disorder, postschizophrenic depression and organic affective disorder. The comparison of objective and subjective evaluations of compliance and a comparative analysis of the level of compliance, with its dependence on the treatment specifics, in different diseases were done. A significant role of efficacy and treatment side-effects was identified. The levels of "mental" and "autonomous" side-effects were highest in the treatment of depression: patients with postschizophrenic depression had the highest risk in respect of maintenance treatment; patients with recurrent depressive disorder and organic (affective) disorder were more tolerant to the treatment side-effects and their treatment, including the maintenance therapy, was rather effective. The compliance of all patients with depression was negatively correlated with the severity of side-effects of pharmacotherapy. The greatest side-effects and the lowest level of compliance were observed in the complex treatment with antidepressants and atypical neuroleptics. The effect of side-effects on the compliance was dependent on their severity and subjective tolerability and, to a lesser extent, on the amount of drugs.

Exploring the associations between drug side-effects and therapeutic indications.

PubMed

Wang, Fei; Zhang, Ping; Cao, Nan; Hu, Jianying; Sorrentino, Robert

2014-10-01

Drug therapeutic indications and side-effects are both measurable patient phenotype changes in response to the treatment. Inferring potential drug therapeutic indications and identifying clinically interesting drug side-effects are both important and challenging tasks. Previous studies have utilized either chemical structures or protein targets to predict indications and side-effects. In this study, we compared drug therapeutic indication prediction using various information including chemical structures, protein targets and side-effects. We also compared drug side-effect prediction with various information sources including chemical structures, protein targets and therapeutic indication. Prediction performance based on 10-fold cross-validation demonstrates that drug side-effects and therapeutic indications are the most predictive information source for each other. In addition, we extracted 6706 statistically significant indication-side-effect associations from all known drug-disease and drug-side-effect relationships. We further developed a novel user interface that allows the user to interactively explore these associations in the form of a dynamic bipartitie graph. Many relationship pairs provide explicit repositioning hypotheses (e.g., drugs causing postural hypotension are potential candidates for hypertension) and clear adverse-reaction watch lists (e.g., drugs for heart failure possibly cause impotence). All data sets and highly correlated disease-side-effect relationships are available at http://astro.temple.edu/∼tua87106/druganalysis.html. Copyright © 2014 Elsevier Inc. All rights reserved.

Effectiveness of increased law enforcement surveillance on work zone safety in Mississippi.

DOT National Transportation Integrated Search

2007-07-01

Increased law enforcement surveillance program is one of the methods currently been implemented by departments of transportation in the United States in an effort to increase safety for both drivers and workers in highway construction zones. Unfortun...

A Quick-Test for Biochar Effects on Seed Germination

EPA Science Inventory

Biochar is being globally evaluated as a soil amendment to improve soil characteristics (e.g. soil water holding, nutrient exchange, microbiology, pesticides and chemical availability) to increase crop yields. Unfortunately, there are no quick tests to determine what biochar type...

Helping Teachers Improve Classroom Assessments

ERIC Educational Resources Information Center

Emberger, Marcella

2007-01-01

Understanding and implementing effective classroom assessments are skills that are essential to increasing student achievement. Unfortunately, many teachers have had little training in assessment strategies in either graduate or undergraduate programs. Administrators, therefore, must find innovative ways to help their teachers think like assessors…

Parental Expectation of Side Effects Following Vaccination Is Self-fulfilling: A Prospective Cohort Study.

PubMed

Smith, Louise E; Weinman, John; Amlôt, Richard; Yiend, Jenny; Rubin, G James

2018-06-02

One of the major factors contributing to parental refusal of vaccinations is the perception that vaccines cause side effects. Although symptoms are commonly reported following vaccinations, their causes are not always straightforward. Although some may be directly attributable to the vaccine itself, others may reflect pre-existing or coincidental symptoms that are misattributed to the vaccine. To investigate psychological factors associated with parental report of side effects following vaccination with the child influenza vaccine, and parental intention to re-vaccinate one's child the following year. A prospective cohort study was run in primary care practices in London in the 2016-2017 influenza season (ClinicalTrials.gov number NCT02909855). Two hundred seventy parents from 14 practices completed a questionnaire before their child's vaccination. Follow-up questionnaires were completed 3 days after vaccination and one month after vaccination. Parental report of side effects and vaccination intention for the subsequent year were measured. Parental report of side effects was strongly associated with pre-vaccination expectation of side effects. Suggestions received from the media, National Health Service (NHS) vaccination leaflet, and health care workers, as well as uncertainty-related beliefs, perceived sensitivity of the child to medicines, pessimism, and anxiety were also associated with reporting side effects. Side effect report was associated with lower vaccination intention for the following influenza season. Side effect perception following vaccination is influenced by psychological factors, in particular expectations. Perceiving side effects reduces future vaccination intention. Future public health communications should aim to decrease unrealistic expectations of side effects to increase vaccine uptake.

Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

PubMed Central

Zielinski, Daniel C.; Filipp, Fabian V.; Bordbar, Aarash; Jensen, Kasper; Smith, Jeffrey W.; Herrgard, Markus J.; Mo, Monica L.; Palsson, Bernhard O.

2015-01-01

Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways dysregulated by drugs are linked to the development of side effects. We show such dysregulated metabolic pathways contain genes with sequence variants affecting side effect incidence, play established roles in pathophysiology, have significantly altered activity in corresponding diseases, are susceptible to metabolic inhibitors and are effective targets for therapeutic nutrient supplementation. Our results indicate that metabolic dysregulation represents a common mechanism underlying side effect pathogenesis that is distinct from the role of metabolism in drug clearance. We suggest that elucidating the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies. PMID:26055627

Radiation Therapy Side Effects

Cancer.gov

Radiation therapy has side effects because it not only kills or slows the growth of cancer cells, it can also affect nearby healthy cells. Many people who get radiation therapy experience fatigue. Other side effects depend on the part of the body that is being treated. Learn more about possible side effects.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care.

PubMed

Jamison, Robert N; Dorado, Kathleen; Mei, Anna; Edwards, Robert R; Martel, Marc O

2017-03-01

There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects ( P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk ( P < 0.001). This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care

PubMed Central

Jamison, Robert N.; Dorado, Kathleen; Mei, Anna; Edwards, Robert R.; Martel, Marc O.

2017-01-01

Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care. PMID:29392205

Side effects of low-dose pyridostigmine bromide are not related to cholinesterase inhibition.

PubMed

Cook, M R; Gerkovich, M M; Sastre, A; Graham, C

2001-12-01

Pretreatment with pyridostigmine bromide (PB) has become part of standard military procedures for protection against the effects of possible chemical warfare attack. The purpose of the work reported here was to quantify the type, intensity and frequency of side effects of low-dose PB, and to examine factors that predict the intensity and frequency of side effects. A double-blind, cross-over, placebo (PL)-controlled design was used. Of the 67 subjects, 33 received 30 mg PB every 8 h for 13 doses, and 34 received 60 mg on the same schedule. Order of PB and PL administration was counterbalanced. Overall, side effects were mild, even at the 60-mg dose level. More side effects were reported when volunteers were taking PB than when they were taking placebo. Women reported more symptoms than men. Neither cholinesterase inhibition nor plasma levels of PB predicted side effect scores during the PB week; the best predictor of side effect scores during the PB week was side effect scores during the PL week. PB is well tolerated by healthy young people, even when twice the recommended military dose is administered.

Factors affecting patient's perception of anticancer treatments side-effects: an observational study.

PubMed

Russo, Stefania; Cinausero, Marika; Gerratana, Lorenzo; Bozza, Claudia; Iacono, Donatella; Driol, Pamela; Deroma, Laura; Sottile, Roberta; Fasola, Gianpiero; Puglisi, Fabio

2014-02-01

Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. There is evidence that patients' perception of the side effects of anticancer treatments changes over time. Aim of this study was to evaluate the cancer patients' perceptions of physical and non-physical side effects of contemporary anticancer therapy. Four hundred and sixty-four patients entered the study (153 men and 311 women). Participants were asked to rank their side effects in order of distress by using two sets of cards naming physical and non-physical effects, respectively. Influencing factors, including treatment and patient characteristics, were also analysed. Patients ranked the non-physical side effect 'Affects my family or partner' first. 'Constantly tired' and 'Loss of hair' were ranked second and third, respectively. Significant differences from previous studies on this topic emerged. In particular, 'Vomiting', a predominant concern in previous studies, almost disappeared, whereas 'Nausea' and 'Loss of hair' remained important side effects in the patients' perception. Interestingly, marital status was predominant in driving patients' perception, being associated with several side effects ('Constantly tired', 'Loss of appetite', 'Affects my work/Home duties', 'Affects my social activities', 'Infertility'). Other significant factors influencing patient's perception of side effects included age, disease characteristics and ongoing anticancer therapy. This study provided information on current status of patients' perceptions of side effects of anticancer treatment. These results could be used in pre-treatment patient education and counselling.

Perceived risk of tamoxifen side effects: a study of the use of absolute frequencies or frequency bands, with or without verbal descriptors.

PubMed

Knapp, Peter; Gardner, Peter H; Raynor, David K; Woolf, Elizabeth; McMillan, Brian

2010-05-01

To investigate the effectiveness of presenting medicine side effect risk information in different forms, including that proposed by UK guidelines [[1] Medicines and Healthcare products Regulatory Agency. Always read the leaflet-Getting the best information with every medicine. (Report of the Committee on Safety of Medicines Working Group on Patient Information). London: The Stationery Office, 2005.]. 134 Cancer Research UK (CRUK) website users were recruited via a 'pop-up'. Using a 2x2 factorial design, participants were randomly allocated to one of four conditions and asked to: imagine they had to take tamoxifen, estimate the risks of 4 side effects, and indicate a presentation mode preference. Those presented with absolute frequencies demonstrated greater accuracy in estimating 2 of 4 side effects, and of any side effect occurring, than those presented with frequency bands. Those presented with combined descriptors were more accurate at estimating the risk of pulmonary embolism than those presented with numeric descriptors only. Absolute frequencies outperform frequency bands when presenting side effect risk information. However, presenting such exact frequencies for every side effect may be much less digestible than all side effects listed under 5 frequency bands. Combined numerical and verbal descriptors may be better than numeric only descriptors when describing infrequent side effects. Information about side effects should be presented in ways that patients prefer, and which result in most accurate risk estimates. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

A multi-port power electronics interface for battery powered electric vehicles: Application of inductively coupled wireless power transfer and hybrid energy storage system

NASA Astrophysics Data System (ADS)

McDonough, Matthew Kelly

Climate change, pollution, and geopolitical conflicts arising from the extreme wealth concentrations caused by fossil fuel deposits are just a few of the side-effects of the way that we fuel our society. A new method to power our civilization is becoming more and more necessary. Research for new, more sustainable fuel sources is already underway due to research in wind, solar, geothermal, and hydro power. However this focus is mainly on stationary applications. A large portion of fossil fuel usage comes from transportation. Unfortunately, the transition to cleaner transportation fuels is being stunted by the inability to store adequate amounts of energy in electro-chemical batteries. The idea of charging while driving has been proposed by many researchers, however several challenges still exist. In this work some of these challenges are addressed. Specifically, the ability to route power from multiple sources/loads is investigated. Special attention is paid to adjusting the time constant of particular converters, namely the battery and ultra-capacitor converters to reduce the high frequency and high magnitude current components applied to the battery terminals. This is done by developing a closed loop model of the entire multi-port converter, including the state of charge of the ultra-capacitors. The development of closed loop models and two experimental testbeds for use as stationary vehicle charging platforms with their unique set of sources/loads are presented along-side an on-board charger to demonstrate the similarities and differences between stationary charging and mobile charging. Experimental results from each are given showing that it is not only possible, but feasible to utilize Inductively Coupled Wireless Power Transfer (ICWPT) to charge a battery powered electric vehicle while driving and still protect the life-span of the batteries under the new, harsher conditions generated by the ICWPT system.

How Can I Improve My Ratings: A Regression Analysis of Student Evaluations of University Professors

ERIC Educational Resources Information Center

Watson, Tyler A.

2011-01-01

Research on the utility of student evaluations to measure teaching effectiveness of university professors could be the largest body of work conducted on pedagogy in the academe. The literature suggests that student evaluations are valid and reliable measures of effective teaching and student learning. Unfortunately, while there have been many…

Great Principals at Scale: Creating District Conditions That Enable All Principals to Be Effective

ERIC Educational Resources Information Center

Ikemoto, Gina; Taliaferro, Lori; Fenton, Benjamin; Davis, Jacquelyn

2014-01-01

School leaders are critical in the lives of students and to the development of their teachers. Unfortunately, in too many instances, principals are effective in spite of--rather than because of--district conditions. To truly improve student achievement for all students across the country, well-prepared principals need the tools, support, and…

How to Effectively Use Social Media as In-Class Teaching Tools

ERIC Educational Resources Information Center

Simplicio, Joseph

2015-01-01

Every day all across America teachers assign their students stories to read and summarize. Unfortunately, many of these students find this to be an exercise in futility. Lacking the skills to effectively analyze the material, these students often struggle to properly summarize what they have read because they have never mastered the correct…

Restoring Self-Esteem in Adolescent Males

ERIC Educational Resources Information Center

Hendel, Andrea

2006-01-01

When presented with the words self-esteem, it is most common in our society to immediately think of girls. It is not often that people ponder the effects of body image, athleticism, success, or even friendships for boys. Unfortunately in overlooking these concepts, we are doing a disservice to our male youth. This article addresses the effects of…

Robust Evaluation Matrix: Towards a More Principled Offline Exploration of Instructional Policies

ERIC Educational Resources Information Center

Doroudi, Shayan; Aleven, Vincent; Brunskill, Emma

2017-01-01

The gold standard for identifying more effective pedagogical approaches is to perform an experiment. Unfortunately, frequently a hypothesized alternate way of teaching does not yield an improved effect. Given the expense and logistics of each experiment, and the enormous space of potential ways to improve teaching, it would be highly preferable if…

Medication Side Effects among People with Epilepsy Taking Phenobarbital in Zambia

PubMed Central

Elafros, Melissa A.; Bui, Esther; Birbeck, Gretchen L.

2014-01-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool Adverse Events Profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman’s correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1 mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4–8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the WHO report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects in routine care in low income settings is warranted. PMID:25219354

Medication side effects among people with epilepsy taking phenobarbital in Zambia.

PubMed

Elafros, Melissa A; Bui, Esther; Birbeck, Gretchen L

2014-11-01

Phenobarbital remains one of the most widely used antiepileptic drugs worldwide, yet there are limited data regarding side effects associated with its use in routine clinical care settings in low-income countries. Available data suggests that phenobarbital is as effective as other first-line drugs for treating tonic-clonic seizures, but side effect reports differ widely between high and low-income settings. A better understanding of phenobarbital side effect profile and severity in low-income settings is warranted given its role in efforts to decrease the epilepsy treatment gap. We used the Liverpool adverse events profile (LEAP) to assess side effects in consecutive patients with epilepsy on phenobarbital seeking care in rural Zambia. Data regarding age, gender, medication dose, and medication adherence were also collected. T-tests and Spearman's correlation coefficient were used to assess predictors of LEAP score and medication adherence. Thirty-five patients receiving a mean dose of 2.1mg/kg/day (SD: 2.78 mg/kg/day) of phenobarbital were assessed. All participants reported at least one side effect in the previous four weeks with a median of 6 symptoms (IQR: 4-8) and a mean side effects score of 28/76 (SD: 5.38). Over half reported sleepiness and dizziness. Memory problems and depression were also common (both 46%). Total LAEP score was not associated with age (p=0.88), gender (p=0.17), or phenobarbital dose (p=0.13). Medication adherence was not associated with side effects total score (p=0.56). Rural Zambian adults taking phenobarbital at doses recommended by the World Health Organization report a significant number of side effects. The most common side effects reported were similar to those reported in high-income countries. The significant burden of phenobarbital-associated side effects in this African cohort is in contrast to data from non-randomized clinical trials in China that reported phenobarbital to be well-tolerated with few side effects. Additional investigations regarding phenobarbital side effects during routine care in low income settings is warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Reducing Aversion to Side Effects in Preventive Medical Treatment Decisions

ERIC Educational Resources Information Center

Waters, Erika A.; Weinstein, Neil D.; Colditz, Graham A.; Emmons, Karen M.

2007-01-01

Laypeople tend to be overly sensitive to side effects of treatments that prevent illness, possibly leading them to refuse beneficial therapies. This Internet-based study attempted to reduce such side effect aversion by adding graphic displays to the numerical risk probabilities. It also explored whether graphics reduce side effect aversion by…

Systematic identification of proteins that elicit drug side effects

PubMed Central

Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica; Jensen, Lars Juhl; Gross, Cornelius; Gavin, Anne-Claude; Bork, Peer

2013-01-01

Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug–target relations to identify overrepresented protein–side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause side effects. Of 1428 side effects studied, 732 were predicted to be predominantly caused by individual proteins, at least 137 of them backed by existing pharmacological or phenotypic data. We prove this concept in vivo by confirming our prediction that activation of the serotonin 7 receptor (HTR7) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations. PMID:23632385

Prediction of Central Nervous System Side Effects Through Drug Permeability to Blood-Brain Barrier and Recommendation Algorithm.

PubMed

Fan, Jun; Yang, Jing; Jiang, Zhenran

2018-04-01

Drug side effects are one of the public health concerns. Using powerful machine-learning methods to predict potential side effects before the drugs reach the clinical stages is of great importance to reduce time consumption and protect the security of patients. Recently, researchers have proved that the central nervous system (CNS) side effects of a drug are closely related to its permeability to the blood-brain barrier (BBB). Inspired by this, we proposed an extended neighborhood-based recommendation method to predict CNS side effects using drug permeability to the BBB and other known features of drug. To the best of our knowledge, this is the first attempt to predict CNS side effects considering drug permeability to the BBB. Computational experiments demonstrated that drug permeability to the BBB is an important factor in CNS side effects prediction. Moreover, we built an ensemble recommendation model and obtained higher AUC score (area under the receiver operating characteristic curve) and AUPR score (area under the precision-recall curve) on the data set of CNS side effects by integrating various features of drug.

An Ensemble Approach for Drug Side Effect Prediction

PubMed Central

Jahid, Md Jamiul; Ruan, Jianhua

2014-01-01

In silico prediction of drug side-effects in early stage of drug development is becoming more popular now days, which not only reduces the time for drug design but also reduces the drug development costs. In this article we propose an ensemble approach to predict drug side-effects of drug molecules based on their chemical structure. Our idea originates from the observation that similar drugs have similar side-effects. Based on this observation we design an ensemble approach that combine the results from different classification models where each model is generated by a different set of similar drugs. We applied our approach to 1385 side-effects in the SIDER database for 888 drugs. Results show that our approach outperformed previously published approaches and standard classifiers. Furthermore, we applied our method to a number of uncharacterized drug molecules in DrugBank database and predict their side-effect profiles for future usage. Results from various sources confirm that our method is able to predict the side-effects for uncharacterized drugs and more importantly able to predict rare side-effects which are often ignored by other approaches. The method described in this article can be useful to predict side-effects in drug design in an early stage to reduce experimental cost and time. PMID:25327524

The use of fungal entomopathogens as endophytes in biological control: a review

USDA-ARS?s Scientific Manuscript database

Fungal entomopathogens have been proposed as environmentally friendly alternatives to chemical control. Unfortunately, their effectiveness continues to be limited by their susceptibility to UV light, low moisture, etc. A relatively recent development, the use of fungal entomopathogens as endophytes,...

Migration effects on population dynamics of the honeybee-mite interactions

USDA-ARS?s Scientific Manuscript database

Honeybees are amazing and highly beneficial insect species that play important roles in undisturbed and agricultural ecosystems. Unfortunately, honeybees are increasingly threatened by numerous factors, most notably the parasitic Varroa mite (Varroa destructor Anderson and Trueman). A recent field s...

A PORTABLE MICROREACTOR SYSTEM TO SYNTHESIZE HYDROGEN PEROXIDE - PHASE I

EPA Science Inventory

In the event that vehicles of buildings become contaminated by hazardous chemical or biological materials, a well-studied and effective decontaminant is hydrogen peroxide vapor (HPV).  Unfortunately, the current technology for generating HPV requires 35 weight percent hydro...

Encyclopedia of Terrorism.

ERIC Educational Resources Information Center

Combs, Cindy C.; Slann, Martin

As recent terrorist attacks on the United States, such as the Oklahoma City (Oklahoma) bombing, and the ongoing conflicts in the Middle East have shown, terrorism is an unfortunate reality that can have potentially devastating effects on governments, businesses, and individuals. This encyclopedia provides students, researchers, journalists, and…

Bernoulli? Perhaps, but What about Viscosity?

ERIC Educational Resources Information Center

Eastwell, Peter

2007-01-01

Bernoulli's principle is being misunderstood and consequently misused. This paper clarifies the issues involved, hypothesises as to how this unfortunate situation has arisen, provides sound explanations for many everyday phenomena involving moving air, and makes associated recommendations for teaching the effects of moving fluids.

A Systematic Framework for Addressing Treatment Integrity in School Settings

ERIC Educational Resources Information Center

Kupzyk, Sara; Shriver, Mark D.

2016-01-01

School psychologists are tasked with ensuring treatment integrity because the level of intervention implementation affects decisions about student progress. Treatment integrity includes multiple dimensions that may impact the effectiveness of an intervention including adherence, dosage, quality, and engagement. Unfortunately, treatment integrity…

The side-effects to CPAP treatment inventory: the development and initial validation of a new tool for the measurement of side-effects to CPAP treatment.

PubMed

Broström, Anders; Arestedt, Kristofer Franzén; Nilsen, Per; Strömberg, Anna; Ulander, Martin; Svanborg, Eva

2010-12-01

Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea syndrome (OSAS), but side-effects are common. No validated self-rating scale measuring side-effects to CPAP treatment exists today. The aim was to develop the side-effects to CPAP treatment inventory (SECI), and investigate the validity and reliability of the instrument among patients with OSAS. SECI was developed on the basis of: (1) in-depth interviews with 23 patients; (2) examination of the scientific literature and (3) consensus agreement of a multi-professional expert panel. This yielded 15 different types of side-effects related to CPAP treatment. Each side-effect has three sub-questions (scales): perceived frequency (a) and magnitude (b) of the side-effect, as well as its perceived impact on CPAP use (c). A cross-sectional descriptive design was used. A total of 329 patients with OSAS with an average use of CPAP treatment for 39 months (2 weeks to 182 months) were recruited. Data were collected with SECI, and obtained from medical records (clinical variables and data related to CPAP treatment). Construct validity was confirmed with factor analysis (principal component analysis with orthogonal rotation). A logical two-factor solution, the device subscale and symptom subscale, emerged across all three scales. The symptom subscale describing physical and psychological side-effects and the device subscale described mask and device-related side-effects. Internal consistency reliability of the three scales was good (Cronbach's α = 0.74-0.86) and acceptable for the subscales (Cronbach's α = 0.62-0.86). The satisfactory measurement properties of this new instrument are promising and indicate that SECI can be used to measure side-effects to CPAP treatment. © 2010 European Sleep Research Society.

Relating drug–protein interaction network with drug side effects

PubMed Central

Mizutani, Sayaka; Pauwels, Edouard; Stoven, Véronique; Goto, Susumu; Yamanishi, Yoshihiro

2012-01-01

Motivation: Identifying the emergence and underlying mechanisms of drug side effects is a challenging task in the drug development process. This underscores the importance of system–wide approaches for linking different scales of drug actions; namely drug-protein interactions (molecular scale) and side effects (phenotypic scale) toward side effect prediction for uncharacterized drugs. Results: We performed a large-scale analysis to extract correlated sets of targeted proteins and side effects, based on the co-occurrence of drugs in protein-binding profiles and side effect profiles, using sparse canonical correlation analysis. The analysis of 658 drugs with the two profiles for 1368 proteins and 1339 side effects led to the extraction of 80 correlated sets. Enrichment analyses using KEGG and Gene Ontology showed that most of the correlated sets were significantly enriched with proteins that are involved in the same biological pathways, even if their molecular functions are different. This allowed for a biologically relevant interpretation regarding the relationship between drug–targeted proteins and side effects. The extracted side effects can be regarded as possible phenotypic outcomes by drugs targeting the proteins that appear in the same correlated set. The proposed method is expected to be useful for predicting potential side effects of new drug candidate compounds based on their protein-binding profiles. Supplementary information: Datasets and all results are available at http://web.kuicr.kyoto-u.ac.jp/supp/smizutan/target-effect/. Availability: Software is available at the above supplementary website. Contact: yamanishi@bioreg.kyushu-u.ac.jp, or goto@kuicr.kyoto-u.ac.jp PMID:22962476

Variations in judgments of intentional action and moral evaluation across eight cultures.

PubMed

Robbins, Erin; Shepard, Jason; Rochat, Philippe

2017-07-01

Individuals tend to judge bad side effects as more intentional than good side effects (the Knobe or side-effect effect). Here, we assessed how widespread these findings are by testing eleven adult cohorts of eight highly contrasted cultures on their attributions of intentional action as well as ratings of blame and praise. We found limited generalizability of the original side-effect effect, and even a reversal of the effect in two rural, traditional cultures (Samoa and Vanuatu) where participants were more likely to judge the good side effect as intentional. Three follow-up experiments indicate that this reversal of the side-effect effect is not due to semantics and may be linked to the perception of the status of the protagonist. These results highlight the importance of factoring cultural context in our understanding of moral cognition. Copyright © 2017. Published by Elsevier B.V.

Side-effects of topical steroids: A long overdue revisit.

PubMed

Coondoo, Arijit; Phiske, Meghana; Verma, Shyam; Lahiri, Koushik

2014-10-01

The introduction of topical steroids (TS) of varying potency have rendered the therapy of inflammatory cutaneous disorders more effective and less time-consuming. However the usefulness of these has become a double edged sword with constantly rising instances of abuse and misuse leading to serious local, systemic and psychological side effects. These side effects occur more with TS of higher potency and on particular areas of the body like face and genitalia. The article reviews the side effects of TS with special mention about peadiatric age group, also includes the measures for preventing the side effects.

Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens

PubMed Central

Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

2015-01-01

Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn’t mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the “old” IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues guiding treatment indication in the next future. The sooner we will change our mind with respect to an a priori obstacle for anti-HCV treatment in the elderly, the sooner we will begin to spare many aged HCV patients from avoidable liver-related complications. PMID:26139987

Hepatitis C treatment in the elderly: New possibilities and controversies towards interferon-free regimens.

PubMed

Vespasiani-Gentilucci, Umberto; Galati, Giovanni; Gallo, Paolo; De Vincentis, Antonio; Riva, Elisabetta; Picardi, Antonio

2015-06-28

Due to the progressive aging of the hepatitis C virus (HCV) population which have acquired the infection during its maximum spread after the Second World War, the management of the elderly HCV-infected patient is emerging as a hot topic. Unfortunately, although it is recognized that the progression of HCV-related liver disease gets faster with aging, and that even extra-hepatic manifestations of HCV infection are probably worse in the elderly, till now, treatment attempts in this population have been significantly limited by the well-known contraindications and side effects of interferon (IFN). The arrival of several new anti-HCV drugs, and the possibility to combine them in safe and effective anti-viral regimens, is relighting the hope of a cure for many elderly patients who had been cut out of IFN-based treatments. However, although these new regimens will be certainly more manageable, it should be underscored that IFN-free doesn't mean free from any contraindication or side-effect. Moreover, one issue which promises to become central is that of the possible interactions between antiviral therapy and the multiple drugs frequently assumed by elderly patients because of comorbidities. In this review, we will revise the epidemiology pointing to HCV as an infection of the elderly, the evidences that HCV harms the health of the aged patient more than that of the young one, and the available experiences of HCV treatment in the elderly with the "old" IFN-based regimens and with the newer drugs. We will conclude that the availability of IFN-free regimens should prompt us to change our mind and consider a significantly larger number of possible candidates among elderly patients, who would take significant advantage from viral eradication. Rather than the anagraphic age, drug-drug interactions and, mainly in case of economic restrictions, an evaluation of life expectancy dependent on liver disease with respect to that dependent on comorbidities, are likely to be the key issues guiding treatment indication in the next future. The sooner we will change our mind with respect to an a priori obstacle for anti-HCV treatment in the elderly, the sooner we will begin to spare many aged HCV patients from avoidable liver-related complications.

Effectiveness and side-effect profile of stimulant therapy as monotherapy and in combination in the central hypersomnias in clinical practice.

PubMed

Thakrar, Chiraag; Patel, Kishankumar; D'ancona, Grainne; Kent, Brian D; Nesbitt, Alexander; Selsick, Hugh; Steier, Joerg; Rosenzweig, Ivana; Williams, Adrian J; Leschziner, Guy D; Drakatos, Panagis

2017-10-19

Effectiveness and side-effect profile data on pharmacotherapy for daytime sleepiness in central hypersomnias are based largely upon randomized controlled trials. Evidence regarding the use of combination therapy is scant. The aim of this study was to examine the effectiveness and occurrence of drug-related side effects of these drugs in routine clinical practice. Adult patients diagnosed with a central hypersomnia during a 54-month period at a tertiary sleep disorders centre were identified retrospectively. Side effects were recorded at every follow-up visit. A total of 126 patients, with 3275 patient-months of drug exposure, were categorized into narcolepsy type 1 (n = 70), narcolepsy type 2 (n = 47) and idiopathic hypersomnia (n = 9). Modafinil was the most common drug used as a first-line treatment (93%) and in combination therapy (70%). Thirty-nine per cent of the patients demonstrated a complete, 25% partial and 36% a poor response to treatment. Combination treatment improved daytime sleepiness in 55% of the patients with residual symptoms despite monotherapy. Sixty per cent of patients reported side effects, and 30% reported treatment-limiting side effects. Drugs had similar side-effect incidence (P = 0.363) and their side-effect profile met those reported in the literature. Twenty-seven per cent of the patients received combination treatment and had fewer side effects compared to monotherapy (29.4% versus 60%, respectively, P = 0.001). Monotherapy appears to achieve satisfactory symptom control in most patients with central hypersomnia, but significant side effects are common. Combination therapy appears to be a useful and safe option in patients with refractory symptoms. © 2017 European Sleep Research Society.

Comparison of various approaches for the treatment of fractures of the mandibular condylar process.

PubMed

Handschel, Jörg; Rüggeberg, Tim; Depprich, Rita; Schwarz, Frank; Meyer, Ulrich; Kübler, Norbert R; Naujoks, Christian

2012-12-01

Fractures of the mandibular condyle process are the most common fractures of the lower jaw. Unfortunately, the type of treatment is still a matter of debate. The aim of this investigation was to compare the outcome of different treatment approaches regarding function and surgical side-effects. 111 fractures of the mandibular condyle representing all types according to the classification of Spiessl and Schroll were included. Both closed reduction (CR) and open reduction with internal fixation (ORIF) including the retromandibular/transparotid, submandibular, preauricular and intraoral approach were performed. The clinical examination included functional and aesthetic aspects at least 1 year after the fracture. The majority of fractures (45%) were classified into Type II and IV according to Spiessl and Schroll followed by fractures without any displacement or dislocation (29.7%). The submandibular approach showed the worst outcome regarding permanent palsy of the facial nerve and hypertrophic scarring. No significant differences between the various approaches were detected in the functional status in any diagnosis group. Inferior condylar neck fractures benefit from ORIF by an intraoral approach whereas in high condylar neck fractures the retromandibular/transparotid approach shows the best results. Fractures of the condylar head were almost all treated by CR and our results cannot contribute to the debate of CR vs. ORIF in this type of fracture. Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

An analysis of the 'legal high' mephedrone.

PubMed

Gibbons, Simon; Zloh, Mire

2010-07-15

'Legal highs' are compounds, plant or fungal material which can be readily bought from the internet without legal restriction and the single chemicals may be structurally related to illegal drugs of abuse such as the amphetamines. Several recent deaths in the UK have been attributed to these legal highs and unfortunately there is little chemical or biological literature on these materials or certified standards. Here, we detail the analysis of the widely consumed synthetic N-methyl-cathinone analogue known as mephedrone ((1) 2-aminomethyl-1-tolyl-propan-1-one (4'-methylmethcathinone)) and report its spectral data and molecular properties. Material was purchased from an internet site and examined by extensive one- and two-dimensional NMR studies, high-resolution mass spectrometry, elemental analysis and optical rotation, which demonstrated the sample to be of high purity and racemic in nature. Additionally, we report the molecular modelling properties of methyl-cathinones and compare them to their corresponding methyl-amphetamine series. This indicated that the methyl-cathinones are considerably more hydrophilic than the methyl-amphetamines which may account for the higher doses that are needed to demonstrate similar effects. The presence of a ketone in the side chain introduces a far more planar quality to the methyl-cathinones which is absent in the methyl-amphetamine series, and this planarity may contribute to toxicity. 2010 Elsevier Ltd. All rights reserved.

Moving from recycling to waste prevention: A review of barriers and enables.

PubMed

Bartl, Andreas

2014-09-01

Current European waste policy does not mainly aim to treat waste streams but rather place in the foreground of interest the complete supply chain of a product. Waste prevention and re-use do have the highest priority and they take effect before the end-of-life phase of a product or a material is reached. Recycling only takes the third place whereas recovery and disposal represent the least favourable options. Recycling can help to decrease the consumption of primary resources but it does not tackle the causes but only the symptoms. In principle, recycling processes require energy and will generate side streams (i.e. waste). Furthermore, there are insuperable barriers and the practice is far from 100% recycling. The philosophy of waste prevention and re-use is completely different since they really tackle the causes. It is self-evident that a decrease of waste will also decrease the consumption of resources, energy and money to process the waste. However, even if European legislation is proceeding in the right direction, a clear decrease in waste generation did not occur up to now. Unfortunately, waste generation represents a positive factor of economic growth. Basically, waste generation is a huge business and numerous stakeholders are not interested to reduce waste. More sophisticated incentives are required to decouple economic growth from waste generation. © The Author(s) 2014.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management.

PubMed

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%.

Hepatitis C infection in patients with hereditary bleeding disorders: epidemiology, natural history, and management

PubMed Central

Papadopoulos, Nikolaos; Argiana, Vasiliki; Deutsch, Melanie

2018-01-01

Hereditary bleeding disorders include a group of diseases with abnormalities of coagulation. Prior to 1990, infection with hepatitis C virus (HCV) was mainly transmitted via pooled plasma products as a treatment for hereditary bleeding disorders. Anti-HCV positivity in these patients may be as high as >70% in some areas, while some of them have also been coinfected with human immunodeficiency virus. Since about 20% of HCV-infected patients clear the infection naturally, chronic HCV infection represents a significant health problem in this group of patients. Mortality due to chronic HCV infection is estimated to be >10 times higher in patients with hemophilia than in the general population, and is mainly due to liver cirrhosis and hepatocellular carcinoma. The antiviral treatment of HCV in patients with hereditary bleeding disorders is not different from that of any other infected patients. Nevertheless, many patients with hereditary bleeding disorders have declined (Peg)interferon-based treatment because of side effects. In recent years, multiple orally administrated direct-acting antivirals (DAAs) have been approved for HCV treatment. Unfortunately, there is not much experience from treating these patients with DAA regimens, as major studies and real-life data did not include adequate numbers of patients with inherited hemorrhagic disorders. However, the available data indicate that DAAs have an excellent safety profile with a sustained virological response rate of >90%. PMID:29333065

Pharmacological treatment of diabetes in older people.

PubMed

Valencia, W M; Florez, H

2014-12-01

The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents. © 2014 John Wiley & Sons Ltd.

High frequency source localization in a shallow ocean sound channel using frequency difference matched field processing.

PubMed

Worthmann, Brian M; Song, H C; Dowling, David R

2015-12-01

Matched field processing (MFP) is an established technique for source localization in known multipath acoustic environments. Unfortunately, in many situations, particularly those involving high frequency signals, imperfect knowledge of the actual propagation environment prevents accurate propagation modeling and source localization via MFP fails. For beamforming applications, this actual-to-model mismatch problem was mitigated through a frequency downshift, made possible by a nonlinear array-signal-processing technique called frequency difference beamforming [Abadi, Song, and Dowling (2012). J. Acoust. Soc. Am. 132, 3018-3029]. Here, this technique is extended to conventional (Bartlett) MFP using simulations and measurements from the 2011 Kauai Acoustic Communications MURI experiment (KAM11) to produce ambiguity surfaces at frequencies well below the signal bandwidth where the detrimental effects of mismatch are reduced. Both the simulation and experimental results suggest that frequency difference MFP can be more robust against environmental mismatch than conventional MFP. In particular, signals of frequency 11.2 kHz-32.8 kHz were broadcast 3 km through a 106-m-deep shallow ocean sound channel to a sparse 16-element vertical receiving array. Frequency difference MFP unambiguously localized the source in several experimental data sets with average peak-to-side-lobe ratio of 0.9 dB, average absolute-value range error of 170 m, and average absolute-value depth error of 10 m.

Oxaliplatin-induced Oxidative Stress Provokes Toxicity in Isolated Rat Liver Mitochondria.

PubMed

Tabassum, Heena; Waseem, Mohammad; Parvez, Suhel; Qureshi, M Irfan

2015-11-01

Oxaliplatin is a widely employed platinum-derived chemotherapeutic agent commonly used for the treatment of colorectal cancer. Unfortunately, the benefit of this important drug is compromised by severe side effects such as neuropathy, ototoxicity, gastrointestinal toxicity, and hematological toxicity. Recently, few studies have also suggested the occurrence of hepatotoxicity in oxaliplatin-treated patients. Mitochondria have emerged as targets for anticancer drugs in various kinds of toxicity including hepatotoxicity that can lead to neoplastic disease. Oxidative stress is a well-established biomarker of mitochondrial toxicity. The purpose of this study was to investigate the dose-dependent damage caused by oxaliplatin on isolated liver mitochondria under in vitro conditions. The study was conducted in mitochondria isolated from liver of Wistar rats. Oxaliplatin was incubated with mitochondria in a dose-dependent manner under in vitro conditions. Oxidative stress indexes, non-enzymatic and enzymatic antioxidants were evaluated, looking at the overall armamentarium against the toxicity induced by oxaliplatin. Oxaliplatin caused a significant rise in the mitochondrial oxidative stress indexes lipid peroxidation and protein carbonyl. Alterations in the levels of non-enzymatic antioxidants and activities of enzymatic antioxidants were also observed. Oxidative stress plays an important role in the mitochondrial toxicity of oxaliplatin. The integrity of the hepatic tissue is compromised by the reactive oxygen species-mediated lipid peroxidation and protein carbonyl formation. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Winter cover crop effect on corn seedling pathogens

USDA-ARS?s Scientific Manuscript database

Cover crops are an excellent management tool to improve the sustainability of agriculture. Winter rye cover crops have been used successfully in Iowa corn-soybean rotations. Unfortunately, winter rye cover crops occasionally reduce yields of the following corn crop. We hypothesize that one potential...

Improving Teaching, One Conversation at a Time

ERIC Educational Resources Information Center

Arneson, Shelly

2015-01-01

Both speaking and listening are essential to effective communication. Unfortunately, meaningful two-way exchanges are largely absent from conversations about improving professional practice. Instead, many teachers say that they feel the observation and evaluation process is something that is done "to" them--at the post-observation…

How chemical ripeners of sugarcane affect the starch and color quality of juices

USDA-ARS?s Scientific Manuscript database

The application of chemical ripeners is an important component of sugarcane cultivation management to increase sucrose concentrations. Unfortunately, very little information is available concerning the effects of ripener on quality parameters which are critical to both factory and refinery processi...

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Health care resource use and costs associated with possible side effects of high oral corticosteroid use in asthma: a claims-based analysis.

PubMed

Luskin, Allan T; Antonova, Evgeniya N; Broder, Michael S; Chang, Eunice Y; Omachi, Theodore A; Ledford, Dennis K

2016-01-01

The objective of this study was to estimate the prevalence of possible oral corticosteroid (OCS)-related side effects and health care resource use and costs in patients with asthma. This was a cross-sectional, matched-cohort, retrospective study using a commercial claims database. Adults with asthma diagnosis codes and evidence of asthma medication use were studied. Patients with high OCS use (≥30 days of OCS annually) were divided into those who did versus those who did not experience OCS-related possible side effects. Their health care resource use and costs were compared using linear regression or negative binomial regression models, adjusting for age, sex, geographic region, Charlson Comorbidity Index score, and chronic obstructive pulmonary disease status. After adjustment, high OCS users with possible side effects were more likely to have office visits (23.0 vs 19.6; P <0.001) and hospitalizations (0.44 vs 0.22; P <0.001) than those without possible side effects. Emergency department visits were similar between the groups. High OCS users with possible side effects had higher adjusted total annual mean health care costs ($25,168) than those without such side effects ($21,882; P =0.009). Among high OCS users, patients with possible OCS-related side effects are more likely to use health care services than those without such side effects. Although OCS may help control asthma and manage exacerbations, OCS side effects may result in additional health care resource use and costs, highlighting the need for OCS-sparing asthma therapies.

An infrared divergence in the cosmological measure theory and the anthropic reasoning

NASA Astrophysics Data System (ADS)

Yurov, A. V.; Yurov, V. A.; Astashenok, A. V.; Shpilevoi, A. A.

2011-10-01

An anthropic principle has made it possible to answer the difficult question of why the observable value of cosmological constant ( Λ˜10-47 GeV4) is so disconcertingly tiny compared to the predicted value of vacuum energy density ρ SUSY˜1012 GeV4. Unfortunately, there is a darker side to this argument; being combined with the cosmic heat death scenario, it consequently leads to another absurd prediction: the probability of randomly selected observer observing Λ=0 ends up being exactly equal to 1. We shall call this controversy an infrared divergence problem. It is shown that the IRD prediction can be avoided with the help of a singular runaway measure coupled with the calculation of relative Bayesian probabilities by the means of the doomsday argument. Moreover, it is shown that while the IRD problem occurs for the prediction stage of value of Λ, it disappears at the explanatory stage when Λ has already been measured by the observer.

High-reliability GaAs image intensifier with unfilmed microchannel plate

NASA Astrophysics Data System (ADS)

Bender, Edward J.; Estrera, Joseph P.; Ford, C. E.; Giordana, A.; Glesener, John W.; Lin, P. P.; Nico, A. J.; Sinor, Timothy W.; Smithson, R. H.

1999-07-01

Current GaAs image intensifier technology requires that the microchannel plate (MCP) have a thin dielectric film on the side facing the photocathode. This protective coating substantially reduces the amount of outgassing of ions and neutral species from the microchannels. The prevention of MCP outgassing is necessary in order to prevent the `poisoning' of the Cs:O surface on the GaAs photocathode. Many authors have experimented with omitting the MCP coating. The results of such experiments invariably lead to an intensifier with a reported useful life of less than 100 hours, due to contamination of the Cs:O layer on the photocathode. Unfortunately, the MCP film is also a barrier to electron transport within the intensifier. Substantial enhancement of the image intensifier operating parameters is the motivation for the removal of the MCP film. This paper presents results showing for the first time that it is possible to fabricate a long lifetime image intensifier with a single uncoated MCP.

Aid in a city at war: the case of Mogadishu, Somalia.

PubMed

Grünewald, François

2012-07-01

Mogadishu, the capital of Somalia, has been central to life, war, and peace in the country for almost two decades. Its urban characteristics, though, have been put to one side for the most part. In recent years, Mogadishu-related issues have been merged mostly into a global agenda for South and Central Somalia, resulting in the technical and coordination approaches employed in the city largely being reproductions of solutions utilised in refugee camps and rural areas. Unfortunately, urban problems require urban solutions. The aid system is just starting to discover how specific aid in cities at war should be, both from an organisational and a technical standpoint. The enhancement of aid practices in an urban setting implies, among other things, a more strategic approach to the specific spatial characteristics of the city, a more fine-tuned analysis of the technical requirements of the urban service delivery systems, and a better understanding of the role of urban institutions. © 2012 The Author(s). Journal compilation © Overseas Development Institute, 2012.

Coming Climate Crisis? Perhaps, but Beware the Solutions

NASA Technical Reports Server (NTRS)

Parkinson, Claire L.

2010-01-01

Over the past several decades, there has been a growing awareness that climate changes in substantial ways, that human activities are having an impact on climate change, and that climate change can have major consequences for human societies. Unfortunately, along with this realization has come a strong polarization within the scientific community and outside of it regarding what if anything should be done to reduce negative human impacts and/or to attempt to control climate. This book places recent climate change in the context of the very long term history of change on planet Earth and warns that our understanding of climate change remains sufficiently incomplete that we should be extremely cautious about implementing proposed massive geoengineering schemes intended to alter future climate conditions. The book treats with respect the various viewpoints in the highly polarized discussions regarding climate change, following a basic assumption that the major scientists on each side of the issues have valuable points to bring to the table. The topic is too important to become endlessly mired in contentious polarization.

The economic cost of adverse health effects from wildfire-smoke exposure: A review

Treesearch

Ikuho Kochi; Geoffrey H. Donovan; Patricia A. Champ; John B. Loomis

2010-01-01

The economic costs of adverse health effects associated with exposure to wildfire smoke should be given serious consideration in determining the optimal wildfire management policy. Unfortunately, the literature in this research area is thin. In an effort to better understand the nature of these economic costs, we review and synthesise the relevant literature in three...

Great Principals at Scale: Creating District Conditions That Enable All Principals to Be Effective. Executive Summary

ERIC Educational Resources Information Center

Ikemoto, Gina; Taliaferro, Lori; Fenton, Benjamin; Davis, Jacquelyn

2014-01-01

School leaders are critical in the lives of students and to the development of their teachers. Unfortunately, in too many instances, principals are effective in spite of--rather than because of--district conditions. To truly improve student achievement for all students across the country, well-prepared principals need the tools, support, and…

Can Good Principals Keep Teachers in Disadvantaged Schools? Linking Principal Effectiveness to Teacher Satisfaction and Turnover in Hard-to-Staff Environments

ERIC Educational Resources Information Center

Grissom, Jason A.

2011-01-01

Background: High rates of teacher turnover likely mean greater school instability, disruption of curricular cohesiveness, and a continual need to hire inexperienced teachers, who typically are less effective, as replacements for teachers who leave. Unfortunately, research consistently finds that teachers who work in schools with large numbers of…

Environmental effects on pine tree carbon budgets and resistance to bark beetles

Treesearch

Richard T. Wilkens; Matthew P. Ayres; Peter L. Lorio; John D. Hodges

1998-01-01

Our results indicate that increased nutrient availability leads to an increase in growth and a reduction in resin-based defenses.Because of this, we recommend that foresters and planners consider the effect of fertilization and site fertility on both tree growth and SPB risk.Unfortunately, increased tree growth may frequently be associated with increased SPB risk.The...

Physical Education Teachers' Perceptions about the Effectiveness and Acceptability of Strategies Used to Increase Relevance and Choice for Students in Physical Education Classes

ERIC Educational Resources Information Center

Bennie, Andrew; Peralta, Louisa; Gibbons, Sandra; Lubans, David; Rosenkranz, Richard

2017-01-01

School physical education (PE) aims to develop students' knowledge and skills for lifelong participation in physical activity (PA). Unfortunately, many PE teachers report that motivating students is a significant challenge. The purpose of this study was to explore PE teacher perceptions about the effectiveness and acceptability of three…

Microcomputer software for calculating an elk habitat effectiveness index on Blue Mountain winter ranges.

Treesearch

Mark Hitchcock; Alan Ager

1992-01-01

National Forests in the Pacific Northwest Region have incorporated elk habitat standards into Forest plans to ensure that elk habitat objectives are met on multiple use land allocations. Many Forests have employed versions of the habitat effectiveness index (HEI) as a standard method to evaluate habitat. Field application of the HEI model unfortunately is a formidable...

Immunotoxin Targeting Glypican-3 Effective against Liver Tumors | Center for Cancer Research

Cancer.gov

Worldwide, liver cancer is the fifth most common malignancy, and hepatocellular carcinoma (HCC) makes up about two-thirds of those cases. Unfortunately, surgery is still the most effective treatment for HCC but is only available to patients diagnosed at early stages. HCC is known for being particularly drug resistant, sorafenib being the only FDA-approved chemotherapy

'Designer drugs'. Recognizing and managing their toxic effects.

PubMed

Sternbach, G L; Varon, J

1992-06-01

"Adam," "Eve," "ecstasy," "China white." Illicit street drugs such as these are called designer drugs because they are designed to elicit certain effects and to bypass legal classification. Unfortunately, use and abuse of such substances can lead to serious medical problems and even death. Drs Sternbach and Varon describe the best-known compounds and discuss clinical characteristics and management of designer drug intoxication.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia.

PubMed

Dibonaventura, Marco; Gabriel, Susan; Dupclay, Leon; Gupta, Shaloo; Kim, Edward

2012-03-20

Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia.

A patient perspective of the impact of medication side effects on adherence: results of a cross-sectional nationwide survey of patients with schizophrenia

PubMed Central

2012-01-01

Background Antipsychotic medications often have a variety of side effects, however, it is not well understood how the presence of specific side effects correlate with adherence in a real-world setting. The aim of the current study was to examine the relationship between these variables among community-dwelling patients with schizophrenia. Methods Data were analyzed from a 2007-2008 nationwide survey of adults who self-reported a diagnosis of schizophrenia and were currently using an antipsychotic medication (N = 876). The presence of side effects was defined as those in which the patient reported they were at least "somewhat bothered". Adherence was defined as a score of zero on the Morisky Medication Adherence Scale. To assess the relationship between side effects and adherence, individual logistic regression models were fitted for each side effect controlling for patient characteristics. A single logistic regression model assessed the relationship between side effect clusters and adherence. The relationships between adherence and health resource use were also examined. Results A majority of patients reported experiencing at least one side effect due to their medication (86.19%). Only 42.5% reported complete adherence. Most side effects were associated with a significantly reduced likelihood of adherence. When grouped as side effect clusters in a single model, extra pyramidal symptoms (EPS)/agitation (odds ratio (OR) = 0.57, p = 0.0007), sedation/cognition (OR = 0.70, p = 0.033), prolactin/endocrine (OR = 0.69, p = 0.0342), and metabolic side effects (OR = 0.64, p = 0.0079) were all significantly related with lower rates of adherence. Those who reported complete adherence to their medication were significantly less likely to report a hospitalization for a mental health reason (OR = 0.51, p = 0.0006), a hospitalization for a non-mental health reason (OR = 0.43, p = 0.0002), and an emergency room (ER) visit for a mental health reason (OR = 0.60, p = 0.008). Conclusions Among patients with schizophrenia, medication side effects are highly prevalent and significantly associated with medication nonadherence. Nonadherence is significantly associated with increased healthcare resource use. Prevention, identification, and effective management of medication-induced side effects are important to maximize adherence and reduce health resource use in schizophrenia. PMID:22433036

Development of a New Self-Reporting Instrument Measuring Benefits and Side Effects of Corticosteroids in Duchenne Muscular Dystrophy: Report from a Pilot Study.

PubMed

Hendriksen, Ruben G F; Lionarons, Judith M; Hendriksen, Jos G M; Vles, Johan S H; McAdam, Laura C; Biggar, W Douglas

There is no cure for Duchenne Muscular Dystrophy (DMD); treatment is symptomatic and corticosteroids slow the progression. Side effects of corticosteroids - especially the physical effects - have been described, however patients' and caregivers perception on chronic corticosteroid treatment and their side effects is less well known, in particular with regards to cognition, behaviour, and emotional functioning. The primary aim of this pilot study was to (i) construct a self-report questionnaire to assess the perceived benefits and side effects of corticosteroids for patients with DMD and their parents. Furthermore we aimed to (ii) investigate the psychometric qualities of this questionnaire, (iii) whether there was a difference between parents' and patient's perceptions, and finally (iv) to what extent reported side effects may alter over time. A 23-item questionnaire (SIDECORT: side effect of corticosteroids) was constructed to assess the perception of these benefits and side effects in a systematic manner. In total, 86 patients (aged 5 - 28 years) and 125 of their parents completed the questionnaire. Internal consistency was good. Using factor analyses on the side effect items as reported by parents, two underlying factors were found, with the first factor describing cognitive, behavioural and emotional functioning, and the second factor describing physical functioning. The potential benefits of corticosteroids were highly rated among both parents and patients, although parents rated the importance of the benefits higher than their sons (p = 0.002). Similarly, parents rated the severity of the side effects generally higher than their sons (p = 0.011), especially with regards to the physical side effects (p = 0.014). Based on the parent's perception, the neurodevelopmental side effects generally appeared to decline the longer corticosteroids were used. To our knowledge, this is the first explicit study on perceived cognitive-, behavioural-, and emotional side effects and the allocation of benefits to corticosteroids in DMD. On the basis of our research we suggest a short form questionnaire, which proves to be reliable and valid for research- and clinical practice. This questionnaire could provide useful insights for the care of boys and men with DMD.

Central nervous system side effects associated with zolpidem treatment.

PubMed

Toner, L C; Tsambiras, B M; Catalano, G; Catalano, M C; Cooper, D S

2000-01-01

Zolpidem is one of the newer medications developed for the treatment of insomnia. It is an imidazopyridine agent that is an alternative to the typical sedative-hypnotic agents. Zolpidem use is gaining favor because of its efficacy and its side effect profile, which is milder and less problematic than that of the benzodiazepines and barbiturates used to treat insomnia. Still, side effects are not uncommon with zolpidem use. We report a series of cases in which the patients developed delirium, nightmares and hallucinations during treatment with zolpidem. We will review its pharmacology, discuss previous reports of central nervous system side effects, examine the impact of drug interactions with concurrent use of antidepressants, examine gender differences in susceptibility to side effects, and explore the significance of protein binding in producing side effects.

"Side effects affected my daily activities a lot": a qualitative exploration of the impact of contraceptive side effects in Bangladesh.

PubMed

Jain, Aparna; Reichenbach, Laura; Ehsan, Iqbal; Rob, Ubaidur

2017-01-01

In a country like Bangladesh that has made great progress in contraceptive use with one of the lowest levels of fertility and highest levels of contraceptive use, understanding what factors influence women's decisions to discontinue a contraceptive method and not switch to a new method is critical in designing interventions and programs that will help enable Bangladesh to reach its FP2020 goals. Research on side effects has focused on physical manifestations like headaches, moodiness, abdominal pain, and menstrual irregularities. While physical effects alone may stop women from continuing a contraceptive method, less is known about how side effects influence women's daily activities and lives. The purpose of this study is to understand the ways that side effects affect Bangladeshi women's participation in different social settings. Thirty-five in-depth interviews with married women who recently discontinued or switched to a different contraceptive method were conducted in Sylhet and Khulna Divisions. Interviews explored reasons for discontinuation including experience of side effects and impact of side effects on women's lives. Key themes emerged including that side effects are not only experienced physically but are barriers to women's participation in many aspects of their lives. The spheres of life that most commonly appeared to be influenced by side effects include religion, household, and sexual intimacy irrespective of method used or residence. Family planning providers need to be aware of these additional consequences associated with contraceptive side effects to provide tailored counseling that recognizes these issues and helps women to mitigate them. For Bangladesh to achieve its FP2020 goals, understanding the broader context in which family planning decisions are made vis-à-vis side effects is critical to design programs and interventions that meet all the needs of women beyond just their fertility intentions.

Morin protects gastric mucosa from nonsteroidal anti-inflammatory drug, indomethacin induced inflammatory damage and apoptosis by modulating NF-κB pathway.

PubMed

Sinha, Krishnendu; Sadhukhan, Pritam; Saha, Sukanya; Pal, Pabitra Bikash; Sil, Parames C

2015-04-01

Deregulation in prostaglandin (PG) biosynthesis, severe oxidative stress, inflammation and apoptosis contribute to the pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. Unfortunately, most of the prescribed anti-ulcer drugs generate various side effects. In this scenario, we could consider morin as a safe herbal potential agent against IND-gastropathy and rationalize its action systematically. Rats were pretreated with morin for 30 min followed by IND (48 mgkg(-1)) administration for 4 h. The anti-ulcerogenic nature of morin was assessed by morphological and histological analysis. Its effects on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COXs, PGE(2)), and signaling parameters (NF-κB and apoptotic signaling) were assessed by biochemical, RP-HPLC, immunoblots, IHC, RT-PCR, and ELISA at the time points of their maximal changes due to IND administration. IND induced NF-κB and apoptotic signaling in rat's gastric mucosa. These increased proinflammatory responses, but reduced the antioxidant enzymes and other protective factors. Morin reversed all the adverse effects to prevent IND-induced gastric ulceration in a PGE2 independent manner. Also, it did not affect the absorption and/or primary pharmacological activity of IND. The gastroprotective action of morin is primarily attributed to its potent antioxidant nature that also helps in controlling several IND-induced inflammatory responses. For the first time, the study reveals a mechanistic basis of morin mediated protective action against IND-induced gastropathy. As morin is a naturally abundant safe antioxidant, future detailed pharmacokinetic and pharmacodynamic studies are expected to establish it as a gastroprotective agent. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase.

PubMed

Tan, Gabriel; Rintala, Diana H; Jensen, Mark P; Richards, J Scott; Holmes, Sally Ann; Parachuri, Rama; Lashgari-Saegh, Shamsi; Price, Larry R

2011-01-01

Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes. Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain. Multi-site, double-blind, sham-controlled study. Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES. Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess 'as-needed' CES use. Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment. The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal-Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59). On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief.

Side Effects (Management)

MedlinePlus

... cancer care is relieving side effects, called symptom management, palliative care, or supportive care. It is important ... treat them. To learn about the symptoms and management of the long-term side effects of cancer ...

What side effects are problematic for patients prescribed antipsychotic medication? The Maudsley Side Effects (MSE) measure for antipsychotic medication.

PubMed

Wykes, T; Evans, J; Paton, C; Barnes, T R E; Taylor, D; Bentall, R; Dalton, B; Ruffell, T; Rose, D; Vitoratou, S

2017-10-01

Capturing service users' perspectives can highlight additional and different concerns to those of clinicians, but there are no up to date, self-report psychometrically sound measures of side effects of antipsychotic medications. Aim To develop a psychometrically sound measure to identify antipsychotic side effects important to service users, the Maudsley Side Effects (MSE) measure. An initial item bank was subjected to a Delphi exercise (n = 9) with psychiatrists and pharmacists, followed by service user focus groups and expert panels (n = 15) to determine item relevance and language. Feasibility and comprehensive psychometric properties were established in two samples (N43 and N50). We investigated whether we could predict the three most important side effects for individuals from their frequency, severity and life impact. MSE is a 53-item measure with good reliability and validity. Poorer mental and physical health, but not psychotic symptoms, was related to side-effect burden. Seventy-nine percent of items were chosen as one of the three most important effects. Severity, impact and distress only predicted 'putting on weight' which was more distressing, more severe and had more life impact in those for whom it was most important. MSE is a self-report questionnaire that identifies reliably the side-effect burden as experienced by patients. Identifying key side effects important to patients can act as a starting point for joint decision making on the type and the dose of medication.

Surgical management of metabolic dysfunction in PCOS.

PubMed

Escobar-Morreale, Héctor F

2012-03-10

Metabolic disturbances are common in women with polycystic ovary syndrome (PCOS). Obesity is the major link in the association of PCOS with diabetes, metabolic syndrome, hypertension, low-grade chronic inflammation and increased body iron stores, among others. Metabolic prevention in PCOS women should start as early as possible, usually meaning at diagnosis. Among preventive strategies, those promoting a healthy life-style based on diet, regular exercising and smoking cessation are possibly the most effective therapies, but also are the most difficult to achieve. To this regard, every effort must be made to avoid weight gain and obesity, given the deleterious impact that obesity exerts on the metabolic and cardiovascular associations of PCOS. Unfortunately, classic strategies that address obesity by life-style modification and dieting are seldom successful on a long-term basis, especially in women with severe obesity. In selected cases, metabolic surgery in severely obese women may resolve signs and symptoms of PCOS restoring insulin sensitivity and fertility, and avoiding the long-term risks associated with PCOS and morbid obesity. Surgical techniques for bariatric surgery have evolved in the past decades and newer procedures do not longer carry the severe side effects associated with earlier bariatric procedures. The choice of bariatric procedure should consider both the severity of obesity and the possibility of future pregnancy, since fertility may be restored by the sustained and marked weight loss usually attained after bariatric surgery. Finally, avoidance of the risks associated with morbid obesity compensate for the possible residual risks for pregnancy derived from the previous bariatric procedure itself. Copyright © 2011 Elsevier Inc. All rights reserved.

Identification of a Novel Non-retinoid Pan Inverse Agonist of the Retinoic Acid Receptors

PubMed Central

Busby, Scott A.; Kumar, Naresh; Kuruvilla, Dana S.; Istrate, Monica A.; Conkright, Juliana J.; Wang, Yongjun; Kamenecka, Theodore M.; Cameron, Michael D.; Roush, William R.; Burris, Thomas P.; Griffin, Patrick R.

2011-01-01

Retinoids are potent forms of vitamin A and are involved in a broad range of physiological processes and the pharmacological effects of retinoids are primarily mediated by the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Several natural and synthetic RAR modulators have proven to be clinically useful for a number of therapeutic indications including cancer, psoriasis, and diabetes. Unfortunately, these agents lead to a number of significant side effects. Most synthetic retinoid ligands are based on the retinoid scaffold and thus have similarities to the natural ligand with all previously disclosed RAR ligands having a carboxylic acid that makes a critical ionic bridge within the ligand binding domain of the receptors. The potential therapeutic value offered from RAR modulation provides the impetus to identify novel ligands based on unique scaffolds that may offer improved toxicity and pharmacokinetic profiles. Here we describe the identification of an atypical RAR inverse agonist that represents the first non-acid, non-retinoid direct modulator of RAR receptor subfamily. SR-0065 functions as a pan-RAR inverse agonist suppressing the basal activity of RARα, RARβ, and RARγ as well as inhibiting agonist induced RAR activity. SR-0065 treatment enhanced receptor interaction with a peptide representative of the corepressor SMRT and in cells SR-0065 enhances recruitment of SMRT to RARγ. The acid form of SR-0065, SR-1758, was inactive in all assays. Thus, SR-0065 represents a new class of non-acid, non-retinoid RAR modulator that may be used as a point to initiate development of improved RAR-targeted drugs. PMID:21381756

MDI with DIY Spacer versus Nebulizer for Bronchodilator Therapy in Children Admitted with Asthmatic Attack.

PubMed

Leelathipkul, Lalit; Tanticharoenwiwat, Pattara; Ithiawatchakul, Jutinan; Prommin, Danu; Sirisalee, Pasu; Junhunee, Parinya; Poachanukoon, Orapan

2016-07-01

Inhaled bronchodilator treatment given via the pressurized metered-dose inhaler (pMDI) with spacer has been recommended for an acute asthma treatment. Unfortunately, most of commercially available spacers are at high cost while a do-it-yourself (DIY) spacer has lower cost as it is made from plastic bottle and siphon pump which are inexpensive and easilyfound materials. This study aims to compare treatment response in nebulizer and DIY spacer used for asthmatic children. A prospective, randomized control study was conducted in children aged 1-15 years old hospitalized for mild to moderate asthmatic attack at Thammasat University Hospital between June 2014 and March 2015. The patients were divided into 2 groups, receiving β2-agonist via nebulization and via pMDI with DIY spacer. Their vital signs and oxygen saturation were monitored and asthma scores were also recorded at admission, 24 hours, 48 hours, and before discharge. The satisfaction of equipment use was evaluated employing questionnaires. 40 childrens were enrolled with male at 72.5% and mean age at 3.1±1.6 years old. There was no significant difference in efficacy of β2-agonist among 2 groups when comparing in consideration of vital signs, oximetry, asthma scores and hospital stay. However, there were significantly different on side effect in which the DIY spacer had less tachycardia and agitation. Satisfaction of parents and healthcare workers were higher in DIY spacer. MDI with DIY spacer was able to be used effectively when compared with nebulization to treat mild to moderate acute exacerbations of asthma in children admitted in hospital.

Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents.

PubMed

Savjani, Jignasa K; Mulamkattil, Suja; Variya, Bhavesh; Patel, Snehal

2017-04-15

Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions. In this study, molecular docking investigations of outlined derivatives were done utilizing Protein Data Bank (PDB ID-4PH9). Synthesis of heterocyclic compounds was carried out utilizing Dicyclohexylcarbodiimide/4-Dimethylaminopyridine (DCC/DMAP) coupling. Acute toxicity prediction was performed using free online GUSAR (General Unrestricted Structure-Activity Relationships) software. The study indicated most of the compounds under safe category. In-vitro pharmacological assessment of heterocyclic compounds was done for COX-1 and COX-2 enzymes for the determination of selectivity. In vivo pharmacological screening for anti-inflammatory activity and ED 50 value were determined utilizing carrageenan induced rat paw edema. Gastro intestinal safety study was carried out on selected compounds and found to be devoid of any gastric ulcer toxicity. Most of the compounds indicated high scores as compared to standard during molecular modelling, analysis and displayed interactions with active amino acids of a COX-2 enzyme. The pharmacological screening uncovered that compound substituted with p-bromophenyl indicated maximum potency. Copyright © 2017 Elsevier B.V. All rights reserved.

Common modeling system for digital simulation

NASA Technical Reports Server (NTRS)

Painter, Rick

1994-01-01

The Joint Modeling and Simulation System is a tri-service investigation into a common modeling framework for the development digital models. The basis for the success of this framework is an X-window-based, open systems architecture, object-based/oriented methodology, standard interface approach to digital model construction, configuration, execution, and post processing. For years Department of Defense (DOD) agencies have produced various weapon systems/technologies and typically digital representations of the systems/technologies. These digital representations (models) have also been developed for other reasons such as studies and analysis, Cost Effectiveness Analysis (COEA) tradeoffs, etc. Unfortunately, there have been no Modeling and Simulation (M&S) standards, guidelines, or efforts towards commonality in DOD M&S. The typical scenario is an organization hires a contractor to build hardware and in doing so an digital model may be constructed. Until recently, this model was not even obtained by the organization. Even if it was procured, it was on a unique platform, in a unique language, with unique interfaces, and, with the result being UNIQUE maintenance required. Additionally, the constructors of the model expended more effort in writing the 'infrastructure' of the model/simulation (e.g. user interface, database/database management system, data journalizing/archiving, graphical presentations, environment characteristics, other components in the simulation, etc.) than in producing the model of the desired system. Other side effects include: duplication of efforts; varying assumptions; lack of credibility/validation; and decentralization in policy and execution. J-MASS provides the infrastructure, standards, toolset, and architecture to permit M&S developers and analysts to concentrate on the their area of interest.

Colon cleansing protocol in children: research conditions vs. clinical practice.

PubMed

Elitsur, Yoram; Balfaqih, Yaslam; Preston, Deborah

2018-04-01

 Colon preparation rates are the limiting factor for a successful diagnostic colonoscopy in children. Different colon cleansing protocols have been published for use in children. Unfortunately, the applicability of those published research protocols has not been formally evaluated in routine clinical practice. We investigated the success rate of our previously published colon cleansing protocol as utilized in our clinical practice.  This was a retrospective study. In the clinical practice, the colon cleansing protocol included PEG-3350 at a dose of 2 g/kg/day plus Dulcolax (Bisacodyl, Boehringer Ingelheim, TX USA) 5 mg/day for 2 days. Adequate colon preparation was graded between 1 - 5, as previously described, and grade ≥ 4.0 was considered an adequate preparation. Patients were instructed to complete a questionnaire that included PEG-3350 dose, number of stools per day, consistency of each stool, and side effects (vomiting, abdominal pain). Clinical and endoscopic results were compared between the protocol under research conditions and routine practice.  The success rate of the colon preparation in our clinical practice was similar to the results observed under our research protocol (75 % vs. 73.6 %). Moreover, the total number of stools, stool consistency, and the intubation rate of the terminal ileum were also similar. We concluded, that in our experience, the colon cleansing protocol used under research conditions was effective and appropriate for use in routine clinical practice.  We recommend testing each new protocol under the routine conditions of clinical practice to confirm its applicability for general practitioners.

Educating Preservice Teachers for Family, School, and Community Engagement

ERIC Educational Resources Information Center

Evans, Michael P.

2013-01-01

Effective family, school, and community partnerships enhance the academic, social, and emotional development of children. As a result, colleges, schools, and departments of education are increasingly addressing the topic. Unfortunately, teachers continue to report that the most significant challenge encountered when entering the profession is the…

Preventing Bullying. ERIC Digest.

ERIC Educational Resources Information Center

Lumsden, Linda

Students who are the target of bullying episodes commonly suffer serious, long-term academic, physical, and emotional consequences. Unfortunately, school personnel often minimize, underestimate, tolerate, or ignore the extent of bullying and the harm it can cause. This digest examines the problem of bullying and some of its effects, and discusses…

Pore water effects on soil erodibility and its implication in ephemeral gully erosion modeling

USDA-ARS?s Scientific Manuscript database

Ephemeral gully erosion is the main source of sediment from the agricultural landscape, unfortunately, it has been overlooked in traditional soil erosion assessment. Field observations, and subsequent support from controlled lab experiments, have shown the linkage between transient soil hydraulic co...

Scarification and gap size have interacting effects on northern temperate seedling establishment

Treesearch

John L. Willis; Michael B. Walters; Kurt W. Gottschalk

2015-01-01

After decades focused on promoting economically valuable species, management of northern temperate forests has increasingly become focused on promoting tree species diversity. Unfortunately, many formerly common species that could contribute to diversity including yellow birch (Betula alleghaniensis Britton.), paper birch (Betula papyrifera...

Communicating Effectively to Obtain Supervision of Professional Practice

ERIC Educational Resources Information Center

Fischetti, Barbara A.; Petry, Bradley; Munch, Jessica Kouvel

2012-01-01

School psychologists are expected by parents, students, and their profession to maintain their competency to ensure the appropriate delivery of psychological services. Supervision by a school psychologist is a prime method for maintaining skill levels and updating professional services. Unfortunately, many school districts do not understand the…

China's Progress toward Gender Equity: From Bound Feet to Boundless Possibilities

ERIC Educational Resources Information Center

Hagedorn, Linda Serra; Zhang, Yi

2010-01-01

Throughout the world, gender defines an omnipresent and personal identity. Historically gender effects have ventured far beyond the biological aspects of reproduction and deep into societal constraints of action, appearance, freedom, and destiny. Gender provides convenient labels, descriptions, and expectations. Unfortunately history provides many…

A Critical Review of Videoconferencing Software to Support School Consultation

ERIC Educational Resources Information Center

Fischer, Aaron J.; Schultz, Brandon K.; Collier-Meek, Melissa A.; Zoder-Martell, Kimberly A.; Erchul, William P.

2018-01-01

With recent advances in technology, several viable options now exist for school consultants to communicate with teachers via synchronous online videoconferencing (VC) without the need for specialized equipment. Unfortunately, few studies have evaluated the effectiveness of school consultation through VC, so practitioners are provided little…

A Theoretical Framework for the Associations between Identity and Psychopathology

ERIC Educational Resources Information Center

Klimstra, Theo A.; Denissen, Jaap J. A.

2017-01-01

Identity research largely emerged from clinical observations. Decades of empirical work advanced the field in refining existing approaches and adding new approaches. Furthermore, the existence of linkages of identity with psychopathology is now well established. Unfortunately, both the directionality of effects between identity aspects and…

A BRIEF OVERVIEW OF RESEARCH TO ASSESS THE EFFECTIVENESS OF STREAM RESTORATION AT USEPA

EPA Science Inventory

Numerous stream and riparian restoration projects are being undertaken across the nation at a variety of scales and for disparate reasons. Unfortunately, there are very few studies associated with these restoration efforts which provide a consistent and practical methodology to e...

Managing Chemotherapy Side Effects: Constipation

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Constipation Take these steps: Eat high-fiber foods ... SERVICES National Institutes of Health Managing Chemotherapy Side Effects: Constipation These foods may help if you are ...

HIV Medicines and Side Effects

MedlinePlus

... Apps skip to content Side Effects of HIV Medicines Home Understanding HIV/AIDS Fact Sheets HIV Medicines ... p.m. ET) Send us an email HIV Medicines and Side Effects Last Reviewed: October 9, 2017 ...

The fundamental unit of pain is the cell.

PubMed

Reichling, David B; Green, Paul G; Levine, Jon D

2013-12-01

The molecular/genetic era has seen the discovery of a staggering number of molecules implicated in pain mechanisms [18,35,61,69,96,133,150,202,224]. This has stimulated pharmaceutical and biotechnology companies to invest billions of dollars to develop drugs that enhance or inhibit the function of many these molecules. Unfortunately this effort has provided a remarkably small return on this investment. Inevitably, transformative progress in this field will require a better understanding of the functional links among the ever-growing ranks of "pain molecules," as well as their links with an even larger number of molecules with which they interact. Importantly, all of these molecules exist side-by-side, within a functional unit, the cell, and its adjacent matrix of extracellular molecules. To paraphrase a recent editorial in Science magazine [223], although we live in the Golden age of Genetics, the fundamental unit of biology is still arguably the cell, and the cell is the critical structural and functional setting in which the function of pain-related molecules must be understood. This review summarizes our current understanding of the nociceptor as a cell-biological unit that responds to a variety of extracellular inputs with a complex and highly organized interaction of signaling molecules. We also discuss the insights that this approach is providing into peripheral mechanisms of chronic pain and sex dependence in pain. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Probiotics: Safety and Side Effects

MedlinePlus

... of this page please turn JavaScript on. Feature: Probiotics Safety and Side Effects Past Issues / Winter 2016 ... Says About the Safety and Side Effects of Probiotics Whether probiotics are likely to be safe for ...

Managing Chemotherapy Side Effects: Pain

MedlinePlus

N ational C ancer I nstitute Managing Chemotherapy Side Effects Pain It’s important to treat pain. If ... help to pay for pain medicine. Managing Chemotherapy Side Effects: Pain Keep track of the pain. Each ...

Managing Chemotherapy Side Effects: Memory Changes

MedlinePlus

... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

The Influence of Social Modeling, Gender, and Empathy on Treatment Side Effects.

PubMed

Faasse, Kate; Parkes, Bryony; Kearney, James; Petrie, Keith J

2018-05-31

Social modeling has the capacity to shape treatment outcomes, including side effects. This study investigated the influence of social modeling of treatment side effects, gender, and participant empathy, on side effects of a placebo treatment. Ninety-six participants (48 females) completed a study purportedly investigating the influence of modafinil (actually placebo) on alertness and fatigue. The participants were randomly seated with a male or female confederate and saw this confederate report experiencing side effects or no side effects. Participant empathy was assessed at baseline. Changes in modeled and general symptoms, and misattribution of symptoms, were assessed during the session and at 24-hr follow-up. During the experimental session, seeing side effect modeling significantly increased modeled symptoms (p = .023, d = 0.56) but not general or misattributed symptoms. Regardless of modeling condition, female participants seated with a female model reported significantly more general symptoms during the session. However, response to social modeling did not differ significantly by model or participant gender. At follow-up, the effect of social modeling of side effects had generalized to other symptoms, resulting in significantly higher rates of modeled symptoms (p = .023, d = 0.48), general symptoms (p = .013, d = 0.49), and misattributed symptoms (p = .022, d = 0.50). The experience of modeled symptoms in response to social modeling was predicted by participants' levels of baseline empathy. Social modeling of symptoms can increase the side effects following treatment, and this effect appears to generalize to a broader range of symptoms and symptom misattribution over time. Higher baseline empathy seems to increase response to social modeling.

"Side effects" of ECT are mainly depressive phenomena and are independent of age.

PubMed

Brodaty, H; Berle, D; Hickie, I; Mason, C

2001-10-01

The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.

A hierarchical anatomical classification schema for prediction of phenotypic side effects

PubMed Central

Kanji, Rakesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a ‘hierarchical anatomical classification schema’ which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects. PMID:29494708

A hierarchical anatomical classification schema for prediction of phenotypic side effects.

PubMed

Wadhwa, Somin; Gupta, Aishwarya; Dokania, Shubham; Kanji, Rakesh; Bagler, Ganesh

2018-01-01

Prediction of adverse drug reactions is an important problem in drug discovery endeavors which can be addressed with data-driven strategies. SIDER is one of the most reliable and frequently used datasets for identification of key features as well as building machine learning models for side effects prediction. The inherently unbalanced nature of this data presents with a difficult multi-label multi-class problem towards prediction of drug side effects. We highlight the intrinsic issue with SIDER data and methodological flaws in relying on performance measures such as AUC while attempting to predict side effects.We argue for the use of metrics that are robust to class imbalance for evaluation of classifiers. Importantly, we present a 'hierarchical anatomical classification schema' which aggregates side effects into organs, sub-systems, and systems. With the help of a weighted performance measure, using 5-fold cross-validation we show that this strategy facilitates biologically meaningful side effects prediction at different levels of anatomical hierarchy. By implementing various machine learning classifiers we show that Random Forest model yields best classification accuracy at each level of coarse-graining. The manually curated, hierarchical schema for side effects can also serve as the basis of future studies towards prediction of adverse reactions and identification of key features linked to specific organ systems. Our study provides a strategy for hierarchical classification of side effects rooted in the anatomy and can pave the way for calibrated expert systems for multi-level prediction of side effects.

An Examination of Psychotropic Medication Side Effects: Does Taking a Greater Number of Psychotropic Medications from Different Classes Affect Presentation of Side Effects in adults with ID?

ERIC Educational Resources Information Center

Mahan, Sara; Holloway, Jodie; Bamburg, Jay W.; Hess, Julie A.; Fodstad, Jill C.; Matson, Johnny L.

2010-01-01

This study examined whether the number of psychotropic medications an individual is taking across classes influences side effects among adults with Intellectual Disability (ID). Participants were 80 adults diagnosed with ID. Dependent variables were the composite score and domain scores of the "Matson Evaluation of Drug Side-Effects" ("MEDS"),…

Managing Chemotherapy Side Effects: Anemia

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Anemia “I told my doctor that I was ... exercise a little every day. Managing Chemotherapy Side Effects: Anemia Eat and drink well. ● ● Talk with your ...

Chemotherapy Side Effects: A Cause of Heart Disease?

MedlinePlus

... Can chemotherapy side effects increase the risk of heart disease? Answers from Timothy J. Moynihan, M.D. Chemotherapy side effects may increase the risk of heart disease, including weakening of the heart muscle (cardiomyopathy) and ...

Managing Chemotherapy Side Effects: Skin and Nail Changes

MedlinePlus

... ational C ancer I nstitute Managing Chemotherapy Side Effects Skin and Nail Changes “I was glad to ... services national institutes of health Managing Chemotherapy Side Effects: Skin and Nail Changes Protect your skin from ...

Cutaneous side effects of doxycycline: a pediatric case series.

PubMed

Bayhan, Gulsum Iclal; Akbayram, Sinan; Ozaydin Yavuz, Goknur; Oner, Ahmet Fayik

2017-06-01

Brucellosis is highly endemic in Turkey and doxycycline is commonly used for its treatment. The present study aimed at documenting the cutaneous side effects of doxycycline in pediatric brucellosis patients in Turkey. Pediatric patients with brucellosis that were treated between February 2014 and January 2016 were analyzed retrospectively, and those that developed doxycycline-related cutaneous side effects were identified. Demographic data, epidemiological history, physical examination findings, laboratory test results, anti-brucellosis treatment regimen, duration of follow up and outcome were recorded. Among the 189 brucellosis patients, 141 treated with doxycycline plus rifampicin. Seven patients (5%) (two female and five male) developed doxycycline-related cutaneous side effects. Mean duration of treatment before the onset of cutaneous side effects was 9.5 weeks. Doxycycline therapy was continued in five of these patients and was changed in two patients. In the patients that continued to receive doxycycline the cutaneous side effects gradually improved. Cutaneous side effects of doxycycline should always be a consideration, especially in regions in which brucellosis is endemic and doxycycline is commonly used to treat it.

Influence of Side Effects on ART Adherence Among PLWH in China: The Moderator Role of ART-Related Knowledge.

PubMed

Zhou, Guangyu; Li, Xiaoming; Qiao, Shan; Shen, Zhiyong; Zhou, Yuejiao

2018-03-01

Despite the medical advancements in HIV treatment, realities of side effects are faced by people living with HIV (PLWH) who receive antiretroviral therapy (ART). Mixed findings have been reported on the association between side effects and ART adherence. However, few studies have explored the combined side effects and behavior-related information on medication adherence. The aim of the current study is to examine moderator role of ART-related knowledge between side effects and ART adherence. A cross-sectional survey was conducted among 2987 PLWH from October 2012 to August 2013 in China. Of the total sample, 2095 patients had received ART and provided ART adherence. Side effects, ART-related knowledge, and ART adherence, as well as potential covariates were assessed. The results revealed that there was a negative relationship of side effects and ART adherence existed among low and medium levels of ART-related knowledge, but not among high level of knowledge. Future interventions to promote HIV medication adherence should focus on providing behavior-related information education among PLWH.

Cancer Treatment Side Effects: A Meta-analysis of the Relationship Between Response Expectancies and Experience.

PubMed

Devlin, Elise J; Denson, Linley A; Whitford, Hayley S

2017-08-01

Although previous research has, overall, suggested a moderate relationship between response expectancies (REs) and cancer treatment-related side effects, empirical results have been mixed. We aimed to further explore these relationships, hypothesizing that REs would predict subsequent toxicities with the inclusion of more recent studies, across a broader range of side effects, while incorporating the impact of potential moderators including patients' experience with treatment and measurement methods. We further investigated the impact of REs across individual toxicities. A systematic search and analysis were conducted across four databases (PsychInfo, PubMed, CINAHL, and Embase) and reference lists, from 1985 to February 2016. This provided 27 eligible studies with 4474 participants, through which the main analysis, moderator analyses, and individual side-effect analyses were explored. REs were moderately related to side effects overall (r = 0.26), and effect sizes were significantly influenced by sample diagnostic homogeneity, whereas differences between type and timing of measurement showed trends. Of the 16 toxicities examined, 15 demonstrated significant relationships between REs and side-effect experience, with hair loss (r = 0.48) the strongest. No clear difference emerged between objective and subjective side effects; however, significant differences across individual toxicities were revealed. Findings support a relationship between REs and a wide range of subsequent side effects, yet differences between individual RE-toxicity associations emerged. These findings provide direction for the measurement of side effects and REs and support REs as potential targets for intervention during the informed consent process. Copyright © 2017 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Anaesthesiological considerations on tocolytic and uterotonic therapy in obstetrics.

PubMed

Vercauteren, M; Palit, S; Soetens, F; Jacquemyn, Y; Alahuhta, S

2009-07-01

Significant side effects of tocolytic and uterotonic substances may be of concern to the anaesthesiologist. Recently, new drugs have been introduced having less side effects for both the mother and the neonate. A literature search was undertaken mainly focusing on meta-analyses, to review the possible side effects that might affect the course of anaesthesia and to suggest which precautions should be considered to prevent the occurrence of significant interactions with anaesthetic manipulations and drugs. Magnesium sulphate has a proven benefit in lowering systolic blood pressure and preventing the occurrence of eclampsia, but not as a tocolytic. beta-adrenergic agonists are being abandoned due to the availability of tocolytic agents causing less side effects. Calcium channel blockers (CCB) are frequently used but can cause major maternal cardiovascular complications. Nitroglycerin seems to be appreciated as an acute tocolytic rather than a routine substance during pre-term labour. Cyclo-oxygenase-2 inhibitors are still under investigation but their tocolytic benefit is questionable mainly due to foetal side effects. Atosiban is considered the first-choice tocolytic. With respect to oxytocic drugs, oxytocine, prostaglandines and methylergometrine may all cause serious side effects especially when combined. The cardiovascular side effects of prostaglandins and methylergometrine can be life-threatening. Both oxytocin and carbetocin have a rather low risk for maternal complications. Atosiban and CCB are at least as effective tocolytic agents as beta-mimetics but have significantly less side effects. Magnesium sulphate can cause neuromuscular blockade, especially when combined with CCB. Concerning oxytocic agents, short-acting oxyctocin and long-acting carbetocin have the least side effects as compared with prostaglandins and methylergometrine.

Transfer of Learning in Leadership Development: Lived Experiences of HPI Practitioners

ERIC Educational Resources Information Center

Johnstal, Susan P.

2010-01-01

Recent research showed developing leadership matters a great deal for organizations seeking a competitive advantage. Unfortunately, despite numerous resources devoted to leadership development, confidence in leaders was plummeting and development programs were failing to meet the goal of more effective leadership. Research suggested these failures…

Training Physicians for Public Health Careers

ERIC Educational Resources Information Center

Hernandez, Lyla M., Ed.; Munthali, A. Wezi, Ed.

2007-01-01

Public health efforts have resulted in tremendous improvements in the health of individuals and communities. The foundation for effective public health interventions rests, in large part, on a well-trained workforce. Unfortunately there is a major shortage of public health physicians who are prepared to face today's public health challenges.…

Effective Analysis of Reaction Time Data

ERIC Educational Resources Information Center

Whelan, Robert

2008-01-01

Most analyses of reaction time (RT) data are conducted by using the statistical techniques with which psychologists are most familiar, such as analysis of variance on the sample mean. Unfortunately, these methods are usually inappropriate for RT data, because they have little power to detect genuine differences in RT between conditions. In…

Designing for Sustained Adoption: A Model of Developing Educational Innovations for Successful Propagation

ERIC Educational Resources Information Center

Khatri, Raina; Henderson, Charles; Cole, Renée; Froyd, Jeffrey E.; Friedrichsen, Debra; Stanford, Courtney

2016-01-01

The physics education research community has produced a wealth of knowledge about effective teaching and learning of college level physics. Based on this knowledge, many research-proven instructional strategies and teaching materials have been developed and are currently available to instructors. Unfortunately, these intensive research and…

Exploring the Effects of Professional Development for the Interactive Whiteboard on Teachers' Technology Self-Efficacy

ERIC Educational Resources Information Center

DeSantis, Joshua D.

2013-01-01

Identifying means of assisting teachers in integrating technology during their instruction is becoming more important as the rate new technologies enter the classroom accelerates. The primary means of helping in-service teachers employ new technologies in their classrooms is frequently professional development. Unfortunately, professional…

Great Principals at Scale: Toolkit

ERIC Educational Resources Information Center

Ikemoto, Gina; Taliaferro, Lori; Fenton, Benjamin; Davis, Jacquelyn

2014-01-01

School leaders are critical in the lives of students and to the development of their teachers. Unfortunately, in too many instances, principals are effective in spite of--rather than because of--district conditions. To truly improve student achievement for all students across the country, well-prepared principals need the tools, support, and…

Rural Canadian Youth Exposed to Physical Violence

ERIC Educational Resources Information Center

Laye, Adele M.; Mykota, David B.

2014-01-01

Exposure to physical violence is an unfortunate reality for many Canadian youth as it is associated with numerous negative psychosocial effects. The study aims to assist in understanding resilience in rural Canadian youth exposed to physical violence. This is accomplished by identifying the importance of protective factors, as measured by the…

Guidelines for whitebark pine planting prescriptions

Treesearch

Glenda L. Scott; Ward W. McCaughey; Kay Izlar

2011-01-01

Whitebark pine (Pinus albicaulis) is a keystone species in high-elevation ecosystems of the western United States. Unfortunately many fragile subalpine ecosystems are losing whitebark pine as a functional community component due to the combined effects of an introduced disease, insects and succession. Planting whitebark pine is one part of a multifaceted restoration...

Vouchers and Public Policy: When Ideology Trumps Evidence

ERIC Educational Resources Information Center

Belfield, Clive; Levin, Henry M.

2005-01-01

The economic model of education policy assumes that there is a substantial consensus on educational goals among constituencies and that the major challenge is to determine the most effective strategies for reaching those goals. Unfortunately, the debate over educational vouchers is complicated by the presence of multiple and competing goals, and…

Professional Development to Increase Teacher Behavior-Specific Praise: A Single-Case Design Replication

ERIC Educational Resources Information Center

Gage, Nicholas A.; Grasley-Boy, Nicolette M.; MacSuga-Gage, Ashley S.

2018-01-01

Effective classroom instruction is contingent upon successful classroom management. Unfortunately, not all teachers successfully manage classroom behavior and need in-service professional development. In this study, we replicated a targeted professional development approach that included a brief one-on-one training session and emailed visual…

Characteristics of an Effective Writing Literacy Program

ERIC Educational Resources Information Center

Mascia Reed, Candi

2012-01-01

Learning to write is an arduous undertaking for every student; for deaf and hard of hearing students, it can be particularly difficult. Too often, they arrive in school with minimal literacy skills, experience subsequent difficulties in writing standard English, and, unfortunately, still graduate with reading levels below those of their hearing…

A New Electropositive Filter for Concentrating Enterovirus and Norovirus from Large Volumes of Water - MCEARD

EPA Science Inventory

The detection of enteric viruses in environmental water usually requires the concentration of viruses from large volumes of water. The 1MDS electropositive filter is commonly used for concentrating enteric viruses from water but unfortunately these filters are not cost-effective...

Effects of Trans-cinnamaldehyde on Campylobacter and Sperm Viability in Chicken Semen after in vitro Storage

USDA-ARS?s Scientific Manuscript database

Campylobacter is one of the leading causes of bacterial human acute gastroenteritis. These microorganisms are highly prevalent in poultry semen and may contribute to vertical transmission between the breeder hen and offspring. Unfortunately, strategies to reduce or eliminate these pathogens in poult...

Teaching Writing for Keeps

ERIC Educational Resources Information Center

Alber-Morgan, Sheila R.; Hessler, Terri; Konrad, Moira

2007-01-01

Proficiency with written expression is critical for students' academic success. Unfortunately, writing presents a challenge for both students and teachers. Recent data suggest that many students in U.S. schools fail to meet even the most basic writing standards. And even when students receive effective (i.e., evidence-based) writing instruction,…

Evidence-Based Practices Project for Suicide Prevention

ERIC Educational Resources Information Center

Rodgers, Philip L.; Sudak, Howard S.; Silverman, Morton M.; Litts, David A.

2007-01-01

Suicide continues to be a serious public health problem. In response to this problem, a myriad of suicide prevention programs have been developed and employed across the United States. Unfortunately, the effectiveness of many of these programs is unknown because they have not been evaluated using rigorous methods. The Evidence-Based Practices…

Determining effective riparian buffer width for nonnative plant exclusion and habitat enhancement

Treesearch

Gavin Ferris; Vincent D' Amico; Christopher K. Williams

2012-01-01

Nonnative plants threaten native biodiversity in landscapes where habitats are fragmented. Unfortunately, in developed areas, much of the remaining forested habitat occurs in fragmented riparian corridors. Because forested corridors of sufficient width may allow forest interior specializing native species to retain competitive advantage over edge specialist and...

Using Decision Support to Address Racial Disparities in Mental Health Service Utilization

ERIC Educational Resources Information Center

Rawal, Purva H.; Anderson, Tanya R.; Romansky, Jill R.; Lyons, John S.

2008-01-01

Unfortunately, racial disparities are well documented in the delivery of behavioral health services. This study examines the effects of implementing a decision support process, integrating clinical information into the administration of mental health services, on racial disparities in psychiatric hospital admissions for children in state custody.…

Increasing Student-Learning Team Effectiveness with Team Charters

ERIC Educational Resources Information Center

Hunsaker, Phillip; Pavett, Cynthia; Hunsaker, Johanna

2011-01-01

Because teams are a ubiquitous part of most organizations today, it is common for business educators to use team assignments to help students experientially learn about course concepts and team process. Unfortunately, students frequently experience a number of problems during team assignments. The authors describe the results of their research and…

Urban School Challenges: Implementation and Sustainability of Positive Behavioral Interventions and Supports

ERIC Educational Resources Information Center

Rusk, Christina N.

2016-01-01

Educators are under increasing pressure to improve the climate and safety in urban schools. Unfortunately, schools have addressed school safety concerns by increasing exclusionary measures such as suspensions and expulsions. Knowing that exclusionary measures can have detrimental effects, state legislatures have called for more proactive…

Mathematics Problems from Ancient Egyptian Papyri

ERIC Educational Resources Information Center

Howard, Christopher A.

2009-01-01

Most high school mathematics teachers completed a mathematics history course in college, and many of them likely found it intriguing. Unfortunately, very few of them find the time to allow much, if any, mathematics history to trickle into their instruction. However, if mathematics history is taught effectively, students can see the connections…

Assessor Training: Its Effects on Criterion-Based Assessment in a Medical Context

ERIC Educational Resources Information Center

Pell, Godfrey; Homer, Matthew S.; Roberts, Trudie E.

2008-01-01

Increasingly, academic institutions are being required to improve the validity of the assessment process; unfortunately, often this is at the expense of reliability. In medical schools (such as Leeds), standardized tests of clinical skills, such as "Objective Structured Clinical Examinations" (OSCEs) are widely used to assess clinical…

Writing Our Wrongs.

ERIC Educational Resources Information Center

Rothschild, Jeffrey

In writing, as with tools, form must always follow function. From this perspective there can be no "good" writing, only effective writing. Unfortunately, in most instructional situations the function of communicating to an audience is often neglected. Most so-called poor writing falls into the category of writer-based prose. Once student writing…

An Investigation into the Effectiveness of Using a Smart Classroom Teaching Platform to Manage Educational Outcomes

ERIC Educational Resources Information Center

Carter, Bobbi Jo

2012-01-01

Utilization of technology in the classroom has become the norm in higher education. Technology has been advocated as a means of improving learning and students expect it to be present so schools have adopted it in order to stay competitive. Unfortunately, the effectiveness of the technology is frequently either unknown or falls short due to a…

Type and frequency of side effects during PC6 acupuncture: observations from therapists and patients participating in clinical efficacy trials of acupuncture.

PubMed

Enblom, Anna; Johnsson, Anna

2017-12-01

Many therapists practise PC6 acupuncture for emesis (nausea and vomiting) during pregnancy, different cancer therapies, palliative care, after surgery, or to induce relaxing effects in general. Knowledge of side effects is central to shared decision-making. To describe the type and frequency of side effects and the level of needle-induced pain during PC6 acupuncture. We included 1298 PC6 acupuncture treatments, delivered to 221 participants (77% women, mean age 52.5, range 18-91 years). The subjects had received genuine PC6 acupuncture, in one of two previous randomised controlled trials, aimed at inducing antiemetic (n=100, with 100 providing data on side effects and 94 on needle-induced pain, respectively) or relaxing (n=121, with 120 providing data) effects. Side effects during and after the acupuncture treatments were registered in structured treatment protocols and study diaries. No serious complications occurred. Side effects during the acupuncture sessions included minor bleeding in 5.0%, tiredness in 4.9%, numbness in 4.5% and dizziness in 1.4% of the 1298 treatments. After treatment, the mean proportions of participants reporting side effects each week were: tiredness 25.8%; feeling cold 17.8%; dizziness 9.7%; sweating 9.3%; haematoma 8.8%; and soreness at the needling sites 4.3%. Participants perceived the needling to be not painful (47.4% of participants), or mildly (39.1%), moderately (11.6%) or very painful (1.4%). Few side effects occurred and those that did were mild. Nearly 90% found PC6 acupuncture to be not painful or only mildly painful. Healthcare professionals may consider the observed levels of side effects when informing patients about side effects of PC6 acupuncture. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Side-gate modulation effects on high-quality BN-Graphene-BN nanoribbon capacitors

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

Wang, Yang; Chen, Xiaolong; Ye, Weiguang

High-quality BN-Graphene-BN nanoribbon capacitors with double side-gates of graphene have been experimentally realized. The double side-gates can effectively modulate the electronic properties of graphene nanoribbon capacitors. By applying anti-symmetric side-gate voltages, we observed significant upward shifting and flattening of the V-shaped capacitance curve near the charge neutrality point. Symmetric side-gate voltages, however, only resulted in tilted upward shifting along the opposite direction of applied gate voltages. These modulation effects followed the behavior of graphene nanoribbons predicted theoretically for metallic side-gate modulation. The negative quantum capacitance phenomenon predicted by numerical simulations for graphene nanoribbons modulated by graphene side-gates was not observed,more » possibly due to the weakened interactions between the graphene nanoribbon and side-gate electrodes caused by the Ga{sup +} beam etching process.« less

Subjective experience and mental side-effects of antipsychotic treatment.

PubMed

Gerlach, J; Larsen, E B

1999-01-01

Many schizophrenic patients have a negative attitude towards antipsychotic drugs. This attitude is not only due to lack of insight into the disease, lack of recognition of the beneficial effects of the drugs, and to objective side-effects. The negative attitude is to a high degree due to mental side-effects and a sceptical opinion about antipsychotic medication in general. In a study of 53 chronic schizophrenic out-patients receiving maintenance depot antipsychotic treatment, we found that 60% were positive about the treatment, 32% were ambivalent and 8% had a negative attitude. Only 60% complained of side-effects, even though 94% had objective side-effects. Mental side-effects such as subjective akathisia, dysphoria and emotional indifference were most often observed by the patients, while hypokinesia and hyperkinesia were least noticed by them, but most often observed by the physician. No correlation was found between the patients' subjective assessment of their quality of life and the degree of psychosis and side-effects. With the new atypical antipsychotics this situation seems to be changing. These new drugs are primarily characterized by a lower level of motor extrapyramidal side-effects (EPS), and with fewer motor EPS, fewer mental EPS can be expected. In recent studies comparing the new antipsychotics with haloperidol, better effects have been observed with regard to negative symptoms and depression, and this may at least in part be a reflection of a lower level of mental side-effects of the atypical antipsychotics. This improved clinical profile of new antipsychotics is extremely valuable in the context of an integrated treatment in schizophrenia, consisting of early intervention, psychosocial rehabilitation and family/patient psycho-education.

Ayurveda for chemo-radiotherapy induced side effects in cancer patients.

PubMed

Metri, Kashinath; Bhargav, Hemant; Chowdhury, Praerna; Koka, Prasad S

2013-01-01

Chemotherapy drugs and radiotherapy are highly toxic and both damage adjacent healthy cells. Side effects may be acute (occurring within few weeks after therapy), intermediate or late (occurring months or years after the therapy). Some important side effects of chemotherapy are: nausea, vomiting, diarrhea, mucositis, alopecia, constipation etc; whereas radiation therapy though administered locally, can produce systemic side effects such as fatigue, anorexia, nausea, vomiting, alteration in the taste, sleep disturbance, headache, anemia, dry skin, constipation etc. Late complications of these therapies also include pharyngitis, esophagitis, laryngitis, persistent dysphagia, fatigue, hepatotoxicity, infertility and cognitive deficits. These arrays of side effects have a devastating effect on the quality of life of cancer survivors. Due to the inadequacy of most of the radio-protectors and chemo-protectors in controlling the side effects of conventional cancer therapy the complementary and alternative medicines have attracted the view of researchers and medical practitioners more recently. This review aims at providing a comprehensive management protocol of above mentioned chemo-radiotherapy induced side effects based on Ayurveda, which is an ancient system of traditional medicine practiced in Indian peninsula since 5000 BC. When the major side effects of chemo-radiotherapy are looked through an ayurvedic perspective, it appears that they are the manifestations of aggravated pitta dosha, especially under the group of disorders called Raktapitta (haemorrhage) or Raktadushti (vascular inflammation). Based on comprehensive review of ancient vedic literature and modern scientific evidences, ayurveda based interventions are put forth. This manuscript should help clinicians and people suffering from cancer to combat serious chemo-radiotherapy related side effects through simple but effective home-based ayurveda remedies. The remedies described are commonly available and safe. These simple ayurveda based solutions may act as an important adjuvant to chemo-radiotherapy and enhance the quality of life of cancer patients.

Martian "Gullies": Unfortunate Use of a Terrestrial Term

NASA Astrophysics Data System (ADS)

Dixon, J. C.; Coleman, K. A.

2008-03-01

It is unfortunate that the hillslope forms identified on Mars are referred to as "gullies" as they bear little resemblance to their namesake in the terrestrial realm. It is necessary to identify more appropriate terrestrial analogs of the forms.

Dissatisfaction with opioid maintenance treatment partly explains reported side effects of medications.

PubMed

Muller, Ashley Elizabeth; Bjørnestad, Ronny; Clausen, Thomas

2018-03-29

Drop-out is a core problem in opioid maintenance treatment (OMT), but patients' reactions to and acceptance of the various OMT medications are insufficiently investigated. In Norway, there has been vocal patient resistance to the newest medication, buprenorphine-naloxone (BNX), and complaints have focused on the side effect profile. There has been no comparison of patient satisfaction and side effects of the three most common OMT medications. To compare patient satisfaction with OMT and side effects of BNX, buprenorphine monopreparate (BUP), and methadone (MET) as reported by patients. Data were drawn from a national peer-to-peer survey developed by a patient advocacy group. The survey engaged more than 1000 OMT patients, corresponding to one seventh of OMT patients in Norway. The associations between side effects, treatment satisfaction, and patient characteristics were tested in multinomial logistic regressions. High patient satisfaction with OMT overall was reported despite lower satisfaction with medication itself and widely prevalent side effects. Among each medication group, dissatisfaction with medications or OMT in general along with poor health status increased the relative risk ratio of reporting the heaviest side effect burden. MET users reported the highest side effect burden and BNX users the lightest, but BNX users were more dissatisfied with their medication. Side effects are a concern for nearly all OMT patients, and they do not appear to accumulate with age or length of treatment. BNX users' dissatisfaction with their medication is of particular concern, and expectations and preferences of medication may be influencing their dissatisfaction. Copyright © 2018. Published by Elsevier B.V.

Selective serotonin reuptake inhibitor discontinuation: side effects and other factors that influence medication adherence.

PubMed

Goethe, John W; Woolley, Stephen B; Cardoni, Alex A; Woznicki, Brenda A; Piez, Deborah A

2007-10-01

Patients with major depression discontinue taking their antidepressants for many reasons. Although side effects are often cited as the reason for discontinuation, few prospective studies have addressed this question, and none has specifically examined discontinuation in patients with severe depression. Inpatients and outpatients treated with a selective serotonin reuptake inhibitor for major depressive disorder were identified after admission. Three months later, patients were contacted and interviewed to determine antidepressant usage and the side effects experienced, including when these were experienced and their severity. Between October 2001 and April 2003, 406 English- or Spanish-speaking patients aged 18 to 75 years were followed up. One in 4 patients discontinued the index antidepressant. Among specific side effects noted, only "change in weight" and "anxiety" were significant predictors of discontinuation after controlling for confounders. Experiencing 1 or more "extremely" bothersome side effects was associated with more than a doubling of the risk of discontinuation, but the presence of side effects and side effects less severe than "extremely" bothersome were not significant predictors. There were no differences among selective serotonin reuptake inhibitor antidepressants in either the presence/absence of side effects or in the discontinuation rates. The results suggest that the contribution of side effects to antidepressant discontinuation is more complex than previously suggested. Disparate findings from earlier studies may reflect aspects of study design, such as examining populations whose severity of depression varied widely or not controlling for important confounding factors. Future research should separately examine high-risk groups (or control for severity of depression) and carefully rule out other potential contributors to discontinuation.

Effects of side lying on lung function in older individuals.

PubMed

Manning, F; Dean, E; Ross, J; Abboud, R T

1999-05-01

Body positioning exerts a strong effect on pulmonary function, but its effect on other components of the oxygen transport pathway are less well understood, especially the effects of side-lying positions. This study investigated the interrelationships between side-lying positions and indexes of lung function such as spirometry, alveolar diffusing capacity, and inhomogeneity of ventilation in older individuals. Nineteen nonsmoking subjects (mean age=62.8 years, SD=6.8, range=50-74) with no history of cardiac or pulmonary disease were tested over 2 sessions. The test positions were sitting and left side lying in one session and sitting and right side lying in the other session. In each of the positions, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), single-breath pulmonary diffusing capacity (DLCO/VA), and the slope of phase III (DN2%/L) of the single-breath nitrogen washout test to determine inhomogeneity of ventilation were measured. Compared with measurements obtained in the sitting position, FVC and FEV1 were decreased equally in the side-lying positions, but no change was observed in DLCO/VA or DN2%/L. Side-lying positions resulted in decreases in FVC and FEV1, which is consistent with the well-documented effects of the supine position. These findings further support the need for prescriptive rather than routine body positioning of patients with risks of cardiopulmonary compromise and the need to use upright positions in which lung volumes and capacities are maximized.

Effects and Side Effects of Flemish School Inspection

ERIC Educational Resources Information Center

Penninckx, Maarten; Vanhoof, Jan; De Maeyer, Sven; Van Petegem, Peter

2016-01-01

Despite the increased importance of school inspection in recent years, the current knowledge base does not provide a clear view on the effects and side effects of being inspected. More evidence is needed in more diverse educational contexts. This article responds to this need with a quantitative study on the effects and side effects of school…

Chemotherapy

MedlinePlus

... cells to get better. Because everyone's different, some people will have fewer side effects than others. Common side effects of chemo are ... infections easily. Medicines are available that can help people feel better if they have side effects from chemo. Doctors, nurses, and other members of ...

Predicting new drug indications from network analysis

NASA Astrophysics Data System (ADS)

Mohd Ali, Yousoff Effendy; Kwa, Kiam Heong; Ratnavelu, Kurunathan

This work adapts centrality measures commonly used in social network analysis to identify drugs with better positions in drug-side effect network and drug-indication network for the purpose of drug repositioning. Our basic hypothesis is that drugs having similar phenotypic profiles such as side effects may also share similar therapeutic properties based on related mechanism of action and vice versa. The networks were constructed from Side Effect Resource (SIDER) 4.1 which contains 1430 unique drugs with side effects and 1437 unique drugs with indications. Within the giant components of these networks, drugs were ranked based on their centrality scores whereby 18 prominent drugs from the drug-side effect network and 15 prominent drugs from the drug-indication network were identified. Indications and side effects of prominent drugs were deduced from the profiles of their neighbors in the networks and compared to existing clinical studies while an optimum threshold of similarity among drugs was sought for. The threshold can then be utilized for predicting indications and side effects of all drugs. Similarities of drugs were measured by the extent to which they share phenotypic profiles and neighbors. To improve the likelihood of accurate predictions, only profiles such as side effects of common or very common frequencies were considered. In summary, our work is an attempt to offer an alternative approach to drug repositioning using centrality measures commonly used for analyzing social networks.

[Cardiovascular side effects of non-steroidal anti-inflammatory drugs in the light of recent recommendations. Diclofenac is not more dangerous].

PubMed

Horváth, Viktor József; Tabák, Gy Ádám; Szabó, Gergely; Putz, Zsuzsanna; Koós, Csaba Géza; Lakatos, Péter

2015-03-29

Among their beneficial effects, non-steroidal anti-inflammatory drugs may also exert several side effects which depend on the dosage and the type of these medications. The most frequent gastrointestinal side effects usually develop shortly after the beginning of their administration, but others such as cardiovascular interactions (which are present much less frequently than gastrointestinal side effects) can also occur after the beginning of drug administration without a latency period. For a long-term treatment, non-steroidal anti-inflammatory drugs are most frequently used in the elderly population where patients typically have high cardiovascular risk and take other medicines, e.g. low dose acetylsalicylic acid that can interact with non-steroidal anti-inflammatory drugs; in this aspect diclofenac may cause less side effects. In this review, the authors briefly review cardiovascular side effects of non-steroidal anti-inflammatory drugs, the processes which potentially influence them, therapeutic consequences and their interaction with acetylsalicylic acid.

The impact of tamoxifen brand switch on side effects and patient compliance in hormone receptor positive breast cancer patients.

PubMed

Zeidan, B; Anderson, K; Peiris, L; Rainsbury, D; Laws, S

2016-10-01

In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Consecutive disease free ER positive patients (stage I-III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects (p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms (p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects (p = 0.001), yet this did not translate into discontinuation or non-adherence (p = 0.8 and 0.08 respectively). Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy.

PubMed

Erdogan, Suat; Turkekul, Kader; Serttas, Rıza; Erdogan, Zeynep

2017-04-01

Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death among men. Development of chemoresistance, tumor relapse and metastasis remain major barriers to effective treatment and all been identified to be associated with cancer stem cells (CSCs). Natural flavonoids such as apigenin have been shown to have the ability to improve the therapeutic efficacy of common chemotherapy agents through CSCs sensitization. Thus, the aim of this study was to evaluate the combination of apigenin with cisplatin on CD44 + PCa stem cell growth and migration. Platinum-based anti-neoplastic drugs have been used to treat a number of malignancies including PCa. However, acquired resistance and side effects unfortunately have limited cisplatin's use. A CD44 + subpopulation was isolated from human androgen-independent PC3 PCa cells by using human CD44-PE antibody. IC 50 values were determined by MTT test. RT-qPCR, Western blot analyses and image-based cytometer were used to investigate apoptosis, cell cycle and their underlying molecular mechanisms. Cell migration was evaluated by wound healing test. The combination of the IC 50 doses of apigenin (15μM) and cisplatin (7.5μM) for 48h significantly enhanced cisplatin's cytotoxic and apoptotic effects through downregulation of Bcl-2, sharpin and survivin; and upregulation of caspase-8, Apaf-1 and p53 mRNA expression. The combined therapy suppressed the phosphorylation of p-PI3K and p-Akt, inhibited the protein expression of NF-κB, and downregulated the cell cycle by upregulating p21, as well as cyclin dependent kinases CDK-2, -4, and -6. Apigenin significantly increased the inhibitory effects of cisplatin on cell migration via downregulation of Snail expression. In conclusion, our study showed the possible therapeutic approach of using apigenin to potentially increase the effects of cisplatin by targeting CSCs subset in prostate cancer. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of 5-fluorouracil in nuclear and cellular morphology, proliferation, cell cycle, apoptosis, cytoskeletal and caveolar distribution in primary cultures of smooth muscle cells.

PubMed

Filgueiras, Marcelo de Carvalho; Morrot, Alexandre; Soares, Pedro Marcos Gomes; Costa, Manoel Luis; Mermelstein, Cláudia

2013-01-01

Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. The anti-metabolite 5- fluorouracil (5-FU) is widely used in the treatment of patients with colon cancer and other cancer types. 5-FU-based chemotherapy has been shown to be very efficient in the improvement of overall survival of the patients and for the eradication of the disease. Unfortunately, common side effects of 5-FU include severe alterations in the motility of the gastrointestinal tissues. Nevertheless, the molecular and cellular effects of 5-FU in smooth muscle cells are poorly understood. Primary smooth muscle cell cultures are an important tool for studies of the biological consequences of 5-FU at the cellular level. The avian gizzard is one of the most robust organs of smooth muscle cells. Here we studied the molecular and cellular effects of the chemotherapic drug 5-FU in a primary culture of chick gizzard smooth muscle cells. We found that treatment of smooth muscle cells with 5-FU inhibits cell proliferation by the arrest of cells in the G1 phase of cell cycle and induce apoptosis. 5-FU induced a decrease in the percentage of histone H3-positive cells. Treatment of cells with 5-FU induced changes in cellular and nuclear morphology, a decrease in the number of stress fibers and a major decrease in the number of caveolin-3 positive cells. Our results suggest that the disorganization of the actin cytoskeleton and the reduction of caveolin-3 expression could explain the alterations in contractility observed in patients treated with 5-FU. These findings might have an impact in the understanding of the cellular effects of 5-FU in smooth muscle tissues and might help the improvement of new therapeutic protocols for the treatment of colon cancer.

Effects of 5-Fluorouracil in Nuclear and Cellular Morphology, Proliferation, Cell Cycle, Apoptosis, Cytoskeletal and Caveolar Distribution in Primary Cultures of Smooth Muscle Cells

PubMed Central

Filgueiras, Marcelo de Carvalho; Morrot, Alexandre; Soares, Pedro Marcos Gomes; Costa, Manoel Luis; Mermelstein, Cláudia

2013-01-01

Colon cancer is one of the most prevalent types of cancer in the world and is one of the leading causes of cancer death. The anti-metabolite 5- fluorouracil (5-FU) is widely used in the treatment of patients with colon cancer and other cancer types. 5-FU-based chemotherapy has been shown to be very efficient in the improvement of overall survival of the patients and for the eradication of the disease. Unfortunately, common side effects of 5-FU include severe alterations in the motility of the gastrointestinal tissues. Nevertheless, the molecular and cellular effects of 5-FU in smooth muscle cells are poorly understood. Primary smooth muscle cell cultures are an important tool for studies of the biological consequences of 5-FU at the cellular level. The avian gizzard is one of the most robust organs of smooth muscle cells. Here we studied the molecular and cellular effects of the chemotherapic drug 5-FU in a primary culture of chick gizzard smooth muscle cells. We found that treatment of smooth muscle cells with 5-FU inhibits cell proliferation by the arrest of cells in the G1 phase of cell cycle and induce apoptosis. 5-FU induced a decrease in the percentage of histone H3-positive cells. Treatment of cells with 5-FU induced changes in cellular and nuclear morphology, a decrease in the number of stress fibers and a major decrease in the number of caveolin-3 positive cells. Our results suggest that the disorganization of the actin cytoskeleton and the reduction of caveolin-3 expression could explain the alterations in contractility observed in patients treated with 5-FU. These findings might have an impact in the understanding of the cellular effects of 5-FU in smooth muscle tissues and might help the improvement of new therapeutic protocols for the treatment of colon cancer. PMID:23646193

The effect of substrate on electric field enhancement of Tip-enhanced Raman spectroscopy (TERS)

NASA Astrophysics Data System (ADS)

Bahreini, Maryam

2018-01-01

The characterization of materials down to a few-molecule level is a key challenge in nanotechnology. Raman spectroscopy is a powerful method that provides chemical information via nondestructive vibrational fingerprinting. Unfortunately, this method suffers from signal weakness which prevents the study of small quantities. Tip-enhanced Raman spectroscopy (TERS) which combines the chemical sensitivity of Raman spectroscopy (RS) with high spatial resolution of scanning probe microscopy (SPM), provides chemical images of surfaces at the nanometer scale. In this method, irradiation of an SPM tip by a focused laser beam results in enhancement of local electric field via two reasons of localized surface plasmon resonance and lightning rod effect. This enhancement leads to the enhancement in Raman intensity from the sample surface in the vicinity of tip. In all TERS measurements, samples should be located on a substrate. In this paper, the dependence of the electric field enhancement to the substrate has been investigated. In simulations, three-dimensional finite-difference time-domain (3D-FDTD) method is used for numerical solution of Maxwell's equations. Our results show that the electric field enhancement is weak for the tip alone case. Introducing a substrate provides further electric field enhancement via near field electromagnetic dipole-dipole coupling between the tip and substrate. Since the side-illumination geometry is used for laser irradiation, the vertical component of the incident field plays a dominant role in the electric field enhancement. Therefore, the coupling effect between the tip and the substrate is the key contribution to the enhancement. For the case of silicon tip and the gold substrate, the electric field enhancement is improved considerably. There is an optimal tip size for TERS because of the competing effects of the radiation damping and the surface scattering of the tip. The results show the substrate as an effective tool for the improvement of the TERS detection sensitivity.

The Association of Long-term Treatment-related Side Effects With Cancer-specific and General Quality of Life Among Prostate Cancer Survivors

PubMed Central

Davis, Kimberly M.; Kelly, Scott P.; Luta, George; Tomko, Catherine; Miller, Anthony B.; Taylor, Kathryn L.

2018-01-01

OBJECTIVE To examine the association between treatment-related side effects and cancer-specific and general quality of life (QOL) among long-term prostate cancer survivors. MATERIALS AND METHODS Within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we conducted telephone interviews with prostate cancer survivors (N = 518) who were 5-10 years after diagnosis. We assessed demographic and clinical information, sexual, urinary, and bowel treatment-related side effects (Expanded Prostate Cancer Index Composite), cancer-specific QOL (Functional Assessment of Cancer Therapy—total score), and general QOL (the Medical Outcomes Study Short Form 12’s physical and mental subscales). RESULTS Participants were aged 74.6 years on average, primarily White (88.4%), and married (81.7%). Pearson correlation coefficients between the 3 treatment-related side effect domains (urinary, sexual, and bowel) and QOL ranged between 0.14 and 0.42 (P <.0001). Multivariable linear regression analyses revealed that poorer urinary and sexual functioning and greater bowel side effects were independently associated with poorer cancer-specific QOL (P <.0001). Bowel and urinary functions were also associated with poorer general QOL on the Medical Outcomes Study Short Form 12’s physical component summary and mental component summary (P <.05). Bowel side effects demonstrated the strongest association with all QOL outcomes. CONCLUSION Treatment-related side effects persisted for up to 10 years after diagnosis and continued to be associated with men’s QOL. These results suggest that each of the treatment-related side effects was independently associated with cancer-specific QOL. Compared with the other Expanded Prostate Cancer Index Composite domains, bowel side effects had the strongest association with cancer-specific and general QOL. These associations emphasize the tremendous impact that bowel side effects continue to have for men many years after their initial diagnosis. PMID:24975711

Consumer confusion between prescription drug precautions and side effects.

PubMed

Amoozegar, Jacqueline B; Rupert, Douglas J; Sullivan, Helen W; O'Donoghue, Amie C

2017-06-01

Multiple studies have identified consumers' difficulty correctly interpreting risk information provided about prescription drugs, whether in printed format or online. This study's purpose was to explore whether consumers can distinguish between prescription drug precautions and side effects presented on brand-name drug websites. Participants (n=873) viewed fictitious drug websites that presented both precautions and side effects for one of four drugs, and they completed a survey assessing recall and comprehension. We coded open-ended recall data to identify whether drug precautions were mentioned and, if so, how they were interpreted. Approximately 15% of participants mentioned at least one drug precaution. The majority (59.7%) misinterpreted precautions as potential side effects. Participants who misinterpreted precautions rated the drugs as significantly more likely to cause side effects than participants who accurately interpreted the precautions. Age, education, literacy, and other factors did not appear to predict precaution interpretation. At least some consumers are likely to interpret precautions on drug websites as potential side effects, which might affect consumer preferences, treatment decisions, and medication safety. Healthcare providers should be aware of this potential confusion, assess patients' understanding of precautions and potential side effects, and address any misunderstandings. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Ocular side-effects associated with imatinib mesylate (Gleevec).

PubMed

Fraunfelder, Frederick W; Solomon, Jonathan; Druker, Brian J; Esmaeli, Bita; Kuyl, Jennifer

2003-08-01

This retrospective case series describes ocular side-effects associated with imatinib mesylate (Gleevec) and the clinical characteristics of these adverse reactions. A chart review of 104 patients on imatinib mesylate therapy from Oregon Health & Science University's Cancer Center were studied with regard to ocular side-effects. In addition, spontaneous reports from the Food and Drug Administration, the World Health Organization, and the National Registry of Drug-Induced Ocular Side-Effects databases were reviewed, including a Medline literature search. Seventy-three (70%) of the patients at OHSU developed periorbital edema and 19 patients (18%) developed epiphora after receiving imatinib mesylate. Average dose was 407.5+/-60 mg. Periorbital edema occurred an average of 68+/-48 days after initiation of therapy. WHO classification of side-effects is as follows: certain: periorbital edema; probable: epiphora; possible: extraocular muscle palsy, ptosis, blepharoconjunctivitis; unlikely: glaucoma, papilledema, retinal hemorrhage, photosensitivity, abnormal vision, and increased intraocular pressure. Periorbital edema and epiphora are the two most common ocular side-effects related to imatinib mesylate therapy. Clinical characteristics of imatinib mesylate induced periorbital edema are described. Management of ocular side-effects is conservative except in very rare cases of visually significant periorbital edema.

Fast image decompression for telebrowsing of images

NASA Technical Reports Server (NTRS)

Miaou, Shaou-Gang; Tou, Julius T.

1993-01-01

Progressive image transmission (PIT) is often used to reduce the transmission time of an image telebrowsing system. A side effect of the PIT is the increase of computational complexity at the viewer's site. This effect is more serious in transform domain techniques than in other techniques. Recent attempts to reduce the side effect are futile as they create another side effect, namely, the discontinuous and unpleasant image build-up. Based on a practical assumption that image blocks to be inverse transformed are generally sparse, this paper presents a method to minimize both side effects simultaneously.

A potential role for adjunctive vitamin D therapy in the management of weight gain and metabolic side effects of second-generation antipsychotics

PubMed Central

Nwosu, Benjamin U.; Meltzer, Bruce; Maranda, Louise; Ciccarelli, Carol; Reynolds, Daniel; Curtis, Laura; King, Jean; Frazier, Jean A.; Lee, Mary M.

2014-01-01

Second-generation antipsychotic (SGA) medications introduced about 20 years ago are increasingly used to treat psychiatric illnesses in children and adolescents. There has been a five-fold increase in the use of these medications in U.S. children and adolescents in the past decade. However, there has also been a parallel rise in the incidence of side effects associated with these medications, such as obesity, dyslipidemia, insulin resistance, and diabetes mellitus. Despite the severity of these complications and their financial impact on the national healthcare budget, there is neither a clear understanding of the mechanisms contributing to these side effects nor the best ways to address them. Studies that examined lifestyle modification and pharmaceutical agents have yielded mixed results. Therefore, clinical studies using agents, such as vitamin D, which are inexpensive, readily available, with low side effects profile, and have mechanisms to counteract the metabolic side effects of SGA agents, are warranted. Vitamin D is a prohormone with skeletal and extraskeletal properties that could potentially reduce the severity of these metabolic side effects. Its role as an adjunctive therapy for the management of metabolic side effects of SGA agents has not been adequately studied. Effective strategies to curb these side effects will improve the overall health of youths with psychiatric illnesses who receive SGAs. Herein we present a pilot study on the use of vitamin D in patients on treatment with SGAs. PMID:22145446

Choreatic Side Effects of Deep Brain Stimulation of the Anteromedial Subthalamic Nucleus for Treatment-Resistant Obsessive-Compulsive disorder.

PubMed

Mulders, Anne E P; Leentjens, Albert F G; Schruers, Koen; Duits, Annelien; Ackermans, Linda; Temel, Yasin

2017-08-01

Patients with treatment-resistant obsessive-compulsive disorder (OCD) are potential candidates for deep brain stimulation (DBS). The anteromedial subthalamic nucleus (STN) is among the most commonly used targets for DBS in OCD. We present a patient with a 30-year history of treatment-resistant OCD who underwent anteromedial STN-DBS. Despite a clear mood-enhancing effect, stimulation caused motor side effects, including bilateral hyperkinesia, dyskinesias, and sudden large amplitude choreatic movements of arms and legs when stimulating at voltages greater than approximately 1.5 V. DBS at lower amplitudes and at other contact points failed to result in a significant reduction of obsessions and compulsions without inducing motor side effects. Because of this limitation in programming options, we decided to reoperate and target the ventral capsule/ventral striatum (VC/VS), which resulted in a substantial reduction in key obsessive and compulsive symptoms without serious side effects. Choreatic movements and hemiballismus have previously been linked to STN dysfunction and have been incidentally reported as side effects of DBS of the dorsolateral STN in Parkinson disease (PD). However, in PD, these side effects were usually transient, and they rarely interfered with DBS programming. In our patient, the motor side effects were persistent, and they made optimal DBS programming impossible. To our knowledge, such severe and persistent motor side effects have not been described previously for anteromedial STN-DBS. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement of Side Effects of Drugs

PubMed Central

Huskisson, E. C.; Wojtulewski, J. A.

1974-01-01

In a clinical trial of two antirheumatic agents two methods of collection of side effects were used, one with and the other without a check list of possible symptoms. Findings suggested that the use of a check list interfered with the collection of side effects. Known side effects of aspirin—tinnitus, deafness, and gastrointestinal disturbance—were more efficiently shown and symptoms not included in the check list were more likely to be reported when a check list was not used. PMID:4853118

Comparison of hair removal efficacy and side effect of neodymium:Yttrium-aluminum-garnet laser and intense pulsed light systems (18-month follow-up).

PubMed

Szima, Georgina Zita; Janka, Eszter Anna; Kovács, Anikó; Bortély, Blanka; Bodnár, Edina; Sawhney, Irina; Szabó, Éva; Remenyik, Éva

2017-06-01

Photothermal destruction of hair shaft melanin with intense pulsed light (IPL) and neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has become an effective treatment of hair removal. Our aim was to compare efficacy, satisfactory levels, safety, and side effects of Nd:YAG and IPL in hair reduction. This was a prospective randomized intrapatient, right-left, assessor-blinded comparison of Nd:YAG vs IPL. There were 38 volunteers recruited. Seven sessions were performed. Hair count, efficacy, and side effects were compared before and after each treatment and 6 months after the last treatment. In respect of 12 volunteers, we have examined the reduction in hair after 18 months. Initially, there was no significant difference between the numbers of hair follicles. There was significant hair reduction after each treatment on the Nd:YAG-treated side. The hair reduction became significant after the third treatment with IPL. Comparison of the efficacy of the two devices on each visits showed no significant difference. There was statistically lower pain score on the IPL-treated side and statistically higher erythema, burning sensation, and edema on the Nd:YAG-treated side. Statistically lower side effect score was observed on the IPL-treated side. Eight months after the last treatment, there was significant hair reduction both on the Nd:YAG and on the IPL-treated side, and there was no difference between the efficacy. The patient satisfaction scores were higher with the IPL. Unwanted hair can be reduced by both systems safely and effectively; however, IPL has less side effects and higher satisfaction scores. © 2017 Wiley Periodicals, Inc.

Side effects during subcutaneous immunotherapy in children with allergic diseases.

PubMed

Tophof, Max A; Hermanns, Anne; Adelt, Thomas; Eberle, Peter; Gronke, Christine; Friedrichs, Frank; Knecht, Roland; Mönter, Ernst; Schöpfer, Helmut; Schwerk, Nicolaus; Steinbach, Jörg; Umpfenbach, Hans-Ulrich; Weißhaar, Christian; Wilmsmeyer, Brigitte; Bufe, Albrecht

2018-05-01

Allergen-specific immunotherapy is the only causal form of therapy for IgE-mediated allergic diseases. Subcutaneous immunotherapy (SCIT) is considered safe and well tolerated in adults, yet there is less evidence of safety in the pediatric population. A non-interventional prospective observing longitudinal study was carried out to determine the incidence of local and systemic side effects by SCIT, routinely performed in pediatric patients. A total of 581 pediatric patients were observed in 18 study centers between March 2012 and October 2014, recording 8640 treatments and 10 015 injections. A total of 54.6% of the patients experienced immediate local side effects at least once; delayed local side effects were seen in 56.1%. Immediate systemic adverse reactions occurred in 2.2% of patients; 7.4% experienced delayed systemic side effects. However, severe systemic side effects (grade III in the classification of Ring and Messmer) were seen in 0.03% of all treatments, all appearing within 30 minutes after the injections. No grade IV reactions were observed. In addition, many potential risk factors were investigated, yet only a few were found to be associated with the occurrence of side effects. Subcutaneous immunotherapy is a safe form of therapy in pediatric patients, with similar rates of local side effects compared to adult patients and low rates of severe systemic side effects. However, local and systemic reactions occurring later than 30 minutes after injection were observed more often than expected, which makes it essential to be attentive on behalf of pediatricians, patients, and parents. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

PubMed

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Specific expectancies are associated with symptomatic outcomes and side effect burden in a trial of chamomile extract for Generalized Anxiety Disorder

PubMed Central

Keefe, John R.; Amsterdam, Jay; Li, Qing S; Soeller, Irene; DeRubeis, Robert; Mao, Jun J

2017-01-01

Objective Patient expectancies are hypothesized to contribute to the efficacy and side effects of psychiatric treatments, but little research has investigated this hypothesis in the context of psychopharmacological therapies for anxiety. We prospectively investigated whether expectancies predicted efficacy and adverse events in oral therapy for Generalized Anxiety Disorder (GAD), controlling for confounding patient characteristics correlating with outcomes. Methods Expectancies regarding treatment efficacy and side effects were assessed at baseline of an eight week open-label phase of a trial of chamomile for Generalized Anxiety Disorder (GAD). The primary outcome was patient-reported GAD-7 scores, with clinical response and treatment-emergent side-effects as secondary outcomes. Expectancies were used to predict symptomatic and side-effect outcomes. Results Very few baseline patient characteristics predicted either type of expectancy. Controlling for a patient’s predicted recovery based on their baseline characteristics, higher efficacy expectancies at baseline predicted greater change on the GAD-7 (adjusted β = −0.19, p = 0.011). Efficacy expectancies also predicted a higher likelihood of attaining clinical response (adjusted odds ratio = 1.69, p = 0.002). Patients with higher side effect expectancies reported more side effects (adjusted log expected count = 0.26, p = 0.038). Efficacy expectancies were unrelated to side effect reports (log expected count = −0.05, p = 0.680), and side effect expectancies were unrelated to treatment efficacy (β = 0.08, p = 0.306). Conclusions Patients entering chamomile treatment for GAD with more favorable self-generated expectancies for the treatment experience greater improvement and fewer adverse events. Aligning patient expectancies with treatment selections may optimize outcomes. PMID:27716513

Melting in the Arctic: Preparing Now for Possibilities in the Future

DTIC Science & Technology

2016-04-04

shipping, exploration, research, tourism , military patrols, and unfortunately the potential for conflict. So far, climate change, diplomacy, and economic...presence such as shipping, exploration, research, tourism , military patrols, and unfortunately the potential for conflict. So far, climate change...3 Tourism

[Extrapyramidal side-effects: avoidance, diagnosis and treatment].

PubMed

Fleischhacker, W Wolfgang; Widschwendter, Christian

2005-04-01

Acute extrapyramidal side-effects (EPS) are a common phenomenon of treatment with antipsychotics. They are associated with a substantial reduction of the patient's quality of life and of compliance with the treatment. This article gives an overview of the different forms of EPS. It outlines strategies to avoid these side-effects and discusses problems in diagnosis and treatment. In comparison to conventional compounds, the clearest advantage of new generation antipsychotics is a reduced risk of the occurrence of extrapyramidal side-effects (EPS). Many studies have found that newer antipsychotics have a lesser propensity to causes EPS. Nevertheless, there are some conflicting results on this topic. This article discusses some of these results and sheds light on methodological problems in the evaluation of side-effects of antipsychotic treatment.

Chemotherapy: the effect of oral cryotherapy on the development of mucositis.

PubMed

Karagözoğlu, Serife; Filiz Ulusoy, Mehlika

2005-07-01

The aim of this study is to investigate the effect of oral cryotherapy on the development of chemotherapy-induced mucositis in patients administered combined chemotherapy. Mucositis has been of interest to scientists for more than 20 years. Unfortunately, this has not resulted in the development of standard procedures for prevention and management. To cope with this side-effect and to prevent opportunistic infections that may emerge during treatment, attempts are taken to provide preventative and comfort measures. In this context, cryotherapy (oral cooling) has become popular as a cheap and readily applicable method in preventing the developing due the rapid infusion of chemotherapy agents, or decreasing its severity. Study involved 60 patients, 30 of whom were in the study group and 30 in the control group. Ice cubes at a size that can be moved easily in the mouth and whose corners have been smoothed in order that they will not cause irritation in the mouth has been used in oral cryotherapy in the study group. Oral chemotherapy was initiated five minutes before chemotherapy and maintained during venous infusions of etoposide (Vepesid), platinol (Cisplatin), mitomycin (Mitomycin-C) and vinblastin (Velbe) depending on the chemotherapy course. According to Patient-Judged Mucositis Grading, the rate of mucositis is 36.7% in study group and 90.0% in control group, the difference between two groups being statistically significant (P < 0.05). According to Physician-Judged Mucositis Grading, the rate of mucositis is 10.0% in the study group and 50.0% in the control group, the difference between two groups being statistically significant (P < 0.05). Oral pH values decreased in 90% of the subjects in study group, i.e. mucositis risk was reduced whereas oral pH values remained unchanged or decreased in 86.7% of the subjects in the control group, namely mucositis risk increased. The difference between study and control groups in terms of the change in pH values after chemotherapy was found to be statistically significant (P < 0.05). Our findings have demonstrated that oral cryotherapy makes an important contribution to the protection of oral health by reducing the mucositis score according to patient- and physician-judged mucositis score and by increasing oral pH values. Aggressive cancer therapy places patients at greater risk for oral complications and treatment-related consequences. Unfortunately, prevention and/or treatment of such oral sequelae have often become overlooked as priorities of the treatment team. Effective approaches for the prevention or treatment of oral mucositis have not been standardized, and vary considerably among institutions. Prophylactic measures begin with an increased emphasis on improved oral status. Oral cryotherapy, the therapeutic administration of cold, is a prophylactic measure for oral inflammation. The relevance for clinical practice will be to understand the content of mucositis; comprehensive care should focus on the prevention of this complication in the clinical practice.

Beyond Job Satisfaction: A Five-Year Prospective Analysis of the Dispositional Approach to Work Attitudes

ERIC Educational Resources Information Center

Bowling, Nathan A.; Beehr, Terry A.; Lepisto, Lawrence R.

2006-01-01

Mounting evidence indicates a dispositional component to global job satisfaction. Unfortunately, however, relatively little attention has been given to the potential effects of dispositions on work-related attitudes other than global job satisfaction. We used a five-year prospective design to investigate the relationships of affective disposition…

Business Intelligence: The Smart Way to Track Academic Collections

ERIC Educational Resources Information Center

Kelly, Debra

2005-01-01

University collections are a vital source of knowledge for researchers and often a source of pride for universities. Without an effective way to manage and query them, however, collections often go underutilized. Parts of a collection can remain untapped for years, and the larger it grows, the more difficult management becomes. Unfortunately,…

The Effects of a Model Developmental Mathematics Program on Elementary and Middle School Preservice Teachers

ERIC Educational Resources Information Center

Gerber, Lindsey N.

2012-01-01

Teacher quality is instrumental in improving student performance. Unfortunately, discrepancies between teacher preparation programs and national and state K-12 student standards have contributed to the difficult task of producing quality teachers. The contemporary mathematics education paradigm used at most colleges and universities relies on…

Behavior of class-level landscape metrics across gradients of class aggregation and area

Treesearch

Maile C. Neel; Kevin McGarigal; Samuel A. Cushman

2004-01-01

Habitat loss and fragmentation processes strongly affect biodiversity conservation in landscapes undergoing anthropogenic land use changes. Many attempts have been made to use landscape structure metrics to quantify the independent and joint effects of these processes. Unfortunately, ecological interpretation of those metrics has been plagued by lack of thorough...

Anti-Tobacco School-Based Programming for Deaf Youth

ERIC Educational Resources Information Center

Berman, Barbara A.; Guthmann, Debra S.

2007-01-01

As part of the effort to reduce cigarette smoking--the single most preventable cause of death in the society--researchers have tried for over half a century to identify effective school-based anti-tobacco education that can discourage tobacco use among children and adolescents. Unfortunately, deaf and hard of hearing young people have been largely…

An Evaluation of Observational Methods for Measuring Response to Classwide Intervention

ERIC Educational Resources Information Center

Briesch, Amy M.; Hemphill, Elizabeth M.; Volpe, Robert J.; Daniels, Brian

2015-01-01

Although there is much research to support the effectiveness of classwide interventions aimed at improving student engagement, there is also a great deal of variability in terms of how response to group-level intervention has been measured. The unfortunate consequence of this procedural variability is that it is difficult to determine whether…

Brain Gym: Pseudoscientific Practice

ERIC Educational Resources Information Center

Kroeze, Kevin; Hyatt, Keith J.; Lambert, M. Chuck

2016-01-01

There is an abundance of scams and pseudoscientific practices promising seemingly magical cures for whatever ails a person. A short viewing of late night television will readily reveal a whole host of scams that may be more effective at relieving the viewer of the cash in his or her pocket than alleviating any unwanted symptoms. Unfortunately,…

Requirements, Benefits, and Concerns of Technology Education Cooperating Teachers: An Exploratory Study among Nine Midwest Universities

ERIC Educational Resources Information Center

Busby, Joe R.; Mupinga, Davison M.

2007-01-01

Student teaching experience is important in the professional preparation of teachers. Successful teaching practice hinges on the effectiveness of cooperating teachers (CTs) who spend considerable time supervising and mentoring student teachers. Unfortunately, the welfare of the cooperating teachers is often neglected, and this is detrimental to…

Promoting Leisure-Time Physical Activity for Students with Visual Impairments Using Generalization Tactics

ERIC Educational Resources Information Center

Haegele, Justin A.

2015-01-01

Important and favorable health effects of physical activity have been well documented. Unfortunately, school-aged individuals who are visually impaired tend to be less physically active than their peers without visual impairments. Although students with visual impairments learn skills to participate in physical activities during their PE classes,…

Cultivating Efficacious Teachers: A Case Study of the Impact of Socialization on Self-Efficacy Belief Development

ERIC Educational Resources Information Center

Lowder, Garrett

2017-01-01

Education preparation institutions have long sought the most effective preparation practices for preparing tomorrow's educators. Unfortunately, understanding best practices in teacher preparation is fraught with ambiguity. Key facets of instruction on theory and clinical experience are understood to be necessary elements of preparation, and…

Counting on COUNTER: The Current State of E-Resource Usage Data in Libraries

ERIC Educational Resources Information Center

Welker, Josh

2012-01-01

Any librarian who has managed electronic resources has experienced the--for want of words--"joy" of gathering and analyzing usage statistics. Such statistics are important for evaluating the effectiveness of resources and for making important budgeting decisions. Unfortunately, the data are usually tedious to collect, inconsistently organized, of…

Bayesian Analysis of Recognition Memory: The Case of the List-Length Effect

ERIC Educational Resources Information Center

Dennis, Simon; Lee, Michael D.; Kinnell, Angela

2008-01-01

Recognition memory experiments are an important source of empirical constraints for theories of memory. Unfortunately, standard methods for analyzing recognition memory data have problems that are often severe enough to prevent clear answers being obtained. A key example is whether longer lists lead to poorer recognition performance. The presence…

Current Juvenile Corrections Professional Development Practices and Future Directions

ERIC Educational Resources Information Center

Gagnon, Joseph C.; Houchins, David E.; Murphy, Kristin M.

2012-01-01

Personnel in juvenile corrections (JC) work with students who have challenging academic, behavioral, and mental health needs. The complexity of the JC setting requires personnel to be highly skilled in effective practices to meet the demands of their job. Unfortunately, juvenile correctional personnel are neglected as an important link in the…

Effects of Violent Media on Verbal Task Performance in Gifted and General Cohort Children

ERIC Educational Resources Information Center

Çetin, Yakup; Wai, Jonathan; Altay, Cengiz; Bushman, Brad J.

2016-01-01

"Retraction Notice--Joseph Hilgard, postdoctoral fellow at the Annenberg Public Policy Center at the University of Pennsylvania, contacted the journal with questions regarding the pattern of results and conducted reanalyses of the data that called into question the credibility of the data. Unfortunately, the data collection procedures could…

Ten Tips for Using Co-Planning Time More Efficiently

ERIC Educational Resources Information Center

Murawski, Wendy W.

2012-01-01

In this era of collaboration, educators are frequently expected to co-plan with one another on a regular basis. Unfortunately, the expectation of co-planning is not often accompanied by the time required or by the strategies necessary to plan effectively and efficiently for the inclusive classroom. This article provides 10 concrete tips for…

Digital Image Correlation of Flapping Wings for Micro-Technologies

DTIC Science & Technology

2011-08-01

polyethylene ( LDPE ) 0.03-mm-thick plastic was used for the wing skin, which was tautly stretched and taped to a solid surface. The LDPE is adhered to the wing...simplicity purposes and to maintain minimal skin thickness. Unfortunately, the effect of adding the paint to the LDPE is unknown since the wing must

Invasions by Harmonia axyridis (Pallas) (Coleoptera: Coccinellidae) in the Western Hemisphere: implications for South America

Treesearch

Robert L. Koch; Robert C. Venette; William D. Hutchison

2006-01-01

The multicolored Asian lady beetle, Harmonia axyridis (Pallas), native to Asia, has recently been detected in South America after successfully invading North America and Europe. This coccinellid is a voracious predator; therefore, it is popular and effective in biological control. Unfortunately, H. axyridis also has associated...

Establishing Internationally-Competent Leaders for the Future: Promoting an Agenda for Social Justice, Equity, and Intercultural Sensitivity

ERIC Educational Resources Information Center

Talbert-Johnson, Carolyn

2009-01-01

To be successful in a global economy, U.S. candidates must possess international knowledge, intercultural communication skills, and global perspectives to effectively teach diverse student populations. Unfortunately, teacher education programs have not prepared candidates to be internationally competent leaders for the future. Schools of education…

When Others' Performance Just Isn't Good Enough: Educational Leaders' Framing of Concerns in Private and Public

ERIC Educational Resources Information Center

Sinnema, Claire E. L.; Le Fevre, Deidre; Robinson, Viviane M. J.; Pope, Denyse

2013-01-01

Effective instructional leadership demands that leaders address the inevitable problems and concerns that exist in any educational organization. Unfortunately, much evidence suggests that many important concerns, including teacher performance issues, continue to be unaddressed and unresolved. This article portrays the nature of concerns facing 77…

Promising Strategies for Attracting and Retaining Successful Urban Teachers

ERIC Educational Resources Information Center

Stotko, Elaine M.; Ingram, Rochelle; Beaty-O'Ferrall, Mary Ellen

2007-01-01

In the debate about urban school effectiveness and teacher quality, one proposition has emerged as indisputable: The success of urban schools depends heavily on the quality of the teachers who serve the schools and the administrators who support the teachers. Unfortunately, urban school district recruitment policies are often not aligned with…

Time for a Plant Clinostat: Effects of Light and Gravity on Plants

ERIC Educational Resources Information Center

Hershey, David R.

2005-01-01

Plant tropisms--their directional movement in response to stimuli--are a fundamental concept in plant science and excite students because they are the observable signs of life in plants. Unfortunately, the precollege teaching literature is full of tropism misconceptions. An inexpensive clock clinostat is invaluable for student gravitropism and…

Intracloacal inoculation, an effective screening method for determining the efficacy of probiotic bacterial isolates against Campylobacter colonization in broiler chickens

USDA-ARS?s Scientific Manuscript database

Campylobacter is a leading cause of foodborne illness worldwide. It is common in poultry, and human infections are often associated with consumption of contaminated poultry products. One strategy to reduce Campylobacter colonization in poultry is by using oral probiotics. Unfortunately, oral probiot...

The Effect of Physical Training on Static Balance in Young People with Intellectual Disability

ERIC Educational Resources Information Center

Jankowicz-Szymanska, A.; Mikolajczyk, E.; Wojtanowski, W.

2012-01-01

Intellectual disability affects all spheres of people's lives who suffer from it. It lowers the level of intellectual functioning, often stigmatizes, characteristically changing features, and decreases motor performance. Unfortunately, modern medicine cannot cure intellectual disability; however, there is a chance to improve the quality of life of…

Bringing Mental Health Needs into Focus through School Counseling Program Transformation

ERIC Educational Resources Information Center

Gruman, Diana H.; Marston, Toby; Koon, Holly

2013-01-01

Professional school counselors are educational leaders with training and expertise to address the mental health concerns of students. Unfortunately, work conditions at some schools can create barriers to the delivery of effective mental health services. This article presents a case of one rural, diverse high school that transformed its school…

Diagnosing Causes of Teacher Retention, Mobility and Turnover: Guidelines for TIF Grantees

ERIC Educational Resources Information Center

Finster, Matthew

2015-01-01

To effectively address teacher turnover, Teacher Incentive Fund (TIF) grantees need to follow an approach that entails aligning the tracking, diagnosing, and intervening processes. Unfortunately, too often retention strategies are implemented without regard to the various types of teacher turnover and specific data about the causes of turnover.…

Using Repetition to Make Ideas Stick

ERIC Educational Resources Information Center

Lykins, Alicia N.

2015-01-01

In elementary school, the use of repetitive songs to help children remember concepts is commonplace and is usually very effective. Unfortunately for many students, this strategy is generally not used in later grades. A group of mathematics teachers at Westerville South High School in Westerville, Ohio, have taken this approach to a new creative…

Causes and Management of Treatment-Resistant Panic Disorder and Agoraphobia: A Survey of Expert Therapists

ERIC Educational Resources Information Center

Sanderson, William C.; Bruce, Timothy J.

2007-01-01

Cognitive behavior therapy (CBT) is recognized as an effective psychological treatment for panic disorder (PD). Despite its efficacy, some clients do not respond optimally to this treatment. Unfortunately, literatures on the prediction, prevention, and management of suboptimal response are not well developed. Considering this lack of empirical…

Practical Applications of Reading Research.

ERIC Educational Resources Information Center

Harris, Albert J.

There are three main reasons why reading research has not had a stronger influence on what goes on in schools. The first reason is the powerful impact of social forces such as the bandwagon effect, the pendulum swing, and the prevailing climate of opinion. These factors determine to an unfortunately large degree whether or not particular research…

Development of an Online Hazards Atlas to Improve Disaster Awareness

ERIC Educational Resources Information Center

Battersby, Sarah E.; Mitchell, Jerry T.; Cutter, Susan L.

2011-01-01

Understanding the causes, effects and geographic patterns of local hazards is important for helping individuals make educated decisions about how to respond to their threat. Unfortunately, it is often difficult to find comprehensive sources of information about local hazards. In this paper, we discuss the development of an online hazards atlas for…

Bits, Bangs, or Bucks? The Coming Information Crisis

DTIC Science & Technology

2001-01-01

information is becoming increasingly important, but unfortunately the OR profession’s ability to measure its contribution is still primitive. We are not ... good at deciding whether information is cost/effective or whether information is more important than firepower, and yet precisely these questions will be asked more and more frequently as budgets shrink.

Evaluating the Validity and Reliability of a Student Self-Advocacy Teacher Rating Scale

ERIC Educational Resources Information Center

Walick, Christopher M.

2017-01-01

Self-advocacy skills are critical to high school and post-secondary success. Unfortunately, students with disabilities often times struggle with self-advocacy. While there are effective, evidence-based programs to teach self-advocacy skills, there are few scales that directly measure self-advocacy. The current research study was conducted to…

The Effectiveness of Blended Instruction in Core Postsecondary Mathematics Courses

ERIC Educational Resources Information Center

Bargagliotti, Anna; Botelho, Fernanda; Gleason, Jim; Haddock, John; Windsor, Alistair

2012-01-01

Most students in U.S. universities are required to take a collection of core courses regardless of their degree or major. These courses are known as "general education" courses. The general education requirements typically include at least one mathematics course. Unfortunately each year hundreds of thousands of students in the US do not…

Open the Windows: Design New Spaces for Learning

ERIC Educational Resources Information Center

Johnson, Christopher

2011-01-01

As a technologist, the author is interested in how the digital world is changing the educational landscape. As he began to research effective learning spaces, he discovered that the architecture, design, and school facilities communities are making a great deal of progress in creating better classrooms and school buildings. Unfortunately, many in…

Lexical Inferencing in First and Second Language Listening

ERIC Educational Resources Information Center

Van Zeeland, Hilde

2014-01-01

Lexical inferencing is an important vocabulary learning strategy. Unfortunately, almost all research on this issue has been carried out in the reading context. This study is the first to directly measure lexical inferencing success in listening, by both native (N?=?47) and nonnative (N?=?30) speakers of English. It analysed the effects of…

Symposium: Talking about Race and Whiteness in "Crash"

ERIC Educational Resources Information Center

Middleton, Joyce Irene

2007-01-01

Teaching films like "Crash" gives teachers and researchers the opportunity to discuss films as social texts that engage students in critical thinking and self-reflection. This particular movie is especially effective in its use of a pulp-fiction visual rhetoric. Unfortunately, the film equates and replaces the term "race" with the term "prejudice"…

Integrating a Social Behavior Intervention during Small Group Academic Instruction Using a Total Group Criterion Intervention

ERIC Educational Resources Information Center

Rodriguez, Billie Jo; Anderson, Cynthia M.

2014-01-01

Total group contingencies, a variation of interdependent group contingencies, provide educators with an efficient and effective mechanism to improve social behavior and increase academic skills. Their utility has not been examined in small educational groups. This is unfortunate as supplemental instruction frequently is delivered in small group…

Oral health impacts of medications used to treat mental illness.

PubMed

Cockburn, N; Pradhan, A; Taing, M W; Kisely, S; Ford, P J

2017-12-01

Many psychotropic medications affect oral health. This review identified oral side effects for antidepressant, antipsychotic, anticonvulsant, antianxiety and sedative drugs that are recommended in Australia for the management of common mental illnesses and provides recommendations to manage these side-effects. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat common mental health conditions. For each medication, the generic name, class, and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (eMIMs) and UpToDate databases. Meyler's Side Effect of Drugs Encyclopaedia was used to identify additional oral adverse reactions to these medications. Fifty-seven drugs were identified: 23 antidepressants, 22 antipsychotics or mood stabilisers, and 12 anxiolytic or sedative medications. Xerostomia (91%) the most commonly reported side effect among all classes of medications of the 28 identified symptoms. Other commonly reported adverse effects included dysguesia (65%) for antidepressants, and tardive dyskinesia (94%) or increased salivation (78%) for antipsychotic medications. While xerostomia has often been reported as a common adverse effect of psychotropic drugs, this review has identified additional side effects including dysguesia from antidepressants and tardive dyskinesia and increased salivation from antipsychotics. Clinicians should consider oral consequences of psychotropic medication in addition to other side-effects when prescribing. For antidepressants, this would mean choosing duloxetine, agomelatine and any of the serotonin re-uptake inhibitors except sertraline. In the case of antipsychotics and mood stabilisers, atypical agents have less oral side effects than older alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting drug side-effect profiles: a chemical fragment-based approach

PubMed Central

2011-01-01

Background Drug side-effects, or adverse drug reactions, have become a major public health concern. It is one of the main causes of failure in the process of drug development, and of drug withdrawal once they have reached the market. Therefore, in silico prediction of potential side-effects early in the drug discovery process, before reaching the clinical stages, is of great interest to improve this long and expensive process and to provide new efficient and safe therapies for patients. Results In the present work, we propose a new method to predict potential side-effects of drug candidate molecules based on their chemical structures, applicable on large molecular databanks. A unique feature of the proposed method is its ability to extract correlated sets of chemical substructures (or chemical fragments) and side-effects. This is made possible using sparse canonical correlation analysis (SCCA). In the results, we show the usefulness of the proposed method by predicting 1385 side-effects in the SIDER database from the chemical structures of 888 approved drugs. These predictions are performed with simultaneous extraction of correlated ensembles formed by a set of chemical substructures shared by drugs that are likely to have a set of side-effects. We also conduct a comprehensive side-effect prediction for many uncharacterized drug molecules stored in DrugBank, and were able to confirm interesting predictions using independent source of information. Conclusions The proposed method is expected to be useful in various stages of the drug development process. PMID:21586169

Impact of present and past antipsychotic side effects on attitude toward typical antipsychotic treatment and adherence.

PubMed

Lambert, M; Conus, P; Eide, P; Mass, R; Karow, A; Moritz, S; Golks, D; Naber, D

2004-11-01

(1) determine which antipsychotic side effects (SE) schizophrenic patients consider the most distressing during treatment with typical antipsychotics, (2) measure the impact of actual and past SE on patients' attitude toward antipsychotics and (3) assess the influence of both on adherence. The 213 schizophrenics, treated with conventional antipsychotics, were recruited in two psychiatric hospitals in Hamburg. Subjects were assessed about type and severity of present and past side effects and their attitude and adherence to antipsychotic treatment. The 82 (39%) patients presented present SE while 131 (61%) did not. Sexual dysfunctions (P < 0.001), extrapyramidal (P < 0.05) and psychic side effects (P < 0.05) were rated as significantly subjectively more distressing than sedation or vegetative side effects. Patients presenting with present SE compared with patients without present SE had a significantly more negative general attitude toward antipsychotics (P < 0.05), were more doubtful about their efficacy (P < 0.01) and were less likely to encourage a relative to take such a medication in case of need (P < 0.001). A regression analysis indicated that nonadherence was mainly influenced by negative general and efficacy attitudes toward antipsychotics and the experience of past or present antipsychotic side effects. All antipsychotic side effects, present or past, can have a durable negative impact on patient's attitude toward antipsychotic treatment and adherence. Non-adherence is mainly determined, among other factors, by these negative attitudes, which are partly influenced by the experience of past or present antipsychotic-induced side effects.