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.

Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain

PubMed Central

Olson, Keith M.; Lei, Wei; Keresztes, Attila; LaVigne, Justin; Streicher, John M.

2017-01-01

Opioid drugs like morphine and fentanyl are the gold standard for treating moderate to severe acute and chronic pain. However, opioid drug use can be limited by serious side effects, including constipation, tolerance, respiratory suppression, and addiction. For more than 100 years, we have tried to develop opioids that decrease or eliminate these liabilities, with little success. Recent advances in understanding opioid receptor signal transduction have suggested new possibilities to activate the opioid receptors to cause analgesia, while reducing or eliminating unwanted side effects. These new approaches include designing functionally selective ligands, which activate desired signaling cascades while avoiding signaling cascades that are thought to provoke side effects. It may also be possible to directly modulate downstream signaling through the use of selective activators and inhibitors. Separate from downstream signal transduction, it has also been found that when the opioid system is stimulated, various negative feedback systems are upregulated to compensate, which can drive side effects. This has led to the development of multi-functional molecules that simultaneously activate the opioid receptor while blocking various negative feedback receptor systems including cholecystokinin and neurokinin-1. Other novel approaches include targeting heterodimers of the opioid and other receptor systems which may drive side effects, and making endogenous opioid peptides druggable, which may also reduce opioid mediated side effects. Taken together, these advances in our molecular understanding provide a path forward to break the barrier in producing an opioid with reduced or eliminated side effects, especially addiction, which may provide relief for millions of patients. PMID:28356897

Older People's Preferences for Side Effects Associated with Antimuscarinic Treatments of Overactive Bladder: A Discrete-Choice Experiment.

PubMed

Decalf, Veerle H; Huion, Anja M J; Benoit, Dries F; Denys, Marie-Astrid; Petrovic, Mirko; Everaert, Karel C M M

2017-08-01

Understanding the importance older people attribute to the different side effects associated with oral antimuscarinic treatments for overactive bladder (OAB) could help inform prescribers, healthcare policy makers and the drug industry. Our objective was to quantify the importance of the most prevalent cognitive and side effects of oral antimuscarinic treatments for OAB in older people. We conducted a discrete-choice experiment (DCE) with the assistance of an interviewer with community-dwelling and hospitalized older people aged >65 years. The DCE involved two hypothetical drugs for imaginary OAB, with three levels of four side effects for each drug, and the International Consultation on Incontinence Questionnaire-Overactive Bladder and EuroQol 5-Dimensions (EQ-5D) questionnaire were also administered. Data were analysed using a conditional logit model. In total, 276 older people participated in the study. The median age was 75 years (interquartile range [IQR] 69-80), 63% were women and 21% had OAB syndrome. The most unwanted side effect in the choice of antimuscarinics for OAB was severe cognitive effects, followed by severe constipation, severe blurred vision, severe dry mouth, moderate cognitive effects and moderate constipation. Severe cognitive effects were at least 1.7 times as important as severe constipation. Exploratory subgroup analysis showed that none of the attributes was found to be significant in people who scored as anxious or depressed on the EQ-5D, and preferences about cognitive effects, constipation and blurred vision were equal in people with and without OAB. Older people attribute more importance to loss of cognitive function as a possible side effect of antimuscarinic treatment than to the three most prevalent possible side effects of this treatment.

Mesoscopic modeling of the response of human dental enamel to mid-infrared radiation

NASA Astrophysics Data System (ADS)

Vila Verde, Ana; Ramos, Marta; Stoneham, A. M.

2006-03-01

Ablation of human dental enamel, a composite biomaterial with water pores, is of significant importance in minimally invasive laser dentistry but progress in the area is hampered by the lack of optimal laser parameters. We use mesoscopic finite element models of this material to study its response to mid-infrared radiation. Our results indicate that the cost-effective, off-the-shelf CO2 laser at λ = 10.6 μm may in fact ablate enamel precisely, reproducibly and with limited unwanted side effects such as cracking or heating, provided that a pulse duration of 10 μs is used. Furthermore, our results also indicate that the Er:YAG laser (λ = 2.94 μm), currently popular for laser dentistry, may in fact cause unwanted deep cracking in the enamel when regions with unusually high water content are irradiated, and also provide an explanation for the large range of ablation threshold values observed for this material. The model may be easily adapted to study the response of any composite material to infrared radiation and thus may be useful for the scientific community.

Nanoparticles and the blood coagulation system. Part II: safety concerns

PubMed Central

Ilinskaya, Anna N; Dobrovolskaia, Marina A

2014-01-01

Nanoparticle interactions with the blood coagulation system can be beneficial or adverse depending on the intended use of a nanomaterial. Nanoparticles can be engineered to be procoagulant or to carry coagulation-initiating factors to treat certain disorders. Likewise, they can be designed to be anticoagulant or to carry anticoagulant drugs to intervene in other pathological conditions in which coagulation is a concern. An overview of the coagulation system was given and a discussion of a desirable interface between this system and engineered nanomaterials was assessed in part I, which was published in the May 2013 issue of Nanomedicine. Unwanted pro- and anti-coagulant properties of nanoparticles represent significant concerns in the field of nanomedicine, and often hamper the development and transition into the clinic of many promising engineered nanocarriers. This part will focus on the undesirable effects of engineered nanomaterials on the blood coagulation system. We will discuss the relationship between the physicochemical properties of nanoparticles (e.g., size, charge and hydrophobicity) that determine their negative effects on the blood coagulation system in order to understand how manipulation of these properties can help to overcome unwanted side effects. PMID:23730696

Examining the effects of drinking and interpersonal protective behaviors on unwanted sexual experiences in college women.

PubMed

Sell, Nichole M; Turrisi, Rob; Scaglione, Nichole M; Hultgren, Brittney A; Mallett, Kimberly A

2016-03-01

Recent evidence suggests interpersonal protective behaviors (IPBs) may be more effective than alcohol-based strategies at decreasing alcohol-related sexual consequences. However, no studies have examined individual IPBs to assess their unique influences on specific sexual consequences. The current study used a longitudinal design to examine the direct effects of typical weekly drinking and specific IPBs on unwanted sex. IPBs were also examined as moderators of the relationship between drinking and unwanted sex. Randomly sampled female drinkers attending a northeastern university (N=191) completed a baseline survey measuring typical weekly drinking and IPBs and a six-month follow-up assessing unwanted sex. Bootstrapped regression examined the effects. Drinking predicted unwanted sex after accounting for IPBs (range of bs=.008-.009, SE=.005, 95% CI [.000, .02]). Vigilance-related IPBs were negatively associated with unwanted sex after controlling for drinking (b=-.052, SE=.025, 95% CI [-.107, -.008]). The IPB "Talking to people who know one's potential dating or sexual partner to find out what s/he is like" significantly moderated the drinking-unwanted sex relationship (b=-.009, SE=.004, 95% CI [-.018, -.003]). At above-average drinking levels, women who used this IPB more frequently reported fewer episodes of unwanted sex. Findings revealed obtaining information about a potential partner significantly reduced the impact of drinking on unwanted sex for heavier drinkers. Future research examining how women implement this IPB may clarify its role in reducing unwanted sex. Copyright © 2015 Elsevier Ltd. All rights reserved.

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors

PubMed Central

Butler, Jason M.; Kobayashi, Hideki; Rafii, Shahin

2010-01-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an ‘angiocrine’ mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents. PMID:20094048

Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors.

PubMed

Butler, Jason M; Kobayashi, Hideki; Rafii, Shahin

2010-02-01

The precise mechanisms whereby anti-angiogenesis therapy blocks tumour growth or causes vascular toxicity are unknown. We propose that endothelial cells establish a vascular niche that promotes tumour growth and tissue repair not only by delivering nutrients and O2 but also through an 'angiocrine' mechanism by producing stem and progenitor cell-active trophogens. Identification of endothelial-derived instructive angiocrine factors will allow direct tumour targeting, while diminishing the unwanted side effects associated with the use of anti-angiogenic agents.

Design of joint source/channel coders

NASA Technical Reports Server (NTRS)

1991-01-01

The need to transmit large amounts of data over a band limited channel has led to the development of various data compression schemes. Many of these schemes function by attempting to remove redundancy from the data stream. An unwanted side effect of this approach is to make the information transfer process more vulnerable to channel noise. Efforts at protecting against errors involve the reinsertion of redundancy and an increase in bandwidth requirements. The papers presented within this document attempt to deal with these problems from a number of different approaches.

Single mode levitation and translation

NASA Technical Reports Server (NTRS)

Barmatz, Martin B. (Inventor); Allen, James L. (Inventor)

1988-01-01

A single frequency resonance mode is applied by a transducer to acoustically levitate an object within a chamber. This process allows smooth movement of the object and suppression of unwanted levitation modes that would urge the object to a different levitation position. A plunger forms one end of the chamber, and the frequency changes as the plunger moves. Acoustic energy is applied to opposite sides of the chamber, with the acoustic energy on opposite sides being substantially 180 degrees out of phase.

Knowledge, attitude and practice of pharmacists and health-care workers regarding oral contraceptives correct usage, side-effects and contraindications.

PubMed

Sattari, M; Mokhtari, Z; Jabari, H; Mashayekhi, S O

2013-06-01

Despite the success of the Iranian family planning programme, the number of unwanted pregnancies remains high. To investigate whether health workers in Tabriz are providing correct information and counselling about OCP use, the current study was planned to examine the level of knowledge, attitude and practice of OCP providers. A sample of 150 health-care workers in health houses and 150 community/hospital pharmacists answered a questionnaire about knowledge of correct use of OCP, side-effects, contraindications, danger signs/symptoms and non-contraceptive benefits, and whether they counselled patients about these subjects. Knowledge of pharmacists and health workers was not as high as expected and in many topics they were counselling patients even when they had incorrect knowledge and in other areas they were not providing information to patients despite having the correct knowledge. Better continuing education for OCP providers and especially for pharmacists seems necessary.

Chronic neuropathic facial pain after intense pulsed light hair removal. Clinical features and pharmacological management.

PubMed

Gay-Escoda, Cosme; Párraga-Manzol, Gabriela; Sánchez-Torres, Alba; Moreno-Arias, Gerardo

2015-10-01

Intense Pulsed Light (IPL) photodepilation is usually performed as a hair removal method. The treatment is recommended to be indicated by a physician, depending on each patient and on its characteristics. However, the use of laser devices by medical laypersons is frequent and it can suppose a risk of damage for the patients. Most side effects associated to IPL photodepilation are transient, minimal and disappear without sequelae. However, permanent side effects can occur. Some of the complications are laser related but many of them are caused by an operator error or mismanagement. In this work, we report a clinical case of a patient that developed a chronic neuropathic facial pain following IPL hair removal for unwanted hair in the upper lip. The specific diagnosis was painful post-traumatic trigeminal neuropathy, reference 13.1.2.3 according to the International Headache Society (IHS). Neuropathic facial pain, photodepilation, intense pulse light.

Identification and characterization of carprofen as a multitarget fatty acid amide hydrolase/cyclooxygenase inhibitor.

PubMed

Favia, Angelo D; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2012-10-25

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the nonsteroidal anti-inflammatory drug carprofen as a multitarget-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2, and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several derivatives of carprofen, sharing this multitarget activity. This may result in improved analgesic efficacy and reduced side effects (Naidu et al. J. Pharmacol. Exp. Ther.2009, 329, 48-56; Fowler, C. J.; et al. J. Enzyme Inhib. Med. Chem.2012, in press; Sasso et al. Pharmacol. Res.2012, 65, 553). The new compounds are among the most potent multitarget FAAH/COX inhibitors reported so far in the literature and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs.

Correlates of Unwanted Births in Bangladesh: A Study through Path Analysis.

PubMed

Roy, Tapan Kumar; Singh, Brijesh P

2016-01-01

Unwanted birth is an important public health concern due to its negative association with adverse outcomes of mothers and children as well as socioeconomic development of a country. Although a number of studies have been investigated the determinants of unwanted births through logistic regression analysis, an extensive assessment using path model is lacking. In the current study, we applied path analysis to know the important covariates for unwanted births in Bangladesh. The study used data extracted from Bangladesh Demographic and Health Survey (BDHS) 2011. It considered sub-sample consisted of 7,972 women who had given most recent births five years preceding the date of interview or who were currently pregnant at survey time. Correlation analysis was used to find out the significant association with unwanted births. This study provided the factors affecting unwanted births in Bangladesh. The path model was used to determine the direct, indirect and total effects of socio-demographic factors on unwanted births. The result exhibited that more than one-tenth of the recent births were unwanted in Bangladesh. The differentials of unwanted births were women's age, education, age at marriage, religion, socioeconomic status, exposure of mass-media and use of family planning. In correlation analysis, it showed that unwanted births were positively correlated with women age and place of residence and these relationships were significant. On the contrary, unwanted births were inversely significantly correlated with education and social status. The total effects of endogenous variables such as women age, place of residence and use of family planning methods had favorable effect on unwanted births. Policymakers and program planners need to design programs and services carefully to reduce unwanted births in Bangladesh, especially, service should focus on helping those groups of women who were identified in the analysis as being at increased risks of unwanted births- older women, illiterate, low socioeconomic status, early age at marriage and rural poor susceptible women.

Examining the Effects of Drinking and Interpersonal Protective Behaviors on Unwanted Sexual Experiences in College Women

PubMed Central

Sell, Nichole M.; Turrisi, Rob; Scaglione, Nichole M.; Hultgren, Brittney A.; Mallett, Kimberly A.

2015-01-01

Introduction Recent evidence suggests interpersonal protective behaviors (IPBs) may be more effective than alcohol-based strategies at decreasing alcohol-related sexual consequences. However, no studies have examined individual IPBs to assess their unique influences on specific sexual consequences. The current study used a longitudinal design to examine the direct effects of typical weekly drinking and specific IPBs on unwanted sex. IPBs were also examined as moderators of the relationship between drinking and unwanted sex. Methods Randomly sampled female drinkers attending a northeastern university (N = 191) completed a baseline survey measuring typical weekly drinking and IPBs and a six-month follow-up assessing unwanted sex. Bootstrapped regression examined the effects. Results Drinking predicted unwanted sex after accounting for IPBs (range of bs = .008-.009, SE = .005, 95% CI [.000, .02]). Vigilance-related IPBs were negatively associated with unwanted sex after controlling for drinking (b = −.052, SE = .025, 95% CI [−.107, −.008]). The IPB “Talking to people who know one’s potential dating or sexual partner to find out what s/he is like” significantly moderated the drinking - unwanted sex relationship (b = −.009, SE = .004, 95% CI [−.018, −.003]). At above- average drinking levels, women who used this IPB more frequently reported fewer episodes of unwanted sex. Conclusion Findings revealed obtaining information about a potential partner significantly reduced the impact of drinking on unwanted sex for heavier drinkers. Future research examining how women implement this IPB may clarify its role in reducing unwanted sex. PMID:26706612

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy

PubMed Central

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P.; Alexiou, Christoph; Janko, Christina

2017-01-01

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient’s body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications. PMID:28661430

Analysis of Hypericin-Mediated Effects and Implications for Targeted Photodynamic Therapy.

PubMed

Mühleisen, Laura; Alev, Magdalena; Unterweger, Harald; Subatzus, Daniel; Pöttler, Marina; Friedrich, Ralf P; Alexiou, Christoph; Janko, Christina

2017-06-29

The phototoxic effect of hypericin can be utilized for Photodynamic Therapy (PDT) of cancer. After intravenous application and systemic distribution of the drug in the patient's body, the tumor site is exposed to light. Subsequently, toxic reactive oxygen species (ROS) are generated, inducing tumor cell death. To prevent unwanted activation of the drug in other regions of the body, patients have to avoid light during and after the treatment cycles, consequently impairing quality of life. Here, we characterize toxicity and hypericin-mediated effects on cancer cells in vitro and confirm that its effect clearly depends on concentration and illumination time. To reduce side effects and to increase therapy success, selective accumulation of hypericin in the tumor region is a promising solution. Loading hypericin on superparamagnetic iron oxide nanoparticles (SPIONs) and guiding them to the desired place using an external magnetic field might accomplish this task (referred to as Magnetic Drug Targeting (MDT)). Thus, using a double targeting strategy, namely magnetic accumulation and laser induced photoactivation, might improve treatment effectivity as well as specificity and reduce toxic side effects in future clinical applications.

Effects of pyrazole partial agonists on HCA(2) -mediated flushing and VLDL-triglyceride levels in mice.

PubMed

Li, Zhaosha; Blad, Clara C; van der Sluis, Ronald J; de Vries, Henk; Van Berkel, Theo J C; Ijzerman, Adriaan P; Hoekstra, Menno

2012-10-01

Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect. In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo. Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver. The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Infantile hemangioma: treatment with short course systemic corticosteroid therapy as an alternative for propranolol.

PubMed

Nieuwenhuis, Klaske; de Laat, Peter C J; Janmohamed, Sherief R; Madern, Gerard C; Oranje, Arnold P

2013-01-01

Infantile hemangiomas (IHs) are increasingly being treated with propranolol or other beta-blockers, but before this therapeutic option was available, oral glucocorticosteroids (GCSs) were the criterion standard treatment and are still the alternative modality in problematic cases. Nevertheless, there is no standard treatment protocol for the dose and duration of GCSs. Long-term treatment with GCSs is associated with unwanted side effects such as growth suppression, behavioral changes, and reflux. Twenty-one children with troublesome IHs were treated according to an algorithm with 3 mg/kg/day of oral prednisolone divided three times per day with varying duration and number of GCS courses. Two blinded investigators independently interpreted therapy results using the Hemangioma Activity Score (HAS). Side effects were determined according to reports in patient charts and parental questionnaires. The median duration of a short course of GCSs was 2 weeks (range 1-6 weeks). The number of courses was 2 (range 1-5). The median cumulative dose was 91 mg/kg. Growth stabilized in all patients, with a good response (>50% reduction in HAS) in 62% and a favorable response (30-50% reduction is HAS) in 23%. Twelve of the 21 children (57%) had minor side effects. Persistent side effects did not occur. Intermittent short course, systemic, high-dose GCS therapy is an effective and safe treatment modality for IH, with a substantially lower cumulative dose of GCSs compared to prolonged therapy and no major side effects. This treatment is an alternative in cases in which propranolol fails or is contraindicated. © 2012 Wiley Periodicals, Inc.

Bulk-scaffolded hydrogen storage and releasing materials and methods for preparing and using same

DOEpatents

Autrey, S Thomas [West Richland, WA; Karkamkar, Abhijeet J [Richland, WA; Gutowska, Anna [Richland, WA; Li, Liyu [Richland, WA; Li, Xiaohong S [Richland, WA; Shin, Yongsoon [Richland, WA

2011-06-21

Compositions are disclosed for storing and releasing hydrogen and methods for preparing and using same. These hydrogen storage and releasing materials exhibit fast release rates at low release temperatures without unwanted side reactions, thus preserving desired levels of purity and enabling applications in combustion and fuel cell applications.

Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: Recommendations for patient information☆☆☆

PubMed Central

Barron, Anthony J.; Zaman, Nabeela; Cole, Graham D.; Wensel, Roland; Okonko, Darlington O.; Francis, Darrel P.

2013-01-01

Background Patients trying life-preserving agents such as beta-blockers may be discouraged by listings of harmful effects provided in good faith by doctors, drug information sheets, and media. We systematically review the world experience of side-effect information in blinded, placebo-controlled beta-blockade in heart failure. We present information for a physician advising a patient experiencing an unwanted symptom and suspecting the drug. Methods We searched Medline for double-blinded randomized trials of beta-blocker versus placebo in heart failure reporting side-effects. We calculated, per 100 patients reporting the symptom on beta-blockade, how many would have experienced it on placebo: the “proportion of symptoms non-pharmacological”. Results 28 of the 33 classically-described side-effects are not significantly more common on beta-blockers than placebo. Of the 100 patients developing dizziness on beta-blockers, 81 (95% CI 73–89) would have developed it on placebo. For diarrhoea this proportion is 82/100 (70–95), and hyperglycaemia 83/100 (68–98). For only two side-effects is this under half (i.e. predominantly due to beta-blocker): bradycardia (33/100, CI 21–44) and intermittent claudication (41/100, 2–81). At least 6 so-called side-effects are less common on beta-blocker than placebo, including depression (reduced by 35%, p < 0.01) and insomnia (by 27%, p = 0.01). Conclusions Clinicians might reconsider whether it is scientifically and ethically correct to warn a patient that a drug might cause them a certain side-effect, when randomized controlled trials show no significant increase, or indeed a significant reduction. A better informed consultation could, in patients taking beta-blockers, alleviate suffering. In patients who might otherwise not take the drug, it might prevent deaths. PMID:23796325

Effect of fronto-orbital advancement on astigmatism in patients with anterior plagiocephaly.

PubMed

Song, Hyun Beom; Yang, Hee Kyung; Baek, Rong-Min; Hwang, Jeong-Min; Kim, Namju; Wang, Kyu-Chang; Kim, Sukwha

2016-10-01

The purpose of this study was to determine the effect of unilateral fronto-orbital advancement (FOA) or bilateral FOA on ocular aspects of plagiocephaly. A retrospective review of ocular findings in 16 patients with plagiocephaly was performed. Patients were divided into 2 groups: 12 patients who underwent bilateral FOA (bFOA) and 4 patients who underwent unilateral FOA (uFOA), and ocular findings were compared. One-half of patients showed strabismus in both groups, and all had exotropia. Hypertropia was found only on the same side of the plagiocephaly in 17% of the bFOA group and 25% of the uFOA group. One-third of the patients in the bFOA group and one-half of patients in the uFOA group had oblique muscle dysfunction. In terms of astigmatism, the degree of with-the-rule astigmatism on the contralateral side was larger in the bFOA group compared to the uFOA group (p = 0.030). The degree of with-the-rule astigmatism was larger on the contralateral side than the ipsilateral side (p = 0.005) in the bFOA group. Patients with abnormalities in ductions/versions had larger astigmatism on the contralateral side than those without abnormalities in ductions/versions. In conclusion, bilateral FOA could induce unwanted outcomes of larger astigmatism on the contralateral side. Astigmatism should be carefully evaluated after bilateral FOA. Copyright © 2016 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Ex-vivo multiphoton analysis of rabbit corneal wound healing following photorefractive keratectomy

NASA Astrophysics Data System (ADS)

Wang, Tsung-Jen; Lo, Wen; Dong, Chen-Yuan; Hu, Fung-Rong

2008-02-01

The aim of this study is to assess the application of multiphoton autofluorescence and second harmonic generation (SHG) microscopy for investigating corneal wound healing after high myopic (-10.0D) photorefractive keratectomy (PRK) procedures on the rabbit eyes. The effect of PRK on the morphology and distribution of keratocytes were investigated using multiphoton excited autofluorescence imaging, while the effect of PRK on the arrangement of collagen fibers was monitored by second-harmonic generation imaging. Without histological processing, multiphoton microscopy is able to characterize corneal damage and wound healing from PRK. Our results show that this technique has potential application in the clinical evaluation of corneal damage due to refractive surgery, and may be used to study the unwanted side effects of these procedures.

Chronic neuropathic facial pain after intense pulsed light hair removal. Clinical features and pharmacological management

PubMed Central

Párraga-Manzol, Gabriela; Sánchez-Torres, Alba; Moreno-Arias, Gerardo

2015-01-01

Intense Pulsed Light (IPL) photodepilation is usually performed as a hair removal method. The treatment is recommended to be indicated by a physician, depending on each patient and on its characteristics. However, the use of laser devices by medical laypersons is frequent and it can suppose a risk of damage for the patients. Most side effects associated to IPL photodepilation are transient, minimal and disappear without sequelae. However, permanent side effects can occur. Some of the complications are laser related but many of them are caused by an operator error or mismanagement. In this work, we report a clinical case of a patient that developed a chronic neuropathic facial pain following IPL hair removal for unwanted hair in the upper lip. The specific diagnosis was painful post-traumatic trigeminal neuropathy, reference 13.1.2.3 according to the International Headache Society (IHS). Key words:Neuropathic facial pain, photodepilation, intense pulse light. PMID:26535105

Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

PubMed Central

Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2013-01-01

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

Effects of the pelvic compression belt on gluteus medius, quadratus lumborum, and lumbar multifidus activities during side-lying hip abduction.

PubMed

Park, Kyung-Mi; Kim, Suhn-Yeop; Oh, Duck-Won

2010-12-01

The aims of this study were to assess the effect of the pelvic compression belt on the electromyographic (EMG) activities of gluteus medius (GM), quadratus lumborum (QL), and lumbar multifidus (LM) during side-lying hip abduction. Thirty-one volunteers (15 men and 16 women) with no history of pathology volunteered for this study. Subjects were instructed to perform hip abduction in side-lying position with and without applying the pelvic compression belt. The pelvic compression belt was adjusted just below the anterior superior iliac spines with the stabilizing pressure using elastic compression bands. Surface EMG data were collected from the GM, QL, and LM of the dominant limb. Significantly decreased EMG activity in the QL (without the pelvic compression belt, 60.19±23.66% maximal voluntary isometric contraction [MVIC]; with the pelvic compression belt, 51.44±23.00% MVIC) and significantly increased EMG activity in the GM (without the pelvic compression belt, 26.71±12.88% MVIC; with the pelvic compression belt, 35.02±18.28% MVIC) and in the LM (without the pelvic compression belt, 30.28±14.60% MVIC; with the pelvic compression belt, 37.47±18.94% MVIC) were found when the pelvic compression belt was applied (p<0.05). However, there were no significant differences of the EMG activity between male and female subjects. The findings suggest that the pelvic compression belt may be helpful to prevent unwanted substitution movement during side-lying hip abduction, through increasing the GM and LM and decreasing the QL. Copyright © 2010 Elsevier Ltd. All rights reserved.

Understanding the side effects of emission trading: implications for waste management.

PubMed

Braschel, Nina; Posch, Alfred; Pierer, Magdalena

2014-01-01

The trading of emission allowances is an important market instrument in climate policy. However, the inclusion of certain branches of industry in the trading system not only provides incentives for emission reduction, it also entails unwanted side effects. Thus, the objective of the present study is to identify such side effects-positive and negative-by examining the potential impact of waste management inclusion in the European Union Emissions Trading Scheme (EU ETS). Desk research was supplemented with qualitative and quantitative empirical analysis (based on expert interviews and a questionnaire) in order to analyse the related perceptions and expectations of actors and stakeholders. The impact of waste management inclusion in the EU ETS is analysed in terms of the following three areas: (i) costs and cost pass-through, (ii), competitiveness and market position, and (iii) carbon leakage. Concerning expectations in the area of costs, both the interviewed experts and the practitioners surveyed thought that costs were likely to increase or that they could be passed on to customers. However, experts and practitioners differed with respect to the possibility of carbon leakage. Clearly, increased knowledge of the possible impact arising from inclusion of the waste sector in the EU ETS would enable managers to become more proactive and to manage waste streams and treatment options more economically.

Gender scripts and unwanted pregnancy among urban Kenyan women.

PubMed

Izugbara, Chimaraoke O; Ochako, Rhoune; Izugbara, Chibuogwu

2011-10-01

Women's lived experiences and lay accounts of unwanted pregnancy remain poorly interrogated. We investigated portrayals of unwanted pregnancy using narrative data gathered from 80 women in Nairobi, Kenya. Unwanted pregnancy had a diversity of significance for the women. Pregnancies were not simply unwanted because they occurred when women became pregnant without wanting to. Rather, pregnancies were considered unwanted largely because they had occurred in contexts that did not reinforce socially-sanctioned notions of motherhood and 'proper' procreation and/or revealed women's use of their sexuality in ways deemed culturally-inappropriate. Kenyan women's invocation of femininity scripts to explain unwanted pregnancy; the centrality of gender in everyday life in contemporary Kenya; women's and girls' poor access to effective family planning services; growing female poverty; and Kenya's restrictive abortion policy imply that unwanted pregnancy and its consequences will persist in the country. Addressing unwanted pregnancy and its consequences requires making accessible quality contraceptive and abortion services as well as sexuality information. It also calls for providers who understand the socio-cultural norms that circumscribe fertility and reproductive behaviours.

Efficacy and safety of fractional carbon dioxide laser for treatment of unwanted facial freckles in phototypes II-IV: a pilot study.

PubMed

El Zawahry, Bakr; Zaki, Naglaa; Hafez, Vanessa; Abdel Hay, Rania; Hay, Rania Abdel; Fahim, Aya

2014-11-01

Facial freckles are a cosmetic concern to Egyptians, particularly young females. Several therapeutic lines exist with variable response rates and limitations. Fractional carbon dioxide (FCO2) laser provides minimal ablation and therefore less down time and less side effects. The efficacy and safety of this laser technology have still not been studied in freckles. The aim of this study is to assess the efficacy and safety of FCO2 laser in the treatment of unwanted facial freckles in Egyptians. Twenty patients undergone a single session of FCO2 laser and then were followed up clinically a month later. Photographs were taken before treatment and at follow-up visit and were assessed by three blinded investigators. Percent of global improvement was measured on a 4-point grading scale. Patient's satisfaction and adverse events were recorded. Two patients (10 %) showed grade 1 improvement, while eight patients (40 %) showed grade 2 improvement. Nine patients (45 %) showed grade 3 improvement, and only one patient (5 %) showed grade 4 improvement. FCO2 laser resurfacing is effective and safe in treatment of facial freckles in skin phototypes II-IV. It can offer a more practical alternative to topical treatments, and a cheaper alternative to Q-switched lasers.

Iatrogenic Damage to the Periodontium Caused by Orthodontic Treatment Procedures: An Overview

PubMed Central

Rafiuddin, Syed; YG, Pradeep Kumar; Biswas, Shriparna; Prabhu, Sandeep S; BM, Chandrashekar; MP, Rakesh

2015-01-01

In orthodontic treatment, teeth are moved in to new positions and relationships and the soft tissue and underlying bone are altered to accommodate changes in esthetics and function. Function is more important than esthetics. The speciality of orthodontics has in addition to its benefits, complications as well as risks associated with its procedures. However the benefits outweigh the risks & complications in most of the treatment cases. Few of the unwanted side effects associated with treatment are tooth discolorations, enamel decalcification, periodontal complications like open gingival embrasures, root resorption, allergic reactions to nickel & chromium as well as treatment failure in the form of relapse. PMID:26312093

Targeted traction of impacted teeth with C-tube miniplates.

PubMed

Chung, Kyu-Rhim; Kim, Yong; Ahn, Hyo-Won; Lee, Dongjoo; Yang, Dong-Min; Kim, Seong-Hun; Nelson, Gerald

2014-09-01

Orthodontic traction of impacted teeth has typically been performed using full fixed appliance as anchorage against the traction force. This conventional approach can be difficult to apply in the mixed dentition if the partial fixed appliance offers an insufficient anchor unit. In addition, full fixed appliance can induce unwanted movement of adjacent teeth. This clinical report presents 3 cases where impacted teeth were recovered in the mixed or transitional dentition with skeletal anchorage on the opposite arch without full fixed appliance. Instead, intermaxillary traction was used to bring the impacted teeth into position. With this approach, side effects on teeth and periodontal tissues adjacent to the impaction were minimized.

Targeting Mitogen-activated Protein Kinase-activated Protein Kinase 2 (MAPKAPK2, MK2): Medicinal Chemistry Efforts to Lead Small Molecule Inhibitors to Clinical Trials

PubMed Central

Fiore, Mario; Forli, Stefano; Manetti, Fabrizio

2015-01-01

The p38/MAPK-activated kinase 2 (MK2) pathway is involved in a series of pathological conditions (inflammation diseases and metastasis) and in the resistance mechanism to antitumor agents. None of the p38 inhibitors entered advanced clinical trials because of their unwanted systemic side effects. For this reason, MK2 was identified as an alternative target to block the pathway, but avoiding the side effects of p38 inhibition. However, ATP-competitive MK2 inhibitors suffered from low solubility, poor cell permeability, and scarce kinase selectivity. Fortunately, non-ATP-competitive inhibitors of MK2 have been already discovered that allowed circumventing the selectivity issue. These compounds showed the additional advantage to be effective at lower concentrations in comparison to the ATP-competitive inhibitors. Therefore, although the significant difficulties encountered during the development of these inhibitors, MK2 is still considered as an attractive target to treat inflammation and related diseases, to prevent tumor metastasis, and to increase tumor sensitivity to chemotherapeutics. PMID:26502061

Amorfrutins are potent antidiabetic dietary natural products

PubMed Central

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

The role of intravenous immunoglobulin in treatment of mucous membrane pemphigoid: A review of literature

PubMed Central

Tavakolpour, Soheil

2016-01-01

Background: Mucous membrane pemphigoid (MMP) is considered an autoimmune blistering disease that predominantly affects mucous membranes. Various treatments are available for controlling the diseases, but not all of them may respond. Materials and Methods: PubMed and Google Scholar were searched for all the associated studies until 2015, using the keywords such as “cicatricial pemphigoid” or “ocular pemphigoid” or “mucous membrane pemphigoid” or “MMP” and “intravenous immunoglobulin” or “IVIg” to find all the relevant studies. The last search update was for September 2, 2015. Among the searched items, only English studies were included in the review. Results: After excluding nonrelevant studies, 13 studies with a total number of seventy patients with MMP who were under treatment with IVIg were analyzed. The 65 patients responded completely, one did not respond, two had partially responded, and the remaining two patients stopped IVIg therapy, which resulted in ocular cicatricial pemphigoid progression. Majority of the studies reported mild adverse effects while two of them did not report any unwanted side effect. The most common side effect was headache, followed by nausea. Most of the patients who had a cessation of IVIg therapy before achieving clinical remission experienced the disease progression. Conclusion: Overall, it can be concluded that IVIg therapy was very helpful in treatment of MMP patients who did not respond to conventional therapy or stopped using them for various side effects. Adverse effects associated with IVIg therapy were considerably lower than conventional therapy that can lead toward treatment with this agent in patients who suffer from severe side effects. PMID:27904583

[Unwanted children].

PubMed

Sulová, L; Fait, T

2009-06-01

Aim of the study is review of knowledges about psychosocial aspects of unwanted pregnancy for child. Literary review. Department of psychology, Faculty of psychology, Charles University Prague. In our review article we give results of studies which evaluate physical, psychological and social aspects of beeing unwanted baby. Especially we show unique results of Prague study. The majority of studies confirm that unwanted children are significantly discriminated against wanted children. Unwanted children have more diseases, worse school result with identical inteligence quotient, higher frequency of nervous and psychosomatic disables and worse social adaptibility. Results of studies confirm order to find for every women safe and effective method for familly planning.

Unwanted sexual activity among married women in urban China.

PubMed

Parish, William L; Luo, Ye; Laumann, Edward O; Kew, Melissa; Yu, Zhiyuan

2007-05-01

This paper examines the prevalence, precursors, and consequences of unwanted marital sex activities in a national sample of 1,127 married urban Chinese women aged 20-64. During the lifetime of their current marriage, 32% reported ever experiencing unwanted spousal intercourse, with about one-fifth reporting that this unwanted intercourse ever involved force. Reports for the past year were 21% unwanted intercourse, 22% unwanted sex act(s), and 72% sex only to please the husband. The major risk factors for these activities were poor relationship quality (hitting, lack of daily intimacy and foreplay, and husband insensitivity to wife's sexual needs); a woman's negative attitudes towards sex, and weak bargaining position (low income share, husband's family of superior economic status, and no additional adults in home). In addition, unwanted activity was more common when women reported sexual dysfunctions (dryness, pain, low arousal, inorgasmia), were more educated, and had more permissive sex attitudes. Net of feedback effects, unwanted sexual activity diminished women's psychological well-being.

Microbial production of next-generation stevia sweeteners.

PubMed

Olsson, Kim; Carlsen, Simon; Semmler, Angelika; Simón, Ernesto; Mikkelsen, Michael Dalgaard; Møller, Birger Lindberg

2016-12-07

The glucosyltransferase UGT76G1 from Stevia rebaudiana is a chameleon enzyme in the targeted biosynthesis of the next-generation premium stevia sweeteners, rebaudioside D (Reb D) and rebaudioside M (Reb M). These steviol glucosides carry five and six glucose units, respectively, and have low sweetness thresholds, high maximum sweet intensities and exhibit a greatly reduced lingering bitter taste compared to stevioside and rebaudioside A, the most abundant steviol glucosides in the leaves of Stevia rebaudiana. In the metabolic glycosylation grid leading to production of Reb D and Reb M, UGT76G1 was found to catalyze eight different reactions all involving 1,3-glucosylation of steviol C 13 - and C 19 -bound glucoses. Four of these reactions lead to Reb D and Reb M while the other four result in formation of side-products unwanted for production. In this work, side-product formation was reduced by targeted optimization of UGT76G1 towards 1,3 glucosylation of steviol glucosides that are already 1,2-diglucosylated. The optimization of UGT76G1 was based on homology modelling, which enabled identification of key target amino acids present in the substrate-binding pocket. These residues were then subjected to site-saturation mutagenesis and a mutant library containing a total of 1748 UGT76G1 variants was screened for increased accumulation of Reb D or M, as well as for decreased accumulation of side-products. This screen was performed in a Saccharomyces cerevisiae strain expressing all enzymes in the rebaudioside biosynthesis pathway except for UGT76G1. Screening of the mutant library identified mutations with positive impact on the accumulation of Reb D and Reb M. The effect of the introduced mutations on other reactions in the metabolic grid was characterized. This screen made it possible to identify variants, such as UGT76G1 Thr146Gly and UGT76G1 His155Leu , which diminished accumulation of unwanted side-products and gave increased specific accumulation of the desired Reb D or Reb M sweeteners. This improvement in a key enzyme of the Stevia sweetener biosynthesis pathway represents a significant step towards the commercial production of next-generation stevia sweeteners.

Social support and pregnancy: II. Its relationship with depressive symptoms among Japanese women.

PubMed

Kitamura, T; Toda, M A; Shima, S; Sugawara, K; Sugawara, M

1998-02-01

In a questionnaire survey among 1329 first-trimester pregnant women, both the husband support measures and unwanted pregnancy ('stressor' agent in pregnancy) showed significant effects on an elevated score of the cognitive disturbance subscale of the Zung's self-rating depression scale (SDS), while only unwanted pregnancies showed an effect on an elevated score of the dysphoric mood subscale of the SDS. However, no interaction was observed between the husband support measures and unwanted pregnancy, therefore the effect of the husband's social support on the cognitive disturbance score was not that of a buffer, but rather a main effector. Finally, multiple regression analyses showed that the dysphoric mood score was preceded by unwanted pregnancy, premenstrual irritability, public self-consciousness, and maternal overprotection; while the cognitive disturbance score was preceded by unwanted pregnancy, husband reduced 'given' and 'giving' support, maternal reduced care and overprotection, paternal reduced care, low annual income, low private self-consciousness, and smoking. These findings suggest that the husband's support for a pregnant woman is effective only in reducing cognitive symptoms, and that different symptomatic constellations have different sets of psychosocial correlates.

Multiscale image fusion using the undecimated wavelet transform with spectral factorization and nonorthogonal filter banks.

PubMed

Ellmauthaler, Andreas; Pagliari, Carla L; da Silva, Eduardo A B

2013-03-01

Multiscale transforms are among the most popular techniques in the field of pixel-level image fusion. However, the fusion performance of these methods often deteriorates for images derived from different sensor modalities. In this paper, we demonstrate that for such images, results can be improved using a novel undecimated wavelet transform (UWT)-based fusion scheme, which splits the image decomposition process into two successive filtering operations using spectral factorization of the analysis filters. The actual fusion takes place after convolution with the first filter pair. Its significantly smaller support size leads to the minimization of the unwanted spreading of coefficient values around overlapping image singularities. This usually complicates the feature selection process and may lead to the introduction of reconstruction errors in the fused image. Moreover, we will show that the nonsubsampled nature of the UWT allows the design of nonorthogonal filter banks, which are more robust to artifacts introduced during fusion, additionally improving the obtained results. The combination of these techniques leads to a fusion framework, which provides clear advantages over traditional multiscale fusion approaches, independent of the underlying fusion rule, and reduces unwanted side effects such as ringing artifacts in the fused reconstruction.

Flirting with disaster: short-term mating orientation and hostile sexism predict different types of sexual harassment.

PubMed

Diehl, Charlotte; Rees, Jonas; Bohner, Gerd

2012-01-01

We combine evolutionary and sociocultural accounts of sexual harassment, proposing that sexuality-related and hostility-related motives lead to different types of harassment. Specifically, men's short-term mating orientation (STMO) was hypothesized to predict only unwanted sexual attention but not gender harassment, whereas men's hostile sexism (HS) was hypothesized to predict both unwanted sexual attention and gender harassment. As part of an alleged computer-chat task, 100 male students could send sexualized personal remarks (representing unwanted sexual attention), sexist jokes (representing gender harassment), or nonharassing material to an attractive female target. Independently, participants' STMO, HS, and sexual harassment myth acceptance (SHMA) were assessed. Correlational and path analyses revealed that STMO specifically predicted unwanted sexual attention, whereas HS predicted both unwanted sexual attention and gender harassment. Furthermore, SHMA fully mediated the effect of HS on gender harassment, but did not mediate effects of STMO or HS on unwanted sexual attention. Results are discussed in relation to motivational explanations for sexual harassment and antiharassment interventions. © 2012 Wiley Periodicals, Inc.

Novel pharmacological approaches for the treatment of acne vulgaris.

PubMed

Valente Duarte de Sousa, Isabel Cristina

2014-10-01

Acne vulgaris is the most common skin disease worldwide; yet, current treatment options, although effective, are associated with unwanted side effects, chronicity, relapses and recurrences. The adequate control of the four pathogenic mechanisms, involved in the appearance of acne lesions, is paramount to treatment success. The authors discuss and evaluate the pathogenic pathways related to the mechanisms of action of novel molecules, which are currently under investigation for the treatment of acne vulgaris. The manuscript is based on comprehensive searches made through PubMed, GoogleScholar and ClinicalTrial.gov, using different combination of key words, which include acne vulgaris, pathogenesis, treatment, sebogenesis and Propionibacterium acnes. In the near future, more effective treatments with fewer side effects are expected. The use of topical antiandrogens, acetylcholine inhibitors and PPAR modulators seem to be promising options for controlling sebum production. Retinoic acid metabolism-blocking agents and IL-1α inhibitors have the potential to become legitimate alternative options to retinoid therapy in the management of infundibular dyskeratosis. Indeed, the authors believe that there will likely be a decline in the use of antibiotics for controlling P. acnes colonization and targeting the inflammation cascade.

Sexual activity and contraceptive use among young female students of tertiary educational institutions in Ilorin, Nigeria.

PubMed

Abiodun, Omoniyi M; Balogun, Olayinka R

2009-02-01

A survey was conducted to evaluate the pattern of sexual behavior and contraceptive use among female students aged 15 to 24 years attending tertiary institutions in Ilorin, Nigeria. A valid and reliable semistructured questionnaire was self-administered to a sampled population of 600 students aged 15 to 24 years. Of the 600 students, 562 (93.7%) completed the questionnaire. Most (98.6%) of the respondents were unmarried, 77.6% have had sexual intercourse, 67.8% have had an unwanted pregnancy while 63.5% have had induced abortion. All the respondents were aware of contraceptives, but only 25.4% have ever used any contraceptive method. The most common sources of information about contraception among the respondents were friends/relatives (73.7%), while the fear of side effects of modern contraceptives was the most common reason (77.5%) for nonuse. The fear of side effects is the main reason for low contraceptive prevalence among young female students of tertiary institutions in Ilorin. Reproductive health services should focus more on delivery of adequate and accurate information about contraceptives to improve use among young women.

Students’ Perceptions of Contraceptives in University of Ghana

PubMed Central

Kayi, Esinam Afi

2013-01-01

Objective This study sought to explore University of Ghana Business School diploma student's knowledge of contraceptives, types of contraceptives, attitudes towards contraceptive users, preference for contraceptives, benefits, and side-effects of contraceptives. Materials and methods Data was conducted with three sets of focus group discussions. Participants were systematically sampled from accounting and public administration departments. Results Findings showed that students had little knowledge of contraceptives. The male and female condoms were the main contraceptive types reported out of the many modern and traditional methods of contraceptives. The main benefits of contraceptives were; ability to protect against STIs, abortions, unwanted pregnancy and psychological trauma. Whilst most respondents preferred future use of pills, side-effects of contraceptives were mostly reported for condoms than other contraceptive methods. Results showed that participants had bad attitudes towards unmarried contraceptive users. Conclusion Generally, our findings show that detailed knowledge about contraceptives is low. There is a little gap of information on contraception knowledge, timing, and contraceptive types among university diploma students. Reproductive and maternal services should be available and accessible for tertiary students. PMID:24971101

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

PubMed

Grundmann-Kollmann, Marcella; Martin, Hans; Ludwig, Ralf; Klein, Stefan; Boehncke, Wolf-Henning; Hoelzer, Dieter; Kaufmann, Roland; Podda, Maurizio

2002-12-15

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622.

PubMed

Uslaner, Jason M; Kuduk, Scott D; Wittmann, Marion; Lange, Henry S; Fox, Steve V; Min, Chris; Pajkovic, Natasa; Harris, Dawn; Cilissen, Caroline; Mahon, Chantal; Mostoller, Kate; Warrington, Steve; Beshore, Douglas C

2018-06-01

The current standard of care for treating Alzheimer's disease is acetylcholinesterase inhibitors, which nonselectively increase cholinergic signaling by indirectly enhancing activity of nicotinic and muscarinic receptors. These drugs improve cognitive function in patients, but also produce unwanted side effects that limit their efficacy. In an effort to selectively improve cognition and avoid the cholinergic side effects associated with the standard of care, various efforts have been aimed at developing selective M 1 muscarinic receptor activators. In this work, we describe the preclinical and clinical pharmacodynamic effects of the M 1 muscarinic receptor-positive allosteric modulator, MK-7622. MK-7622 attenuated the cognitive-impairing effects of the muscarinic receptor antagonist scopolamine and altered quantitative electroencephalography (qEEG) in both rhesus macaque and human. For both scopolamine reversal and qEEG, the effective exposures were similar between species. However, across species the minimum effective exposures to attenuate the scopolamine impairment were lower than for qEEG. Additionally, there were differences in the spectral power changes produced by MK-7622 in rhesus versus human. In sum, these results are the first to demonstrate translation of preclinical cognition and target modulation to clinical effects in humans for a selective M 1 muscarinic receptor-positive allosteric modulator. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Glucocorticoid receptor modulators.

PubMed

Meijer, Onno C; Koorneef, Lisa L; Kroon, Jan

2018-06-01

The glucocorticoid hormone cortisol acts throughout the body to support circadian processes and adaptation to stress. The glucocorticoid receptor is the target of cortisol and of synthetic glucocorticoids, which are used widely in the clinic. Both agonism and antagonism of the glucocorticoid receptor may be beneficial in disease, but given the wide expression of the receptor and involvement in various processes, beneficial effects are often accompanied by unwanted side effects. Selective glucocorticoid receptor modulators are ligands that induce a receptor conformation that allows activation of only a subset of downstream signaling pathways. Such molecules thereby combine agonistic and antagonistic properties. Here we discuss the mechanisms underlying selective receptor modulation and their promise in treating diseases in several organ systems where cortisol signaling plays a role. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Cannabidiol as potential anticancer drug

PubMed Central

Massi, Paola; Solinas, Marta; Cinquina, Valentina; Parolaro, Daniela

2013-01-01

Over the past years, several lines of evidence support an antitumourigenic effect of cannabinoids including Δ9-tetrahydrocannabinol (Δ9-THC), synthetic agonists, endocannabinoids and endocannabinoid transport or degradation inhibitors. Indeed, cannabinoids possess anti-proliferative and pro-apoptotic effects and they are known to interfere with tumour neovascularization, cancer cell migration, adhesion, invasion and metastasization. However, the clinical use of Δ9-THC and additional cannabinoid agonists is often limited by their unwanted psychoactive side effects, and for this reason interest in non-psychoactive cannabinoid compounds with structural affinity for Δ9-THC, such as cannabidiol (CBD), has substantially increased in recent years. The present review will focus on the efficacy of CBD in the modulation of different steps of tumourigenesis in several types of cancer and highlights the importance of exploring CBD/CBD analogues as alternative therapeutic agents. PMID:22506672

Immunization with Small Amyloid-β-derived Cyclopeptide Conjugates Diminishes Amyloid-β-Induced Neurodegeneration in Mice.

PubMed

Mulder, Cornelis K; Dong, Yun; Brugghe, Humphrey F; Timmermans, Hans A M; Tilstra, Wichard; Westdijk, Janny; van Riet, Elly; van Steeg, Harry; Hoogerhout, Peter; Eisel, Ulrich L M

2016-01-01

Soluble oligomeric (misfolded) species of amyloid-β (Aβ) are the main mediators of toxicity in Alzheimer's disease (AD). These oligomers subsequently form aggregates of insoluble fibrils that precipitate as extracellular and perivascular plaques in the brain. Active immunization against Aβ is a promising disease modifying strategy. However, eliciting an immune response against Aβ in general may interfere with its biological function and was shown to cause unwanted side-effects. Therefore, we have developed a novel experimental vaccine based on conformational neo-epitopes that are exposed in the misfolded oligomeric Aβ, inducing a specific antibody response. Here we investigate the protective effects of the experimental vaccine against oligomeric Aβ1-42-induced neuronal fiber loss in vivo. C57BL/6 mice were immunized or mock-immunized. Antibody responses were measured by enzyme-linked immunosorbent assay. Next, mice received a stereotactic injection of oligomeric Aβ1-42 into the nucleus basalis of Meynert (NBM) on one side of the brain (lesion side), and scrambled Aβ1-42 peptide in the contralateral NBM (control side). The densities of choline acetyltransferase-stained cholinergic fibers origination from the NBM were measured in the parietal neocortex postmortem. The percentage of fiber loss in the lesion side was determined relative to the control side of the brain. Immunized responders (79%) showed 23% less cholinergic fiber loss (p = 0.01) relative to mock-immunized mice. Moreover, fiber loss in immunized responders correlated negatively with the measured antibody responses (R2 = 0.29, p = 0.02). These results may provide a lead towards a (prophylactic) vaccine to prevent or at least attenuate (early onset) AD symptoms.

Safety evaluation for a cell-based immune support system in an ex vivo rat model of gram-negative sepsis.

PubMed

Sauer, Martin; Altrichter, Jens; Kreutzer, Hans-Jürgen; Schmidt, Heidrun; Nöldge-Schomburg, Gabriele; Schmidt, Reinhard; Mitzner, Steffen R

2009-10-01

Granulocyte dysfunction is a central component of immunodeficiency in septic patients. Granulocyte transfusions appear to be pathophysiologically useful; however, they cause unwanted side-effects in the lungs and other organs. This study evaluates the safety of an extracorporeal immune support system with granulocytic cells in a rat model of Gram-negative sepsis. Three groups of male CD rats received either saline (control group, I), a dose of Escherichia coli O7:K1 lethal to 90% of the animals (LD90) (septic group, II), or an LD90 dose of E. coli that was incubated with the human promyelocytic leukemia cell line (HL-60) (differentiated into the granulocytic direction) for 20 min prior to infusion (second septic group, III). The animals were observed for seven days. Pre-treatment with HL-60 cells resulted in no adverse effects in the group III animals. Significantly lower bacterial counts and endotoxin levels in the plasma were detected after 24 h as compared to group II (P < 0.05). Group III animals had better weight gain and more stable hemodynamics than group II animals (P < 0.01). Seven day survival was 0/8 in group II, 6/8 in group III, and 8/9 in group I (log-rank test: II-III: P < 0.001). The data suggest that extracorporeal use of granulocytes allows the therapeutic use of these cells while avoiding unwanted effects resulting from direct contact to internal organs.

Pharmacokinetic Studies of Gel System Containing Ibuprofen Solid Nanoparticles.

PubMed

Nagai, Noriaki; Tanino, Tadatoshi; Ito, Yoshimasa

2016-12-01

In the therapy of rheumatoid arthritis, ibuprofen (IBU) is widely used; however, it has been limited the clinical use by its systemic side effect, such as gastrointestinal lesions. Therefore, we prepared topical gel ointment used IBU solid nanoparticles (IBU nano -gel formulation). In addition, we demonstrated their anti-inflammatory effect by using arthritis model rat (adjuvant-induced arthritis rat, AA rat). The gel formulations were prepared using additives (Carbopol 934, 2-hydroxypropyl-β-cyclodextrin and methylcellulose) and bead mill-method. The IBU particle size in the IBU nano -gel formulation was 208 nm. The increase in inflammation of the hind feet of AA rats was attenuated by the treatment with the IBU nano -gel formulation, and preventive effect was higher than that of a gel formulation containing IBUmicroparticles (IBU micro -gel formulation, mean particle size 85.4 μm); the accumulation and permeability through the skin of IBU from the IBU nano -gel formulation were significantly larger in comparison with the IBU micro -gel formulation. Further, no gastrointestinal lesions were observed in AA rats following the repetitive administration of the 5% IBU nano -gel formulation (0.30 g) for 42 days (once a day). These results suggest that the dermal application of IBU-nanoparticles provide effective and efficient therapy that spares patients from unwanted side effects.

Resisting Unwanted Sexual and Social Advances: Perspectives of College Women and Men.

PubMed

Orchowski, Lindsay M; Gidycz, Christine A; Kraft, Kathryn

2018-06-01

This study examines college men's ( N = 635) and women's ( N = 650) reports of women's resistance against unwanted sexual and social advances. Men completed surveys to assess (a) initiation of unwanted sexual contact with a female partner, (b) initiation of unwanted sexual intercourse with a female partner, (c) sexual situations where a female partner decided she did not want to proceed, (d) encouraging a woman to drink when they were aware that the woman did not want to, and (e) attempting to take a woman to an isolated location against her will. Women completed corresponding questionnaires regarding the receipt of such unwanted advances, the outcome of the situation, and the resistance tactics utilized. Many men (5%-46%) and women (15%-38%) initiated or experienced, respectively, at least one of the five unwanted sexual or social advances. Unwanted sexual and social advances most often stopped as a result of women's verbal and physical resistance. Few advances (0%-8%) stopped as a result of bystander intervention. In addition to decreasing men's likelihood of engaging in unwanted sexual and social advances, these data highlight the importance of educating women on the effectiveness of verbal and physical resistance tactics, and increasing the frequency of prosocial bystander action on college campuses.

Characteristics and Use of a Parametric End-Fired Array for Acoustics in Air

DTIC Science & Technology

2007-03-01

as a sonar application for underwater use. The vast majority of the research for parametric arrays was devoted to underwater applications until the...and also for the calibration of hydrophones and receivers for wide band sonar . All of the researchers mentioned above mainly focused their efforts on...features, which include very high directivity at low frequencies without unwanted side lobes. They are generally used as a wide band sonar system

Depressive symptoms as a side effect of the sustained release form of methylphenidate in a 7-year-old boy with attention-deficit hyperactivity disorder.

PubMed

Lakić, Aneta

2012-02-01

Hyperkinetic disorder or attention-deficit hyperactivity disorder (ADHD) is a clinical entity consisting of a cluster of symptoms including hyperactivity, attention disorder and impulse control disorder group. In the context of ADHD etiology we may say that genetic, clinical and imaging studies point out a disruption of the brain dopamine system, which is corroborated by the clinical effectiveness of stimulant drugs, which increase extracellular dopamine in the brain. Basically, it is a biological and not psychological disorder, which is important both for the comprehension and therapeutical approach to this problem. Today, the best recommended approach regarding children with ADHD is a combination of two therapeutic modalities: pharmacotherapy and behavioral treatment. The first-choice drugs for this disorder belong to the group of sympathomimetics--psychostimulants and atomoxetine (more recently). As the first-choice therapy, methylphenydate in sustained release form has numerous advantages. Like all drugs, methylphenidate has its unwanted side effects. Most common are: loss of appetite, weight loss, sleeping disorders, irritability, headache. These side effects are well-known and documented in the literature. By analysing the available literature we have found cases of psychiatric side effects such as: psychosis, mania, visual hallucinations, agitation, suicidal ideas. We have not found examples of ADHD in children who use increased dosage of sustained release of methylphenidate leading to depressive symptomatology. On the other side, methylphenidate may be prescribed for off-label use in treatment-resistant cases of depression. The case of a 7-year-old boy diagnosed with ADHD was on a minimal dose of sustained release form of methylphenidate. After initial titration of the drug, i.e. after raising the dose to the next level the boy developed clinical signs of depression. The treatment was ceased and depressive symptoms were withdrawed. Manifestation of depressive symptomatology after dose increasement of sustained release form of methylphenidate in a 7-year-old boy with ADHD represents an uncommon side effect. Precise drug activity mechanisms responsible for the appearance of these symptoms remains to be explained.

Adjustable speed drive study, part 1

NASA Astrophysics Data System (ADS)

Wallace, A.

1989-08-01

Advances in speed control for motors in recent years, notably those in power electronics, have widened the range of application for several adjustable speed drive (ASD) types to include the smaller horsepower sizes. The dc motor drive, formerly in almost universal use for speed control, is being challenged by the high efficiency induction motor/pulse width modulation (PWM) drive; and for special small horsepower size applications, by the permanent magnet motor/PWM inverter drive or by the switched reluctance motor drive. The main characteristics of the several ASD types suitable for small horsepower size applications are discussed, as well as their unwanted side effects: poor power factor, harmonic distortion of the supply, acoustic noise, and electromagnetic interference. A procedure is recommended for determining which, if any, ASD to use.

Alternative approaches to conventional antiepileptic drugs in the management of paediatric epilepsy

PubMed Central

Kneen, R; Appleton, R E

2006-01-01

Over the last two decades, there has been a rapid expansion in the number and types of available antiepileptic drugs (AEDs), but there is increasing concern amongst parents and carers about their unwanted side effects. Seizure control is achieved in approximately 75% of children treated with conventional AEDs, but non‐conventional (or non‐standard) medical treatments, surgical procedures, dietary approaches, and other non‐pharmacological treatment approaches may have a role to play in those with intractable seizures or AED toxicity. Many of the approaches are largely common sense and are already incorporated into our current practice, including, for example, avoidance techniques and lifestyle advice, while others require further investigation or appear to be impractical in children. PMID:17056869

Design and manufacture of monoclonal antibodies for radioimmunotherapy.

PubMed

Hale, G; Berrie, E; Bird, P

2004-12-01

antibodies is fundamental to their use for radioimmunotherapy. Besides the right selection of antibody specificity and affinity, recombinant antibodies can be designed to simplify manufacture and minimise unwanted side effects. Although many innovative new technologies have been developed in recent years, antibodies are still most commonly produced from mammalian cells and purified by column chromatography. Purification methods have to be designed and validated to remove potential contaminants, especially retroviruses, which in principle might be present in mammalian cell lines. Adherence to relevant ''Good Manufacturing Practices'' is mandatory in the production of any medicinal product and there are numerous guidelines regarding the manufacture of antibodies. This article outlines some methods used for fermentation, purification and quality control of antibodies intended for radiolabelling.

Impact of Modafinil Add-on with Atypical Anti-psychotics on Excessive Daytime Drowsiness

PubMed Central

Prasuna, P Lakshmi; Sudhakar, TP

2015-01-01

Background: Atypical antipsychotic drugs are known to cause many side effects which include daytime drowsiness. So many add on drugs are tried to reduce the same. Materials and Methods: 72 patients who were on atypical antipsychotic drugs were randomly assigned to either Modafinil or placebo and were followed for a period of 12 weeks. Daytime drowsiness, was taken at baseline, week 3, and at week 12 by using VAS, EDD scales. Results: The results were analyzed and showed that the Modafinil add on therapy significantly reduced the daytime Drowsiness. Conclusions: Modafinil could be a potential candidate in selected group of patients to decrease some of the unwanted adverse events like daytime drowsiness produced by atypical antipsychotics. PMID:26702168

Genotoxicity Assessment of Water Samples from the Sungai Dua River in Pulau Pinang, Malaysia, Using the Allium cepa Test

PubMed Central

Akinboro, Akeem; Mohammed, Kamaruzaman; Rathnasamy, Selestin; Muniandy, Vijay Raj

2011-01-01

Unwanted side effects from a polluted water body may not be limited to the flora and fauna, they may also be transferred to the organisms along the food chain. Four water samples collected immediately and five days after rainfall from two locations inside the polluted Sungai Dua River (SGD) were tested for toxicity using the Allium cepa assay. The samples were analysed for metal content and were both macroscopically and microscopically evaluated. The water samples contained more sodium (Na+) and calcium (Ca2+) than the control tap water, and they showed root growth and mitotic inhibitions (MI) in A. cepa. However, the inhibitory effects were not dose-dependent. No chromosomal aberration (CA) was induced at 100.00% (undiluted water sample). These results suggest the water samples from SGD had weak mitodepressive and genotoxic effects on the A. cepa cells. PMID:24575215

Vaccines and animal welfare.

PubMed

Morton, D B

2007-04-01

Vaccination promotes animal welfare by protecting animal health, but it also has other welfare benefits, e.g. recent investigations have looked at the potential of vaccines in immunoneutering such as immunocastration--a humane alternative to the painful traditional methods. Similarly, vaccination can be used during disease outbreaks as a viable alternative to stamping-out, thus avoiding the welfare problems that on-farm mass slaughter can cause. Protecting animal health through vaccination leads to improved animal welfare, and maintaining good welfare ensures that animals can respond successfully to vaccination (as poor welfare can lead to immunosuppression, which can affect the response to vaccination). It is clear that vaccination has tremendous advantages for animal welfare and although the possible side effects of vaccination can have a negative effect on the welfare of some individual animals, the harm caused by these unwanted effects must be weighed against the undoubted benefits for groups of animals.

Phytoremediation of metals contaminated dredged sediments: Use of synthetic chelates in metals phytoextraction

NASA Astrophysics Data System (ADS)

Sahut, C.; Geniaut, G.; Lillo, M. P.

2003-05-01

(in Times 10 points) The waterways maintenance leads to a large volume of dredged polluted sediments, to be disposed of, every year. As the economic disposal of dredged sediment is a single line along the stream they can behave as a sink of pollutant and a migration in the environment is observed. Chelate-enhanced phytoremediation has been proposed as an effective tool for the extraction of heavy metals from dredged sediment by plants. Lysimeters studies were conducted to study the phytoremediation of sediments with EDTA and lactic acid used as synthetic chelators. EDTA appeared to enhance metal solubility by plant uptake did not increase accordingly. Futhermore EDTA enhance metal leaching which could lead 10 groungwater pollution. To prevent these unwanted side-effects, careful management of phytoremediation and of the use of EDTA seems necessary.

Adjunctive aripiprazole in the treatment of risperidone-induced hyperprolactinemia: A randomized, double-blind, placebo-controlled, dose-response study.

PubMed

Chen, Jing-Xu; Su, Yun-Ai; Bian, Qing-Tao; Wei, Li-He; Zhang, Rong-Zhen; Liu, Yan-Hong; Correll, Christoph; Soares, Jair C; Yang, Fu-De; Wang, Shao-Li; Zhang, Xiang-Yang

2015-08-01

Hyperprolactinemia is an unwanted adverse effect associated with several antipsychotics. The addition of partial dopamine receptor agonist aripiprazole may attenuate antipsychotic-induced hyperprolactinemia effectively. However, the ideal dosing regimen for this purpose is unknown. We aimed to evaluate the dose effects of adjunctive treatment with aripiprazole on prolactin levels and hyperprolactinemia in schizophrenia patients. Stable subjects 18-45 years old with schizophrenia and hyperprolactinemia (i.e., >24 ng/ml for females and >20 ng/ml for males) were randomly assigned to receive 8 weeks of placebo (n=30) or oral aripiprazole 5mg/day (n=30), 10mg/day (n=29), or 20mg/day (n=30) added on to fixed dose risperidone treatment. Serum prolactin levels were measured at baseline and after 2, 4 and 8 weeks; clinical symptoms and side effects were assessed at baseline and week 8 using the Positive and Negative Syndrome Scale, Clinical Global Impressions Severity scale, Barnes Akathisia Scale, Simpson-Angus Scale and UKU Side Effects Rating Scale. Of 119 randomized patients, 107 (89.9%) completed the 8-week study. At study end, all three aripiprazole doses resulted in significantly lower prolactin levels (beginning at week 2), higher response rates (≥30% prolactin reduction) and higher prolactin normalization rates than placebo. Effects were significantly greater in the 10 and 20mg/day groups than the 5mg/day group. No significant changes were observed in any treatment groups regarding psychopathology and adverse effect ratings. Adjunctive aripiprazole treatment was effective and safe for resolving risperidone-induced hyperprolactinemia, producing significant and almost maximal improvements by week 2 without significant effects on psychopathology and side effects. Copyright © 2015 Elsevier Ltd. All rights reserved.

Controlling satellite communication system unwanted emissions in congested RF spectrum

NASA Astrophysics Data System (ADS)

Olsen, Donald; Heymann, Roger

2007-09-01

The International Telecommunication Union (ITU), a United Nations (UN) agency, is the agency that, under an international treaty, sets radio spectrum usage regulations among member nations. Within the United States of America (USA), the organization that sets regulations, coordinates an application for use, and provides authorization for federal government/agency use of the radio frequency (RF) spectrum is the National Telecommunications and Information Administration (NTIA). In this regard, the NTIA defines which RF spectrum is available for federal government use in the USA, and how it is to be used. The NTIA is a component of the United States (U.S.) Department of Commerce of the federal government. The significance of ITU regulations is that ITU approval is required for U.S. federal government/agency permission to use the RF spectrum outside of U.S. boundaries. All member nations have signed a treaty to do so. U.S. federal regulations for federal use of the RF spectrum are found in the Manual of Regulations and Procedures for Federal Radio Frequency Management, and extracts of the manual are found in what is known as the Table of Frequency Allocations. Nonfederal government and private sector use of the RF spectrum within the U.S. is regulated by the Federal Communications Commission (FCC). There is a need to control "unwanted emissions" (defined to include out-of-band emissions, which are those immediately adjacent to the necessary and allocated bandwidth, plus spurious emissions) to preclude interference to all other authorized users. This paper discusses the causes, effects, and mitigation of unwanted RF emissions to systems in adjacent spectra. Digital modulations are widely used in today's satellite communications. Commercial communications sector standards are covered for the most part worldwide by Digital Video Broadcast - Satellite (DVB-S) and digital satellite news gathering (DSNG) evolutions and the second generation of DVB-S (DVB-S2) standard, developed by the European Telecommunications Standards Institute (ETSI). In the USA, the Advanced Television Systems Committee (ATSC) has adopted Europe's DVB-S and DVB-S2 standards for satellite digital transmission. With today's digital modulations, RF spectral side lobes can extend out many times the modulating frequency on either side of the carrier at excessive power levels unless filtered. Higher-order digital modulations include quadrature phase shift keying (QPSK), 8 PSK (8-ary phase shift keying), 16 APSK (also called 12-4 APSK (amplitude phase shift keying)), and 16 QAM (quadrature amplitude modulation); they are key for higher spectrum efficiency to enable higher data rate transmissions in limited available bandwidths. Nonlinear high-power amplifiers (HPAs) can regenerate frequency spectral side lobes on input-filtered digital modulations. The paper discusses technologies and techniques for controlling these spectral side lobes, such as the use of square root raised cosine (SRRC) filtering before or during the modulation process, HPA output power back-off (OPBO), and RF filters after the HPA. Spectral mask specifications are a common method of the NTIA and ITU to define spectral occupancy power limits. They are intended to reduce interference among RF spectrum users by limiting excessive radiation at frequencies beyond the regulatory allocated bandwidth.The focus here is on the communication systems of U.S. government satellites used for space research, space operations, Earth exploration satellite services (EESS), meteorological satellite services (METSATS), and other government services. The 8025 to 8400 megahertz (MHz) X band can be used to illustrate the "unwanted emissions" issue. 8025 to 8400 MHz abuts the 8400 to 8450 MHz band allocated by the NTIA and ITU to space research for space-to-Earth transmissions such as receiving very weak Deep Space Network signals. The views and ideas expressed in this paper are those of the authors and do not necessarily reflect those of The Aerospace Corporation or The National Oceanic and Atmospheric Administration (NOAA) and its National Environmental Satellite Service (NESDIS).

St. John's wort: a new alternative for depression?

PubMed

Josey, E S; Tackett, R L

1999-03-01

The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an acceptable alternative to traditional antidepressant therapy, although trials on a larger scale are warranted in this area. Hypericum is available to the lay public as an over-the-counter preparation and may be misused if not fully understood.

Reasons why undergraduate women comply with unwanted, non-coercive sexual advances: A serial indirect effect model integrating sexual script theory and sexual self-control perspectives.

PubMed

Quinn-Nilas, Christopher; Kennett, Deborah J

2018-01-16

This study explored the predictors of young women's compliance with unwanted sexual activities, integrating the social with the cognitive and behavioral correlates of sexual compliance. In total, 222 young heterosexual women completed measures examining the Sexual Self-Control model, including reasons for consenting, sexual resourcefulness, and compliance with unwanted sex, as well as gender role measures pertaining to sexual script theory, including the sexual double standard, gender role stress, and virginity scripts. An exploratory analysis of serial indirect effects demonstrated that women scoring lower in sexual resourcefulness endorsed higher female gender role stress, which in turn was associated with higher endorsement of reasons for consent, translating into more frequent compliance with unwanted sexual activities. The relationship between one's ability to refuse and their decision to refuse appears quite complex. Understanding one's decision requires consideration of the social aspects of gender role endorsement.

Aptamer delivery of siRNA, radiopharmaceutics and chemotherapy agents in cancer.

PubMed

de Almeida, Carlos E B; Alves, Lais Nascimento; Rocha, Henrique F; Cabral-Neto, Januário Bispo; Missailidis, Sotiris

2017-06-20

Aptamers are oligonucleotide reagents with high affinity and specificity, which among other therapeutic and diagnostic applications have the capability of acting as delivery agents. Thus, aptamers are capable of carrying small molecules, nanoparticles, radiopharmaceuticals or fluorescent agents as well as nucleic acid therapeutics specifically to their target cells. In most cases, the molecules may possess interesting therapeutic properties, but their lack of specificity for a particular cell type, or ability to internalise in such a cell, hinders their clinical development, or cause unwanted side effects. Thus, chemotherapy or radiotherapy agents, famous for their side effects, can be coupled to aptamers for specific delivery. Equally, siRNA have great therapeutic potential and specificity, but one of their shortcomings remain the delivery and internalisation into cells. Various methodologies have been proposed to date, including aptamers, to resolve this problem. Therapeutic or imaging reagents benefit from the adaptability and ease of chemical manipulation of aptamers, their high affinity for the specific marker of a cell type, and their internalisation ability via cell mediated endocytosis. In this review paper, we explore the potential of the aptamers as delivery agents and offer an update on current status and latest advancements. Copyright © 2017 Elsevier B.V. All rights reserved.

Visualization of laser tattoo removal treatment effects in a mouse model by two-photon microscopy

PubMed Central

Jang, Won Hyuk; Yoon, Yeoreum; Kim, Wonjoong; Kwon, Soonjae; Lee, Seunghun; Song, Duke; Choi, Jong Woon; Kim, Ki Hean

2017-01-01

Laser tattoo removal is an effective method of eliminating tattoo particles in the skin. However, laser treatment cannot always remove the unwanted tattoo completely, and there are risks of either temporary or permanent side effects. Studies using preclinical animal models could provide detailed information on the effects of laser treatment in the skin, and might help to minimize side effects in clinical practices. In this study, two-photon microscopy (TPM) was used to visualize the laser treatment effects on tattoo particles in both phantom specimens and in vivo mouse models. Fluorescent tattoo ink was used for particle visualization by TPM, and nanosecond (ns) and picosecond (ps) lasers at 532 nm were used for treatment. In phantom specimens, TPM characterized the fragmentation of individual tattoo particles by tracking them before and after the laser treatment. These changes were confirmed by field emission scanning electron microscopy (FE-SEM). TPM was used to measure the treatment efficiency of the two lasers at different laser fluences. In the mouse model, TPM visualized clusters of tattoo particles in the skin and detected their fragmentation after the laser treatment. Longitudinal TPM imaging observed the migration of cells containing tattoo particles after the laser treatment. These results show that TPM may be useful for the assessment of laser tattoo removal treatment in preclinical studies. PMID:28856046

Reducing unwanted trauma memories by imaginal exposure or autobiographical memory elaboration: An analogue study of memory processes

PubMed Central

Ehlers, Anke; Mauchnik, Jana; Handley, Rachel

2012-01-01

Unwanted memories of traumatic events are a core symptom of post-traumatic stress disorder. A range of interventions including imaginal exposure and elaboration of the trauma memory in its autobiographical context are effective in reducing such unwanted memories. This study explored whether priming for stimuli that occur in the context of trauma and evaluative conditioning may play a role in the therapeutic effects of these procedures. Healthy volunteers (N = 122) watched analogue traumatic and neutral picture stories. They were then randomly allocated to 20 min of either imaginal exposure, autobiographical memory elaboration, or a control condition designed to prevent further processing of the picture stories. A blurred picture identification task showed that neutral objects that preceded traumatic pictures in the stories were subsequently more readily identified than those that had preceded neutral stories, indicating enhanced priming. There was also an evaluative conditioning effect in that participants disliked neutral objects that had preceded traumatic pictures more. Autobiographical memory elaboration reduced the enhanced priming effect. Both interventions reduced the evaluative conditioning effect. Imaginal exposure and autobiographical memory elaboration both reduced the frequency of subsequent unwanted memories of the picture stories. PMID:21227404

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans.

PubMed

Singh, Nisha; Sharpley, Ann L; Emir, Uzay E; Masaki, Charles; Herzallah, Mohammad M; Gluck, Mark A; Sharp, Trevor; Harmer, Catherine J; Vasudevan, Sridhar R; Cowen, Philip J; Churchill, Grant C

2016-06-01

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood-brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials.

An Effect of Oak-Wood Extract (Robuvit®) on Energy State of Healthy Adults—A Pilot Study

PubMed Central

Országhová, Zuzana; Waczulíková, Iveta; Burki, Carolina; Rohdewald, Peter; Ďuračková, Zdeňka

2015-01-01

The purpose of our study was to examine the psychological benefits of the treatment with Robuvit® (Horphag Research Ltd.) – polyphenolic extract obtained from the wood of oak Quercus robur – on the healthy elderly individuals using energy subscale scores of the Activation – Deactivation Adjective Check List. Analysis was focused on the comparison of pre-post treatment effect of Robuvit on symptoms of fatigue. In the total group of volunteers, significant increase of average question scores was found in three of four subscales of feelings (energy, tiredness, and tension) after 4 weeks of Robuvit administration. Effects of extract were observed mainly after stratification of total group of volunteers according to the level of feeling at the pre-treatment questionnaire. Our results demonstrate positive effect of Robuvit on mental and energy level in healthy human without any unwanted side effects. © 2015 The Authors Phytotherapy Research Published by John Wiley & Sons Ltd. PMID:25981190

The roles of safety and compliance in determining effectiveness of topical therapy for psoriasis.

PubMed

Stein Gold, Linda; Corvari, Linda

2007-01-01

Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil.

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas; Okonogi, Siriporn

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO.

Self-microemulsifying drug delivery system and nanoemulsion for enhancing aqueous miscibility of Alpinia galanga oil

PubMed Central

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Müllertz, Anette; Rades, Thomas

2017-01-01

Alpinia galanga oil (AGO) possesses various activities but low aqueous solubility limits its application particularly in aquatic animals. AGO has powerful activity on fish anesthesia. Ethanol used for enhancing water miscible of AGO always shows severe side effects on fish. The present study explores the development of self-microemulsifying drug delivery systems (SMEDDS) and nanoemulsions (NE) to deliver AGO for fish anesthesia with less or no alcohol. Pseudoternary phase diagrams were constructed to identify the best SMEDDS-AGO formulation, whereas NE-AGO were developed by means of high-energy emulsification. The mean droplet size of the best SMEDDS-AGO was 82 ± 0.5 nm whereas that of NE-AGO was 48 ± 1.6 nm. The anesthetic effect of the developed SMEDDS-AGO and NE-AGO in koi (Cyprinus carpio) was evaluated and compared with AGO ethanolic solution (EtOH-AGO). It was found that the time of induction the fish to reach the surgical stage of anesthesia was dose dependent. NE-AGO showed significantly higher activity than SMEDDS-AGO and EtOH-AGO, respectively. EtOH-AGO caused unwanted hyperactivity in the fish. This side effect did not occur in the fish anesthetized with SMEDDS-AGO and NE-AGO. In conclusion, SMEDDS and NE are promising delivery systems for AGO. PMID:29190663

Quantum key distribution with untrusted detectors

NASA Astrophysics Data System (ADS)

González, P.; Rebón, L.; Ferreira da Silva, T.; Figueroa, M.; Saavedra, C.; Curty, M.; Lima, G.; Xavier, G. B.; Nogueira, W. A. T.

2015-08-01

Side-channel attacks currently constitute the main challenge for quantum key distribution (QKD) to bridge theory with practice. So far two main approaches have been introduced to address this problem, (full) device-independent QKD and measurement-device-independent QKD. Here we present a third solution that might exceed the performance and practicality of the previous two in circumventing detector side-channel attacks, which arguably is the most hazardous part of QKD implementations. Our proposal has, however, one main requirement: the legitimate users of the system need to ensure that their labs do not leak any unwanted information to the outside. The security in the low-loss regime is guaranteed, while in the high-loss regime we already prove its robustness against some eavesdropping strategies.

A rapid, Web-based method for obtaining patient views on effects and side-effects of antidepressants.

PubMed

Rizo, Carlos; Deshpande, Amol; Ing, Alton; Seeman, Neil

2011-04-01

This project was undertaken to develop a rapid method for obtaining a widespread sample of patient views on the efficacy and side-effects of antidepressants. A Web-based method is described for rapidly and objectively obtaining patient views on the effects and side-effects of treatment with antidepressants. The method entails a systematized search of many URLs (Uniform Resource Locators, or Web page addresses), using keywords and phrases to extract the named drug and symptom that are reliably relevant to the medication being taken by the individual reporting the experience online. Unwanted medical conditions (e.g., cancer) are excluded. Three successive searches of thousands of Web pages revealed a cumulative total of 835 "mentions" of patient experience on duloxetine, 756 for venlafaxine, 637 for citalopram, 636 for sertraline, 559 for paroxetine, 457 for fluoxetine, 318 for desvenlafaxine, 289 for fluvoxamine, and 210 for mirtazapine, in association with various symptoms. A comparison of the associated symptoms for each of the antidepressants found that the prevalence of the combined factor of fatigue, drowsiness, tiredness or lethargy ranged from 6.4±0.8% down to 2.9±0.15% of the mentions, where the S.E. was derived from three repeats of the Web-based analysis. The prevalence of dizziness or vertigo ranged from 7.6±0.8% down to 1.9±0.3% of the mentions. Given the increasing number of patient narratives about drug experiences on open-access Web forums, this rapid novel method will have increasing utility in post-marketing surveillance and in comparing the effects of psychiatric medications. Copyright © 2010 Elsevier B.V. All rights reserved.

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

PubMed

Hu, Ming; Zhao, Jixian; Ai, Xiangzhao; Budanovic, Maja; Mu, Jing; Webster, Richard D; Cao, Qian; Mao, Zongwan; Xing, Bengang

2016-09-13

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

A FRET-guided, NIR-responsive bubble-generating liposomal system for in vivo targeted therapy with spatially and temporally precise controlled release.

PubMed

Chuang, Er-Yuan; Lin, Chia-Chen; Chen, Ko-Jie; Wan, De-Hui; Lin, Kun-Ju; Ho, Yi-Cheng; Lin, Po-Yen; Sung, Hsing-Wen

2016-07-01

The nonspecific distribution of therapeutic agents and nontargeted heating commonly produce undesirable side effects during cancer treatment since the optimal timing of triggering the carrier systems is unknown. This work proposes a multifunctional liposomal system that can intracellularly and simultaneously deliver the therapeutic drug doxorubicin (DOX), heat, and a bubble-generating agent (ammonium bicarbonate, ABC) into targeted tumor cells to have a cytotoxic effect. Gold nanocages that are encapsulated in liposomes effectively convert near-infrared light irradiation into localized heat, which causes the decomposition of ABC and generates CO2 bubbles, rapidly triggering the release of DOX. Additionally, a hybridized Mucin-1 aptamer is conjugated on the surface of the test liposomes, which then function as a recognition probe to enhance the uptake of those liposomes by cells, and as a molecular beacon to signal when the internalized particles have been maximized, which is the optimal time for photothermally triggering the release of the drug following the systemic administration of the liposomes. Empirical results reveal that this combined treatment effectively controls targeted drug release in a spatially and temporally precise fashion and so significantly increases the potency of the drug while minimizing unwanted side effects, making it a promising treatment for cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

PubMed

Khan, Haroon; Khan, Murad Ali; Hussain, Sajid; Gaffar, Rukhsana; Ashraf, Nadeem

2016-05-01

Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models. © The Author(s) 2013.

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

PubMed Central

Viola, Joana R.; Rafael, Diana F.; Wagner, Ernst; Besch, Robert; Ogris, Manfred

2013-01-01

Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed. PMID:23634303

Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting.

PubMed

Aziz, Fahad

2012-07-01

Chemotherapy can be a life-prolonging treatment for many cancer patients, but it is often associated with profound nausea and vomiting that is so distressing that patients may delay or decline treatment to avoid these side effects. The discovery of several NK1 receptor antagonists is a big revolution to dealt this problem. NK1 receptor antagonists prevent both acute and delayed chemotherapy-induced nausea and vomiting (CINV). These agents act centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy. By controlling nausea and vomiting, these agents help improve patients' daily living and their ability to complete multiple cycles of chemotherapy. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.

Effects of planned, mistimed and unwanted pregnancies on the use of prenatal health services in sub-Saharan Africa: a multicountry analysis of Demographic and Health Survey data.

PubMed

Amo-Adjei, Joshua; Anamaale Tuoyire, Derek

2016-12-01

We analysed the extent of planned, mistimed and unwanted pregnancies and how they predict optimal use of prenatal (timing and number of antenatal) care services in 30 African countries. We pooled data from Demographic and Health Surveys conducted in 30 African countries between 2006 and 2015. We described the extent of mistimed and unwanted pregnancies and further used mixed effects logistic and Poisson regression estimation techniques to examine the impacts of planned, mistimed and unwanted pregnancies on the use of prenatal health services. In total, 73.65% of pregnancies in all countries were planned. Mistimed pregnancy ranged from 7.43% in Burkina Faso to 41.33% in Namibia. Unwanted pregnancies were most common in Swaziland (39.54%) and least common in Niger (0.74%). Timely (first trimester) initiation of ANC was 37% overall in all countries; the multicountry average number of ANC visits was optimal [4.1; 95% CI: 4.1-4.2] but with notable disparities between countries. Overall, mistimed and unwanted pregnancies were strongly associated with late ANC attendance and fewer visits women made in the pooled analysis. Unintended pregnancies are critical risks to achieving improved maternal health in respect of early and optimal ANC coverage for women in Africa. Programmes targeted at advancing coverage of ANC in Africa need to deploy contextually appropriate mechanisms to prevent unintended pregnancies. © 2016 John Wiley & Sons Ltd.

Adjustable speed drive study, June 1985 to September 1988. Part 2: Appendices

NASA Astrophysics Data System (ADS)

Wallace, Alan

1989-08-01

Advances in speed control for motors in recent years, notably those in power electronics, have widened the range of application for several adjustable speed drive (ASD) types to include the smaller horsepower sizes. The dc motor drive, formerly in almost universal use for speed control, is being challenged by the high efficiency induction motor/pulse width modulation (PWM) drive; and for special small horsepower size applications, by the permanent magnet motor/PWM inverter drive or by the switched reluctance motor drive. The main characteristics of the several ASD types suitable for small horsepower size applications are discussed, as well as their unwanted side effects: poor power factor, harmonic distortion of the supply, acoustic noise, and electromagnetic interference. A procedure is recommended for determining which, if any, ASD to use.

Understanding drug targets: no such thing as bad news.

PubMed

Roberts, Ruth A

2018-05-24

How can small-to-medium pharma and biotech companies enhance the chances of running a successful drug project and maximise the return on a limited number of assets? Having a full appreciation of the safety risks associated with proposed drug targets is a crucial element in understanding the unwanted side-effects that might stop a project in its tracks. Having this information is necessary to complement knowledge about the probable efficacy of a future drug. However, the lack of data-rich insight into drug-target safety is one of the major causes of drug-project failure today. Conducting comprehensive target-safety reviews early in the drug discovery process enables project teams to make the right decisions about which drug targets to take forward. Copyright © 2018 Elsevier Ltd. All rights reserved.

A fabrication guide for planar silicon quantum dot heterostructures

NASA Astrophysics Data System (ADS)

Spruijtenburg, Paul C.; Amitonov, Sergey V.; van der Wiel, Wilfred G.; Zwanenburg, Floris A.

2018-04-01

We describe important considerations to create top-down fabricated planar quantum dots in silicon, often not discussed in detail in literature. The subtle interplay between intrinsic material properties, interfaces and fabrication processes plays a crucial role in the formation of electrostatically defined quantum dots. Processes such as oxidation, physical vapor deposition and atomic-layer deposition must be tailored in order to prevent unwanted side effects such as defects, disorder and dewetting. In two directly related manuscripts written in parallel we use techniques described in this work to create depletion-mode quantum dots in intrinsic silicon, and low-disorder silicon quantum dots defined with palladium gates. While we discuss three different planar gate structures, the general principles also apply to 0D and 1D systems, such as self-assembled islands and nanowires.

Androgen receptor and immune inflammation in benign prostatic hyperplasia and prostate cancer

PubMed Central

Izumi, Kouji; Li, Lei; Chang, Chawnshang

2014-01-01

Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are frequent diseases in middle-aged to elderly men worldwide. While both diseases are linked to abnormal growth of the prostate, the epidemiological and pathological features of these two prostate diseases are different. BPH nodules typically arise from the transitional zone, and, in contrast, PCa arises from the peripheral zone. Androgen deprivation therapy alone may not be sufficient to cure these two prostatic diseases due to its undesirable side effects. The alteration of androgen receptor-mediated inflammatory signals from infiltrating immune cells and prostate stromal/epithelial cells may play key roles in those unwanted events. Herein, this review will focus on the roles of androgen/androgen receptor signals in the inflammation-induced progression of BPH and PCa. PMID:26594314

Analysis of cryogenic propellant behavior in microgravity and low thrust environments

NASA Technical Reports Server (NTRS)

Fisher, Mark F.; Schmidt, George R.; Martin, James J.

1991-01-01

Predictions of a CFD program calculating a fluid-free surface shape and motion as a function of imposed acceleration are validated against the drop-tower test data collected to support design and performance assessments of the Saturn S-IVB stage liquid-hydrogen tank. The drop-tower facility, experimental package, and experiment procedures are outlined, and the program is described. It is noted that the validation analysis confirms the program's suitability for predicting low-g fluid slosh behavior, and that a similar analysis could examine the effect of incorporating baffles and screens to impede initiation of any unwanted side loads due to slosh. It is concluded that in actual vehicle applications, the engine thrust tailoff profile should be included in computer simulations if the precise interface versus time definition is needed.

Control of Maillard Reactions in Foods: Strategies and Chemical Mechanisms.

PubMed

Lund, Marianne N; Ray, Colin A

2017-06-14

Maillard reactions lead to changes in food color, organoleptic properties, protein functionality, and protein digestibility. Numerous different strategies for controlling Maillard reactions in foods have been attempted during the past decades. In this paper, recent advances in strategies for controlling the Maillard reaction and subsequent downstream reaction products in food systems are critically reviewed. The underlying mechanisms at play are presented, strengths and weaknesses of each strategy are discussed, and reasonable reaction mechanisms are proposed to reinforce the evaluations. The review includes strategies involving addition of functional ingredients, such as plant polyphenols and vitamins, as well as enzymes. The resulting trapping or modification of Maillard targets, reactive intermediates, and advanced glycation endproducts (AGEs) are presented with their potential unwanted side effects. Finally, recent advances in processing for control of Maillard reactions are discussed.

Exploring Different Strategies for Efficient Delivery of Colorectal Cancer Therapy

PubMed Central

Lin, Congcong; Ng, Huei Leng Helena; Pan, Weisan; Chen, Hubiao; Zhang, Ge; Bian, Zhaoxiang; Lu, Aiping; Yang, Zhijun

2015-01-01

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. Much emphasis is being laid on the development of effective drug delivery systems for achieving selective delivery of the active moiety at the anticipated site of action with minimized unwanted side effects. Researchers have employed various techniques (dependent on pH, time, pressure and/or bacteria) for targeting drugs directly to the colonic region. On the other hand, systemic drug delivery strategies to specific molecular targets (such as FGFR, EGFR, CD44, EpCAM, CA IX, PPARγ and COX-2) overexpressed by cancerous cells have also been shown to be effective. This review aims to put forth an overview of drug delivery technologies that have been, and may be developed, for the treatment of CRC. PMID:26569228

Social and religious dimensions of unwanted pregnancy: an Islamic perspective.

PubMed

Kasule, O H

2003-03-01

The concept of 'unwanted pregnancy' is a recent in human history and is associated with social stresses of modern life. The purposes of the law, maqasid al shari'at, and its principles, qawa'id a shari'at, focus on preventing 'unwanted pregnancy', protecting the rights of the fetus and infant, and mitigating the adverse effects of 'unwanted pregnancy' by social measures. 'Unwanted pregnancy' is associated with general social determinants (hedonistic life styles, sexual transgression, addiction to drugs, fear of poverty, and low female status) and specific antecedent causes (sexual crimes, egoistic greed, maternal/fetal disease, and gender discrimination). It is prevented by sexual hygiene, marriage, contraception, deterring sexual crimes, and raising the status of women. The adverse sequelae of 'unwanted pregnancy' (feticide, infanticide, or child abuse and neglect) can be prevented by defending the basic human right of the fetus and infant to life, promoting social institutions for child welfare (nuclear family, extended family, foster care, and open adoption). Closed adoption is forbidden by Law but care in a foster home is allowed and is encouraged if the nuclear and extended families are unwilling or are unable to care for children. Abortion at any stage of pregnancy is a crime against humanity. It is not a solution to the problem but is part of the problem. It will encourage more 'unwanted pregnancies'.

The Women'S Perceptions About Unwanted Pregnancy: A Qualitative Study in Iran.

PubMed

Akbarzadeh, Marzieh; Yazdanpanahi, Zahra; Zarshenas, Ladan; Sharif, Farkhondeh

2015-09-28

Unwanted pregnancy has affected different aspects of our life. Researchers point out if a child's birth is unwanted, an increase in maternal issues can be observed. The aim of this study was to describe the women's viewpoints regarding unwanted pregnancy. This qualitative study using content analysis was employed in Shiraz University in 2013-2014. 20 women with unwanted pregnancy were chosen using purposeful sampling. Data were gathered through semi-structured interviews and trustworthiness of them was evaluated. Findings of this study, according to the participants' experience, revealed maternal emotions like embarrassment for getting pregnant, mother's own negative affection, concerns about missing family and other children, and terminating the pregnancy through illegal abortion, the husband's disagreement about the termination, blaming themselves for thinking about abortion or illegal abortion, and concern about their guilt feeling. Another finding was family problems like husband's behavior and his negative outlook towards his child and fetus. The next category belonged to anxiety about the future of their child, including economic, social and relational problems, and suppression of the children's logical expectations. The last finding was the lack of maternal emotional support. Unwanted pregnancy's effects on the mothers and infants' health are considerable. A closer observation by family and health care providers for unwanted pregnancies and its results is recommended; therefore, they should be taken care of as high risk pregnancies, requiring family support.

Principles of a multistack electrochemical wastewater treatment design

NASA Astrophysics Data System (ADS)

Elsahwi, Essam S.; Dawson, Francis P.; Ruda, Harry E.

2018-02-01

Electrolyzer stacks in a bipolar architecture (cells connected in series) are desirable since power provided to a stack can be transferred at high voltages and low currents and thus the losses in the power bus can be reduced. The anode electrodes (active electrodes) considered as part of this study are single sided but there are manufacturing cost advantages to implementing double side anodes in the future. One of the main concerns with a bipolar stack implementation is the existence of leakage currents (bypass currents). The leakage current is associated with current paths that are not between adjacent anode and cathode pairs. This leads to non uniform current density distributions which compromise the electrochemical conversion efficiency of the stack and can also lead to unwanted side reactions. The objective of this paper is to develop modelling tools for a bipolar architecture consisting of two single sided cells that use single sided anodes. It is assumed that chemical reactions are single electron transfer rate limited and that diffusion and convection effects can be ignored. The design process consists of the flowing two steps: development of a large signal model for the stack, and then the extraction of a small signal model from the large signal model. The small signal model facilitates the design of a controller that satisfies current or voltage regulation requirements. A model has been developed for a single cell and two cells in series but can be generalized to more than two cells in series and to incorporate double sided anode configurations in the future. The developed model is able to determine the leakage current and thus provide a quantitative assessment on the performance of the cell.

The application of "double isolation" in Fourier transform ion cyclotron resonance sustained off-resonance irradiation collisionally-induced dissociation tandem mass spectrometry to remove labile isobaric impurities.

PubMed

Gates, Paul J; Lopes, Norberto P; Pinto, Emani; Colepicolo, Pio; Cardozo, Karina H M

2011-01-01

This study reports the application of "double isolation" in sustained off-resonance irradiation collisionally-induced dissociation tandem mass spectrometry (SORI-CID-MS/MS) to remove radio- frequency (RF) fragment ions of very close mass isobaric ions (0.02 m/z apart). Analyses were performed with a fraction of a biological extract isolated from a macroalgae containing the mycosporine-like amino acid asterina-330. Direct isolation of the precursor ion by narrowing the isolation window proved ineffective as it impinged upon the required ion thus substantially reducing its intensity. By increasing the correlated sweep time, ejection efficiency of the isolation was improved, but caused the unwanted side-effect of RF fragmentation of labile ions. Finally, by skipping the ion activation step and performing a second isolation (in the MS(3) module) the RF fragments from the first isolation were removed leaving a very pure isolation of the required precursor ion and allowed a very clean CID fragmentation. We demonstrated that the m/z 272.1351 ion is derived from the loss of NH(3) from m/z 289.1620 isobaric impurity and is not related to asterina-330. This application represents a powerful tool to remove unwanted ions in the MS/MS spectrum that result from fragmentation of isobaric ions.

Neuroticism explains unwanted variance in Implicit Association Tests of personality: possible evidence for an affective valence confound.

PubMed

Fleischhauer, Monika; Enge, Sören; Miller, Robert; Strobel, Alexander; Strobel, Anja

2013-01-01

Meta-analytic data highlight the value of the Implicit Association Test (IAT) as an indirect measure of personality. Based on evidence suggesting that confounding factors such as cognitive abilities contribute to the IAT effect, this study provides a first investigation of whether basic personality traits explain unwanted variance in the IAT. In a gender-balanced sample of 204 volunteers, the Big-Five dimensions were assessed via self-report, peer-report, and IAT. By means of structural equation modeling (SEM), latent Big-Five personality factors (based on self- and peer-report) were estimated and their predictive value for unwanted variance in the IAT was examined. In a first analysis, unwanted variance was defined in the sense of method-specific variance which may result from differences in task demands between the two IAT block conditions and which can be mirrored by the absolute size of the IAT effects. In a second analysis, unwanted variance was examined in a broader sense defined as those systematic variance components in the raw IAT scores that are not explained by the latent implicit personality factors. In contrast to the absolute IAT scores, this also considers biases associated with the direction of IAT effects (i.e., whether they are positive or negative in sign), biases that might result, for example, from the IAT's stimulus or category features. None of the explicit Big-Five factors was predictive for method-specific variance in the IATs (first analysis). However, when considering unwanted variance that goes beyond pure method-specific variance (second analysis), a substantial effect of neuroticism occurred that may have been driven by the affective valence of IAT attribute categories and the facilitated processing of negative stimuli, typically associated with neuroticism. The findings thus point to the necessity of using attribute category labels and stimuli of similar affective valence in personality IATs to avoid confounding due to recoding.

Complementary and alternative medicine for multiple sclerosis.

PubMed

Schwarz, S; Knorr, C; Geiger, H; Flachenecker, P

2008-09-01

We analyzed characteristics, motivation, and effectiveness of complementary and alternative medicine in a large sample of people with multiple sclerosis. A 53-item survey was mailed to the members of the German Multiple Sclerosis Society, chapter of Baden-Wuerttemberg. Surveys of 1573 patients (48.5 +/- 11.7 years, 74% women, duration of illness 18.1 +/- 10.5 years) were analyzed. In comparison with conventional medicine, more patients displayed a positive attitude toward complementary and alternative medicine (44% vs 38%, P < 0.05), with 70% reporting lifetime use of at least one method. Among a wide variety of complementary and alternative medicine, diet modification (41%), Omega-3 fatty acids (37%), removal of amalgam fillings (28%), vitamins E (28%), B (36%), and C (28%), homeopathy (26%), and selenium (24%) were cited most frequently. Most respondents (69%) were satisfied with the effects of complementary and alternative medicine. Use of complementary and alternative medicine was associated with religiosity, functional independence, female sex, white-collar job, and higher education (P < 0.05). Compared with conventional therapies, complementary and alternative medicine rarely showed unwanted side effects (9% vs 59%, P < 0.00001). A total of 52% stated that the initial consultation with their physician lasted less than 15 min. To conclude, main reasons for the use of complementary and alternative medicine include the high rate of side effects and low levels of satisfaction with conventional treatments and brief patients/physicians contacts.

Improved anti-tumor activity and safety profile of a paclitaxel-loaded glycyrrhetinic acid-graft-hyaluronic acid conjugate as a synergistically targeted drug delivery system.

PubMed

Zhang, Li; Zhou, Jian-Ping; Yao, Jing

2015-12-01

The present study was designed to develop and evaluate glycyrrhetinic acid-graft-hyaluronic acid (HGA) conjugate for intravenous paclitaxel (PTX) delivery. Lyophilized PTX-loaded self-assembled HGA nanoparticles (PTX/HGAs) were prepared and characterized by dynamic light scattering measurements. Hemolysis test, intravenous irritation assessment, and in vitro and in vivo pharmacodynamic studies were carried out. B16F10 and HepG2 cells were used in the cell apoptosis analysis. The mouse MDA-MB-231 xenograft model was used for the evaluation of in vivo anticancer activity of the drugs, by the analysis of tumor growth and side effects on other tissues. PTX/HGAs showed high stability and good biocompability. Compared with PTX plus GA plus HA solution, PTX/HGAs displayed obvious superiority in inducing the apoptosis of the cancer cells. Following systemic administration, PTX/HGAs efficiently suppressed tumor growth, with mean tumor inhibition ratio (TIR) being 65.08%, which was significantly higher than that of PTX plus GA plus HA treatment. In conclusion, PTX/HGAs demonstrated inhibitory effects tumor growth without unwanted side effects, suggesting that HGA conjugates hold a great potential as a delivery carrier for cancer chemotherapeutics to improve therapeutic efficacy and minimize adverse effects. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Metabolic and Structural Effects of Phosphatidylcholine and Deoxycholate Injections on Subcutaneous Fat

PubMed Central

Reeds, Dominic N.; Mohammed, B. Selma; Klein, Samuel; Boswell, Craig Brian

2013-01-01

Background: Phosphatidylcholine and deoxycholate (PC-DC) injections are a popular nonsurgical method to eliminate unwanted fat. The safety and efficacy of this approach is uncertain. Objective: The authors evaluate the effects of PC-DC treatments on body composition, adipocyte function, and mechanisms responsible for fat loss. Methods: This randomized, open-label study enrolled 13 women with a body mass index (BMI) ≤30 kg/m2 and lower abdominal subcutaneous fat suitable for small-volume liposuction. Patients were randomized by the final digit of their Social Security numbers and received between 2 and 4 PC-DC treatments, spaced 8 weeks apart. One side below the umbilicus was injected with PC-DC. The contralateral, control side received no treatment. Adipose tissue biopsies were performed on the treated side at baseline, 1 week after the first treatment, and 8 weeks after the final treatment. The primary outcome was change in adipose tissue thickness at baseline and 8 weeks after the final treatment. Results: Seven women completed the study. Treatment with PC-DC significantly reduced the thickness of the anterior subcutaneous abdominal fat (P = .004). Adipose tissue showed rapid increases in crown-like structures, macrophage infiltration, and reduced expression of leptin, hormone-sensitive lipase, adipose tissue triglyceride lipase, and CD36. Plasma C-reactive protein, lipid profile, and plasma glucose concentrations were unchanged. Conclusions: PC-DC injections can effectively reduce abdominal fat volume and thickness by inducing adipocyte necrosis. These treatments do not appear to increase circulating markers of inflammation or affect glucose and lipid metabolism. Level of Evidence: 3 PMID:23439063

Fixed, low radiant exposure vs. incremental radiant exposure approach for diode laser hair reduction: a randomized, split axilla, comparative single-blinded trial.

PubMed

Pavlović, M D; Adamič, M; Nenadić, D

2015-12-01

Diode lasers are the most commonly used treatment modalities for unwanted hair reduction. Only a few controlled clinical trials but not a single randomized controlled trial (RCT) compared the impact of various laser parameters, especially radiant exposure, onto efficacy, tolerability and safety of laser hair reduction. To compare the safety, tolerability and mid-term efficacy of fixed, low and incremental radiant exposures of diode lasers (800 nm) for axillary hair removal, we conducted an intrapatient, left-to-right, patient- and assessor-blinded and controlled trial. Diode laser (800 nm) treatments were evaluated in 39 study participants (skin type II-III) with unwanted axillary hairs. Randomization and allocation to split axilla treatments were carried out by a web-based randomization tool. Six treatments were performed at 4- to 6-week intervals with study subjects blinded to the type of treatment. Final assessment of hair reduction was conducted 6 months after the last treatment by means of blinded 4-point clinical scale using photographs. The primary endpoint was reduction in hair growth, and secondary endpoints were patient-rated tolerability and satisfaction with the treatment, treatment-related pain and adverse effects. Excellent reduction in axillary hairs (≥ 76%) at 6-month follow-up visit after receiving fixed, low and incremental radiant exposure diode laser treatments was obtained in 59% and 67% of study participants respectively (Z value: 1.342, P = 0.180). Patients reported lower visual analogue scale (VAS) pain score on the fixed (4.26) than on the incremental radiant exposure side (5.64) (P < 0.0003). The only side-effect was mild and transient erythema. Subjects better tolerated the fixed, low radiant exposure protocol (P = 0.03). The majority of the study participants were satisfied with both treatments. Both low and incremental radiant exposures produced similar hair reduction and high and comparable patient satisfaction. However, low radiant exposure diode laser treatments were less painful and better tolerated. © 2015 European Academy of Dermatology and Venereology.

Unintended pregnancy in the life-course perspective.

PubMed

Helfferich, Cornelia; Hessling, Angelika; Klindworth, Heike; Wlosnewski, Ines

2014-09-01

In this contribution unintended pregnancies are studied as a multidimensional concept from a life-course perspective. Standardized data on the prevalence of unwanted pregnancies in different stages of women's life course are combined with a qualitative analysis of the subjective meaning of "unwanted" and of subjective explanations of getting pregnant unintentionally. The study "frauen leben 3" on family planning in the life course of 20-44 year old women was conducted on behalf of the Federal Centre for Health Education (BZgA) from 2011 until 2014 in four federal states in Germany. A standardized questionnaire was used to collect retrospective information on 4794 pregnancies (including induced abortions), and biographical in-depth interviews provide qualitative information on 103 unwanted pregnancies. The standardized data were analyzed with bivariate methods and multivariate logistic regression models. The qualitative procedure to construct typologies of subjective meanings consisted of contrasting cases according to the generative approach of Grounded Theory. In contrast to unwanted pregnancies, mistimed pregnancies are characterized to a greater extent by negligence in the use of contraceptives, by a positive reaction to the pregnancy and by a more general desire to have a child. Four different subjective meanings of "unwanted" are constructed in qualitative analysis. The logistic regressions show that the selected factors that increase the likelihood of an unwanted pregnancy vary according to age and stage in the life course. The quantitative analysis reveals furthermore that relationship with a partner had a significant effect in all stages of the life course. The qualitative interviews specify the age- and life course-related aspects of these effects. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diagnosis and management of fluid overload in heart failure and cardio-renal syndrome: the "5B" approach.

PubMed

Ronco, Claudio; Kaushik, Manish; Valle, Roberto; Aspromonte, Nadia; Peacock, W Frank

2012-01-01

Cardio-Renal syndrome may occur as a result of either primarily renal or cardiac dysfunction. This complex interaction requires a tailored approach to manage the underlying pathophysiology while optimizing the patient's symptoms and thus providing the best outcomes. Patients often are admitted to the hospital for signs and symptoms of congestion and fluid overload is the most frequent cause of subsequent re-admission. Fluid management is of paramount importance in the strategy of treatment for heart failure patients. Adequate fluid status should be obtained but a target value should be set according to objective indicators and biomarkers. Once the fluid excess is identified, a careful prescription of fluid removal by diuretics or extracorporeal therapies must be made. While delivering these therapies, adequate monitoring should be performed to prevent unwanted effects such as worsening of renal function or other complications. There is a very narrow window of optimal hydration for heart failure patients. Overhydration can result in myocardial stretching and potential decompensation. Inappropriate dehydration or relative reduction of circulating blood volume may result in distant organ damage caused by inadequate perfusion. We suggest consideration of the "5B" approach. This stands for balance of fluids (reflected by body weight), blood pressure, biomarkers, bioimpedance vector analysis, and blood volume. Addressing these parameters ensures that the most important issues affecting symptoms and outcomes are addressed. Furthermore, the patient is receiving the best possible care while avoiding unwanted side effects of the treatment. Copyright © 2012 Elsevier Inc. All rights reserved.

Trends in youth reports of sexual solicitations, harassment and unwanted exposure to pornography on the Internet.

PubMed

Mitchell, Kimberly J; Wolak, Janis; Finkelhor, David

2007-02-01

This study was designed to track trends in reports of unwanted sexual solicitations, harassment, and unwanted exposure to pornography via the Internet between 2000 and 2005 across various demographic sub-groups of youth. Cross-sectional data was collected in two equivalent national telephone surveys of 1500 Internet users, ages 10 through 17 years. Bivariate and multivariate analyses were used to determine whether the percentage of youth reporting specific unwanted Internet experiences had changed in 2005, as compared with 2000. The overall incidence and 5-year trends of reporting unwanted sexual solicitations, harassment, and unwanted exposure to pornography varied by age, gender, race, and household income. In particular, the decline in the percentage of youth reporting sexual solicitations was apparent for both boys and girls, all age groups, but not among minority youth and those living in less affluent households. The increase in harassment among particular sub-groups of youth was largely explained by increases in amount of Internet use over the past five years. The increase in unwanted exposure to pornography was particularly apparent among 10- to 12-year-olds, 16- to 17-year-olds, boys, and White, non-Hispanic youth. The decline in the percentage of youth reporting sexual solicitations may be the effect of education and law enforcement activity on this issue in the intervening years. Targeted prevention efforts for minority youth and those living in less affluent households need to be developed. The rise in unwanted pornography exposure may reflect technological changes such as digital photography, faster Internet connections and computer storage capacities, as well as the more aggressive marketing strategies of pornography merchants.

The Women’S Perceptions About Unwanted Pregnancy: A Qualitative Study in Iran

PubMed Central

Akbarzadeh, Marzieh; Yazdanpanahi, Zahra; Zarshenas, Ladan; Sharif, Farkhondeh

2016-01-01

Background: Unwanted pregnancy has affected different aspects of our life. Researchers point out if a child’s birth is unwanted, an increase in maternal issues can be observed. The aim of this study was to describe the women’s viewpoints regarding unwanted pregnancy. Method: This qualitative study using content analysis was employed in Shiraz University in 2013-2014. 20 women with unwanted pregnancy were chosen using purposeful sampling. Data were gathered through semi-structured interviews and trustworthiness of them was evaluated. Results: Findings of this study, according to the participants’ experience, revealed maternal emotions like embarrassment for getting pregnant, mother’s own negative affection, concerns about missing family and other children, and terminating the pregnancy through illegal abortion, the husband’s disagreement about the termination, blaming themselves for thinking about abortion or illegal abortion, and concern about their guilt feeling. Another finding was family problems like husband’s behavior and his negative outlook towards his child and fetus. The next category belonged to anxiety about the future of their child, including economic, social and relational problems, and suppression of the children’s logical expectations. The last finding was the lack of maternal emotional support. Conclusions: Unwanted pregnancy’s effects on the mothers and infants’ health are considerable. A closer observation by family and health care providers for unwanted pregnancies and its results is recommended; therefore, they should be taken care of as high risk pregnancies, requiring family support. PMID:26652070

BIOCOMPATIBLE TARGETING HYDROGELS FOR BREAST CANCER TREATMENT.

PubMed

Cassano, R; Mellace, S; Pellegrino, M; Ricchio, E; Mauro, L; Andò, S; Picci, N; Trombino, S

2016-01-01

Hydrogels have received growing attention as materials for drug delivery systems (DDS) because of their biodegradable and biocompatible properties. DDS were developed to optimize the therapeutic properties of drug products and to render them more safe, effective, and reliable. In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of administration, new dosage forms, DDS, containing the drugs were introduced. They can deliver drugs directly to the intended site of action and can also improve treatment efficacy, while minimizing unwanted side effects elsewhere in the body, which often limit the long-term use of many drugs, and provide better efficacy of treatment. Biocompatible hydrogels are an example of such systems available for therapeutic use. In this review, results from recent publications concerning these systems are discussed. Hydrogels show superior effectiveness over conventional methods of treatment providing controlled release of active substances. They are of interest in medical applications such as breast cancer treatment.

Chronic cannabinoid CB2 activation reverses paclitaxel neuropathy without tolerance or CB1-dependent withdrawal

PubMed Central

Deng, Liting; Guindon, Josée; Cornett, Benjamin L.; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G.

2014-01-01

Background Mixed cannabinoid CB1/CB2 agonists such as Δ9-tetrahydrocannabinol (Δ9-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. Methods We evaluated anti-allodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1KO, CB2KO, and WT mice. Comparisons were made with the prototypic classical cannabinoid Δ9-THC. We also explored the site and possible mechanism of action of AM1710. Results Paclitaxel-induced mechanical and cold allodynia developed equivalently in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ9-THC suppressed established paclitaxel-induced allodynia in WT mice. Unlike Δ9-THC, chronic AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Anti-allodynic efficacy of systemic AM1710 was absent in CB2KO mice or WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal AM1710 also attenuated paclitaxel-induced allodynia in WT but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 anti-allodynic efficacy. Finally, both acute and chronic treatment with AM1710 decreased mRNA levels of tumor necrosis factor alpha and monocyte chemoattractant protein-1 in lumbar spinal cord of paclitaxel-treated WT mice. Conclusions Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. PMID:24853387

Effectiveness of Family Planning Policies: The Abortion Paradox

PubMed Central

Bajos, Nathalie; Le Guen, Mireille; Bohet, Aline; Panjo, Henri; Moreau, Caroline

2014-01-01

Objective The relation between levels of contraceptive use and the incidence of induced abortion remains a topic of heated debate. Many of the contradictions are likely due to the fact that abortion is the end point of a process that starts with sexual activity, contraceptive use (or non-use), followed by unwanted pregnancy, a decision to terminate, and access to abortion. Trends in abortion rates reflect changes in each step of this process, and opposing trends may cancel each other out. This paper aims to investigate the roles played by the dissemination of contraception and the evolving norms of motherhood on changes in abortion rates. Methods Drawing data from six national probability surveys that explored contraception and pregnancy wantedness in France from 1978 through 2010, we used multivariate linear regression to explore the associations between trends in contraceptive rates and trends in (i) abortion rates, (ii) unwanted pregnancy rates, (iii) and unwanted birth rates, and to determine which of these 3 associations was strongest. Findings The association between contraceptive rates and abortion rates over time was weaker than that between contraception rates and unwanted pregnancy rates (p = 0.003). Similarly, the association between contraceptive rates and unwanted birth rates over time was weaker than that between contraceptive rates and unwanted pregnancy rates (p = 0.000). PMID:24670784

Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

PubMed Central

Stip, E

2000-01-01

The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

Selective antitumor activity of roscovitine in head and neck cancer

PubMed Central

Biktasova, Asel; Bellinger, Gary; Yarbrough, Wendell G.; Issaeva, Natalia

2016-01-01

Radiation and chemotherapy that are commonly used to treat human cancers damage cellular DNA. DNA damage appears to be more toxic to cancer cells than normal cells, most likely due to deregulated checkpoint activation and/or deficiency in DNA repair pathways that are characteristics of many tumors. However, unwanted side effects arise as a result of DNA damage to normal cells during the treatment. Here, we show that roscovitine, a cyclin-dependent kinase (CDK) inhibitor that inhibits CDK-1, CDK-2, CDK-5, CDK-7, and CDK-9 due to competitive binding to the ATP site on the kinases, causes significant DNA damage followed by p53-dependent cell death in human papilloma virus (HPV)-positive, but not in HPV-negative, head and neck cancer cells. Since HPV positivity was a molecular marker for increased sensitivity of cells to roscovitine, we reasoned that systemic roscovitine administration would not be toxic to healthy HPV-negative tissue. Indeed, low roscovitine doses significantly inhibited the growth of HPV-associated xenografted tumors in mice without causing any detectable side effects. Given that inhibition of CDKs has been shown to inhibit replication of several viruses, we suggest that roscovitine treatment may represent a selective and safe targeted therapeutic option against HPV-positive head and neck cancer. PMID:27233076

Strategies of targeting oral drug delivery systems to the colon and their potential use for the treatment of colorectal cancer.

PubMed

Krishnaiah, Yellela S R; Khan, Mansoor A

2012-01-01

Colorectal cancer (CRC) is the third most common cause of cancer-related death in both men and women. Often, surgical intervention remains the choice in treating CRC. Traditional dosage forms used for treating CRC deliver drug to wanted as well as unwanted sites of drug action resulting in several adverse side effects. Targeted oral drug delivery systems are being investigated to target and deliver chemotherapeutic and chemopreventive agents directly to colon and rectum. Site-specific delivery of a drug to colon increases its concentration at the target site, and thus requires a lower dose with reduced incidence of side effects. The major obstacle to be overcome for successful targeting of drug to colon through oral route is that drug absorption/degradation must be avoided in stomach and small intestine before the dosage form reaches colon. The review includes discussion of physiological factors that must be considered when targeting drugs directly to colorectal region, an outline on drugs used for treatment and prevention of CRC, and a brief description of various types of colon-targeted oral drug delivery systems. The focus is on the assessment of various formulation approaches being investigated for oral colon-specific delivery of drugs used in the treatment and prevention of CRC.

Role of Principal Ionotropic and Metabotropic Receptors in Visceral Pain

PubMed Central

Kannampalli, Pradeep; Sengupta, Jyoti N

2015-01-01

Visceral pain is the most common form of pain caused by varied diseases and a major reason for patients to seek medical consultation. It also leads to a significant economic burden due to workdays lost and reduced productivity. Further, long-term use of non-specific medications is also associated with side effects affecting the quality of life. Despite years of extensive research and the availability of several therapeutic options, management of patients with chronic visceral pain is often inadequate, resulting in frustration for both patients and physicians. This is, most likely, because the mechanisms associated with chronic visceral pain are different from those of acute pain. Accumulating evidence from years of research implicates several receptors and ion channels in the induction and maintenance of central and peripheral sensitization during chronic pain states. Understanding the specific role of these receptors will facilitate to capitalize on their unique properties to augment the therapeutic efficacy while at the same time minimizing unwanted side effects. The aim of this review is to provide a concise review of the recent literature that reports on the role of principal ionotropic receptors and metabotropic receptors in the modulation visceral pain. We also include an overview of the possibility of these receptors as potential new targets for the treatment of chronic visceral pain conditions. PMID:25843070

You Wouldn't Sober, You Shouldn't Drunk: A Behavioural Change Approach to Changing Attitudes and Responses to Unwanted Sexual Attention in Pubs and Clubs.

PubMed

Wood, Matthew; Shukla, Paurav

2017-11-01

The objective was to evaluate a campaign designed to influence social norms and re-establish boundaries around the issue of unwanted sexual attention in pubs and clubs. In particular, the campaign aimed to raise awareness, and reduce the acceptability, of unwanted sexual attention when drunk. A before-after-with-control group study design was used to evaluate campaign effectiveness. The data was further segmented to explore gender differences and between individuals who reported enjoying going out to get drunk and those who did not. The experimental group with campaign recall demonstrated a significant change in their attitudes to harmful drinking behaviours and unwanted sexual attention compared to the control group. A number of gender differences as well as drink-enjoyment-related differences pre- and post-campaign were observed. Female respondents who were able to recall the campaign demonstrated a significantly lower tolerance of unwanted sexual attention than those who were unable to recall it in either the experimental or control regions. The campaign had limited impact on people who enjoy drunken night outs (DNOs). However, those who do not enjoy DNOs demonstrated significantly higher negative attitudes towards harmful drinking post-campaign recall. The campaign was effective in shifting attitudes towards unwanted sexual attention and harmful drinking behaviour. This was particularly observed among female respondents and those who do not enjoy DNOs. Drinkaware's 'You Wouldn't Sober, You Shouldn't Drunk' behavioural change campaign targets young adults living in North-West England participating in 'drunken nights out'. The experimental group with campaign recall demonstrated a significant change in their attitudes to harmful drinking behaviours and unwanted sexual attention compared to the control group. © The Author 2017. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Risk factors and consequences of unwanted sex among university students: hooking up, alcohol, and stress response.

PubMed

Flack, William F; Daubman, Kimberly A; Caron, Marcia L; Asadorian, Jenica A; D'Aureli, Nicole R; Gigliotti, Shannon N; Hall, Anna T; Kiser, Sarah; Stine, Erin R

2007-02-01

This is the first study of unwanted sexual experiences in the collegiate "hooking-up" culture. In a representative sample of 178 students at a small liberal arts university. Twenty-three percent of women and 7% of men surveyed reported one or more experiences of unwanted sexual intercourse. Seventy-eight percent of unwanted vaginal, anal, and oral incidents took place while--"hooking up,"--whereas 78% of unwanted fondling incidents occurred at parties or bars. The most frequently endorsed reason for unwanted sexual intercourse was impaired judgment due to alcohol. The most frequently endorsed reason for unwanted fondling was that it happened before the perpetrator could be stopped. Of those affected by unwanted sexual intercourse or unwanted fondling, 46.7% and 19.2% reported unwanted memories, 50% and 32.7% reported avoidance and numbing responses, and 30% and 26.9% reported hyperarousal responses, respectively. A preliminary model of unwanted sex and collegiate social dynamics is proposed to provide a heuristic for further research.

Robust cladding light stripper for high-power fiber lasers using soft metals.

PubMed

Babazadeh, Amin; Nasirabad, Reza Rezaei; Norouzey, Ahmad; Hejaz, Kamran; Poozesh, Reza; Heidariazar, Amir; Golshan, Ali Hamedani; Roohforouz, Ali; Jafari, S Naser Tabatabaei; Lafouti, Majid

2014-04-20

In this paper we present a novel method to reliably strip the unwanted cladding light in high-power fiber lasers. Soft metals are utilized to fabricate a high-power cladding light stripper (CLS). The capability of indium (In), aluminum (Al), tin (Sn), and gold (Au) in extracting unwanted cladding light is examined. The experiments show that these metals have the right features for stripping the unwanted light out of the cladding. We also find that the metal-cladding contact area is of great importance because it determines the attenuation and the thermal load on the CLS. These metals are examined in different forms to optimize the contact area to have the highest possible attenuation and avoid localized heating. The results show that sheets of indium are very effective in stripping unwanted cladding light.

Women's Responses to Unwanted Sexual Advances: The Role of Alcohol and Inhibition Conflict

ERIC Educational Resources Information Center

Davis, Kelly Cue; George, William H.; Norris, Jeanette

2004-01-01

In this study we investigated how alcohol consumption affects women's responses to unwanted sexual advances in a hypothetical dating situation. Sixty female social drinkers participated in a 2 times 2 between-subjects experiment, which examined the effects of moderate alcohol intoxication and relationship characteristics on behavioral responses to…

Flux Recovery of a Forward Osmosis Membrane After a Fouling Process

NASA Technical Reports Server (NTRS)

Romero-Mangado, Jaione; Parodi, Jurek; Gamboa-Vazquez, Sonia; Stefanson, Ofir; Diaz-Cartagena, Diana C.; Flynn, Michael

2016-01-01

Wastewater treatment through forward osmosis (FO) membranes is a process that has been evaluated in the past years as an innovative technology for the Next Generation Life Support Systems. FO technologies are cost effective, and require very low energy consumption, but are subject to membrane fouling. Membrane fouling occurs when unwanted materials accumulate on the active side of the membrane during the wastewater treatment process, which leads to a decrease in membrane flux rate. The aim of this study is to identify the materials that cause flux rate reduction due to membrane fouling, as well as to evaluate the flux rate recovery after membrane treatment using commercially available antifoulants. Fourier Transform Infrared (FTIR) spectrometry results identified possible compounds that cause membrane fouling and FO testing results demonstrated flux rate recovery after membrane treatment using antifoulants.

Passenger strand loading in overexpression experiments using microRNA mimics.

PubMed

Søkilde, Rolf; Newie, Inga; Persson, Helena; Borg, Åke; Rovira, Carlos

2015-01-01

MicroRNAs (miRNAs) are important regulators of gene function and manipulation of miRNAs is a central component of basic research. Modulation of gene expression by miRNA gain-of-function can be based on different approaches including transfection with miRNA mimics; artificial, chemically modified miRNA-like small RNAs. These molecules are intended to mimic the function of a miRNA guide strand while bypassing the maturation steps of endogenous miRNAs. Due to easy accessibility through commercial providers this approach has gained popularity, and accuracy is often assumed without prior independent testing. Our in silico analysis of over-represented sequence motifs in microarray expression data and sequencing of AGO-associated small RNAs indicate, however, that miRNA mimics may be associated with considerable side-effects due to the unwanted activity of the miRNA mimic complementary strand.

Preclinical safety assessments of nano-sized constructs on cardiovascular system toxicity: A case for telemetry.

PubMed

Cheah, Hoay Yan; Kiew, Lik Voon; Lee, Hong Boon; Japundžić-Žigon, Nina; Vicent, Marίa J; Hoe, See Ziau; Chung, Lip Yong

2017-11-01

While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Potential of glyburide to reduce intracerebral edema in brain metastases.

PubMed

Boggs, Drexell Hunter; Simard, J Marc; Steven, Andrew; Mehta, Minesh P

2014-04-01

Metastatic disease to the brain results in significant morbidity because of edema in the central nervous system. Current anti-edema therapies are either expensive or result in unwanted long-term side effects. Sulfonylurea receptor 1 (Sur1) is a transmembrane protein that, when activated in the central nervous system, allows for unregulated sodium influx into cells, a process that has been linked to cytotoxic edema formation in ischemic stroke, subarachnoid hemorrhage, spinal cord injury, traumatic brain injury, and, most recently, brain metastases. In this focused review, we explore preclinical data linking Sur1 channel formation to development of edema and reference evidence suggesting that the antidiabetic sulfonylurea drug glyburide (a Sur1 inhibitor) is an inexpensive and well-tolerated agent that can be clinically tested to reduce or prevent malignancy and/or treatment-associated edema.

The Antitumor Effect of Single-domain Antibodies Directed Towards Membrane-associated Catalase and Superoxide Dismutase.

PubMed

Bauer, Georg; Motz, Manfred

2016-11-01

Neutralizing single-domain antibodies directed towards catalase or superoxide dismutase (SOD) caused efficient reactivation of intercellular reactive oxygen species/reactive nitrogen species (ROS/RNS)-dependent apoptosis-inducing signaling specifically in human tumor cells. Single-domain antibodies targeted tumor cell-specific membrane-associated SOD and catalase, but not the corresponding intracellular enzymes. They were shown to be about 200-fold more effective than corresponding classical recombinant antigen-binding fragments and more than four log steps more efficient than monoclonal antibodies. Combined addition of single-domain antibodies against catalase and SOD caused a remarkable synergistic effect. Proof-of-concept experiments in immunocompromised mice using human tumor xenografts and single-domain antibodies directed towards SOD showed an inhibition of tumor growth. Neutralizing single-domain antibodies directed to catalase and SOD also caused a very strong synergistic effect with the established chemotherapeutic agent taxol, indicating an overlap of signaling pathways. This effect might also be useful in order to avoid unwanted side-effects and to drastically lower the costs for taxol-based therapy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Dual-function photonic integrated circuit for frequency octo-tupling or single-side-band modulation.

PubMed

Hasan, Mehedi; Maldonado-Basilio, Ramón; Hall, Trevor J

2015-06-01

A dual-function photonic integrated circuit for microwave photonic applications is proposed. The circuit consists of four linear electro-optic phase modulators connected optically in parallel within a generalized Mach-Zehnder interferometer architecture. The photonic circuit is arranged to have two separate output ports. A first port provides frequency up-conversion of a microwave signal from the electrical to the optical domain; equivalently single-side-band modulation. A second port provides tunable millimeter wave carriers by frequency octo-tupling of an appropriate amplitude RF carrier. The circuit exploits the intrinsic relative phases between the ports of multi-mode interference couplers to provide substantially all the static optical phases needed. The operation of the proposed dual-function photonic integrated circuit is verified by computer simulations. The performance of the frequency octo-tupling and up-conversion functions is analyzed in terms of the electrical signal to harmonic distortion ratio and the optical single side band to unwanted harmonics ratio, respectively.

Phosphoproteomics and Bioinformatics Analyses of Spinal Cord Proteins in Rats with Morphine Tolerance

PubMed Central

Liaw, Wen-Jinn; Tsao, Cheng-Ming; Huang, Go-Shine; Wu, Chin-Chen; Ho, Shung-Tai; Wang, Jhi-Joung; Tao, Yuan-Xiang; Shui, Hao-Ai

2014-01-01

Introduction Morphine is the most effective pain-relieving drug, but it can cause unwanted side effects. Direct neuraxial administration of morphine to spinal cord not only can provide effective, reliable pain relief but also can prevent the development of supraspinal side effects. However, repeated neuraxial administration of morphine may still lead to morphine tolerance. Methods To better understand the mechanism that causes morphine tolerance, we induced tolerance in rats at the spinal cord level by giving them twice-daily injections of morphine (20 µg/10 µL) for 4 days. We confirmed tolerance by measuring paw withdrawal latencies and maximal possible analgesic effect of morphine on day 5. We then carried out phosphoproteomic analysis to investigate the global phosphorylation of spinal proteins associated with morphine tolerance. Finally, pull-down assays were used to identify phosphorylated types and sites of 14-3-3 proteins, and bioinformatics was applied to predict biological networks impacted by the morphine-regulated proteins. Results Our proteomics data showed that repeated morphine treatment altered phosphorylation of 10 proteins in the spinal cord. Pull-down assays identified 2 serine/threonine phosphorylated sites in 14-3-3 proteins. Bioinformatics further revealed that morphine impacted on cytoskeletal reorganization, neuroplasticity, protein folding and modulation, signal transduction and biomolecular metabolism. Conclusions Repeated morphine administration may affect multiple biological networks by altering protein phosphorylation. These data may provide insight into the mechanism that underlies the development of morphine tolerance. PMID:24392096

Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans

PubMed Central

Singh, Nisha; Sharpley, Ann L; Emir, Uzay E; Masaki, Charles; Herzallah, Mohammad M; Gluck, Mark A; Sharp, Trevor; Harmer, Catherine J; Vasudevan, Sridhar R; Cowen, Philip J; Churchill, Grant C

2016-01-01

Lithium remains the gold standard in treating bipolar disorder but has unwanted toxicity and side effects. We previously reported that ebselen inhibits inositol monophosphatase (IMPase) and exhibits lithium-like effects in animal models through lowering of inositol. Ebselen has been tested in clinical trials for other disorders, enabling us to determine for the first time the effect of a blood–brain barrier-penetrant IMPase inhibitor on human central nervous system (CNS) function. We now report that in a double-blind, placebo-controlled trial with healthy participants, acute oral ebselen reduced brain myo-inositol in the anterior cingulate cortex, consistent with CNS target engagement. Ebselen decreased slow-wave sleep and affected emotional processing by increasing recognition of some emotions, decreasing latency time in the acoustic startle paradigm, and decreasing the reinforcement of rewarding stimuli. In summary, ebselen affects the phosphoinositide cycle and has CNS effects on surrogate markers that may be relevant to the treatment of bipolar disorder that can be tested in future clinical trials. PMID:26593266

Performance outcomes and unwanted side effects associated with energy drinks.

PubMed

Mora-Rodriguez, Ricardo; Pallarés, Jesús G

2014-10-01

Energy drinks are increasingly popular among athletes and others. Advertising for these products typically features images conjuring great muscle power and endurance; however, the scientific literature provides sparse evidence for an ergogenic role of energy drinks. Although the composition of energy drinks varies, most contain caffeine; carbohydrates, amino acids, herbs, and vitamins are other typical ingredients. This report analyzes the effects of energy drink ingredients on prolonged submaximal (endurance) exercise as well as on short-term strength and power (neuromuscular performance). It also analyzes the effects of energy drink ingredients on the fluid and electrolyte deficit during prolonged exercise. In several studies, energy drinks have been found to improve endurance performance, although the effects could be attributable to the caffeine and/or carbohydrate content. In contrast, fewer studies find an ergogenic effect of energy drinks on muscle strength and power. The existing data suggest that the caffeine dose given in studies of energy drinks is insufficient to enhance neuromuscular performance. Finally, it is unclear if energy drinks are the optimal vehicle to deliver caffeine when high doses are needed to improve neuromuscular performance. © 2014 International Life Sciences Institute.

The Effects of the Stay in School Truancy Program on Academic Success in Harris County, Texas

ERIC Educational Resources Information Center

Rosales, Carol Ann

2013-01-01

Chronic truancy can have dire consequences from crime and unwanted pregnancy to drug abuse and poor economic futures. Mental illness, lack of parental support, unwanted pregnancy or marriage issues, undocumented immigrant status, drug abuse, and crime are reasons students become chronically truant. Accountability measures passed down from the…

Safety and efficacy of low fluence, high repetition rate versus high fluence, low repetition rate 810-nm diode laser for axillary hair removal in Chinese women.

PubMed

Li, Wenhai; Liu, Chengyi; Chen, Zhou; Cai, Lin; Zhou, Cheng; Xu, Qianxi; Li, Houmin; Zhang, Jianzhong

2016-11-01

High-fluence diode lasers with contact cooling have emerged as the gold standard to remove unwanted hair. Lowering the energy should result in less pain and could theoretically affect the efficacy of the therapy. To compare the safety and efficacy of a low fluence high repetition rate 810-nm diode laser to those of a high fluence, low repetition rate diode laser for permanent axillary hair removal in Chinese women. Ninety-two Chinese women received four axillae laser hair removal treatments at 4-week intervals using the low fluence, high repetition rate 810-nm diode laser in super hair removal (SHR) mode on one side and the high fluence, low repetition rate diode laser in hair removal (HR) mode on the other side. Hair counts were done at each follow-up visit and 6-month follow-up after the final laser treatment using a "Hi Quality Hair Analysis Program System"; the immediate pain score after each treatment session was recorded by a visual analog scale. The overall median reduction of hair was 90.2% with the 810-nm diode laser in SHR mode and 87% with the same laser in HR mode at 6-month follow-up. The median pain scores in SHR mode and in HR mode were 2.75 and 6.75, respectively. Low fluence, high repetition rate diode laser can efficiently remove unwanted hair but also significantly improve tolerability and reduce adverse events during the course of treatment.

Effectiveness of unit-based pricing of waste in the Netherlands: applying a general equilibrium model.

PubMed

van Beukering, Pieter J H; Bartelings, Heleen; Linderhof, Vincent G M; Oosterhuis, Frans H

2009-11-01

Differential and variable rates (DVR) in waste collection charging give a price incentive to households to reduce their waste and increase recycling. International empirical evidence confirms the effectiveness of DVR schemes, with limited unwanted side effects. In the Netherlands, currently some 20% of the population is charged at DVR. This is less than in several other countries. Taking into account differences between types of households and dwellings, this study analyses various scenarios for extended use of DVR in the Netherlands. The analysis shows that further penetration of DVR is a cost-effective instrument for waste reduction and more recycling. Moreover, DVR can itself be seen as a necessary condition for the successful implementation of other economic instruments, such as waste taxes. It is therefore recommended to stimulate municipalities to adopt DVR schemes in the Netherlands, accompanied by the provision of adequate facilities for waste separation by households. Before introducing DVR in 'very strongly urbanized' municipalities (i.e. the 12 largest cities in the Netherlands) a pilot experiment in one of them might be useful to test the behavioral response in this category.

Experimental verification of internal parameter in magnetically coupled boost used as PV optimizer in parallel association

NASA Astrophysics Data System (ADS)

Sawicki, Jean-Paul; Saint-Eve, Frédéric; Petit, Pierre; Aillerie, Michel

2017-02-01

This paper presents results of experiments aimed to verify a formula able to compute duty cycle in the case of pulse width modulation control for a DC-DC converter designed and realized in laboratory. This converter, called Magnetically Coupled Boost (MCB) is sized to step up only one photovoltaic module voltage to supply directly grid inverters. Duty cycle formula will be checked in a first time by identifying internal parameter, auto-transformer ratio, and in a second time by checking stability of operating point on the side of photovoltaic module. Thinking on nature of generator source and load connected to converter leads to imagine additional experiments to decide if auto-transformer ratio parameter could be used with fixed value or on the contrary with adaptive value. Effects of load variations on converter behavior or impact of possible shading on photovoltaic module are also mentioned, with aim to design robust control laws, in the case of parallel association, designed to compensate unwanted effects due to output voltage coupling.

Mouthwashes: Do They Work and Should We Use Them? Part 1: Antiplaque Efficacy of Mouthwashes.

PubMed

Hodge, Penny

2016-01-01

This article will focus on the antiplaque efficacy of mouthwashes. An antiplaque agent inhibits the formation of plaque and also reduces gingivitis. There is good evidence that chlorhexidine digluconate, used in the correct concentrations, is the gold standard agent against which all others should be measured. It does, however, have some unwanted side-effects. One of the major problems for antiplaque mouthwashes is that they have a much reduced effect on established plaque within the oral environment. Although they can flow into the biofilm channels and kill bacteria in the superficial layers of dental plaque, they cannot penetrate the biomass and inhibit the pathogenic bacteria adjacent to the tooth surface and gingival margin. There is no evidence that they prevent the progression of periodontitis. Clinical relevance: The evidence supporting the use of ‘over the counter’ antiplaque mouthwashes is evaluated. This provides guidance for dentists and dental care professionals of when it is appropriate to recommend mouthwash use to their patients.

The PPAR-Platelet Connection: Modulators of Inflammation and Potential Cardiovascular Effects

PubMed Central

Spinelli, S. L.; O'Brien, J. J.; Bancos, S.; Lehmann, G. M.; Springer, D. L.; Blumberg, N.; Francis, C. W.; Taubman, M. B.; Phipps, R. P.

2008-01-01

Historically, platelets were viewed as simple anucleate cells responsible for initiating thrombosis and maintaining hemostasis, but clearly they are also key mediators of inflammation and immune cell activation. An emerging body of evidence links platelet function and thrombosis to vascular inflammation. peroxisome proliferator-activated receptors (PPARs) play a major role in modulating inflammation and, interestingly, PPARs (PPARβ/δ and PPARγ) were recently identified in platelets. Additionally, PPAR agonists attenuate platelet activation; an important discovery for two reasons. First, activated platelets are formidable antagonists that initiate and prolong a cascade of events that contribute to cardiovascular disease (CVD) progression. Dampening platelet release of proinflammatory mediators, including CD40 ligand (CD40L, CD154), is essential to hinder this cascade. Second, understanding the biologic importance of platelet PPARs and the mechanism(s) by which PPARs regulate platelet activation will be imperative in designing therapeutic strategies lacking the deleterious or unwanted side effects of current treatment options. PMID:18288284

Gynaecomastia linked to the intake of a herbal supplement fortified with diethylstilbestrol.

PubMed

Toorians, A W F T; Bovee, T F H; De Rooy, J; Stolker, L A A M; Hoogenboom, R L A P

2010-07-01

This study reports the findings of a supplement marketed on the Internet for prostate problems. The supplement was orally taken by a 60-year-old man with divergent hormonal levels and who was surgically treated for gynaecomastia: development of abnormally large mammary glands in males. The supplement showed a strong effect in a yeast oestrogen bioassay, expressing a yeast-enhanced green fluorescent protein (yEGFP) upon exposure to oestrogens. Using both nuclear magnetic resonance (NMR) and a gradient liquid chromatographic time-of-flight mass spectrometric (LC/TOF-MS) method, the response was shown to be caused by very high levels of diethylstilbestrol, known for causing gynaecomastia. The gynaecomastia was most probably caused by this orally taken 'natural' herbal supplement, as the patient's hormonal levels also returned to normal again when stopping the use of it. This case demonstrates that physicians need to be aware of the use of supplements with illegal components that may be responsible for unwanted side-effects.

Delivery of Cancer Therapeutics Using Nanotechnology

PubMed Central

Lim, Eun-Kyung; Jang, Eunji; Lee, Kwangyeol; Haam, Seungjoo; Huh, Yong-Min

2013-01-01

Nanoparticles have been investigated as drug carriers, because they provide a great opportunity due to their advantageous features: (i) various formulations using organic/inorganic materials, (ii) easy modification of targeting molecules, drugs or other molecules on them, (iii) effective delivery to target sites, resulting in high therapeutic efficacy and (iv) controlling drug release by external/internal stimuli. Because of these features, therapeutic efficacy can be improved and unwanted side effects can be reduced. Theranostic nanoparticles have been developed by incorporating imaging agents in drug carriers as all-in-one system, which makes it possible to diagnose and treat cancer by monitoring drug delivery behavior simultaneously. Recently, stimuli-responsive, activatable nanomaterials are being applied that are capable of producing chemical or physical changes by external stimuli. By using these nanoparticles, multiple tasks can be carried out simultaneously, e.g., early and accurate diagnosis, efficient cataloguing of patient groups of personalized therapy and real-time monitoring of disease progress. In this paper, we describe various types of nanoparticles for drug delivery systems, as well as theranostic systems. PMID:24300452

Alien or American? Immigration Laws and Amerasian People.

DTIC Science & Technology

1985-08-01

of birth control . The basic fabric of . individual morality underlies these strongly held . .. . . . . . . * . . - . .*.~-,’..-i*--., 55...intent of this paper to explore the ethical and moral questions that permeate the controversy over birth control . The ethical problem that does...unplanned and unwanted births. Safe, effective birth control would theoretically have the potential to reduce the problem of unwanted ethnically-mixed

Unwanted effects: Is there a negative side of meditation? A multicentre survey

PubMed Central

Demarzo, Marcelo; Martins, Patricia; Soler, Joaquim; Garcia-Campayo, Javier

2017-01-01

Objectives Despite the long-term use and evidence-based efficacy of meditation and mindfulness-based interventions, there is still a lack of data about the possible unwanted effects (UEs) of these practices. The aim of this study was to evaluate the occurrence of UEs among meditation practitioners, considering moderating factors such as the type, frequency, and lifetime duration of the meditation practices. Methods An online survey was developed and disseminated through several websites, such as Spanish-, English- and Portuguese-language scientific research portals related to mindfulness and meditation. After excluding people who did not answer the survey correctly or completely and those who had less than two months of meditation experience, a total of 342 people participated in the study. However, only 87 reported information about UEs. Results The majority of the practitioners were women from Spain who were married and had a University education level. Practices were more frequently informal, performed on a daily basis, and followed by focused attention (FA). Among the participants, 25.4% reported UEs, showing that severity varies considerably. The information requested indicated that most of the UEs were transitory and did not lead to discontinuing meditation practice or the need for medical assistance. They were more frequently reported in relation to individual practice, during focused attention meditation, and when practising for more than 20 minutes and alone. The practice of body awareness was associated with UEs to a lesser extent, whereas focused attention was associated more with UEs. Conclusions This is the first large-scale, multi-cultural study on the UEs of meditation. Despite its limitations, this study suggests that UEs are prevalent and transitory and should be further studied. We recommend the use of standardized questionnaires to assess the UEs of meditation practices. PMID:28873417

Unwanted effects: Is there a negative side of meditation? A multicentre survey.

PubMed

Cebolla, Ausiàs; Demarzo, Marcelo; Martins, Patricia; Soler, Joaquim; Garcia-Campayo, Javier

2017-01-01

Despite the long-term use and evidence-based efficacy of meditation and mindfulness-based interventions, there is still a lack of data about the possible unwanted effects (UEs) of these practices. The aim of this study was to evaluate the occurrence of UEs among meditation practitioners, considering moderating factors such as the type, frequency, and lifetime duration of the meditation practices. An online survey was developed and disseminated through several websites, such as Spanish-, English- and Portuguese-language scientific research portals related to mindfulness and meditation. After excluding people who did not answer the survey correctly or completely and those who had less than two months of meditation experience, a total of 342 people participated in the study. However, only 87 reported information about UEs. The majority of the practitioners were women from Spain who were married and had a University education level. Practices were more frequently informal, performed on a daily basis, and followed by focused attention (FA). Among the participants, 25.4% reported UEs, showing that severity varies considerably. The information requested indicated that most of the UEs were transitory and did not lead to discontinuing meditation practice or the need for medical assistance. They were more frequently reported in relation to individual practice, during focused attention meditation, and when practising for more than 20 minutes and alone. The practice of body awareness was associated with UEs to a lesser extent, whereas focused attention was associated more with UEs. This is the first large-scale, multi-cultural study on the UEs of meditation. Despite its limitations, this study suggests that UEs are prevalent and transitory and should be further studied. We recommend the use of standardized questionnaires to assess the UEs of meditation practices.

Abortion and unwanted pregnancy in Adigrat Zonal Hospital, Tigray, north Ethiopia.

PubMed

Gessessew, Amanuel

2010-09-01

Unwanted pregnancy is associated with increased risk of maternal mortality and morbidity. This study was done to determine the causes of unwanted pregnancy and its impact on maternal health. A cross sectional study (February 1, 2002-January 31, 2004) was conducted on 907 patients with diagnosis of abortion and admitted to the gynecological ward of Adigrat zonal hospital, Tigray Region, Ethiopia. This accounts to 12.6% of all hospital and 60.6% of gynecological admissions. The majority of these women (69.8%) had unwanted pregnancy. Modern contraception methods were not in use in 76.2% of unwanted and 57.7% of wanted pregnancies (P = 0.008). Interference was reported in 81.4% of unwanted pregnancy. High incidence of complication was reported in patients with unwanted pregnancy. In this study it is found that unwanted pregnancy is associated with increased risk of maternal morbidity and mortality. The development and prompt implementation of a strategy that enables women to safely manage unwanted pregnancy is recommended.

State-of-the-art in design rules for drug delivery platforms: lessons learned from FDA-approved nanomedicines.

PubMed

Dawidczyk, Charlene M; Kim, Chloe; Park, Jea Ho; Russell, Luisa M; Lee, Kwan Hyi; Pomper, Martin G; Searson, Peter C

2014-08-10

The ability to efficiently deliver a drug to a tumor site is dependent on a wide range of physiologically imposed design constraints. Nanotechnology provides the possibility of creating delivery vehicles where these design constraints can be decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing targeting efficiency and efficacy. Here we review the design strategies of the two FDA-approved antibody-drug conjugates (Brentuximab vedotin and Trastuzumab emtansine) and the four FDA-approved nanoparticle-based drug delivery platforms (Doxil, DaunoXome, Marqibo, and Abraxane) in the context of the challenges associated with systemic targeted delivery of a drug to a solid tumor. The lessons learned from these nanomedicines provide an important insight into the key challenges associated with the development of new platforms for systemic delivery of anti-cancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Progress Toward In Vivo Use of siRNAs-II

PubMed Central

Rettig, Garrett R; Behlke, Mark A

2012-01-01

RNA interference (RNAi) has been extensively employed for in vivo research since its use was first demonstrated in mammalian cells 10 years ago. Design rules have improved, and it is now routinely possible to obtain reagents that suppress expression of any gene desired. At the same time, increased understanding of the molecular basis of unwanted side effects has led to the development of chemical modification strategies that mitigate these concerns. Delivery remains the single greatest hurdle to widespread adoption of in vivo RNAi methods. However, exciting advances have been made and new delivery systems under development may help to overcome these barriers. This review discusses advances in RNAi biochemistry and biology that impact in vivo use and provides an overview of select publications that demonstrate interesting applications of these principles. Emphasis is placed on work with synthetic, small interfering RNAs (siRNAs) published since the first installment of this review which appeared in 2006. PMID:22186795

[Big data, Roemer's law and avoidable hospital admissions].

PubMed

van der Horst, H E

2016-01-01

From an analysis of data from 23 European countries to determine the impact of primary care on avoidable hospital admissions for uncontrolled diabetes it appeared that, contrary to expectation, countries with strong primary care did not have a lower rate of avoidable hospital admission. It is clear that Roemer's law, 'a bed built is a bed filled,' still applies. However, the validity of this sort of analysis can be questioned, as these data are highly aggregated, and registration quality differs between countries. It is also questionable if these datasets can be considered as 'big data' as there are relatively small numbers per country. Big data analyses are useful for discerning patterns and formulating hypotheses, but not for proving causality. An unwanted side effect of this kind of analysis might be that policymakers use these not so valid results to underpin their policy to their advantage.

Chirality detection of enantiomers using twisted optical metamaterials

NASA Astrophysics Data System (ADS)

Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

2017-01-01

Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies.

Chirality detection of enantiomers using twisted optical metamaterials

PubMed Central

Zhao, Yang; Askarpour, Amir N.; Sun, Liuyang; Shi, Jinwei; Li, Xiaoqin; Alù, Andrea

2017-01-01

Many naturally occurring biomolecules, such as amino acids, sugars and nucleotides, are inherently chiral. Enantiomers, a pair of chiral isomers with opposite handedness, often exhibit similar physical and chemical properties due to their identical functional groups and composition, yet show different toxicity to cells. Detecting enantiomers in small quantities has an essential role in drug development to eliminate their unwanted side effects. Here we exploit strong chiral interactions with plasmonic metamaterials with specifically designed optical response to sense chiral molecules down to zeptomole levels, several orders of magnitude smaller than what is typically detectable with conventional circular dichroism spectroscopy. In particular, the measured spectra reveal opposite signs in the spectral regime directly associated with different chiral responses, providing a way to univocally assess molecular chirality. Our work introduces an ultrathin, planarized nanophotonic interface to sense chiral molecules with inherently weak circular dichroism at visible and near-infrared frequencies. PMID:28120825

Dendrimer-driven neurotrophin expression differs in temporal patterns between rodent and human stem cells.

PubMed

Shakhbazau, Antos; Shcharbin, Dzmitry; Seviaryn, Ihar; Goncharova, Natalya; Kosmacheva, Svetlana; Potapnev, Mihail; Bryszewska, Maria; Kumar, Ranjan; Biernaskie, Jeffrey; Midha, Rajiv

2012-05-07

This study reports the use of a nonviral expression system based on polyamidoamine dendrimers for time-restricted neurotrophin overproduction in mesenchymal stem cells and skin precursor-derived Schwann cells. The dendrimers were used to deliver plasmids for brain-derived neurotrophic factor (BDNF) or neurotrophin-3 (NT-3) expression in both rodent and human stem cells, and the timelines of expression were studied. We have found that, despite the fact that transfection efficiencies and protein expression levels were comparable, dendrimer-driven expression in human mesenchymal stem cells was characterized by a more rapid decline compared to rodent cells. Transient expression systems can be beneficial for some neurotrophins, which were earlier reported to cause unwanted side effects in virus-based long-term expression models. Nonviral neurotrophin expression is a biologically safe and accessible alternative to increase the therapeutic potential of autologous adult stem cells and stem cell-derived functional differentiated cells.

Maternal Identity Formation in a Military Sample: A Longitudinal Perspective

DTIC Science & Technology

2006-06-08

effective interventions. Successful interventions to assist military wives with maternal adaptation and role adjustment will be possible with a greater 7...maternal identity formation and role adaptation. Despite the obvious need for focused interventions to assist women with maternal identity formation and...pregnancies tended to be unwanted and remain unwanted even in late gestation . In her sample, the women describing the greatest number of unplanned

The Unwanted Child.

ERIC Educational Resources Information Center

Safonova, Tamara; Leparsky, E. A.

1998-01-01

This study examined mothers' attitudes toward pregnancy and outcomes of unwanted pregnancies in 1,454 women in Moscow (Russia). Unplanned and unwanted pregnancies greatly increased the risk of unfavorable pregnancy outcomes (especially prematurity and intrauterine developmental delay). The principal factor contributing to an unwanted pregnancy was…

Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures.

PubMed

Johnson, Neil J; Hanson, Leah R; Frey, William H

2010-06-07

Intranasal delivery has been shown to noninvasively deliver drugs from the nose to the brain in minutes along the olfactory and trigeminal nerve pathways, bypassing the blood-brain barrier. However, no one has investigated whether nasally applied drugs target orofacial structures, despite high concentrations observed in the trigeminal nerve innervating these tissues. Following intranasal administration of lidocaine to rats, trigeminally innervated structures (teeth, temporomandibular joint (TMJ), and masseter muscle) were found to have up to 20-fold higher tissue concentrations of lidocaine than the brain and blood as measured by ELISA. This concentration difference could allow intranasally administered therapeutics to treat disorders of orofacial structures (i.e., teeth, TMJ, and masseter muscle) without causing unwanted side effects in the brain and the rest of the body. In this study, an intranasally administered infrared dye reached the brain within 10 minutes. Distribution of dye is consistent with dye entering the trigeminal nerve after intranasal administration through three regions with high drug concentrations in the nasal cavity: the middle concha, the maxillary sinus, and the choana. In humans the trigeminal nerve passes through the maxillary sinus to innervate the maxillary teeth. Delivering lidocaine intranasally may provide an effective anesthetic technique for a noninvasive maxillary nerve block. Intranasal delivery could be used to target vaccinations and treat disorders with fewer side effects such as tooth pain, TMJ disorder, trigeminal neuralgia, headache, and brain diseases.

Bilastine: a new H1 -antihistamine with an optimal profile for updosing in urticaria.

PubMed

Church, M K; Labeaga, L

2017-09-01

This review set out to examine published papers detailing the efficacy of bilastine in skin models and urticaria to assess whether it meets the optimal profile for updosing in urticaria, that is, strong clinical efficacy and freedom from unwanted side effects, particularly sedation. Bilastine is a highly effective H 1 -antihistamine even when used at the basic dose of 20 mg daily. Its facilitated uptake after oral dosage gives it a rapid onset and long duration of action. In both wheal and flare studies and in urticaria updosing fourfold showed increased effectiveness. With respect to somnolence, bilastine is a substrate for P-glycoprotein, a membrane pump which prevents it crossing the blood-brain barrier. Consequently, bilastine is a practically 'non-sedating' H 1 -antihistamine. In conclusion, the excellent profile of bilastine in both efficacy and safety make it the ideal H 1 -antihistamine for updosing the daily dose fourfold in difficult-to-treat urticaria as recommended by the EAACI/GA 2 LEN/EDF/WAO guideline for the management of urticaria. © 2017 European Academy of Dermatology and Venereology.

Prevalence of sexual coercion and its association with unwanted pregnancies among young pregnant females in Kampala, Uganda: a facility based cross-sectional study.

PubMed

Tusiime, Suzan; Musinguzi, Geofrey; Tinkitina, Benjamin; Mwebaza, Norah; Kisa, Rose; Anguzu, Ronald; Kiwanuka, Noah

2015-09-24

Sexual coercion is associated with sexually transmitted infections and unwanted pregnancies with consequential unsafe abortions and increased maternal morbidity and mortality. Current literature focuses mainly on its risk factors but less on its resultant deleterious health effects. We conducted a study to determine the prevalence of sexual coercion and its association with unwanted pregnancies among young pregnant women. In a cross-sectional study, four hundred and sixteen (416) consenting pregnant females aged 15-24 years attending antenatal clinics in Lubaga division Kampala district in Uganda were enrolled using systematic sampling. Quantitative and qualitative data on sexual coercion were collected by female interviewers. Adjusted Prevalence Proportion Ratios (Adj. PPRs) of unwanted pregnancy and associated 95 % confidence intervals were estimated by generalized linear models with log link function and Poisson family distribution using robust variance estimator. Quantitative data were analyzed using Stata version 10.0, while qualitative data were analyzed using manifest content analysis. Prevalence of sexual coercion was 24 % and was higher among those who had non consensual sexual debut (29.0 %) compared with those who had consensual sexual debut (22.6 %). The prevalence of unwanted pregnancy was 18.3 % and was higher among participants who had been sexually coerced relative to their counterparts (p < 0.001). History of sexual coercion in the past 12 months and non consensual sexual debut were associated with unwanted pregnancy [adj.PPR = 2.23, 95 % CI: (1.49-3.32)] and 1.72, 95 % CI: (1.16- 2.54)] respectively. Qualitative results indicated that different forms/contexts of sexual coercion, such as deception, transactional sex and physical force influenced unwanted pregnancies. This study highlights that a quarter of our participants in our quantitative study had experienced sexual coercion in the past twelve months and nearly a third of these, had history of non consensual sexual debut. Unwanted pregnancy was higher among the sexually coerced and those who had non consensual sexual debut. Sexual coercion among pregnant women aged 15-24 years in Kampala, Uganda is high and is significantly associated with unwanted pregnancy. Comprehensive sex education targeting young people (<25 years), along with availability and access to youth friendly centers may be useful in addressing sexual coercion and its negative outcomes.

The making of unwanted sex: gendered and neoliberal norms in college women's unwanted sexual experiences.

PubMed

Bay-Cheng, Laina Y; Eliseo-Arras, Rebecca K

2008-01-01

Building on extant research regarding the role of gendered norms in women's consent to unwanted sex with male partners as well as recent studies of how the sociopolitical discourse of neoliberalism shapes sexuality at the individual level, we conducted a thematic analysis of undergraduate women's (N = 22) descriptions of their experiences of unwanted sex. In accordance with previous research (Gavey, 2005; Martin, 1996; Phillips, 2000; Tolman, 2002), gendered norms (e.g., women's sexual passivity; subordination of women's sexual interests to those of men) played important roles (a) laying the foundation for unwanted sex, and (b) in-the-moment negotiations between partners. In an extension of the established literature regarding unwanted sex, we also noted the emergence of neoliberal norms (e.g., personal responsibility) in participants' discussions of unwanted sex after the fact. We use these results to argue that gender and neoliberal ideologies work in tandem to (re)produce women's consent to unwanted sex.

Sources of and Remedies for Removing Unwanted Reflections in Millimeter Wave Images of Complex SOFI-Covered Space Shuttle Structures

NASA Technical Reports Server (NTRS)

Kharkovsky, S.; Zoughi, R.; Hepburn, Frank L.

2007-01-01

In the recent years, continuous-wave near-field and lens-focused millimeter wave imaging systems have been effectively used to demonstrate their utility for producing high-resolution images of metallic structures covered with spay on foam insulation (SOFI) such as the Space Shuttle external fuel tank. However, for some specific structures a certain interference -pattern may be superimposed on the produced images. There are methods by which the influence of this unwanted interference can be reduced, such as the incorporation of an incidence .angle and the proper use of signal polarization. This paper presents the basics of this problem and describes the use of the methods for reducing this unwanted influence through specific examples.

Emergency contraception - Potential for women's health

PubMed Central

Mittal, Suneeta

2014-01-01

Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent. PMID:25673542

Emergency contraception - potential for women's health.

PubMed

Mittal, Suneeta

2014-11-01

Emergency contraception (EC) is a safe and effective method which is used to prevent unwanted pregnancy after unprotected sexual intercourse. Many of the unwanted pregnancies end in unsafe abortions. The search for an ideal contraceptive, which does not interfere with spontaneity or pleasure of the sexual act, yet effectively controls the fertility, is still continuing. Numerous contraceptive techniques are available, yet contraceptive coverage continues to be poor in India. Thus, even when not planning for a pregnancy, exposure to unprotected sex takes place often, necessitating the use of emergency contraception. This need may also arise due to failure of contraceptive method being used (condom rupture, diaphragm slippage, forgotten oral pills) or following sexual assault. Emergency contraception is an intervention that can prevent a large number of unwanted pregnancies resulting from failure of regular contraception or unplanned sexual activity, which in turn helps in reducing the maternal mortality and morbidity due to unsafe abortions. However, a concern has been expressed regarding repeated and indiscriminate usage of e-pill, currently the rational use of emergency contraception is being promoted as it is expected to make a significant dent in reducing the number of unwanted pregnancies and unsafe abortions. In fact, since the introduction of emergency contraception, the contribution of unsafe abortion towards maternal mortality has declined from 13 to 8 per cent.

Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal.

PubMed

Deng, Liting; Guindon, Josée; Cornett, Benjamin L; Makriyannis, Alexandros; Mackie, Ken; Hohmann, Andrea G

2015-03-01

Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. We evaluated antiallodynic efficacy, possible tolerance, and cannabimimetic side effects of repeated dosing with a CB2-preferring agonist AM1710 in a model of chemotherapy-induced neuropathy produced by paclitaxel using CB1 knockout (CB1KO), CB2 knockout (CB2KO), and wild-type (WT) mice. Comparisons were made with the prototypic classic cannabinoid Δ(9)-THC. We also explored the site and possible mechanism of action of AM1710. Paclitaxel-induced mechanical and cold allodynia developed to an equivalent degree in CB1KO, CB2KO, and WT mice. Both AM1710 and Δ(9)-THC suppressed established paclitaxel-induced allodynia in WT mice. In contrast to Δ(9)-THC, chronic administration of AM1710 did not engage CB1 activity or produce antinociceptive tolerance, CB1-mediated cannabinoid withdrawal, hypothermia, or motor dysfunction. Antiallodynic efficacy of systemic administration of AM1710 was absent in CB2KO mice and WT mice receiving the CB2 antagonist AM630, administered either systemically or intrathecally. Intrathecal administration of AM1710 also attenuated paclitaxel-induced allodynia in WT mice, but not CB2KO mice, implicating a possible role for spinal CB2 receptors in AM1710 antiallodynic efficacy. Finally, both acute and chronic administration of AM1710 decreased messenger RNA levels of tumor necrosis factor-α and monocyte chemoattractant protein 1 in lumbar spinal cord of paclitaxel-treated WT mice. Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma

PubMed Central

Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

2017-01-01

Background: Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. Materials and Methods: This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Results: Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups (P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels (P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Conclusion: Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel. PMID:28299301

Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma.

PubMed

Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

2017-01-01

Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups ( P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels ( P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Unwanted radiation. 95.635 Section 95.635... SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. Link to an amendment... Unwanted radiation. (d) * * * (1) * * * (v) Are more than 2.5 MHz outside of the 2360-2400 MHz band (for...

Efficacy of a biobehavioral intervention for hot flashes: a randomized controlled pilot study.

PubMed

Barton, Debra L; Schroeder, Kelliann C Fee; Banerjee, Tanima; Wolf, Sherry; Keith, Timothy Z; Elkins, Gary

2017-07-01

The need for effective nonhormonal treatments for hot flash management without unwanted side effects continues. The primary aim of this pilot study was to evaluate the effect of combining a nonhormonal pharmacologic agent with a behavioral treatment for hot flash reduction. Seventy-one postmenopausal women were randomized to one of four groups: venlafaxine 75 mg + hypnosis (VH) versus venlafaxine 75 mg + sham hypnosis (VSH) versus a placebo pill + hypnosis (PH) versus placebo pill + sham hypnosis (PSH). Women recorded hot flash severity and frequency in a daily diary, in real time. The intrapatient difference in hot flash score (frequency × severity) at 8 weeks was analyzed using a General Estimating Equation model, using VSH as the referent arm, controlling for baseline hot flashes. The active arms including PH or VH were not statistically significantly different than VSH (P = 0.34, P = 0.05, respectively). Women in each active arm reported hot flash reductions of about 50%, with the PSH group reporting a 25% reduction. Women receiving the PSH reported statistically significantly smaller reductions in hot flash score than women in the referent VSH arm (P = 0.001). There were no significant negative side effects during the course of the study. Hypnosis alone reduced hot flashes equal to venlafaxine alone, but the combination of hypnosis and venlafaxine did not reduce hot flashes more than either treatment alone. More research is needed to clarify whether combining hypnosis with a different antidepressant would provide synergistic benefits.

Analysis and modification of a single-mesh gear fatigue rig for use in diagnostic studies

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Townsend, Dennis P.; Oswald, Fred B.; Decker, Harry J.

1992-01-01

A single-mesh gear fatigue rig was analyzed and modified for use in gear mesh diagnostic research. The fatigue rig allowed unwanted vibration to mask the test-gear vibration signal, making it difficult to perform diagnostic studies. Several possible sources and factors contributing to the unwanted components of the vibration signal were investigated. Sensor mounting location was found to have a major effect on the content of the vibration signal. In the presence of unwanted vibration sources, modal amplification made unwanted components strong. A sensor location was found that provided a flatter frequency response. This resulted in a more useful vibration signal. A major network was performed on the fatigue rig to reduce the influence of the most probable sources of the noise in the vibration signal. The slave gears were machined to reduce weight and increase tooth loading. The housing and the shafts were modified to reduce imbalance, looseness, and misalignment in the rotating components. These changes resulted in an improved vibration signal, with the test-gear mesh frequency now the dominant component in the signal. Also, with the unwanted sources eliminated, the sensor mounting location giving the most robust representation of the test-gear meshing energy was found to be at a point close to the test gears in the load zone of the bearings.

Does non-invasive brain stimulation modify hand dexterity? Protocol for a systematic review and meta-analysis.

PubMed

O'Brien, Anthony Terrence; Torrealba Acosta, Gabriel; Huerta, Rodrigo; Thibaut, Aurore

2017-06-22

Dexterity is described as coordinated hand and finger movement for precision tasks. It is essential for day-to-day activities like computer use, writing or buttoning a shirt. Integrity of brain motor networks is crucial to properly execute these fine hand tasks. When these networks are damaged, interventions to enhance recovery are frequently accompanied by unwanted side effects or limited in their effect. Non-invasive brain stimulation (NIBS) are postulated to target affected motor areas and improve hand motor function with few side effects. However, the results across studies vary, and the current literature does not allow us to draw clear conclusions on the use of NIBS to promote hand function recovery. Therefore, we developed a protocol for a systematic review and meta-analysis on the effects of different NIBS technologies on dexterity in diverse populations. This study will potentially help future evidence-based research and guidelines that use these NIBS technologies for recovering hand dexterity. This protocol will compare the effects of active versus sham NIBS on precise hand activity. Records will be obtained by searching relevant databases. Included articles will be randomised clinical trials in adults, testing the therapeutic effects of NIBS on continuous dexterity data. Records will be studied for risk of bias. Narrative and quantitative synthesis will be done. No private health information is included; the study is not interventional. Ethical approval is not required. The results will be reported in a peer-review journal. PROSPERO International prospective register of systematic reviews registration number: CRD42016043809. © 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.

Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze.

PubMed

Emamghoreishi, Masoumeh; Khasaki, Mohammad; Aazam, Maryam Fath

2005-01-15

The clinical applications of benzodiazepines as anxiolytics are limited by their unwanted side effects. Therefore, the development of new pharmacological agents is well justified. Among medicinal plants, Coriandrum sativum L. has been recommended for relief of anxiety and insomnia in Iranian folk medicine. Nevertheless, no pharmacological studies have thus far evaluated its effects on central nervous system. Therefore, the aim of this study was to examine if the aqueous extract of Coriandrum sativum seed has anxiolytic effect in mice. Additionally, its effect on spontaneous activity and neuromuscular coordination were evaluated. The anxiolytic effect of aqueous extract (10, 25, 50, 100 mg/kg, i.p.) was examined in male albino mice using elevated plus-maze as an animal model of anxiety. The effects of the extract on spontaneous activity and neuromuscular coordination were assessed using Animex Activity Meter and rotarod, respectively. In the elevated plus-maze, aqueous extract at 100 mg/kg showed an anxiolytic effect by increasing the time spent on open arms and the percentage of open arm entries, compared to control group. Aqueous extract at 50, 100 and 500 mg/kg significantly reduced spontaneous activity and neuromuscular coordination, compared to control group. These results suggest that the aqueous extract of Coriandrum sativum seed has anxiolytic effect and may have potential sedative and muscle relaxant effects.

Miniaturized LTCC elliptic-function lowpass filters with side stopbands

DOE PAGES

Hsieh, Lung -Hwa; Dai, Steve Xunhu

2015-05-28

A compact, high-selectivity, and wide stopband lowpass filter is highly demanded in wireless communication systems to suppress adjacent harmonics and unwanted signals. In this letter, a new miniaturized lowpass filter with elliptic-function frequency response is introduced. The filter is fabricated in multilayer low temperature cofired ceramics. The size of the miniaturized filter is 5.5 × 3.9 × 1.72 mm3. As a result, the measured insertion loss of the filter is better than 0.37 dB from DC to 1.28 GHz and the measured stopband of the filter is great than 22 dB from 2.3 to 7.5 GHz.

Oleochemical industry future through biotechnology.

PubMed

Abdelmoez, Wael; Mustafa, Ahmad

2014-01-01

Lipases are the most widely used class of enzymes in organic synthesis. Enzymatic processes have been implemented in a broad range of industries as they are specific, save raw materials, energy and chemicals, environmentally friendly and fast in action compared to conventional processes. The most notable benefit is the moderate process temperature and pressure with no unwanted side reactions. In the past two decades, intensive research was carried out towards enzymatic synthesis of oleochemicals. This review has a sharp focus on the current implemented enzymatic processes for producing different oleochemicals such as fatty acids, glycerin, biodiesel, biolubricant and different alkyl esters via different processes including hydrolysis, esterification, transesterification and intraesterification.

Implicit and explicit appraisals of the importance of intrusive thoughts.

PubMed

Teachman, Bethany A; Woody, Sheila R; Magee, Joshua C

2006-06-01

To evaluate cognitive theories of obsessions, the current study experimentally manipulated appraisals of the importance of intrusive thoughts. Undergraduate students (N = 156) completed measures of obsessive-compulsive disorder (OCD) symptoms and beliefs and were primed with a list of commonly reported unwanted thoughts. Participants were then informed that unwanted thoughts are either (1) significant and indicative of their personal values, or (2) meaningless, or participants (3) received no instructions about unwanted thoughts. Participants then completed implicit and explicit measures of self-evaluation and interpretations of their unwanted thoughts. Results indicated that the manipulation shifted implicit appraisals of unwanted thoughts in the expected direction, but not self-evaluations of morality or dangerousness. Interestingly, explicit self-esteem and beliefs about the significance of unwanted thoughts were associated with measures of OCD beliefs, whereas implicit self-evaluations of dangerousness were better predicted by the interaction of pre-existing OCD beliefs with the manipulation. Results are discussed in terms of divergent predictors of implicit and explicit responses to unwanted thoughts.

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.

Laser speckle imaging to improve clinical outcomes for patients with trigeminal neuralgia undergoing radiofrequency thermocoagulation.

PubMed

Ringkamp, Matthias; Wooten, Matthew; Carson, Benjamin S; Lim, Michael; Hartke, Timothy; Guarnieri, Michael

2016-02-01

Percutaneous treatments for trigeminal neuralgia are safe, simple, and effective for achieving good pain control. Procedural risks could be minimized by using noninvasive imaging techniques to improve the placement of the radiofrequency thermocoagulation probe into the trigeminal ganglion. Positioning of a probe is crucial to maximize pain relief and to minimize unwanted side effects, such as denervation in unaffected areas. This investigation examined the use of laser speckle imaging during probe placement in an animal model. This preclinical safety study used nonhuman primates, Macaca nemestrina (pigtail monkeys), to examine whether real-time imaging of blood flow in the face during the positioning of a coagulation probe could monitor the location and guide the positioning of the probe within the trigeminal ganglion. Data from 6 experiments in 3 pigtail monkeys support the hypothesis that laser imaging is safe and improves the accuracy of probe placement. Noninvasive laser speckle imaging can be performed safely in nonhuman primates. Because improved probe placement may reduce morbidity associated with percutaneous rhizotomies, efficacy trials of laser speckle imaging should be conducted in humans.

HIF Activation Against CVD in CKD: Novel Treatment Opportunities.

PubMed

Tanaka, Tetsuhiro; Eckardt, Kai-Uwe

2018-05-01

Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD. An additional advantage of PHD inhibition may be found in the potential impact on cardiovascular consequences associated with CKD. Several preclinical studies have suggested a potential benefit of HIF activation in myocardial infarction, cardiac remodeling, atherosclerosis, and peripheral artery disease. Ameliorating glucose and lipid metabolism and lowering blood pressure may also contribute to cardiovascular protection. On the other hand, the broad spectrum of HIF-dependent functions also may include unwanted side effects. Clinical application of PHD inhibitors therefore necessitates careful evaluation of the net systemic effect of HIF activation. Copyright © 2018 Elsevier Inc. All rights reserved.

Dual orexin receptor antagonists - promising agents in the treatment of sleep disorders.

PubMed

Pałasz, Artur; Lapray, Damien; Peyron, Christelle; Rojczyk-Gołębiewska, Ewa; Skowronek, Rafał; Markowski, Grzegorz; Czajkowska, Beata; Krzystanek, Marek; Wiaderkiewicz, Ryszard

2014-01-01

Insomnia is a serious medical and social problem, its prevalence in the general population ranges from 9 to 35% depending on the country and assessment method. Often, patients are subject to inappropriate and therefore dangerous pharmacotherapies that include prolonged administration of hypnotic drugs, benzodiazepines and other GABAA receptor modulators. This usually does not lead to a satisfactory improvement in patients' clinical states and may cause lifelong drug dependence. Brain state transitions require the coordinated activity of numerous neuronal pathways and brain structures. It is thought that orexin-expressing neurons play a crucial role in this process. Due to their interaction with the sleep-wake-regulating neuronal population, they can activate vigilance-promoting regions and prevent unwanted sleep intrusions. Understanding the multiple orexin modulatory effects is crucial in the context of pathogenesis of insomnia and should lead to the development of novel treatments. An important step in this process was the synthesis of dual antagonists of orexin receptors. Crucially, these drugs, as opposed to benzodiazepines, do not change the sleep architecture and have limited side-effects. This new pharmacological approach might be the most appropriate to treat insomnia.

Excessive or unwanted hair in women

MedlinePlus

Hypertrichosis; Hirsutism; Hair - excessive (women); Excessive hair in women; Hair - women - excessive or unwanted ... much of this hormone, you may have unwanted hair growth. In most cases, the exact cause is ...

Risk Factors and Consequences of Unwanted Sex among University Students: Hooked up, Alcohol, and Stress Response

ERIC Educational Resources Information Center

Flack, William F., Jr.; Daubman, Kimberly A.; Caron, Marcia L.; Asadorian, Jenica A.; D'Aureli, Nicole R.; Gigliotti, Shannon N.; Hall, Anna T.; Kiser, Sarah; Stine, Erin R.

2007-01-01

This is the first study of unwanted sexual experiences in the collegiate "hooking-up" culture. In a representative sample of 178 students at a small liberal arts university. Twenty-three percent of women and 7% of men surveyed reported one or more experiences of unwanted sexual intercourse. Seventy-eight percent of unwanted vaginal, anal, and oral…

Estimating the Availability of Potential Homes for Unwanted Horses in the United States

PubMed Central

Weiss, Emily; Dolan, Emily D.; Mohan-Gibbons, Heather; Gramann, Shannon; Slater, Margaret R.

2017-01-01

Simple Summary There are approximately 200,000 unwanted horses annually in the United States. Many are shipped to slaughter, enter rescue facilities, or are held on federal lands. This study aimed to estimate a potential number of available homes for unwanted horses in order to examine broadly the viability of pursuing re-homing policies as an option for the thousands of unwanted horses in the U.S. The results of this survey suggest there could be an estimated 1.2 million homes who have both the perceived resources and desire to house an unwanted horse. This number exceeds the approximately 200,000 unwanted horses living each year in the United States. These data suggest that efforts to reduce unwanted horses could involve matching such horses with adoptive homes and enhancing opportunities to keep horses in the homes they already have. Abstract There are approximately 200,000 unwanted horses annually in the United States. This study aimed to better understand the potential homes for horses that need to be re-homed. Using an independent survey company through an Omnibus telephone (land and cell) survey, we interviewed a nationally projectable sample of 3036 adults (using both landline and cellular phone numbers) to learn of their interest and capacity to adopt a horse. Potential adopters with interest in horses with medical and/or behavioral problems and self-assessed perceived capacity to adopt, constituted 0.92% of the total sample. Extrapolating the results of this survey using U.S. Census data, suggests there could be an estimated 1.25 million households who have both the self-reported and perceived resources and desire to house an unwanted horse. This number exceeds the estimated number of unwanted horses living each year in the United States. This study points to opportunities and need to increase communication and support between individuals and organizations that have unwanted horses to facilitate re-homing with people in their community willing to adopt them. PMID:28726730

Discovery of indolylpiperazinylpyrimidines with dual-target profiles at adenosine A2A and dopamine D2 receptors for Parkinson's disease treatment

PubMed Central

Paira, Priyankar; Tan, Aaron; Herr, Deron Raymond; Lim, Kah Leong; Ng, Chee Hoe; Venkatesan, Gopalakrishnan; Klotz, Karl-Norbert; Federico, Stephanie; Spalluto, Giampiero; Cheong, Siew Lee; Chen, Yu Zong

2018-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra of the human brain, leading to depletion of dopamine production. Dopamine replacement therapy remains the mainstay for attenuation of PD symptoms. Nonetheless, the potential benefit of current pharmacotherapies is mostly limited by adverse side effects, such as drug-induced dyskinesia, motor fluctuations and psychosis. Non-dopaminergic receptors, such as human A2A adenosine receptors, have emerged as important therapeutic targets in potentiating therapeutic effects and reducing the unwanted side effects. In this study, new chemical entities targeting both human A2A adenosine receptor and dopamine D2 receptor were designed and evaluated. Two computational methods, namely support vector machine (SVM) models and Tanimoto similarity-based clustering analysis, were integrated for the identification of compounds containing indole-piperazine-pyrimidine (IPP) scaffold. Subsequent synthesis and testing resulted in compounds 5 and 6, which acted as human A2A adenosine receptor binders in the radioligand competition assay (Ki = 8.7–11.2 μM) as well as human dopamine D2 receptor binders in the artificial cell membrane assay (EC50 = 22.5–40.2 μM). Moreover, compound 5 showed improvement in movement and mitigation of the loss of dopaminergic neurons in Drosophila models of PD. Furthermore, in vitro toxicity studies on compounds 5 and 6 did not reveal any mutagenicity (up to 100 μM), hepatotoxicity (up to 30 μM) or cardiotoxicity (up to 30 μM). PMID:29304113

A Review of Nanoparticle Photosensitizer Drug Delivery Uptake Systems for Photodynamic Treatment of Lung Cancer.

PubMed

Gift, Mokwena Mpho; Ann, Kruger Cherie; Ivan, Mfouo-Tynga; Heidi, Abrahamse

2018-03-24

Lung cancer is a leading cause of cancer related deaths worldwide and so current research is focused on trying to improve treatment modalities, such as photodynamic therapy (PDT). PDT has 3 fundamental factors, namely a photosensitizer (PS) drug, light and oxygen. When a PS drug is administered to a patient, it can either passively or actively accumulate within a tumour site and once exposed to a specific wavelength of light, it is stimulated to produce reactive oxygen species (ROS), resulting in tumour destruction. However, the efficacy of ROS generation for tumour destruction is highly dependent on the accumulation of the PS in tumour cells. Thus PS selective / targeted uptake and delivery in tumour cells is a crucial factor in PDT cancer drug absorption studies. Generally, within non-targeted drug delivery mechanisms, only small amounts of PS is able to passively accumulates in tumour sites due to the enhanced permeability and retention (EPR) effect and the remainder distributes into healthy tissues, causing side effects. Thus to improve the efficacy of PDT, research is currently focused on the development of specific receptor based photosynthetic nanocarrier drugs, which promotes the active uptake and absorption of PS drugs in tumour sites only, avoiding unwanted side effects. The aim of this review is to focus on current non-targeted passive versus specifically active targeted PS nanoparticle drug delivery systems, that have been investigated for the PDT treatment of lung cancer and so to deduce its efficacy and recent advancements. Copyright © 2018. Published by Elsevier B.V.

"Come on Baby. You Know I Love You": African American Women's Experiences of Communication with Male Partners and Disclosure in the Context of Unwanted Sex.

PubMed

Gutzmer, Kyle; Ludwig-Barron, Natasha T; Wyatt, Gail E; Hamilton, Alison B; Stockman, Jamila K

2016-05-01

We examined African American women's experiences of communication with their male intimate partners a couple of hours before and after an incident of unwanted sex. We also examined women's experiences of disclosure following an incident of unwanted sex. Semi-structured qualitative interviews were conducted with a community-based sample of sexually active African American women (n = 19) reporting at least one incident of sexual coercion (i.e., being pressured into unwanted sex without consent) by an intimate male partner since the age of 18. Our analysis was guided by "the sexual division of power" from Connell's (1987) theory of gender and power. Data were analyzed inductively by examining the interviews for common themes in the following domains: communication before the unwanted sex, communication after the unwanted sex, and disclosure to others. Men pressured partners for unwanted sex through verbal and non-verbal tactics, ranging from pestering and blunt requests for sex to verbal bullying and violence. Many women responded by clearly saying no. However, many women also described eventually ceasing to resist their partners and engaging in unwanted sex. After the unwanted sex, men actively and passively avoided discussing the incident. Although many women discussed the unwanted sex with family and friends, less women disclosed to trained professionals. In some cases, women did not discuss the incident with anyone at all. These findings indicate that, when addressing sexual violence against women, there is a need to target men as well as the norms of masculinity that underpin physical and sexual violence against women.

“Come on baby. You know I love you”: African American Women's Experiences of Communication with Male Partners and Disclosure in the Context of Unwanted Sex

PubMed Central

Gutzmer, Kyle; Ludwig-Barron, Natasha T.; Wyatt, Gail E.; Hamilton, Alison B.; Stockman, Jamila K.

2016-01-01

We examined African American women's experiences of communication with their male intimate partners a couple of hours before and after an incident of unwanted sex. We also examined women's experiences of disclosure following an incident of unwanted sex. Semi-structured qualitative interviews were conducted with a community-based sample of sexually active African American women (n=19) reporting at least one incident of sexual coercion (i.e., being pressured into unwanted sex without consent) by an intimate male partner since the age of 18. Our analysis was guided by “the sexual division of power” from the Theory of Gender and Power. Data were analyzed inductively by examining the interviews for common themes in the following domains: communication before the unwanted sex, communication after the unwanted sex, and disclosure to others. Men pressured partners for unwanted sex through verbal and nonverbal tactics, ranging from pestering and blunt requests for sex to verbal bullying and violence. Many women responded by clearly saying no. However, many women also described eventually ceasing to resist their partners and engaging in unwanted sex. After the unwanted sex, men actively and passively avoided discussing the incident. Although many women discussed the unwanted sex with family and friends, less women disclosed to trained professionals. In some cases, women did not discuss the incident with anyone at all. These findings indicate that, when addressing sexual violence against women, there is a need to target men as well as the norms of masculinity that underpin physical and sexual violence against women. PMID:26892099

Consequences for children of their birth planning status.

PubMed

Baydar, N

1995-01-01

Of 1,327 children younger than two in 1986 whose mothers were participants in the National Longitudinal Survey of Youth, 61% were wanted, 34% were mistimed and 5% were unwanted. Planning status is associated with the level of developmental resources the child receives at home: At ages one and older, mistimed and unwanted children score significantly lower on a scale measuring opportunity for skill development and on a scale measuring nonauthoritarian parenting style than their wanted peers; by preschool age, they also have significantly less-positive relationships with their mothers. Measures of the direct effects of planning status on development also indicate that mistimed and unwanted children are at a disadvantage: Those younger than two have higher mean scores for fearfulness than wanted infants and lower scores for positive affect; unintended preschoolers score lower on a measure of receptive vocabulary.

Barriers to modern contraceptive methods uptake among young women in Kenya: a qualitative study.

PubMed

Ochako, Rhoune; Mbondo, Mwende; Aloo, Stephen; Kaimenyi, Susan; Thompson, Rachel; Temmerman, Marleen; Kays, Megan

2015-02-10

Young women in Kenya experience a higher risk of mistimed and unwanted pregnancy compared to older women. However, contraceptive use among youth remains low. Known barriers to uptake include side effects, access to commodities and partner approval. To inform a youth focussed behaviour change communication campaign, Population Services Kenya developed a qualitative study to better understand these barriers among young women. The study was carried out in Nyanza, Coast, and Central regions. Within these regions, urban or peri-urban districts were purposively selected based on having contraceptive prevalence rate close to the regional average and having a population with low socioeconomic profiles. In depth interviews were conducted with a sample of sexually active women aged 15-24, both users and non-users, that were drawn from randomly selected households. All the respondents in the study were familiar with modern methods of contraception and most could describe their general mechanisms of action. Condoms were not considered as contraception by many users. Contraception was also associated with promiscuity and straying. Fear of side effects and adverse reactions were a major barrier to use. The biggest fear was that a particular method would cause infertility. Many fears were based on myths and misconceptions. Young women learn about both true side effects and myths from their social networks. Findings from this research confirm that awareness and knowledge of contraception do not necessarily translate to use. The main barriers to modern contraceptive uptake among young women are myths and misconceptions. The findings stress the influence of social network approval on the use of family planning, beyond the individual's beliefs. In such settings, family planning programming should engage with the wider community through mass and peer campaign strategies. As an outcome from this study, Population Services Kenya developed a mass media campaign to address key myths and misconceptions among youth.

Pharmacological and Toxicological Profile of Harmane-β-Carboline Alkaloid: Friend or Foe.

PubMed

Khan, Haroon; Patel, Seema; Kamal, Mohammad A

2017-01-01

The plant secondary metabolites have an outstanding therapeutic potential and success over the years. In fact, it is the foundation of numerous clinically used drugs. Similarly, these is a general perception that these products are inherent safety. However, such products might have toxic/unwanted lethal effects therefore, along with biological relevance, toxicological evaluation is equally important for clinical applications. Therefore, harmane- β-carboline alkaloid was investigated for both therapeutic and toxicological potential. The literature related to the therapeutic/toxicological effects of the alkaloid was searched using various scientific data bases including Google, ScienceDirect, PubMed, SpringerLink, ASC. The peer reviewed articles were only selected. The harmane-β-carboline alkaloid has shown several pharmacological activities such as antianxiety, antidepressant, antiplatelet, antidiabetic, acetylcholinesterase and myeloperoxidase inhibition, antioxidant, antiparasitic, hypotensive, morphine withdrawal syndrome alleviation, and antinociceptive effects. On the other hand, it exhibited tremorogenic effect, for a symptom of Parkinson's disease. Adverse effect of the alkaloid on learning and memory have also been observed. All together, it is, concluded in this review that harmane elicited marked pharmacological effects but simultaneously, it possessed some serious side effects that could be the primary hurdle in the way of its clinical testing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries.

PubMed

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-04-08

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries

NASA Astrophysics Data System (ADS)

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-04-01

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries.

Flux Recovery of a Forward Osmosis Membrane After a Fouling Process

NASA Technical Reports Server (NTRS)

Gamboa-Vázquez, Sonia; Flynn, Michael; Romero Mangado, Jaione; Parodi, Jurek

2016-01-01

Wastewater treatment through Forward Osmosis (FO) membranes is a process that has been evaluated in the past years as an innovative technology for the Next Generation Life Support Systems. FO technologies are cost effective, and require very low energy consumption, but are subject to membrane fouling. Membrane fouling occurs when unwanted materials accumulate on the active side of the membrane during the wastewater treatment process, which leads to a decrease in membrane flow rates. Membrane fouling can be reversed with the use of antifoulant solutions. The aim of this study is to identify the materials that cause flow rate reduction due to membrane fouling, as well as to evaluate the flux recovery after membrane treatment using commercially available antifoulants. 3D Laser Scanning Microscope images were taken to observe the surface of the membrane. Fourier Transform Infrared (FTIR) spectrometry results identified possible compounds that cause membrane fouling and FO testing results demonstrated flow rate recovery after membrane treatment using antifoulants.

Multifunctional semi-interpenetrating polymer network-nanoencapsulated cathode materials for high-performance lithium-ion batteries

PubMed Central

Kim, Ju-Myung; Park, Jang-Hoon; Lee, Chang Kee; Lee, Sang-Young

2014-01-01

As a promising power source to boost up advent of next-generation ubiquitous era, high-energy density lithium-ion batteries with reliable electrochemical properties are urgently requested. Development of the advanced lithium ion-batteries, however, is staggering with thorny problems of performance deterioration and safety failures. This formidable challenge is highly concerned with electrochemical/thermal instability at electrode material-liquid electrolyte interface, in addition to structural/chemical deficiency of major cell components. Herein, as a new concept of surface engineering to address the abovementioned interfacial issue, multifunctional conformal nanoencapsulating layer based on semi-interpenetrating polymer network (semi-IPN) is presented. This unusual semi-IPN nanoencapsulating layer is composed of thermally-cured polyimide (PI) and polyvinyl pyrrolidone (PVP) bearing Lewis basic site. Owing to the combined effects of morphological uniqueness and chemical functionality (scavenging hydrofluoric acid that poses as a critical threat to trigger unwanted side reactions), the PI/PVP semi-IPN nanoencapsulated-cathode materials enable significant improvement in electrochemical performance and thermal stability of lithium-ion batteries. PMID:24710575

Caffeine Toxicity Due to Supplement Use in Caffeine--Naïve Individual: A Cautionary Tale.

PubMed

Lystrup, Robert M; Leggit, Jeffery C

2015-08-01

Thousands of military members self-medicate with dietary supplements containing unknown quantities of pharmacologically active compounds. These poorly regulated substances can cause real harm to the military population, especially when they contain stimulants such as caffeine. When taken regularly, caffeine has several performance-enhancing benefits. However, when used excessively or in vulnerable populations, caffeine can cause several unwanted side effects such as nervousness, sensory disturbances, insomnia, arrhythmia, excitability, inattentiveness, restlessness, mood changes, gastrointestinal disturbances, and even psychosis. Vulnerable patients include the caffeine-naïve, physiologically stressed, young, and mentally ill patients. One such case describes a caffeine-naïve service member who suffered an adverse reaction after taking an allegedly moderate dose of caffeine from a pill he obtained from a teammate. This case highlights the importance of supplement awareness among service members, increased provider vigilance, third party verification, and enhanced regulation on the approval and marketing of dietary supplements. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

The hERG K+ channel: target and antitarget strategies in drug development.

PubMed

Raschi, Emanuel; Vasina, Valentina; Poluzzi, Elisabetta; De Ponti, Fabrizio

2008-03-01

The human ether-à-go-go related gene (hERG) K+ channel is of great interest for both basic researchers and clinicians because its blockade by drugs can lead to QT prolongation, which is a risk factor for torsades de pointes, a potentially life-threatening arrhythmia. A growing list of agents with "QT liability" have been withdrawn from the market or restricted in their use, whereas others did not even receive regulatory approval for this reason. Thus, hERG K+ channels have become a primary antitarget (i.e. an unwanted target) in drug development because their blockade causes potentially serious side effects. On the other hand, the recent identification and functional characterization of hERG K+ channels not only in the heart, but also in several other tissues (e.g. neurons, smooth muscle and cancer cells) may have far reaching implications for drug development for a possible exploitation of hERG as a target, especially in oncology and cardiology.

Use of direct fluorescence labeling and confocal microscopy to determine the biodistribution of two protein therapeutics, Cerezyme and Ceredase.

PubMed

Piepenhagen, Peter A; Vanpatten, Scott; Hughes, Heather; Waire, James; Murray, James; Andrews, Laura; Edmunds, Tim; O'Callaghan, Michael; Thurberg, Beth L

2010-07-01

Efficient targeting of therapeutic reagents to tissues and cell types of interest is critical to achieving therapeutic efficacy and avoiding unwanted side effects due to offtarget uptake. To increase assay efficiency and reduce the number of animals used per experiment during preclinical development, we used a combination of direct fluorescence labeling and confocal microscopy to simultaneously examine the biodistribution of two therapeutic proteins, Cerezyme and Ceredase, in the same animals. We show that the fluorescent tags do not interfere with protein uptake and localization. We are able to detect Cerezyme and Ceredase in intact cells and organs and demonstrate colocalization within target cells using confocal microscopy. In addition, the relative amount of protein internalized by different cell types can be quantified using cell type-specific markers and morphometric analysis. This approach provides an easy and straightforward means of assessing the tissue and cell type-specific biodistribution of multiple protein therapeutics in target organs using a minimal number of animals. (c) 2009 Wiley-Liss, Inc.

Engineered Context-Sensitive Agonism: Tissue-Selective Drug Signaling through a G Protein-Coupled Receptor.

PubMed

Seemann, Wiebke K; Wenzel, Daniela; Schrage, Ramona; Etscheid, Justine; Bödefeld, Theresa; Bartol, Anna; Warnken, Mareille; Sasse, Philipp; Klöckner, Jessica; Holzgrabe, Ulrike; DeAmici, Marco; Schlicker, Eberhard; Racké, Kurt; Kostenis, Evi; Meyer, Rainer; Fleischmann, Bernd K; Mohr, Klaus

2017-02-01

Drug discovery strives for selective ligands to achieve targeted modulation of tissue function. Here we introduce engineered context-sensitive agonism as a postreceptor mechanism for tissue-selective drug action through a G protein-coupled receptor. Acetylcholine M 2 -receptor activation is known to mediate, among other actions, potentially dangerous slowing of the heart rate. This unwanted side effect is one of the main reasons that limit clinical application of muscarinic agonists. Herein we show that dualsteric (orthosteric/allosteric) agonists induce less cardiac depression ex vivo and in vivo than conventional full agonists. Exploration of the underlying mechanism in living cells employing cellular dynamic mass redistribution identified context-sensitive agonism of these dualsteric agonists. They translate elevation of intracellular cAMP into a switch from full to partial agonism. Designed context-sensitive agonism opens an avenue toward postreceptor pharmacologic selectivity, which even works in target tissues operated by the same subtype of pharmacologic receptor. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

NASA Astrophysics Data System (ADS)

Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

2014-08-01

The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

Augmented reality and haptic interfaces for robot-assisted surgery.

PubMed

Yamamoto, Tomonori; Abolhassani, Niki; Jung, Sung; Okamura, Allison M; Judkins, Timothy N

2012-03-01

Current teleoperated robot-assisted minimally invasive surgical systems do not take full advantage of the potential performance enhancements offered by various forms of haptic feedback to the surgeon. Direct and graphical haptic feedback systems can be integrated with vision and robot control systems in order to provide haptic feedback to improve safety and tissue mechanical property identification. An interoperable interface for teleoperated robot-assisted minimally invasive surgery was developed to provide haptic feedback and augmented visual feedback using three-dimensional (3D) graphical overlays. The software framework consists of control and command software, robot plug-ins, image processing plug-ins and 3D surface reconstructions. The feasibility of the interface was demonstrated in two tasks performed with artificial tissue: palpation to detect hard lumps and surface tracing, using vision-based forbidden-region virtual fixtures to prevent the patient-side manipulator from entering unwanted regions of the workspace. The interoperable interface enables fast development and successful implementation of effective haptic feedback methods in teleoperation. Copyright © 2011 John Wiley & Sons, Ltd.

Reducing blood viscosity with magnetic fields

NASA Astrophysics Data System (ADS)

Tao, R.; Huang, K.

2011-07-01

Blood viscosity is a major factor in heart disease. When blood viscosity increases, it damages blood vessels and increases the risk of heart attacks. Currently, the only method of treatment is to take drugs such as aspirin, which has, however, several unwanted side effects. Here we report our finding that blood viscosity can be reduced with magnetic fields of 1 T or above in the blood flow direction. One magnetic field pulse of 1.3 T lasting ˜1 min can reduce the blood viscosity by 20%-30%. After the exposure, in the absence of magnetic field, the blood viscosity slowly moves up, but takes a couple of hours to return to the original value. The process is repeatable. Reapplying the magnetic field reduces the blood viscosity again. By selecting the magnetic field strength and duration, we can keep the blood viscosity within the normal range. In addition, such viscosity reduction does not affect the red blood cells’ normal function. This technology has much potential for physical therapy.

Examining intendedness among pregnancies ending in spontaneous abortion.

PubMed

Flink-Bochacki, Rachel; Meyn, Leslie A; Chen, Beatrice A; Achilles, Sharon L; Chang, Judy C; Borrero, Sonya

2017-08-01

Spontaneous abortion (SAB) affects over 1 million US women each year, yet little is known about the intendedness of these pregnancies. We examined prevalence and correlates of unintended and unwanted pregnancies ending in SAB. We used nationally-representative cross-sectional data of US women aged 15-44 from the 2011-2013 National Survey of Family Growth to examine pregnancies ending in SAB. We used modified Poisson regression models to evaluate associations between demographic and pregnancy characteristics with unintended and unwanted pregnancy. Among 1351 pregnancies ending in SAB, 44.5% were unintended (i.e. unwanted or occurring sooner than desired). Younger women with SAB were more likely to report unintended pregnancies than women 30-44 years, and women 15-19 years reported unintended pregnancy most often [adjusted relative risk (aRR)=3.0; 95% confidence interval (CI): 2.2-4.1]. Unintended pregnancy was two times more likely among unmarried than married women [never married: aRR=2.2; 95% CI: 1.7-2.7; previously married: aRR=2.2; 95% CI: 1.7-3.0]. Other factors associated with unintended pregnancy were multiparity compared to nulliparity [aRR=2.6; 95% CI: 1.7-4.1 for ≥3 children; aRR=1.8; 95% CI: 1.3-2.5 for 2 children] and inter-pregnancy interval ≤12 months compared to >12 months [aRR=1.4; 95% CI: 1.2-1.7]. We found similar associations with unwanted pregnancies ending in SAB (15.3% of pregnancies). Neither race/ethnicity nor socioeconomic indicators were independently associated with unintended or unwanted pregnancy ending in SAB. Many pregnancies ending in spontaneous abortion are unintended and/or unwanted. Women with pregnancy loss, like all reproductive-aged women, should receive comprehensive counseling about reproductive planning and contraception. Similar to all pregnancies, nearly half of pregnancies ending in spontaneous abortion are unintended and/or unwanted, suggesting that many women experiencing spontaneous abortion may benefit from a review of family planning desires and the provision of reproductive planning counseling and effective contraception to prevent future undesired pregnancy. Copyright © 2017 Elsevier Inc. All rights reserved.

Nitric oxide donor augments antineoplastic effects of arginine deprivation in human melanoma cells.

PubMed

Mayevska, Oksana; Chen, Oleh; Karatsai, Olena; Bobak, Yaroslav; Barska, Maryna; Lyniv, Liliana; Pavlyk, Iuliia; Rzhepetskyy, Yuriy; Igumentseva, Natalia; Redowicz, Maria Jolanta; Stasyk, Oleh

2017-06-15

Anticancer therapy based on recombinant arginine-degrading enzymes has been proposed for the treatment of several types of malignant cells deficient in arginine biosynthesis. One of the predicted side effects of such therapy is restricted bioavailability of nitric oxide as arginine catabolic product. Prolonged NO limitation may lead to unwanted disturbances in NO-dependent vasodilation, cardiovascular and immune systems. This problem can be overcome by co-supplementation with exogenous NO donor. However, NO may potentially counteract anticancer effects of therapy based on arginine deprivation. In this study, we evaluate for the first time the effects of an exogenous NO donor, sodium nitroprusside, on viability and metastatic properties of two human melanoma cell lines SK-MEL-28 and WM793 under arginine-deprived conditions. It was revealed that NO did not rescue melanoma cells from specific effects evoked by arginine deprivation, namely decreased viability and induction of apoptosis, dramatically reduced motility, invasiveness and clonogenic potential. Moreover, sodium nitroprusside co-treatment augmented several of these antineoplastic effects. We report that a combination of NO-donor and arginine deprivation strongly and specifically impaired metastatic behavior of melanoma cells. Thus, sodium nitroprusside can be considered as an adjuvant for the more efficient treatment of malignant melanoma and possibly other tumors with arginine-degrading enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

Improvements for extending the time between maintenance periods for the Heidelberg ion beam therapy center (HIT) ion sources.

PubMed

Winkelmann, Tim; Cee, Rainer; Haberer, Thomas; Naas, Bernd; Peters, Andreas; Schreiner, Jochen

2014-02-01

The clinical operation at the Heidelberg Ion Beam Therapy Center (HIT) started in November 2009; since then more than 1600 patients have been treated. In a 24/7 operation scheme two 14.5 GHz electron cyclotron resonance ion sources are routinely used to produce protons and carbon ions. The modification of the low energy beam transport line and the integration of a third ion source into the therapy facility will be shown. In the last year we implemented a new extraction system at all three sources to enhance the lifetime of extraction parts and reduce preventive and corrective maintenance. The new four-electrode-design provides electron suppression as well as lower beam emittance. Unwanted beam sputtering effects which typically lead to contamination of the insulator ceramics and subsequent high-voltage break-downs are minimized by the beam guidance of the new extraction system. By this measure the service interval can be increased significantly. As a side effect, the beam emittance can be reduced allowing a less challenging working point for the ion sources without reducing the effective beam performance. This paper gives also an outlook to further enhancements at the HIT ion source testbench.

The use of lorcaserin in the management of obesity: a critical appraisal

PubMed Central

Bai, Bo; Wang, Yu

2011-01-01

Obesity is a chronic disease with a high prevalence in both developed and developing countries. Effective management of this worldwide epidemic will have a significant impact on the health care system globally. Lifestyle interventions, such as restricting calorie consumption and increasing physical activity, remain a major component of weight-reduction programs. The development of pharmacotherapy for the management of obesity is still at the infancy stage. Side effects have been the key issue for anti-obesity drugs previously withdrawn from the market. The focus of this review, lorcaserin, is a selective serotonin receptor agonist that is currently undergoing Phase III evaluations. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in two recent clinical trials. The available evidence indicates that this drug does not show unwanted effects on heart valves or pulmonary artery pressure, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. Despite these promising results, additional experimental and clinical studies are critical for the approval of lorcaserin as a new anti-obesity monodrug therapy by the US Food and Drug Administration. PMID:21267355

The use of lorcaserin in the management of obesity: a critical appraisal.

PubMed

Bai, Bo; Wang, Yu

2010-12-20

Obesity is a chronic disease with a high prevalence in both developed and developing countries. Effective management of this worldwide epidemic will have a significant impact on the health care system globally. Lifestyle interventions, such as restricting calorie consumption and increasing physical activity, remain a major component of weight-reduction programs. The development of pharmacotherapy for the management of obesity is still at the infancy stage. Side effects have been the key issue for anti-obesity drugs previously withdrawn from the market. The focus of this review, lorcaserin, is a selective serotonin receptor agonist that is currently undergoing Phase III evaluations. The efficacy of this drug in reducing body weight and improving metabolic parameters of obese patients has been demonstrated in two recent clinical trials. The available evidence indicates that this drug does not show unwanted effects on heart valves or pulmonary artery pressure, and the treatment improves the risk factors for type 2 diabetes and cardiovascular diseases. Despite these promising results, additional experimental and clinical studies are critical for the approval of lorcaserin as a new anti-obesity monodrug therapy by the US Food and Drug Administration.

Development of Selective Androgen Receptor Modulators (SARMs)

PubMed Central

Narayanan, Ramesh; Coss, Christopher C.; Dalton, James T.

2018-01-01

The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits. PMID:28624515

The use of sub-anesthetic intravenous ketamine and adjuvant dexmedetomidine when treating acute pain from CRPS.

PubMed

Nama, Sharanya; Meenan, Daniel R; Fritz, William T

2010-01-01

Complex regional pain syndrome (CRPS) is a pain condition of the extremities that presents with pain and allodynia, decreased range of motion, swelling and skin changes. There are 2 forms of CRPS - Type I which does not have demonstrable nerve lesions and Type 2, which has evidence of obvious nerve damage. Management of refractory CRPS has been challenging. Some studies have revealed that the N-methyl-D-aspartic acid receptor (NMDAR) may be involved in the etiology of the pain in CRPS and perhaps that a NMDA receptor antagonist like ketamine is a potential treatment for CRPS. However, the side effect profile of ketamine is concerning, and limiting the adverse effects of the drug is beneficial. Dexmedetomidine is an alpha 2 agonist similar to clonidine with analgesic properties that can be used in combination with ketamine to provide additional analgesia in CRPS. This case describes the treatment of acute pain symptoms from Chronic Regional Pain Syndrome-Type 1 (CRPS-1) with sub-anesthetic intravenous infusion of ketamine with adjunct dexmedetomidine. A 47-year-old female patient presented with severe pain, burning and allodynia from CRPS-1 refractory to conventional therapy. She was then admitted to a monitored bed, received a sub-anesthetic intravenous infusion of ketamine with adjunct dexmedetomidine for 19 hours and subsequently discharged with complete resolution of her pain and associated symptoms. Here, the synergistic effect of the ketamine and dexmedetomidine together is shown to provide excellent symptom relief while decreasing the total ketamine administered. The combination minimized unwanted side effects and eliminated the need for intensive care unit admission secondary to anesthetic doses of ketamine.

Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks.

PubMed

Brynhildsen, Jan

2014-10-01

Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the 'real-life' efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy.

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study.

PubMed

Zhong, Yingjie; Wang, Ye; Guo, Jun; Chu, Haifeng; Gao, Yong; Pang, Limin

2015-11-01

Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.

Presence of Cx43 in extracellular vesicles reduces the cardiotoxicity of the anti-tumour therapeutic approach with doxorubicin

PubMed Central

Martins-Marques, Tania; Pinho, Maria Joao; Zuzarte, Monica; Oliveira, Carla; Pereira, Paulo; Sluijter, Joost P. G.; Gomes, Celia; Girao, Henrique

2016-01-01

Extracellular vesicles (EVs) are major conveyors of biological information, mediating local and systemic cell-to-cell communication under physiological and pathological conditions. These endogenous vesicles have been recognized as prominent drug delivery vehicles of several therapeutic cargoes, including doxorubicin (dox), presenting major advantages over the classical approaches. Although dox is one of the most effective anti-tumour agents in the clinical practice, its use is very often hindered by its consequent dramatic cardiotoxicity. Despite significant advances witnessed in the past few years, more comprehensive studies, supporting the therapeutic efficacy of EVs, with decreased side effects, are still scarce. The main objective of this study was to evaluate the role of the gap junction protein connexin43 (Cx43) in mediating the release of EV content into tumour cells. Moreover, we investigated whether Cx43 improves the efficiency of dox-based anti-tumour treatment, with a concomitant decrease of cardiotoxicity. In the present report, we demonstrate that the presence of Cx43 in EVs increases the release of luciferin from EVs into tumour cells in vitro and in vivo. In addition, using cell-based approaches and a subcutaneous mouse tumour model, we show that the anti-tumour effect of dox incorporated into EVs is similar to the administration of the free drug, regardless the presence of Cx43. Strikingly, we demonstrate that the presence of Cx43 in dox-loaded EVs reduces the cardiotoxicity of the drug. Altogether, these results bring new insights into the concrete potential of EVs as therapeutic vehicles and open new avenues toward the development of strategies that help to reduce unwanted side effects. PMID:27702427

Mental Health and Substance Use Factors Associated with Unwanted Sexual Contact among U.S. Active Duty Service Women

PubMed Central

Stahlman, Shauna; Javanbakht, Marjan; Cochran, Susan; Hamilton, Alison B.; Shoptaw, Steven; Gorbach, Pamina M.

2015-01-01

Many U.S. military women are exposed to unwanted sexual contact during military service, which can have important implications for mental health. Using data from the 2008 Department of Defense Survey of Health Related Behaviors, we employed multiple logistic regression methods to examine whether unwanted sexual contact was associated with stress, screening positive for mental disorders, or substance use, among active duty service women. The sample included 7,415 female military personnel, of whom 13.4% reported unwanted sexual contact (including any touching of genitals) since entering the military. After adjusting for potentially confounding variables, factors independently associated with unwanted sexual contact included military-related stress (Adjusted Odds Ratio [AOR] = 2.44), family/personal life-related stress (AOR = 1.78), and gender-related stress (AOR = 1.98) in the past 12 months. In addition, screening positive for depression, anxiety, posttraumatic stress disorder, psychological distress, and suicidal ideation or attempt were associated with unwanted sexual contact (AOR = 1.57–2.11). For drug/alcohol use, only misuse of tranquilizers/muscle relaxers (past 12 months) was associated with report of unwanted sexual contact (AOR = 1.35). Given the prevalence of unwanted sexual contact and corresponding adverse health outcomes in this sample of active duty women, strategies to create military structural/cultural changes and reduce gender-related stress and sexism are needed. PMID:25976935

A study protocol: using demand-side financing to meet the birth spacing needs of the underserved in Punjab Province in Pakistan.

PubMed

Azmat, Syed Khurram; Ali, Moazzam; Hameed, Waqas; Mustafa, Ghulam; Abbas, Ghazanfer; Ishaque, Muhammad; Bilgrami, Mohsina; Temmerman, Marleen

2014-05-30

High fertility rates, unwanted pregnancies, low modern contraceptive prevalence and a huge unmet need for contraception adversely affect women's health in Pakistan and this problem is compounded by limited access to reliable information and quality services regarding birth spacing especially in rural and underserved areas. This paper presents a study protocol that describes an evaluation of a demand-side financing (DSF) voucher approach which aims to increase the uptake of modern contraception among women of the lowest two wealth quintiles in Punjab Province, Pakistan. This study will use quasi-experimental design with control arm and be implemented in: six government clinics from the Population Welfare Department; 24 social franchise facilities branded as 'Suraj' (Sun), led by Marie Stopes Society (a local non-governmental organization); and 12 private sector clinics in Chakwal, Mianwali and Bhakkar districts. The study respondents will be interviewed at baseline and endline subject to voluntary acceptance and medical eligibility. In addition, health service data will record each client visit during the study period. The study will examine the impact of vouchers in terms of increasing the uptake of modern contraception by engaging private and public sector service providers (mid-level and medical doctors). If found effective, this approach can be a viable solution to satisfying the current demand and meeting the unmet need for contraception, particularly among the poorest socio-economic group.

The co-occurrence of Internet harassment and unwanted sexual solicitation victimization and perpetration: associations with psychosocial indicators.

PubMed

Ybarra, Michele L; Espelage, Dorothy L; Mitchell, Kimberly J

2007-12-01

Previous research in offline environments suggests that there may be an overlap in bullying and sexual harassment perpetration and victimization; however to what extent this may be true for perpetration and victimization of Internet harassment and unwanted sexual solicitation is unknown. The Growing Up with Media survey is a national cross-sectional online survey of 1,588 youth, 10-15 years old, who have used the Internet at least once in the last 6 months. Cluster analysis was conducted with four scales: Internet harassment perpetration, Internet harassment victimization, unwanted sexual solicitation perpetration, and unwanted sexual solicitation victimization. A four-cluster solution was identified: youth with little to no involvement (n = 1326; 81.7%); perpetrator-victims of Internet harassment (n = 205; 14.3%); victims of both Internet harassment and unwanted sexual solicitation (n = 45; 3.1%); and perpetrator-victims of Internet harassment and unwanted sexual solicitation (n = 12; .9%). Involvement in Internet harassment and unwanted sexual solicitation was associated with concurrent reports of psychosocial problems including substance use; involvement in offline victimization and perpetration of relational, physical, and sexual aggression; delinquent peers; a propensity to respond to stimuli with anger; poor emotional bond with caregivers; and poor caregiver monitoring as compared with youth with little to no involvement. This was especially true for perpetrator-victims of Internet harassment and unwanted sexual solicitation. Findings were replicated using a frequency-based definition of involvement, suggesting that cluster analysis is useful in identifying subgroups of youth and can be used to guide frequency-based definitions, which are easier to implement across study samples. The majority of youth are not frequently involved in Internet harassment or unwanted sexual solicitation either as victims or as perpetrators. Among those who are, however, psychosocial problems are apparent. Perpetrator-victims of Internet harassment and unwanted sexual solicitation have emerged as a particularly important group for adolescent health professionals to be aware of, identify, and treat or refer into services immediately.

Emergency contraception: clinical outcomes.

PubMed

Glasier, Anna

2013-03-01

Emergency contraception (EC) is widely used to prevent unwanted pregnancy. This review considers the safety and efficacy of three commonly used methods -- levonorgestrel (LNG-EC), ulipristal acetate (UPA) and the copper intrauterine device. All are extremely safe, and side effects are minimal. Concerns about increased risks of ectopic pregnancy after EC use have proved unfounded, and possible teratogenic effects seem unlikely. Although the true effectiveness of EC is impossible to estimate, recent research suggests that LNG-EC prevents around 50% of expected pregnancies in women using the method within 72 h of intercourse, whereas UPA appeared to prevent almost two thirds of pregnancies. Emergency intrauterine device insertion probably prevents over 95% of pregnancies. However, although improved accessibility of EC has clearly led to increased use, it does not appear to have had any public health benefit in reducing unintended pregnancy rates. Most of the data on sexual behavior following improved access to EC do not show any detrimental effect on subsequent use of other more effective methods of contraception or on the incidence of unintended pregnancy or sexually transmitted infection. However, unless these other methods of contraception are also made easily available from pharmacies, improved access to EC risks unlinking its use with use of subsequent ongoing contraception. Copyright © 2013 Elsevier Inc. All rights reserved.

The Discovery and Development of Drug Combinations for the Treatment of Various Diseases from Patent Literature (1980-Present).

PubMed

Kleczkowska, Patrycja; Kowalczyk, Agnieszka; Lesniak, Anna; Bujalska-Zadrozny, Magdalena

2017-01-01

The search for a miracle drug that would help to alleviate multiple ailments, dates back many thousands of years before our era and continues until today. Various techniques have been used to obtain a formulation, that would give the desired therapeutic effect. The most popular approach includes drug coctails and multicomponent drugs. Polytherapy is widely accapted as an effective tool for the treatment of several diseases, however it is often faced with important drawbacks that may sometimes result in fatal adverse effects associated with unpredictable drug interactions. Conversly, hybrid compounds were found to be an attractive way to counterbalance the unwanted side effects derived from the administration of individual drug components. Futhermore, they can serve as effective and improved remedies for patients suffering from several diseases simultaneously, as different receptorrelated pharmacophores are used as structural components. This review covers patent literature from 1980 till now that highlights the progress that has been made in the discovery of hybrid compounds potentially useful in the treatment on various disorders, including pain states, neurodegenerative or infectious diseases. Additionally, this review was further enriched with findings from original research papers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Is biotechnology a victim of anti-science bias in scientific journals?

PubMed

Miller, Henry I; Morandini, Piero; Ammann, Klaus

2008-03-01

Primarily outside the scientific community, misapprehensions and misinformation about recombinant DNA-modified (also known as 'genetically modified', or 'GM') plants have generated significant 'pseudo-controversy' over their safety that has resulted in unscientific and excessive regulation (with attendant inflated development costs) and disappointing progress. But pseudo-controversy and sensational claims have originated within the scientific community as well, and even scholarly journals' treatment of the subject has been at times unscientific, one-sided and irresponsible. These shortcomings have helped to perpetuate 'The Big Lie' - that recombinant DNA technology applied to agriculture and food production is unproven, unsafe, untested, unregulated and unwanted. Those misconceptions, in turn, have given rise to unwarranted opposition and tortuous, distorted public policy.

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

47 CFR 95.635 - Unwanted radiation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Unwanted radiation. 95.635 Section 95.635 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Technical Regulations Technical Standards § 95.635 Unwanted radiation. (a) In addition to the...

Sentinel events predicting later unwanted sex among girls: A national survey in Haiti, 2012.

PubMed

Sumner, Steven A; Marcelin, Louis H; Cela, Toni; Mercy, James A; Lea, Veronica; Kress, Howard; Hillis, Susan D

2015-12-01

Sexual violence against children is a significant global public health problem, yet limited studies exist from low-resource settings. In Haiti we conducted the country's first, nationally representative survey focused on childhood violence to help inform the development of a national action plan for violence against children. The Haiti Violence Against Children Survey was a household-level, multistage, cluster survey among youth age 13-24. In this analysis we sought to determine whether sexual violence sentinel events (unwanted sexual touching or unwanted attempted sex) were predictive of later unwanted, completed, penetrative sex in Haiti. We also sought to explore characteristics of sentinel events and help-seeking behavior among Haitian children. Multivariable logistic regression was used to test associations between sentinel events and later unwanted, completed, penetrative sex. Overall, 1,457 females reported on experiences of sexual violence occurring in childhood (before age 18). A sentinel event occurred in 40.4% of females who experienced subsequent unwanted completed sex. Females experiencing a sentinel event were approximately two and a half times more likely to experience later unwanted completed sex (adjusted odds ratio=2.40, p=.004) compared to individuals who did not experience a sentinel event. The mean lag time from first sentinel event to first unwanted completed sex was 2.3 years. Only half (54.6%) of children experiencing a sentinel event told someone about their experience of sexual violence. Among children, sentinel events occur frequently before later acts of completed unwanted sex and may represent a useful point of intervention. Reporting of sexual violence by children in Haiti is low and can be improved to better act on sentinel events. Published by Elsevier Ltd.

A cross-sectional study examining the extent of unwanted sexual attention and unhealthy intimate relationships among female university students.

PubMed

Hayden, Kelly; Graham, Melissa; Lamaro, Greer

2016-05-17

Issue addressed: Unwanted sexual attention and unhealthy intimate relationships have the potential to have serious negative health consequences. To date, there has been scant focus on these issues among university students in Australia. The aim of the current study was to describe the extent of unwanted sexual attention and unhealthy intimate relationships experienced in their lifetime by female university students aged 18-25 years. Methods: A cross-sectional study was undertaken involving 465 female students aged 18-25 years. Students were recruited through one faculty within a Victorian university and invited to complete an anonymous online questionnaire. Results: Sixty-seven per cent (n = 312) of female students reported experiencing unwanted sexual attention in their lifetime. The most common form of unwanted sexual attention was kissing or touching over clothes (98%; n = 306). Over 43% (n = 124) of the female students reported that the experience of unwanted sexual experience occurred after their protests were ignored. Thirty per cent (n = 135) of the female students reported experiencing at least one element of an unhealthy intimate relationship. Conclusions: The high rates of unwanted sexual attention and unhealthy intimate relationships among female university students is of concern given the negative impact such events can have on individual's physical, emotional and social well being. So what?: Public health and health promotion action is required to prevent female students from experiencing unwanted sexual attention and unhealthy intimate relationships, and to address the negative health and well being consequences.

Unintended pregnancy and prenatal care: a study from a maternity hospital in Turkey.

PubMed

Erol, Nermin; Durusoy, Raika; Ergin, Işıl; Döner, Banu; Ciçeklioğlu, Meltem

2010-08-01

To evaluate factors associated with pregnancy intention and its effects on source, content and adequacy of prenatal care for women who delivered in a large maternity hospital in Izmir, Turkey. This cross-sectional survey was carried out using a questionnaire administered face-to-face to 351 women who had given birth in Konak Maternity Hospital in May 2002. Nearly half (47.3%) of the pregnancies were unintended: 31.3% were mistimed, and 16.0% unwanted. Women's and husbands' older age and lower education, lower social class, women's recent migration to Izmir, lower household income and absence of social security had a negative impact on pregnancy intention. Women with unwanted pregnancies had started procreating earlier; they had more pregnancies, deliveries, children and intentional abortions (p < 0.05). Number and contents of prenatal visits increased as intention status improved. When controlled for socio-demographic variables, women with unwanted pregnancies had less prenatal care, received less education during prenatal visits and had less iron and vitamin supplementation (p < 0.05) whereas mistimed pregnancies did not significantly differ from intended pregnancies. Unwanted pregnancies constitute a risk group that should be identified early in pregnancy. Ensuring an adequate and satisfactory prenatal care for all requires appropriate measures to be taken by public health authorities.

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

40 CFR 262.208 - Removing containers of unwanted material from the laboratory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Laboratories Owned by Eligible Academic Entities § 262.208 Removing containers of unwanted material from the laboratory. (a) Removing containers of unwanted material on a regular schedule. An eligible academic entity... months of each container's accumulation start date. (b) The eligible academic entity must specify in Part...

Unwanted sexual attention at work and long-term sickness absence: a follow-up register-based study.

PubMed

Hogh, Annie; Conway, Paul Maurice; Clausen, Thomas; Madsen, Ida Elisabeth Huitfeldt; Burr, Hermann

2016-07-30

The current understanding of the relationship between unwanted sexual attention at work and long-term sickness absence (LTSA) is limited for three reasons: 1) the under-researched role of unwanted sexual attention perpetrated by individuals outside the work organization; 2) a widespread use of self-reported measures of sickness absence, with an unclear identification of sickness absence episodes of long duration; 3) the cross-sectional design of most existing studies. The aim of this study was therefore to investigate the relationship between self-reported unwanted sexual attention at work and subsequent LTSA (≥3 weeks), stratifying by gender and source of exposure (i.e., colleagues, managers and/or subordinates vs. clients/customers/patients). This prospective study is based on a pooled sample of 14,605 employees from three Danish surveys conducted in 2000, 2004 and 2005, providing a total of 19,366 observations. A single questionnaire-based item was used to assess exposure to unwanted sexual attention. The pooled dataset was merged with Danish register data on LTSA. The risk of first-onset episode of LTSA (up to 18 months after baseline) in connection with unwanted sexual attention was examined using Cox proportional hazards models. We estimated Hazard ratios (HR) and 95 % confidence intervals (95 % CI) adjusted for age, influence at work, work pace, occupational group and mode of data collection. We also adjusted for repeated measures from individual respondents by stratifying the Cox models by wave of survey. Unwanted sexual attention from colleagues, managers and/or subordinates predicted LTSA among men (HR 2.66; 95 % CI 1.42-5.00). Among women, an elevated but non-statistically significant risk of LTSA (HR 1.18; 95 % CI 0.65-2.14) was found. Unwanted sexual attention from clients/customers/patients did not predict LTSA, neither among men nor among women. The findings indicate a significantly elevated risk of LTSA, among men only, in relation to exposure to unwanted sexual attention from colleagues, managers and/or subordinates. This study therefore suggests both individual and organizational costs associated with unwanted sexual attention at work. Due to the low prevalence of unwanted sexual attention, larger studies with more statistical power are needed to confirm (or disconfirm) the present findings.

Bedside PDA ligation in premature infants less than 28 weeks and 1000 grams.

PubMed

Avsar, Mustafa Kemal; Demir, Tolga; Celiksular, Cem; Zeybek, Cenap

2016-10-04

PDA(Patent ductus arteriosus) is a common and clinically important condition which is presented with a number of hemodynamic and respiratory problems such as intraventricular hemorrhage, pulmonary hemorrhage and necrotizing enterocolitis due to increased pulmonary blood flow and stealing from systemic circulation. The incidence of PDA among the infants that were born before the 28th gestational week is as high as 70 %; and spontaneous closure rates in very-low-birth-weight premature neonates(VLBWPN) is around 34 %. The onset, duration, and repeat number of consecutive courses of the prostaglandin synthesis inhibitor medication for PDA closure are still issues of debate. Bed-side PDA closure is a safe surgical procedure in both mature and premature babies. Here we aim to retrospectively present our 26 cases which were less than 28 weeks and 1000 grams that underwent bed-side PDA ligation. This retrospective study included 26 VLBWPN with PDA that underwent bed-side ligation between 2012 and 2015. Babies were born before the 28th gestational week (23-27 weeks) and less than 1000 grams (489-970 gr). Of the 26, 15 were female and 11 were male. Indomethacin was administered to all of the cases as the medical closing agent. The medication was stopped due to unwanted effects in 6 cases. All of the patients took medical treatment before surgery. No surgical mortality occurred during our study. One case of pneumothorax was recorded as late surgical complication. Five of the 26 patients were lost, and the most common cause of mortality was sepsis (in 3 cases). The remaining 21 cases were discharged on days 86-238. The follow-up periods of the patients were 2 moths - 3 years. The most frequent problems encountered after discharge was chronic lung problems. Bed side PDA ligation surgery in the ICU is a safe method for VLBWPN with clinically significant PDA.

The Effects of Orally Administered Beta-Glucan on Innate Immune Responses in Humans, a Randomized Open-Label Intervention Pilot-Study

PubMed Central

Leentjens, Jenneke; Quintin, Jessica; Gerretsen, Jelle; Kox, Matthijs; Pickkers, Peter; Netea, Mihai G.

2014-01-01

Rationale To prevent or combat infection, increasing the effectiveness of the immune response is highly desirable, especially in case of compromised immune system function. However, immunostimulatory therapies are scarce, expensive, and often have unwanted side-effects. β-glucans have been shown to exert immunostimulatory effects in vitro and in vivo in experimental animal models. Oral β-glucan is inexpensive and well-tolerated, and therefore may represent a promising immunostimulatory compound for human use. Methods We performed a randomized open-label intervention pilot-study in 15 healthy male volunteers. Subjects were randomized to either the β -glucan (n = 10) or the control group (n = 5). Subjects in the β-glucan group ingested β-glucan 1000 mg once daily for 7 days. Blood was sampled at various time-points to determine β-glucan serum levels, perform ex vivo stimulation of leukocytes, and analyze microbicidal activity. Results β-glucan was barely detectable in serum of volunteers at all time-points. Furthermore, neither cytokine production nor microbicidal activity of leukocytes were affected by orally administered β-glucan. Conclusion The present study does not support the use of oral β-glucan to enhance innate immune responses in humans. Trial Registration ClinicalTrials.gov NCT01727895 PMID:25268806

A Novel Nitronyl Nitroxide with Salicylic Acid Framework Attenuates Pain Hypersensitivity and Ectopic Neuronal Discharges in Radicular Low Back Pain.

PubMed

Han, Wen-Juan; Chen, Lei; Wang, Hai-Bo; Liu, Xiang-Zeng; Hu, San-Jue; Sun, Xiao-Li; Luo, Ceng

2015-01-01

Evidence has accumulated that reactive oxygen species and inflammation play crucial roles in the development of chronic pain, including radicular low back pain. Nonsteroid anti-inflammatory drugs (NSAIDs), for example, salicylic acid, aspirin, provided analgesic effects in various types of pain. However, long-term use of these drugs causes unwanted side effects, which limits their implication. Stable nitronyl (NIT) nitroxide radicals have been extensively studied as a unique and interesting class of new antioxidants for protection against oxidative damage. The present study synthesized a novel NIT nitroxide radical with salicylic acid framework (SANR) to provide synergistic effect of both antioxidation and antiinflammation. We demonstrated for the first time that both acute and repeated SANR treatment exerted dramatic analgesic effect in radicular low back pain mimicked by chronic compression of dorsal root ganglion in rats. This analgesic potency was more potent than that produced by classical NSAIDs aspirin and traditional nitroxide radical Tempol alone. Furthermore, SANR-induced behavioral analgesia is found to be mediated, at least in partial, by a reduction of ectopic spontaneous discharges in injured DRG neurons. Therefore, the synthesized NIT nitroxide radical coupling with salicylic acid framework may represent a novel potential therapeutic candidate for treatment of chronic pain, including radicular low back pain.

The stigmatization dilemma in public health policy--the case of MRSA in Denmark.

PubMed

Ploug, Thomas; Holm, Søren; Gjerris, Mickey

2015-07-11

Multi-resistant bacteria pose an increasing and significant public health risk. As awareness of the severity of the problem grows, it is likely that it will become the target for a range of public health interventions. Some of these can intentionally or unintentionally lead to stigmatization of groups of citizens. The article describes the phenomenon of stigmatization within the health care area by discussing the concept in relation to AIDS and psychiatric diagnosis. It unfolds the ethical aspects of using stigmatization as a public health instrument to affect unwanted behaviours e.g. smoking. Moreover it discusses stigmatization as an unintended albeit expected side effect of public health instruments potentially used to counter the challenge of multi-resistant bacteria with particular reference to the Danish case of the growing problems with Methicillin-resistant Staphylococcus aureus (MRSA) within pig production. We argue that using stigmatization as a direct means to achieve public health outcomes is almost always ethically illegitimate. Autonomy and dignity considerations count against it, and the cost-benefit analysis that might by some be taken to outweigh these considerations will be fundamentally uncertain. We further argue that interventions where stigmatization is a side-effect need to fulfil requirements of proportionality, and that they may fall prey to 'the stigmatization dilemma', i.e. the dilemma that arises when all policy options are potentially stigmatizing but stigmatize different groups. When this dilemma obtains the decision-maker should choose the intervention that does not lead to permanent stigmatization and that stigmatizes as few as possible, as briefly as possible, and as little as possible.

Condom use within marriage: a neglected HIV intervention.

PubMed Central

Ali, Mohamed M.; Cleland, John; Shah, Iqbal H.

2004-01-01

OBJECTIVE: To assess the contraceptive effectiveness of condoms versus oral contraceptive pills and estimate the reproductive consequences of a major shift from pill to condom use. METHODS: Secondary analysis was performed on nationally representative cross-sectional surveys of women in 16 developing countries. FINDINGS: In the 16 countries, the median per cent of married couples currently using condoms was 2%, compared with 13% for the pill. Condom users reported a higher 12-month failure and higher method-related discontinuation rates than pill users (9% and 44% vs 6% and 30%, respectively). Condom users were more likely to report subsequent abortion following failure (21% vs 14%), and also more likely to switch rapidly to another method (76% vs 58%). The reproductive consequences, in terms of abortion and unwanted births, of a hypothetical reversal of the relative prevalence of condom and pill were estimated to be minor. The main reason for this unexpected result is that the majority of abortions and unwanted births arise from non-use of any contraceptive method. CONCLUSION: A massive shift from the more effective oral contraceptive pills to the less effective condom would not jeopardize policy goals of reducing abortions and unwanted births. However, such a shift would potentially have an added benefit of preventing human immunodeficiency virus (HIV) infections, especially in countries with generalized HIV epidemics. PMID:15112006

Anticonvulsant effects of structurally diverse GABA(B) positive allosteric modulators in the DBA/2J audiogenic seizure test: Comparison to baclofen and utility as a pharmacodynamic screening model.

PubMed

Brown, Jordan W; Moeller, Achim; Schmidt, Martin; Turner, Sean C; Nimmrich, Volker; Ma, Junli; Rueter, Lynne E; van der Kam, Elizabeth; Zhang, Min

2016-02-01

The GABA(B) receptor has been indicated as a promising target for multiple CNS-related disorders. Baclofen, a prototypical orthosteric agonist, is used clinically for the treatment of spastic movement disorders, but is associated with unwanted side-effects, such as sedation and motor impairment. Positive allosteric modulators (PAM), which bind to a topographically-distinct site apart from the orthosteric binding pocket, may provide an improved side-effect profile while maintaining baclofen-like efficacy. GABA, the major inhibitory neurotransmitter in the CNS, plays an important role in the etiology and treatment of seizure disorders. Baclofen is known to produce anticonvulsant effects in the DBA/2J mouse audiogenic seizure test (AGS), suggesting it may be a suitable assay for assessing pharmacodynamic effects. Little is known about the effects of GABA(B) PAMs, however. The studies presented here sought to investigate the AGS test as a pharmacodynamic (PD) screening model for GABA(B) PAMs by comparing the profile of structurally diverse PAMs to baclofen. GS39783, rac-BHFF, CMPPE, A-1295120 (N-(3-(4-(4-chloro-3-fluorobenzyl)-6-methoxy-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide), and A-1474713 (N-(3-(4-(4-chlorobenzyl)-3,5-dioxo-4,5-dihydro-1,2,4-triazin-2(3H)-yl)phenyl)acetamide) all produced robust, dose-dependent anticonvulsant effects; a similar profile was observed with baclofen. Pre-treatment with the GABA(B) antagonist SCH50911 completely blocked the anticonvulsant effects of baclofen and CMPPE in the AGS test, indicating such effects are likely mediated by the GABA(B) receptor. In addition to the standard anticonvulsant endpoint of the AGS test, video tracking software was employed to assess potential drug-induced motor side-effects during the acclimation period of the test. This analysis was sensitive to detecting drug-induced changes in total distance traveled, which was used to establish a therapeutic index (TI = hypoactivity/anticonvulsant effects). Calculated TIs for A-1295120, CMPPE, rac-BHFF, GS39783, and A-1474713 were 5.31x, 5.00x, 4.74x, 3.41x, and 1.83x, respectively, whereas baclofen was <1. The results presented here suggest the DBA/2J mouse AGS test is a potentially useful screening model for detecting PD effects of GABA(B) PAMs and can provide an initial read-out on target-related motor side-effects. Furthermore, an improved TI was observed for PAMs compared to baclofen, indicating the PAM approach may be a viable therapeutic alternative to baclofen. Copyright © 2015 Elsevier Ltd. All rights reserved.

The role of myofibroblasts in wound healing, contraction and its clinical implications in cleft palate repair.

PubMed

Chitturi, Ravi Teja; Balasubramaniam, A Murali; Parameswar, R Arjun; Kesavan, G; Haris, K T Muhamed; Mohideen, Khadijah

2015-03-01

Myofibroblasts after its discovery in 1971 as the principal cell for wound healing has come a long way as far as research is concerned. The primary focus of research has been regarding preventing certain unwanted effects of this cell such as wound contraction and scarring. As far as the oral and maxillofacial region is concerned, the primary concern of this untoward effect is during repair of cleft palate surgically which results impaired development of palate and the dentoalveolar structures. This review focuses on the basic aspects of myofibroblasts such as its origin, formation, function in wound healing, role in wound contraction and ways by which its unwanted effects can be overcome to improve the quality of the post surgical complications of cleft palate surgery.

Alterations in Taxol production in plant cell culture via manipulation of the phenylalanine ammonia lyase pathway.

PubMed

Brincat, Michelle C; Gibson, Donna M; Shuler, Michael L

2002-01-01

One approach to increasing secondary metabolite production in plant cell culture is to manipulate metabolic pathways to utilize more resources toward production of one desired compound or class of compounds, such as diverting carbon flux from competing secondary pathways. Since phenylalanine provides both the phenylisoserine side chain and the benzoyl moiety at C-2 of Taxol, we speculated that blockage of the phenylpropanoid pathway might divert phenylalanine into Taxol biosynthesis. We used specific enzyme inhibitors to target the first enzyme in the phenylpropanoid pathway, phenylalanine ammonia lyase (PAL), the critical control point for conversion of L-phenylalanine to trans-cinnamic acid. Cinnamic acid acted quickly in reducing PAL activity by 40-50%, without affecting total protein levels, but it generally inhibited the taxane pathway, reducing Taxol by 90% of control levels. Of the taxanes produced, 13-acetyl-9-dihydro-baccatin III and 9-dihydrobaccatin III doubled as a percentage of total taxanes in C93AD and CO93P cells treated with 0.20 and 0.25 mM cinnamic acid, when all other taxanes were lowered. The PAL inhibitor alpha-aminooxyacetic acid (AOA) almost entirely shut down Taxol production at both 0.5 and 1.5 mM, whereas L-alpha-aminooxy-beta-phenylpropionic acid (AOPP) had the opposite effect, slightly enhancing Taxol production at 1 microM but having no effect at 10 microM. The discrepancy in the effectiveness of AOA and AOPP and the lack of effect with addition of phenylalanine or benzoic acid derivatives further indicates that the impact of cinnamic acid on Taxol is related not to its effect on PAL but rather to a specific effect on the taxane pathway. On the basis of these results, a less direct route for inhibiting the phenylpropanoid pathway may be required to avoid unwanted side effects and potentially enhance Taxol production.

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 3 2010-10-01 2010-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or inventor to be dedicated to the public...

45 CFR 650.9 - Unwanted inventions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Unwanted inventions. 650.9 Section 650.9 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION PATENTS § 650.9 Unwanted inventions. (a) The Foundation will normally allow any patent rights not wanted by the awardee or inventor to be dedicated to the public...

40 CFR 262.215 - Unwanted material that is not solid or hazardous waste.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Unwanted material that is not solid or... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Alternative... Eligible Academic Entities § 262.215 Unwanted material that is not solid or hazardous waste. (a) If an...

40 CFR 262.215 - Unwanted material that is not solid or hazardous waste.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Unwanted material that is not solid or... (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS APPLICABLE TO GENERATORS OF HAZARDOUS WASTE Alternative... Eligible Academic Entities § 262.215 Unwanted material that is not solid or hazardous waste. (a) If an...

Wood ash application increases pH but does not harm the soil mesofauna.

PubMed

Qin, Jiayi; Hovmand, Mads Frederik; Ekelund, Flemming; Rønn, Regin; Christensen, Søren; Groot, Gerard Arjen de; Mortensen, Louise Hindborg; Skov, Simon; Krogh, Paul Henning

2017-05-01

Application of bioash from biofuel combustion to soil supports nutrient recycling, but may have unwanted and detrimental ecotoxicological side-effects, as the ash is a complex mixture of compounds that could affect soil invertebrates directly or through changes in their food or habitat conditions. To examine this, we performed laboratory toxicity studies of the effects of wood-ash added to an agricultural soil and the organic horizon of a coniferous plantation soil with the detrivore soil collembolans Folsomia candida and Onychiurus yodai, the gamasid predaceous mite Hypoaspis aculeifer, and the enchytraeid worm Enchytraeus crypticus. We used ash concentrations spanning 0-75 g kg -1 soil. As ash increases pH we compared bioash effects with effects of calcium hydroxide, Ca(OH) 2 , the main liming component of ash. Only high ash concentrations above 15 g kg -1 agricultural soil or 17 t ha -1 had significant effects on the collembolans. The wood ash neither affected H. aculeifer nor E. crypticus. The estimated osmolalities of Ca(OH) 2 and the wood ash were similar at the LC 50 concentration level. We conclude that short-term chronic effects of wood ash differ among different soil types, and osmotic stress is the likely cause of effects while high pH and heavy metals is of minor importance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early experience with endoscopic lumbar sympathectomy for plantar hyperhidrosis.

PubMed

Singh, Sanjay; Kaur, Simranjit; Wilson, Paul

2016-05-01

We describe our endoscopic lumbar sympathectomy technique and our early experience using it to treat plantar hyperhidrosis. We reviewed 20 lumbar sympathectomies performed in our vascular unit for plantar hyperhidrosis in 10 patients from 2011 and 2014. Demographics and outcomes were analyzed and a review of the literature conducted. All procedures were carried out endoscopically with no intraoperative or postoperative morbidity. Plantar anhidrosis was achieved in all the patients, although two patients (20%) suffered a relapse. Unwanted side-effects occurred in the form of compensatory sweating in three patients (30%) and post-sympathectomy neuralgia in two patients (20%). None of the patients experienced sexual dysfunction. Management of plantar hyperhidrosis may be based upon a therapeutic ladder starting with conservative measures and working up to surgery depending on the severity of the disease. Minimally invasive (endoscopic) sympathectomy for the thoracic chain is well established, but minimally invasive sympathectomy for the lumbar chain is a relatively new technique. Endoscopic lumbar sympathectomy provides an effective, minimally invasive method of surgical management, but long-term data are lacking. © 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

Antitumor activity of Chlorella sorokiniana and Scenedesmus sp. microalgae native of Nuevo León State, México.

PubMed

Reyna-Martinez, Raul; Gomez-Flores, Ricardo; López-Chuken, Ulrico; Quintanilla-Licea, Ramiro; Caballero-Hernandez, Diana; Rodríguez-Padilla, Cristina; Beltrán-Rocha, Julio Cesar; Tamez-Guerra, Patricia

2018-01-01

Cancer cases result in 13% of all deaths worldwide. Unwanted side effects in patients under conventional treatments have led to the search for beneficial alternative therapies. Microalgae synthesize compounds with known in vitro and in vivo biological activity against different tumor cell lines. Therefore, native microalgae from the State of Nuevo Leon, Mexico may become a potential source of antitumor agents. The aim of the present study was to evaluate the in vitro cytotoxic effect of Nuevo Leon regional Chlorella sorokiniana (Chlorellales: Chlorellaceae) and Scenedesmus sp. (Chlorococcales: Scenedesmaceae). Native microalgae crude organic extracts cytotoxicity against murine L5178Y-R lymphoma cell line and normal lymphocyte proliferation were evaluated using the MTT reduction colorimetric assay. Cell death pathway was analyzed by acridine orange and ethidium bromide staining, DNA degradation in 2% agarose gel electrophoresis and caspases activity. Results indicated significant ( p  < 0.05) 61.89% ± 3.26% and 74.77% ± 1.84% tumor cytotoxicity by C. sorokiniana and Scenedesmus sp. methanol extracts, respectively, at 500 µg/mL, by the mechanism of apoptosis. This study contributes to Mexican microalgae biodiversity knowledge and their potential as antitumor agent sources.

Lasers for the treatment of psoriasis

NASA Astrophysics Data System (ADS)

Piruzian, A.; Korsunskaya, I.; Goldenkova, I.; Hertsen, A.; Sarkisova, M.; Egorenkova, L.

2005-08-01

Psoriasis is a chronic, genetically-determined disease, characterized by an immuno-mediated pathogenesis. Treatment of psoriasis is often complicated and remains a challenge. Along with the many new immunomodulatory approaches, various laser systems have been employed for chronic plaque psoriasis treatment. Recently, it has been demonstrated that the light produced by xenon-chloride excimers (generated by sophisticated devices with peak emission of 308 nm) is effective in the treatment of several psoriasis forms. We treated patients, ranging in age from 35 to 55 years, affected by plaque-type psoriasis vulgaris with monochromatic excimer light (MEL). We used MEL in a complex with basic treatment. Therapy was administered three times a week. At the end of the 3th week of treatment all patients showed an improvement, as evidenced by flattening of plaques, decreased scaling and erythema, and decreased vesicle and pustule formation. Unwanted side effects such as pain, blistering was not observed. Minimal erythema and a hyperpigmentation were noted in some patients. It was concluded that the MEL therapy may be a valuable option for treatment of plaque-type psoriasis vulgaris in shorter time compare with traditional NB UVB, with exposure to lower cumulative doses

Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22.

PubMed

Krause-Heuer, Anwen M; Fraser-Spears, Rheaclare; Dobrowolski, Jeremy C; Ashford, Mark E; Wyatt, Naomi A; Roberts, Maxine P; Gould, Georgianna G; Cheah, Wai-Ching; Ng, Clarissa K L; Bhadbhade, Mohan; Zhang, Bo; Greguric, Ivan; Wheate, Nial J; Kumar, Naresh; Koek, Wouter; Callaghan, Paul D; Daws, Lynette C; Fraser, Benjamin H

2017-09-08

Herein we describe the synthesis and evaluation of antidepressant properties of seven analogues (1-7) of the low affinity/high capacity transporter blocker decynium-22 (D-22). All analogues (1-7) were synthesized via base promoted coupling reactions between N-alkylated-2-methylquinolinium iodides or N-alkylated-4-methylquinolinium iodides and electrophilic N-alkylated-2-iodoquinolinium iodides. All final compounds were purified by re-crystallization or preparative HPLC and initial evaluation studies included; 1) screening for in vitro α1-adrenoceptor activity (a property that can lead to unwanted side-effects), 2) measuring antidepressant-like activity in a mouse tail suspension test (TST), and 3) measuring effects upon mouse locomotion. The results showed some analogues have lower affinities at α1-adrenoceptors compared to D-22 and showed antidepressant-like activity without the need for co-administration of SSRIs. Additionally, many analogues did not affect mouse locomotion to the same extent as D-22. Plans for additional evaluations of these promising analogues, including measurement of antidepressant-like activity with co-administration of selective serotonin re-uptake inhibitors (SSRIs), are outlined. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Antitumor activity of Chlorella sorokiniana and Scenedesmus sp. microalgae native of Nuevo León State, México

PubMed Central

Beltrán-Rocha, Julio Cesar

2018-01-01

Cancer cases result in 13% of all deaths worldwide. Unwanted side effects in patients under conventional treatments have led to the search for beneficial alternative therapies. Microalgae synthesize compounds with known in vitro and in vivo biological activity against different tumor cell lines. Therefore, native microalgae from the State of Nuevo Leon, Mexico may become a potential source of antitumor agents. The aim of the present study was to evaluate the in vitro cytotoxic effect of Nuevo Leon regional Chlorella sorokiniana (Chlorellales: Chlorellaceae) and Scenedesmus sp. (Chlorococcales: Scenedesmaceae). Native microalgae crude organic extracts cytotoxicity against murine L5178Y-R lymphoma cell line and normal lymphocyte proliferation were evaluated using the MTT reduction colorimetric assay. Cell death pathway was analyzed by acridine orange and ethidium bromide staining, DNA degradation in 2% agarose gel electrophoresis and caspases activity. Results indicated significant (p < 0.05) 61.89% ± 3.26% and 74.77% ± 1.84% tumor cytotoxicity by C. sorokiniana and Scenedesmus sp. methanol extracts, respectively, at 500 µg/mL, by the mechanism of apoptosis. This study contributes to Mexican microalgae biodiversity knowledge and their potential as antitumor agent sources. PMID:29441241

Prediction of unwanted pregnancies using logistic regression, probit regression and discriminant analysis

PubMed Central

Ebrahimzadeh, Farzad; Hajizadeh, Ebrahim; Vahabi, Nasim; Almasian, Mohammad; Bakhteyar, Katayoon

2015-01-01

Background: Unwanted pregnancy not intended by at least one of the parents has undesirable consequences for the family and the society. In the present study, three classification models were used and compared to predict unwanted pregnancies in an urban population. Methods: In this cross-sectional study, 887 pregnant mothers referring to health centers in Khorramabad, Iran, in 2012 were selected by the stratified and cluster sampling; relevant variables were measured and for prediction of unwanted pregnancy, logistic regression, discriminant analysis, and probit regression models and SPSS software version 21 were used. To compare these models, indicators such as sensitivity, specificity, the area under the ROC curve, and the percentage of correct predictions were used. Results: The prevalence of unwanted pregnancies was 25.3%. The logistic and probit regression models indicated that parity and pregnancy spacing, contraceptive methods, household income and number of living male children were related to unwanted pregnancy. The performance of the models based on the area under the ROC curve was 0.735, 0.733, and 0.680 for logistic regression, probit regression, and linear discriminant analysis, respectively. Conclusion: Given the relatively high prevalence of unwanted pregnancies in Khorramabad, it seems necessary to revise family planning programs. Despite the similar accuracy of the models, if the researcher is interested in the interpretability of the results, the use of the logistic regression model is recommended. PMID:26793655

Prediction of unwanted pregnancies using logistic regression, probit regression and discriminant analysis.

PubMed

Ebrahimzadeh, Farzad; Hajizadeh, Ebrahim; Vahabi, Nasim; Almasian, Mohammad; Bakhteyar, Katayoon

2015-01-01

Unwanted pregnancy not intended by at least one of the parents has undesirable consequences for the family and the society. In the present study, three classification models were used and compared to predict unwanted pregnancies in an urban population. In this cross-sectional study, 887 pregnant mothers referring to health centers in Khorramabad, Iran, in 2012 were selected by the stratified and cluster sampling; relevant variables were measured and for prediction of unwanted pregnancy, logistic regression, discriminant analysis, and probit regression models and SPSS software version 21 were used. To compare these models, indicators such as sensitivity, specificity, the area under the ROC curve, and the percentage of correct predictions were used. The prevalence of unwanted pregnancies was 25.3%. The logistic and probit regression models indicated that parity and pregnancy spacing, contraceptive methods, household income and number of living male children were related to unwanted pregnancy. The performance of the models based on the area under the ROC curve was 0.735, 0.733, and 0.680 for logistic regression, probit regression, and linear discriminant analysis, respectively. Given the relatively high prevalence of unwanted pregnancies in Khorramabad, it seems necessary to revise family planning programs. Despite the similar accuracy of the models, if the researcher is interested in the interpretability of the results, the use of the logistic regression model is recommended.

Linking two opposites of pregnancy loss: Induced abortion and infertility in Yoruba society, Nigeria.

PubMed

Koster, Winny

2010-11-01

Involuntary infertility and induced abortion exist on opposite sides of the spectrum: the first being the unwanted loss of childbearing potential while the second is the intentional termination of pregnancy. However, this paper proposes that these two poles of pregnancy loss are in fact related in Yoruba society, Nigeria. This argument is supported by qualitative and quantitative data drawn from an applied research project in communities and health institutions of Lagos State, from 1996 to 1999, where a total of 693 women recounted 1114 personal abortion experiences, and 233 women shared their experiences of fertility problems. Study statistics show that 37% of secondary infertility was most probably the result of induced abortion and that half of women with abortion complications interviewed in a referral hospital will have fertility problems. This paper provides insight into the reasons why single and married women decide to abort, and use unsafe methods, despite awareness of the serious health risks, including infertility. This is paradoxical given that fear of infertility is a major reason why women do not use modern contraceptives when trying to prevent unwanted pregnancy. By analysing the relations between infertility and abortion within the socio-cultural, economic, and services-related structures that influence women's decisions, this paper suggests ways of addressing the problems related to both types of pregnancy loss. Copyright © 2010 Elsevier Ltd. All rights reserved.

Effect of feeders in 3D modeling of low impedance multilayer CPW transmission line

NASA Astrophysics Data System (ADS)

Zaini, R. I.; Kyabaggu, P. B. K.; Sinulingga, E. P.

2018-02-01

Improved characteristics with low dissipation loss MMICs are highly desirable for wireless communications. However, the current industrial MMIC design is mainly based on microstrip concept which suffered from parasitic and unwanted phenomenon especially at higher frequency (>20 GHz). On the other hand, for future wireless technology, higher frequency operation is required and on-wafer microwave characterizations as well as precise modeling of 3D Multilayer CPW components are vital. This project concerns with understanding of the microwave characteristics behavior of Multilayer CPW components in MMIC applications. Feeder effect as unwanted parts in the characteristics has been investigated to determine its relation with the half wavelength resonance of the Multilayer CPW Low Impedance Transmission Line.

Cyber-Defense: A Taxonomy of Tactics for Managing Cyberstalking.

PubMed

Tokunaga, Robert S; Aune, Krystyna S

2015-06-16

Cyberstalking research has revealed information about who is perpetrating what offense to whom. This study adds to research on cyberstalking by exploring how victims respond to the unwanted pursuit. The reflections of cyberstalking victims were content analyzed to answer research questions about different risk management behaviors, their effectiveness, and their relationship with specific cyberstalking behaviors. Findings indicated that victims used seven general management tactics of which ignore/avoidance, active technological disassociation, and help seeking were the most common. Using technology to move away from pursuers was reported as the most effective tactic for managing the unwanted relational pursuit. The results also suggested that victims' management responses were associated with the type of behaviors experienced. © The Author(s) 2015.

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Labeling and management standards for containers of unwanted material in the laboratory. 262.206 Section 262.206 Protection of Environment... the laboratory to assure safe storage of the unwanted material, to prevent leaks, spills, emissions to...

Sex Differences in the Experience of Unwanted Sexual Attention and Behaviors during Childhood

ERIC Educational Resources Information Center

Whealin, Julia M.; Zinzow, Heidi M.; Salstrom, Seoka A.; Jackson, Joan L.

2007-01-01

Girls receive considerable amounts of unwanted sexual attention (UWSA) and behaviors (UWSB). Less is known about boys' unwanted sexual experiences. The primary goal of this study was to obtain a descriptive profile of the types and perpetrators of childhood UWSA/B. Secondary goals were to examine sex differences in emotional reactions to UWSA/B…

Antiallergic effect of ZCR-2060: antihistaminic action.

PubMed

Abe, T; Omata, T; Yoshida, K; Matsumura, T; Ikeda, Y; Segawa, Y; Matsuda, K; Nagai, H

1994-09-01

The antihistaminic effect of 2-[2-[4-(diphenylmethyl)-1-piperadinyl]ethoxy] benzoic acid maleate (ZCR-2060), a newly synthesized antiallergic agent, was investigated in both in vitro and in vivo studies. ZCR-2060 clearly antagonized histamine-induced contraction of isolated guinea pig ileum and trachea. In contrast, carbachol-, BaCl2- and 5-hydroxytryptamine-induced contractions of isolated guinea pig ileum were slightly inhibited by higher concentrations of ZCR-2060. 3H-Mepyramine specific binding to membranes from guinea pig lung and brain were markedly inhibited by ZCR-2060 in a concentration-dependent fashion. In the in vitro studies, the antihistaminic effect of ZCR-2060 was greater than those of cetirizine and terfenadine, but was less than that of ketotifen. In the in vivo studies, ZCR-2060 significantly inhibited the histamine-induced cutaneous reaction in rats, when administered orally 1 hr before the histamine injection. Moreover, ZCR-2060 has a long-lasting antihistaminic effect. In the in vivo studies, the antihistaminic effect of ZCR-2060 was found to be greater than that of cetirizine and terfenadine, and it was the same as that of ketotifen. Thiopental-induced sleep and spontaneous ambulatory activity in mice, however, were unaffected by ZCR-2060 at higher doses. These results indicate that ZCR-2060 has a potent, selective and long acting histamine H1-receptor antagonistic action without causing any unwanted CNS side effect.

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats.

PubMed

Nabeel, Mannalamkunnath Alikunhi; Kathiresan, Kandasamy; Manivannan, Subramanian

2010-06-01

Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long-term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan-induced diabetic rats. The effects of these extracts were compared with the effect of 30-days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Removing inter-subject technical variability in magnetic resonance imaging studies.

PubMed

Fortin, Jean-Philippe; Sweeney, Elizabeth M; Muschelli, John; Crainiceanu, Ciprian M; Shinohara, Russell T

2016-05-15

Magnetic resonance imaging (MRI) intensities are acquired in arbitrary units, making scans non-comparable across sites and between subjects. Intensity normalization is a first step for the improvement of comparability of the images across subjects. However, we show that unwanted inter-scan variability associated with imaging site, scanner effect, and other technical artifacts is still present after standard intensity normalization in large multi-site neuroimaging studies. We propose RAVEL (Removal of Artificial Voxel Effect by Linear regression), a tool to remove residual technical variability after intensity normalization. As proposed by SVA and RUV [Leek and Storey, 2007, 2008, Gagnon-Bartsch and Speed, 2012], two batch effect correction tools largely used in genomics, we decompose the voxel intensities of images registered to a template into a biological component and an unwanted variation component. The unwanted variation component is estimated from a control region obtained from the cerebrospinal fluid (CSF), where intensities are known to be unassociated with disease status and other clinical covariates. We perform a singular value decomposition (SVD) of the control voxels to estimate factors of unwanted variation. We then estimate the unwanted factors using linear regression for every voxel of the brain and take the residuals as the RAVEL-corrected intensities. We assess the performance of RAVEL using T1-weighted (T1-w) images from more than 900 subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI), as well as healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We compare RAVEL to two intensity-normalization-only methods: histogram matching and White Stripe. We show that RAVEL performs best at improving the replicability of the brain regions that are empirically found to be most associated with AD, and that these regions are significantly more present in structures impacted by AD (hippocampus, amygdala, parahippocampal gyrus, enthorinal area, and fornix stria terminals). In addition, we show that the RAVEL-corrected intensities have the best performance in distinguishing between MCI subjects and healthy subjects using the mean hippocampal intensity (AUC=67%), a marked improvement compared to results from intensity normalization alone (AUC=63% and 59% for histogram matching and White Stripe, respectively). RAVEL is promising for many other imaging modalities. Published by Elsevier Inc.

Planning to break unwanted habits: habit strength moderates implementation intention effects on behaviour change.

PubMed

Webb, Thomas L; Sheeran, Paschal; Luszczynska, Aleksandra

2009-09-01

Implementation intention formation promotes effective goal striving and goal attainment. However, little research has investigated whether implementation intentions promote behaviour change when people possess strong antagonistic habits. Experiment 1 developed relatively habitual responses that, after a task switch, had a detrimental impact on task performance. Forming an if-then plan reduced the negative impact of habit on performance. However, the effect of forming implementation intentions was smaller among participants who possessed strong habits as compared to participants who had weaker habits. Experiment 2 provided a field test of the role of habit strength in moderating the relationship between implementation intentions and behaviour in the context of smoking. Implementation intentions reduced smoking among participants with weak or moderate smoking habits, but not among participants with strong smoking habits. In summary, habit strength moderates the effectiveness of if-then plan formation in breaking unwanted habits.

Covalent Surface Modification of Silicon Oxides with Alcohols in Polar Aprotic Solvents.

PubMed

Lee, Austin W H; Gates, Byron D

2017-09-05

Alcohol-based monolayers were successfully formed on the surfaces of silicon oxides through reactions performed in polar aprotic solvents. Monolayers prepared from alcohol-based reagents have been previously introduced as an alternative approach to covalently modify the surfaces of silicon oxides. These reagents are readily available, widely distributed, and are minimally susceptible to side reactions with ambient moisture. A limitation of using alcohol-based compounds is that previous reactions required relatively high temperatures in neat solutions, which can degrade some alcohol compounds or could lead to other unwanted side reactions during the formation of the monolayers. To overcome these challenges, we investigate the condensation reaction of alcohols on silicon oxides carried out in polar aprotic solvents. In particular, propylene carbonate has been identified as a polar aprotic solvent that is relatively nontoxic, readily accessible, and can facilitate the formation of alcohol-based monolayers. We have successfully demonstrated this approach for tuning the surface chemistry of silicon oxide surfaces with a variety of alcohol containing compounds. The strategy introduced in this research can be utilized to create silicon oxide surfaces with hydrophobic, oleophobic, or charged functionalities.

Preventing unsafe abortion and limiting its consequences: what can be done?

PubMed

Misago, C

1994-12-01

The continued illegality of induced abortion in Latin America has led to substantial, preventable maternal mortality and morbidity. The first strategy for preventing unsafe clandestine abortion is to reduce the incidence of unwanted pregnancy through measures such as improved access to effective contraception, post-abortion family planning counseling, health education campaigns aimed at promoting condom use among young people, involvement of men in family planning decision making, biomedical research on safer and more effective male and female contraceptive methods, and empowering women to demand the use of condoms or avoid unwanted intercourse. The second strategy is to reduce abortion-related mortality and morbidity through more effective clinical management of incomplete illegal abortions, introduction of menstrual regulation services, formation of women's solidarity groups aimed at discouraging the practice of self-induced abortion, and, ultimately, abortion legalization.

Less is sometimes more: a comparison of distance-control and navigated-control concepts of image-guided navigation support for surgeons.

PubMed

Luz, Maria; Manzey, Dietrich; Modemann, Susanne; Strauss, Gero

2015-01-01

Image-guided navigation (IGN) systems provide automation support of intra-operative information analysis and decision-making for surgeons. Previous research showed that navigated-control (NC) systems which represent high levels of decision-support and directly intervene in surgeons' workflow provide benefits with respect to patient safety and surgeons' physiological stress but also involve several cost effects (e.g. prolonged surgery duration, reduced secondary-task performance). It was hypothesised that less automated distance-control (DC) systems would provide a better solution in terms of human performance consequences. N = 18 surgeons performed a simulated mastoidectomy with NC, DC and without IGN assistance. Effects on surgical performance, physiological effort, workload and situation awareness (SA) were compared. As expected, DC technology had the same benefits as the NC system but also led to less unwanted side effects on surgery duration, subjective workload and SA. This suggests that IGN systems just providing information analysis support are overall more beneficial than higher automated decision-support. This study investigates human performance consequences of different concepts of IGN support for surgeons. Less automated DC systems turned out to provide advantages for patient safety and surgeons' stress similar to higher automated NC systems with, at the same time, reduced negative consequences on surgery time and subjective workload.

The effect of aeration on the removal of wastewater-derived pharmaceutical residues from groundwater - a laboratory study.

PubMed

Burke, Victoria; Duennbier, Uwe; Massmann, Gudrun

2013-01-01

Several studies on waste- or drinking water treatment processes as well as on groundwater have recently shown that some pharmaceutical residues (PRs) are redox-sensitive. Hence, their (bio)degradation depends on the redox conditions prevalent in the aquifer. Groundwater, providing raw water for drinking water production, is often anoxic and aeration is a widespread treatment method applied mainly to eliminate unwanted iron and manganese from the water. As a side-effect, aeration may trigger the elimination of PRs. Within the present study the influence of aeration on the fate of a number of wastewater derived analgesics and their residues as well as several antimicrobial compounds was investigated. For this purpose, anoxic groundwater was transferred into stainless steel tanks, some of which were aerated while others were continuously kept anoxic. Results prove that the degradation of six phenazone type compounds is dependent on oxygen availability and compounds are efficiently removed under oxic conditions only. Concerning the antimicrobials, doxycycline and trimethoprim were better removed during aeration, whereas a slightly improved removal under anoxic conditions was observed for clindamycin, roxithromycin and clarithromycin. The study provides first laboratory proof of the redox-sensitivity of several organic trace pollutants. In addition, results demonstrate that aeration is an effective treatment for the elimination of a number of wastewater derived PRs.

Effect of Activated Carbon Amendment on Bacterial Community Structure and Functions in a PAH Impacted Urban Soil

PubMed Central

2012-01-01

We collected urban soil samples impacted by polycyclic aromatic hydrocarbons (PAHs) from a sorbent-based remediation field trial to address concerns about unwanted side-effects of 2% powdered (PAC) or granular (GAC) activated carbon amendment on soil microbiology and pollutant biodegradation. After three years, total microbial cell counts and respiration rates were highest in the GAC amended soil. The predominant bacterial community structure derived from denaturing gradient gel electrophoresis (DGGE) shifted more strongly with time than in response to AC amendment. DGGE band sequencing revealed the presence of taxa with closest affiliations either to known PAH degraders, e.g. Rhodococcus jostii RHA-1, or taxa known to harbor PAH degraders, e.g. Rhodococcus erythropolis, in all soils. Quantification by real-time polymerase chain reaction yielded similar dioxygenases gene copy numbers in unamended, PAC-, or GAC-amended soil. PAH availability assessments in batch tests showed the greatest difference of 75% with and without biocide addition for unamended soil, while the lowest PAH availability overall was measured in PAC-amended, live soil. We conclude that AC had no detrimental effects on soil microbiology, AC-amended soils retained the potential to biodegrade PAHs, but the removal of available pollutants by biodegradation was most notable in unamended soil. PMID:22455603

Effect of activated carbon amendment on bacterial community structure and functions in a PAH impacted urban soil.

PubMed

Meynet, Paola; Hale, Sarah E; Davenport, Russell J; Cornelissen, Gerard; Breedveld, Gijs D; Werner, David

2012-05-01

We collected urban soil samples impacted by polycyclic aromatic hydrocarbons (PAHs) from a sorbent-based remediation field trial to address concerns about unwanted side-effects of 2% powdered (PAC) or granular (GAC) activated carbon amendment on soil microbiology and pollutant biodegradation. After three years, total microbial cell counts and respiration rates were highest in the GAC amended soil. The predominant bacterial community structure derived from denaturing gradient gel electrophoresis (DGGE) shifted more strongly with time than in response to AC amendment. DGGE band sequencing revealed the presence of taxa with closest affiliations either to known PAH degraders, e.g. Rhodococcus jostii RHA-1, or taxa known to harbor PAH degraders, e.g. Rhodococcus erythropolis, in all soils. Quantification by real-time polymerase chain reaction yielded similar dioxygenases gene copy numbers in unamended, PAC-, or GAC-amended soil. PAH availability assessments in batch tests showed the greatest difference of 75% with and without biocide addition for unamended soil, while the lowest PAH availability overall was measured in PAC-amended, live soil. We conclude that AC had no detrimental effects on soil microbiology, AC-amended soils retained the potential to biodegrade PAHs, but the removal of available pollutants by biodegradation was most notable in unamended soil. © 2012 American Chemical Society

Wanted and unwanted fertility in Bolivia: does ethnicity matter?

PubMed

McNamee, Catherine B

2009-12-01

In Bolivia, the total fertility rate (TFR) among indigenous populations is higher than that among the nonindigenous population. It is important to investigate whether this difference is attributable to ethnic differences in wanted or unwanted fertility. Data from the 2003 Bolivian Demographic and Health Survey were used to estimate women's wanted and unwanted TFRs. Logistic regression analyses were conducted to examine whether women's, men's and couples' characteristics were associated with use of any contraceptive method and modern methods. The TFRs for indigenous and nonindigenous women were 1.5 and 1.7, [corrected] respectively. The wanted fertility rate for indigenous women was nearly the same as that for nonindigenous women (2.8 and 1.4, [corrected] respectively); virtually all of the ethnic difference in the TFRs was attributable to the ethnic difference in unwanted fertility. The proportion of women in need of contraception was greater among indigenous women than among nonindigenous women (26% vs. 19%). In logistic regression analyses, male fertility preferences explained only a small part of the ethnic difference in contraceptive use. Women's, men's and couples' preferences contribute only marginally to unwanted fertility, suggesting that structural factors act as obstacles to preventing unwanted fertility.

Unwanted sexual experiences and cognitive appraisals that evoke mental contamination.

PubMed

Ishikawa, Ryotaro; Kobori, Osamu; Shimizu, Eiji

2015-01-01

Mental contamination is a psychological sense of contamination that involves an internal, emotional feeling of dirtiness that may be evoked by unwanted thoughts and images, such as sexual assaults. This study aimed to investigate which types of unwanted sexual experiences evoke the strongest mental contamination, and to test the hypothesis that cognitive appraisals of an unwanted sexual experience predict indices of mental contamination (i.e. feeling of dirtiness, urge to wash, internal negative emotions, and external negative emotions). 148 female participants were asked to recall their most distressing unwanted sexual experiences. Indices of mental contamination and cognitive appraisals of the experience were then assessed. Our findings indicated that individuals recalling experiences related to rape felt more intense feelings of dirtiness than individuals recalling other types of unwanted sexual experience, such as verbal sexual assault, visual sexual assault, and forcible touching/frottage. In addition, hierarchical regression analyses demonstrated that a cognitive appraisal of perceived violation predicted all of the indices of mental contamination after controlling anxiety, depression, and fear of contact contamination. The present study demonstrated that an individual is at greatest risk of mental contamination if she has experienced rape/attempted rape, and if she makes a cognitive appraisal of violation regarding the incident.

An overview of unwanted female hair.

PubMed

Blume-Peytavi, U

2011-12-01

Unwanted facial hair (UFH) is an important but often overlooked issue, with over 40% of women experiencing some degree of UFH. In the female population a wide spectrum of unwanted hair concerns is represented - from biologically normal but undesirable to excessive unwanted hair with an underlying pathology. While women may seek to manage unwanted hair across their bodies, UFH is a particular concern, due to its negative impact on perceived femininity. There may not always be a direct correlation between degree of severity diagnosed objectively by the physician and level of concern and impact upon the patient. This review discusses the spectrum of facial hair experience and outlines the clinical approach to unwanted hair management including UFH. It highlights the importance of a treatment regimen which should respond to the causation factors and needs of the individual. This will lead to a holistic treatment approach including evaluation of the implementation of emotional coping strategies and on-going support, lifestyle modifications, pharmacological interventions (to address underlying pathologies) and the use of cosmetic hair removal methods as either a stand-alone or adjunct treatment as appropriate to the individual. © 2011 The Author. BJD © 2011 British Association of Dermatologists.

Polycation-induced Cell Membrane Permeability Does Not Enhance Cellular Uptake or Expression Efficiency of Delivered DNA

PubMed Central

Prevette, Lisa E.; Mullen, Douglas G.; Banaszak Holl, Mark M.

2010-01-01

Polycationic materials commonly used to delivery DNA to cells are known to induce cell membrane porosity in a charge-density dependent manner. It has been suggested that these pores may provide a mode of entry of the polymer-DNA complexes (polyplexes) into cells. To examine the correlation between membrane permeability and biological activity, we used two-color flow cytometry on two mammalian cell lines to simultaneously measure gene expression of a plasmid DNA delivered with four common nonviral vectors and cellular uptake of normally excluded fluorescent dye molecules of two different sizes, 668 Da and 2 MDa. We also followed gene expression in cells sorted based on the retention of endogenous fluorescein. We have found that cell membrane porosity caused by polycationic vectors does not enhance internalization or gene expression. Based on this single-cell study, membrane permeability is found to be an unwanted side effect that limits transfection efficiency, possibly through leakage of the delivered nucleic acid through the pores prior to transcription and translation and/or activation of cell defense mechanisms that restrict transgene expression. PMID:20349965

Paradigm Shift in the Pharmacological Management of Periodontal Diseases

PubMed Central

Hasturk, Hatice; Kantarci, Alpdogan; Van Dyke, Thomas E.

2015-01-01

It is becoming clear that variations in inflammatory response are a major determinant in susceptibility to periodontitis. However, our understanding of the relationship of the causal agents in periodontitis to the pathogenesis is not as clear as we once thought, and thus therapies based on etiopathogenesis are similarly in question. We are entering a new era of therapeutic discovery that may have a major impact on our management of the periodontal diseases. Fundamentally, periodontitis is an irreversible condition and once both soft and hard tissues are lost, the healthy periodontal architecture cannot be completely or predictably rebuilt. The discovery of new families of lipid mediators of resolution of inflammation (the lipoxins) and eicosapentaenoic-acid-and docosahexaenoic-acid-derived chemical mediators (the resolvins and protectins) opens new avenues to designing resolution-targeted therapies to control the unwanted side effects of excessive inflammation. The novel protective and therapeutic actions of pro-resolution lipid mediators following microbial challenge are mediated by regulation of the local and systemic inflammatory response that has a direct impact on the organization of the biofilm (plaque) and suggests a new paradigm in clinical periodontal therapeutics. PMID:22142963

A new procedure for extraction of collagen from modern and archaeological bones for 14C dating.

PubMed

Maspero, F; Sala, S; Fedi, M E; Martini, M; Papagni, A

2011-10-01

Bones are potentially the best age indicators in a stratigraphic study, because they are closely related to the layer in which they are found. Collagen is the most suitable fraction and is the material normally used in radiocarbon dating. Bone contaminants can strongly alter the carbon isotopic fraction values of the samples, so chemical pretreatment for (14)C dating by accelerator mass spectrometry (AMS) is essential. The most widespread method for collagen extraction is based on the Longin procedure, which consists in HCl demineralization to dissolve the inorganic phase of the samples, followed by dissolution of collagen in a weak acid solution. In this work the possible side effects of this procedure on a modern bone are presented; the extracted collagen was analyzed by ATR-IR spectroscopy. An alternative procedure, based on use of HF instead of HCl, to minimize unwanted degradation of the organic fraction, is also given. A study by ATR-IR spectroscopic analysis of collagen collected after different demineralization times and with different acid volumes, and a study of an archaeological sample, are also presented.

Pt based PEMFC catalysts prepared from colloidal particle suspensions--a toolbox for model studies.

PubMed

Speder, Jozsef; Altmann, Lena; Roefzaad, Melanie; Bäumer, Marcus; Kirkensgaard, Jacob J K; Mortensen, Kell; Arenz, Matthias

2013-03-14

A colloidal synthesis approach is presented that allows systematic studies of the properties of supported proton exchange membrane fuel cell (PEMFC) catalysts. The applied synthesis route is based on the preparation of monodisperse nanoparticles in the absence of strong binding organic stabilizing agents. No temperature post-treatment of the catalyst is required rendering the synthesis route ideally suitable for comparative studies. We report work concerning a series of catalysts based on the same colloidal Pt nanoparticle (NP) suspension, but with different high surface area (HSA) carbon supports. It is shown that for the prepared catalysts the carbon support has no catalytic co-function, but carbon pre-treatment leads to enhanced sticking of the Pt NPs on the support. An unwanted side effect, however, is NP agglomeration during synthesis. By contrast, enhanced NP sticking without agglomeration can be accomplished by the addition of an ionomer to the NP suspension. The catalytic activity of the prepared catalysts for the oxygen reduction reaction is comparable to industrial catalysts and no influence of the particle size is found in the range of 2-5 nm.

The Built Environment and Child Health: An Overview of Current Evidence.

PubMed

Gascon, Mireia; Vrijheid, Martine; Nieuwenhuijsen, Mark J

2016-09-01

Urbanization and the shaping of the built environment have provided a number of socioeconomic benefits, but they have also brought unwanted side effects on health. We aimed to review the current epidemiological evidence of the associations between the built environment, closely related exposures, and child health. We focused on growth and obesity, neuropsychological development, and respiratory and immune health. We used existing review articles and supplemented these with relevant work published and not included in existing reviews. The present review shows that there is good evidence for an association between air pollution and fetal growth restriction and respiratory health, whereas for other exposure and outcome combinations, further evidence is needed. Future studies should make efforts to integrate the different built environment features and to include the evaluation of environments other than home, as well as accessibility, qualitative and perception assessment of the built environment, and, if possible, with improved and standardized tools to facilitate comparability between studies. Efforts are also needed to conduct longitudinal and intervention studies and to understand potential mechanisms behind the associations observed. Finally, studies in low- and middle-income countries are needed.

Sperm-Hybrid Micromotor for Targeted Drug Delivery.

PubMed

Xu, Haifeng; Medina-Sánchez, Mariana; Magdanz, Veronika; Schwarz, Lukas; Hebenstreit, Franziska; Schmidt, Oliver G

2018-01-23

A sperm-driven micromotor is presented as a targeted drug delivery system, which is appealing to potentially treat diseases in the female reproductive tract. This system is demonstrated to be an efficient drug delivery vehicle by first loading a motile sperm cell with an anticancer drug (doxorubicin hydrochloride), guiding it magnetically, to an in vitro cultured tumor spheroid, and finally freeing the sperm cell to deliver the drug locally. The sperm release mechanism is designed to liberate the sperm when the biohybrid micromotor hits the tumor walls, allowing it to swim into the tumor and deliver the drug through the sperm-cancer cell membrane fusion. In our experiments, the sperm cells exhibited a high drug encapsulation capability and drug carrying stability, conveniently minimizing  toxic side effects and unwanted drug accumulation in healthy tissues. Overall, sperm cells are excellent candidates to operate in physiological environments, as they neither express pathogenic proteins nor proliferate to form undesirable colonies, unlike other cells or microorganisms. This sperm-hybrid micromotor is a biocompatible platform with potential application in gynecological healthcare, treating or detecting cancer or other diseases in the female reproductive system.

Suitability of the hydrocarbon-hydroxylating molybdenum-enzyme ethylbenzene dehydrogenase for industrial chiral alcohol production.

PubMed

Tataruch, M; Heider, J; Bryjak, J; Nowak, P; Knack, D; Czerniak, A; Liesiene, J; Szaleniec, M

2014-12-20

The molybdenum/iron-sulfur/heme protein ethylbenzene dehydrogenase (EbDH) was successfully applied to catalyze enantiospecific hydroxylation of alkylaromatic and alkylheterocyclic compounds. The optimization of the synthetic procedure involves use of the enzyme in a crude purification state that saves significant preparation effort and is more stable than purified EbDH without exhibiting unwanted side reactions. Moreover, immobilization of the enzyme on a crystalline cellulose support and changes in reaction conditions were introduced in order to increase the amounts of product formed (anaerobic atmosphere, electrochemical electron acceptor recycling or utilization of ferricyanide as alternative electron acceptor in high concentrations). We report here on an extension of effective enzyme activity from 4h to more than 10 days and final product yields of up to 0.4-0.5g/l, which represent a decent starting point for further optimization. Therefore, we expect that the hydrocarbon-hydroxylation capabilities of EbDH may be developed into a new process of industrial production of chiral alcohols. Copyright © 2014 Elsevier B.V. All rights reserved.

Structure and Thermodynamical Properties of Zirconium Hydrides from First-Principle

NASA Astrophysics Data System (ADS)

Blomqvist, Jakob; Olofsson, Johan; Alvarez, Anna-Maria; Bjerkén, Christina

Zirconium alloys are used as nuclear fuel cladding material due to their mechanical and corrosion resistant properties together with their favorable cross-section for neutron scattering. At running conditions, however, there will be an increase of hydrogen in the vicinity of the cladding surface at the water side of the fuel. The hydrogen will diffuse into the cladding material and at certain conditions, such as lower temperatures and external load, hydrides will precipitate out in the material and cause well known embrittlement, blistering and other unwanted effects. Using phase-field methods it is now possible to model precipitation buildup in metals, for example as a function of hydrogen concentration, temperature and external load, but the technique relies on input of parameters, such as the formation energy of the hydrides and matrix. To that end, we have computed, using the density functional theory (DFT) code GPAW, the latent heat of fusion as well as solved the crystal structure for three zirconium hydride polymorphs: δ-ZrH1.6, γ-ZrH, and Є-ZrH2.

Emergency contraceptive use in Addis Ababa, Ethiopia: Challenging common assumptions about young people's contraceptive practices.

PubMed

Both, Rosalijn

2015-05-01

Drawing on an ethnographic case study of young people's (aged 18-29) use of emergency contraceptives (ECs) in Addis Ababa, Ethiopia, this article highlights areas of disconnect between how reproductive health experts envision EC use and local meanings ascribed to ECs by young people. ECs - designed by reproductive health experts to be used only in case of emergency - were preferred by study participants over other contraceptive methods because of their ease of use, discreetness, perceived minimal side effects on beauty and future fertility, and usefulness in navigating reproductive intentions. The findings point to features that young people find desirable when it comes to contraceptive methods and suggest that common assumptions of reproductive health experts about young people's contraceptive practices need to be reconsidered, namely: 1) that young people can plan for prevention of unwanted pregnancy by buying a contraceptive method in advance; 2) that existing contraceptive technologies are appropriate for young people; 3) that young people prefer to use modern contraceptive methods; and 4) that young people in premarital relationships aim to prevent unplanned pregnancy. Copyright © 2015. Published by Elsevier Ltd.

Layered Double Hydroxide Nanotransporter for Molecule Delivery to Intact Plant Cells

PubMed Central

Bao, Wenlong; Wang, Junya; Wang, Qiang; O’Hare, Dermot; Wan, Yinglang

2016-01-01

Here we report a powerful method that facilitates the transport of biologically active materials across the cell wall barrier in plant cells. Positively charged delaminated layered double hydroxide lactate nanosheets (LDH-lactate-NS) with a 0.5‒2 nm thickness and 30‒60 nm diameter exhibit a high adsorptive capacity for negatively charged biomolecules, including fluorescent dyes such as tetramethyl rhodamine isothiocyanate (TRITC), fluorescein isothiocyanate isomer I(FITC) and DNA molecules, forming neutral LDH-nanosheet conjugates. These neutral conjugates can shuttle the bound fluorescent dye into the cytosol of intact plant cell very efficiently. Furthermore, typical inhibitors of endocytosis and low temperature incubation did not prevent LDH-lactate-NS internalization, suggesting that LDH-lactate-NS penetrated the plasma membrane via non-endocytic pathways, which will widen the applicability to a variety of plant cells. Moreover, the absence of unwanted side effects in our cytological studies, and the nuclear localization of ssDNA-FITC suggest that nano-LDHs have potential application as a novel gene carrier to plants. PMID:27221055

Comparison between 1% tretinoin peeling versus 70% glycolic acid peeling in the treatment of female patients with melasma.

PubMed

Faghihi, Gita; Shahingohar, Anahita; Siadat, Amir Hossein

2011-12-01

Melasma is an irregular brownish pigmentation observed on the faces of young to middle-aged women, especially of Asian races, which may contribute to various emotional disturbances. Although not any favorable treatment being approved yet, one appropriate approach is peeling by glycolic acid 70% (GA 70%). Considering the efficiency of Tretinoin in lower concentrations as over-the-counter lightening agents, peelings with higher strength Tretinoin may effectively relieve the pigmentation (melasma) sooner than other topical therapies. The main purpose was to compare the efficiency and complications of GA 70% with Tretinoin 1% peeling. A randomized, double-blinded clinical trial performed on 63 female patients with bilateral melasma. One facial side was treated by drug A (GA 70%) and the opposite side by agent B (Tretinoin 1%) peeling for four sessions with 2-week intervals. Descending changes in Melasma Area and Severity Index (MASI) scores, patients' discomfort and untoward complications following peeling all were evaluated and compared during the research period. The efficiency of Tretinoin 1% peelings in declining the MASI score (treatment of melasma) was similar to GA 70%, as well as the rare unwanted complications of them. However, the patients' discomfort following procedures as expressed by their own, was significantly lower with Tretinoin 1% compared to GA 70% peeling. The cases' satisfaction with the intervention was statistically similar to each other. Furthermore, we experienced almost the equal times of beginning the therapeutic responses in both groups.

A study protocol: using demand-side financing to meet the birth spacing needs of the underserved in Punjab Province in Pakistan

PubMed Central

2014-01-01

Background High fertility rates, unwanted pregnancies, low modern contraceptive prevalence and a huge unmet need for contraception adversely affect women’s health in Pakistan and this problem is compounded by limited access to reliable information and quality services regarding birth spacing especially in rural and underserved areas. This paper presents a study protocol that describes an evaluation of a demand-side financing (DSF) voucher approach which aims to increase the uptake of modern contraception among women of the lowest two wealth quintiles in Punjab Province, Pakistan. Methods/Design This study will use quasi-experimental design with control arm and be implemented in: six government clinics from the Population Welfare Department; 24 social franchise facilities branded as ‘Suraj’ (Sun), led by Marie Stopes Society (a local non-governmental organization); and 12 private sector clinics in Chakwal, Mianwali and Bhakkar districts. The study respondents will be interviewed at baseline and endline subject to voluntary acceptance and medical eligibility. In addition, health service data will record each client visit during the study period. Discussion The study will examine the impact of vouchers in terms of increasing the uptake of modern contraception by engaging private and public sector service providers (mid-level and medical doctors). If found effective, this approach can be a viable solution to satisfying the current demand and meeting the unmet need for contraception, particularly among the poorest socio-economic group. PMID:24885657

The Sensitivity of Measures of Unwanted and Unintended Pregnancy Using Retrospective and Prospective Reporting: Evidence from Malawi

PubMed Central

Sennott, Christie

2015-01-01

A thorough understanding of the health implications of unwanted and unintended pregnancies is constrained by our ability to accurately identify them. Commonly used techniques for measuring such pregnancies are subject to two main sources of error: the ex post revision of preferences after a pregnancy and the difficulty of identifying preferences at the time of conception. This study examines the implications of retrospective and prospective measurement approaches, which are vulnerable to different sources of error, on estimates of unwanted and unintended pregnancies. We use eight waves of closely-spaced panel data from young women in southern Malawi to generate estimates of unwanted and unintended pregnancies based on fertility preferences measured at various points in time. We then compare estimates using traditional retrospective and prospective approaches to estimates obtained when fertility preferences are measured prospectively within months of conception. The 1,062 young Malawian women in the sample frequently changed their fertility preferences. The retrospective measures slightly underestimated unwanted and unintended pregnancies compared to the time-varying prospective approach; in contrast the fixed prospective measures overestimated them. Nonetheless, most estimates were similar in aggregate, suggesting that frequent changes in fertility preferences need not lead to dramatically different estimates of unwanted and unintended pregnancy. Greater disagreement among measures emerged when classifying individual pregnancies. Carefully designed retrospective measures are not necessarily more problematic for measuring unintended and unwanted fertility than are more expensive fixed prospective ones. PMID:25636647

Contraceptive methods and use by women aged 35 and over: A qualitative study of perspectives.

PubMed

Godfrey, Emily M; Chin, Nancy P; Fielding, Stephen L; Fiscella, Kevin; Dozier, Ann

2011-02-16

More than 30% of the pregnancies in women aged 35 and over are unintended. This paper compares perceptions about contraceptive methods and use among women with and without an unintended pregnancy after turning age 35. Semi-structured, in-depth interviews were conducted with 17 women. They were all 35 to 49 years old, regularly menstruating, sexually active, not sterilized, not desiring a pregnancy in the near future, and at least 3 months postpartum. We purposely sampled for women who had had at least one unintended pregnancy after age 35 (n = 9) and women who did not (n = 8). We assessed partnership, views of pregnancy and motherhood, desired lifestyle, perceived advantages and disadvantages of using and obtaining currently available well-known reversible contraceptives in the U.S. ''We also assessed contraceptive methods used at any time during their reproductive years, including current method use and, if appropriate, circumstances surrounding an unintended pregnancy after age 35.'' Each interview was taped and transcribed verbatim. Data were analyzed using Grounded Theory. Analysis focused on partnership, views of pregnancy, motherhood, desired lifestyle and perceived advantages and disadvantages of various reversible contraceptive methods. The women without an unintended pregnancy after age 35 were more likely to (1) use contraceptive methods that helped treat a medical condition, (2) consider pregnancy as dangerous, or (3) express concerns about the responsibilities of motherhood. The women who experienced an unintended pregnancy after age 35 were more likely to (1) report unstable partnerships, (2) perceive themselves at lower risk of pregnancy, or (3) report past experiences with unwanted contraceptive side effects. There was a greater likelihood a woman would choose a contraceptive method if it was perceived as easy to use, accessible, affordable and had minimal side effects. Women's perspective on contraceptive use after age 35 varies. Public health messages and health providers' care can help women in this age group by reviewing their fertility risks, as well as all contraceptive methods and their associated side effects. The impact of such interventions on unintended pregnancy rates in this age group should be tested in other areas of evidence-based medicine.

Cannabinoids as Anticancer Drugs.

PubMed

Ramer, Robert; Hinz, Burkhard

2017-01-01

The endocannabinoid system encompassing cannabinoid receptors, endogenous receptor ligands (endocannabinoids), as well as enzymes conferring the synthesis and degradation of endocannabinoids has emerged as a considerable target for pharmacotherapeutical approaches of numerous diseases. Besides palliative effects of cannabinoids used in cancer treatment, phytocannabinoids, synthetic agonists, as well as substances that increase endogenous endocannabinoid levels have gained interest as potential agents for systemic cancer treatment. Accordingly, cannabinoid compounds have been reported to inhibit tumor growth and spreading in numerous rodent models. The underlying mechanisms include induction of apoptosis, autophagy, and cell cycle arrest in tumor cells as well as inhibition of tumor cell invasion and angiogenic features of endothelial cells. In addition, cannabinoids have been shown to suppress epithelial-to-mesenchymal transition, to enhance tumor immune surveillance, and to support chemotherapeutics' effects on drug-resistant cancer cells. However, unwanted side effects include psychoactivity and possibly pathogenic effects on liver health. Other cannabinoids such as the nonpsychoactive cannabidiol exert a comparatively good safety profile while exhibiting considerable anticancer properties. So far experience with anticarcinogenic effects of cannabinoids is confined to in vitro studies and animal models. Although a bench-to-bedside conversion remains to be established, the current knowledge suggests cannabinoid compounds to serve as a group of drugs that may offer significant advantages for patients suffering from cancer diseases. The present review summarizes the role of the endocannabinoid system and cannabinoid compounds in tumor progression. © 2017 Elsevier Inc. All rights reserved.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling.

PubMed

Kremer, Ingrid E H; Evers, Silvia M A A; Jongen, Peter J; van der Weijden, Trudy; van de Kolk, Ilona; Hiligsmann, Mickaël

2016-01-01

Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics-or attributes-of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes' relative importance among patients. First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes' mean relative importance scores (RIS) were calculated. Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48-9.81]), followed by quality of life (RIS = 9.21 [9.00-9.42]), relapse rate (RIS = 7.76 [7.39-8.13]), severity of side effects (RIS = 7.63 [7.33-7.94]) and relapse severity (RIS = 7.39 [7.06-7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences.

Identification and Prioritization of Important Attributes of Disease-Modifying Drugs in Decision Making among Patients with Multiple Sclerosis: A Nominal Group Technique and Best-Worst Scaling

PubMed Central

Kremer, Ingrid E. H.; van der Weijden, Trudy; van de Kolk, Ilona

2016-01-01

Objectives Understanding the preferences of patients with multiple sclerosis (MS) for disease-modifying drugs and involving these patients in clinical decision making can improve the concordance between medical decisions and patient values and may, subsequently, improve adherence to disease-modifying drugs. This study aims first to identify which characteristics–or attributes–of disease-modifying drugs influence patients´ decisions about these treatments and second to quantify the attributes’ relative importance among patients. Methods First, three focus groups of relapsing-remitting MS patients were formed to compile a preliminary list of attributes using a nominal group technique. Based on this qualitative research, a survey with several choice tasks (best-worst scaling) was developed to prioritize attributes, asking a larger patient group to choose the most and least important attributes. The attributes’ mean relative importance scores (RIS) were calculated. Results Nineteen patients reported 34 attributes during the focus groups and 185 patients evaluated the importance of the attributes in the survey. The effect on disease progression received the highest RIS (RIS = 9.64, 95% confidence interval: [9.48–9.81]), followed by quality of life (RIS = 9.21 [9.00–9.42]), relapse rate (RIS = 7.76 [7.39–8.13]), severity of side effects (RIS = 7.63 [7.33–7.94]) and relapse severity (RIS = 7.39 [7.06–7.73]). Subgroup analyses showed heterogeneity in preference of patients. For example, side effect-related attributes were statistically more important for patients who had no experience in using disease-modifying drugs compared to experienced patients (p < .001). Conclusions This study shows that, on average, patients valued effectiveness and unwanted effects as most important. Clinicians should be aware of the average preferences but also that attributes of disease-modifying drugs are valued differently by different patients. Person-centred clinical decision making would be needed and requires eliciting individual preferences. PMID:27812117

Purification of metal-organic framework materials

DOEpatents

Farha, Omar K.; Hupp, Joseph T.

2012-12-04

A method of purification of a solid mixture of a metal-organic framework (MOF) material and an unwanted second material by disposing the solid mixture in a liquid separation medium having a density that lies between those of the wanted MOF material and the unwanted material, whereby the solid mixture separates by density differences into a fraction of wanted MOF material and another fraction of unwanted material.

Purification of metal-organic framework materials

DOEpatents

Farha, Omar K.; Hupp, Joseph T.

2015-06-30

A method of purification of a solid mixture of a metal-organic framework (MOF) material and an unwanted second material by disposing the solid mixture in a liquid separation medium having a density that lies between those of the wanted MOF material and the unwanted material, whereby the solid mixture separates by density differences into a fraction of wanted MOF material and another fraction of unwanted material.

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women.

PubMed

Christofides, Nicola J; Jewkes, Rachel K; Dunkle, Kristin L; McCarty, Frances; Jama Shai, Nwabisa; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Teenage girls, aged 15-18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21-0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05-2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07-0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58-0.83 and OR 0.78; 95% CI 0.64-0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07-6.25, and OR 2.21 95% CI 1.13-4.29). Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented.

Reproductive consequences of unwanted sexual debut among young adult women from Metro Cebu, Philippines.

PubMed

Wiles, Melissa; Agustin, Sonny; Narasimhan, Subasri; Gipson, Jessica D

2018-04-18

The circumstances surrounding sexual debut influence subsequent sexual and reproductive outcomes. We analysed longitudinal data from 397 women who participated in the Cebu Longitudinal Health and Nutrition Survey in Cebu, Philippines to examine associations between unwanted first sex and number of pregnancies, unintended pregnancy, and use of modern contraception. 72% of women reported unwanted first sex. Women whose first sex was unwanted had increased odds of unintended pregnancy compared to women whose first sex was wanted (aOR = 2.2, 95% CI 1.3, 3.6). Nationally-representative surveys should include culturally-relevant questions about sexual debut to inform public health programmes aimed at improving sexual/reproductive health.

Plasminogen binding inhibitors demonstrate unwanted activities on GABAA and glycine receptors in human iPSC derived neurons.

PubMed

Kristensson, Lisbeth; Lundin, Anders; Gustafsson, David; Fryklund, Jan; Fex, Tomas; Louise, Delsing; Ryberg, Erik

2018-05-11

Plasminogen binding inhibitors (PBIs) reduce the risk of bleeding in hemorrhagic conditions. However, generic PBIs are also associated with an increased risk of seizures, an adverse effect linked to unwanted activities towards inhibitory neuronal receptors. Development of novel PBIs serve to remove compounds with such properties, but progress is limited by a lack of higher throughput methods with human translatability. Herein we apply human induced pluripotent stem cell (hiPSC) derived neurons in combination with dynamic mass redistribution (DMR) technology to demonstrate robust and reproducible modulation of both GABA A and glycine receptors. These cells respond to GABA (EC 50 0.33 ± 0.18 μM), glycine (EC 50 11.0 ± 3.7 μM) and additional ligands in line with previous reports from patch clamp technologies. Additionally, we identify and characterize a competitive antagonistic behavior of the prototype inhibitor and drug tranexamic acid (TXA). Finally, we demonstrate proof of concept for effective counter-screening of lead series compounds towards unwanted GABA A receptor activities. No activity was observed for a previously identified PBI candidate drug, AZD6564, whereas a discontinued analog, AZ13267257, could be characterized as a potent GABA A receptor agonist. Copyright © 2018. Published by Elsevier B.V.

Childhood maltreatment history as a risk factor for sexual harassment among U.S. Army soldiers.

PubMed

Rosen, L N; Martin, L

1998-01-01

Four different types of childhood maltreatment were examined as predictors of unwanted sexual experiences and acknowledged sexual harassment among male and female active duty soldiers in the United States Army. Predictor variables included childhood sexual abuse, physical-emotional abuse, physical neglect, and emotional neglect. Three types of unwanted sexual experiences in the workplace were examined as outcome variables: gender harassment, unwanted sexual attention, and coercion. Both sexual and physical-emotional abuse during childhood were found to be predictors of unwanted sexual experiences and of acknowledged sexual harassment in the workplace. Among female soldiers, the most severe type of unwanted experience-coercion-was predicted only by childhood physical-emotional abuse. Among male soldiers childhood sexual abuse was the strongest predictor of coercion. A greater variety of types of childhood maltreatment predicted sexual harassment outcomes for male soldiers. Childhood maltreatment and adult sexual harassment were predictors of psychological well-being for soldiers of both genders.

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events

PubMed Central

Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com. PMID:27331907

Negative Effects of Psychological Treatments: An Exploratory Factor Analysis of the Negative Effects Questionnaire for Monitoring and Reporting Adverse and Unwanted Events.

PubMed

Rozental, Alexander; Kottorp, Anders; Boettcher, Johanna; Andersson, Gerhard; Carlbring, Per

2016-01-01

Research conducted during the last decades has provided increasing evidence for the use of psychological treatments for a number of psychiatric disorders and somatic complaints. However, by focusing only on the positive outcomes, less attention has been given to the potential of negative effects. Despite indications of deterioration and other adverse and unwanted events during treatment, little is known about their occurrence and characteristics. Hence, in order to facilitate research of negative effects, a new instrument for monitoring and reporting their incidence and impact was developed using a consensus among researchers, self-reports by patients, and a literature review: the Negative Effects Questionnaire. Participants were recruited via a smartphone-delivered self-help treatment for social anxiety disorder and through the media (N = 653). An exploratory factor analysis was performed, resulting in a six-factor solution with 32 items, accounting for 57.64% of the variance. The derived factors were: symptoms, quality, dependency, stigma, hopelessness, and failure. Items related to unpleasant memories, stress, and anxiety were experienced by more than one-third of the participants. Further, increased or novel symptoms, as well as lack of quality in the treatment and therapeutic relationship rendered the highest self-reported negative impact. In addition, the findings were discussed in relation to prior research and other similar instruments of adverse and unwanted events, giving credence to the items that are included. The instrument is presently available in eleven different languages and can be freely downloaded and used from www.neqscale.com.

The use of supplements and performance and image enhancing drugs in fitness settings: A exploratory cross-sectional investigation in the United Kingdom.

PubMed

Mooney, Roisin; Simonato, Pierluigi; Ruparelia, Risha; Roman-Urrestarazu, Andres; Martinotti, Giovanni; Corazza, Ornella

2017-05-01

The strive for perfection is prevalent in the fitness industry. This study aimed to explore the use of products to enhance performance alongside exposure to exercise addiction, appearance anxiety and self-esteem in fitness settings. An online survey was prepared and piloted before wider dissemination in fitness clubs via snowballing and selected mailing lists. A list of commonly used products, including Performance and Image Enhancing Drugs (PIEDs) was provided. Exercise addiction (Exercise Addiction Inventory; EAI), anxiety levels (Appearance Anxiety Inventory; AAI) and their self-esteem (Rosenberg's Self-Esteem Scale; RSE) were also measured. 377 questionnaires were completed. A significant number of participants declared the use products either to lose weight (16%) or to reach their fitness goals (41%). The Internet played a major role in both the supply of information and the provision of the enhancement products (33.7%) and side effects were reported (10.5%). Only a limited number of participants sought a medical opinion about taking products (5.1%). EAI scores were high (m=20.02 ± 4.1), AAI (m=15.98 ± 4.8) showed an intermediate level of anxiety, while self-esteem was low (RSE m=12.59 ± 2.2). This pilot study identified the emergence of a new drug trend in fitness settings and showed a potential relationship to exercise addiction, anxiety disorders and low self-esteem. The Internet played a crucial role in disseminating often untested products, including PIEDs without medical supervision and unwanted side-effects were reported. More studies in the field are required in order to safeguard public health and inform policy making. Copyright © 2017 John Wiley & Sons, Ltd.

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

PubMed Central

Lozano, Alysia; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

2010-01-01

Aims Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side-effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7 day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main Methods A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key Findings Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7 days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain. PMID:20176037

Sexual Attitudes and Contraceptive Practices.

ERIC Educational Resources Information Center

Byrne, Donn

1978-01-01

Discusses barriers to effective contraception, such as informational, emotional, and imaginative factors, and what might be done to avoid unwanted pregnancies by using these factors in positive programs and behaviors. (Author/RK)

Parameters affecting mechanical and thermal responses in bone drilling: A review.

PubMed

Lee, JuEun; Chavez, Craig L; Park, Joorok

2018-04-11

Surgical bone drilling is performed variously to correct bone fractures, install prosthetics, or for therapeutic treatment. The primary concern in bone drilling is to extract donor bone sections and create receiving holes without damaging the bone tissue either mechanically or thermally. We review current results from experimental and theoretical studies to investigate the parameters related to such effects. This leads to a comprehensive understanding of the mechanical and thermal aspects of bone drilling to reduce their unwanted complications. This review examines the important bone-drilling parameters of bone structure, drill-bit geometry, operating conditions, and material evacuation, and considers the current techniques used in bone drilling. We then analyze the associated mechanical and thermal effects and their contributions to bone-drilling performance. In this review, we identify a favorable range for each parameter to reduce unwanted complications due to mechanical or thermal effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Unwanted childbearing and household food insecurity in the United States

PubMed Central

Patel, SA; Surkan, PJ

2015-01-01

Household food insecurity is a population health concern disproportionately affecting families with children in the United States. Unwanted childbearing may place unanticipated strain on families to meet basic needs, heightening the risk for household food insecurity. We investigated the association between mother’s and father’s report of unwanted childbearing and exposure to household food insecurity among children residing in two-parent households in the United States. Data from the Early Childhood Longitudinal Study - Birth Cohort, a nationally representative cohort of US children (n~6,150) were used to estimate the odds of household food insecurity when children were aged 9 months and 2 years, separately, based on parental report of unwanted childbearing. The majority of children were reported as wanted by both parents (74.4%). Of the sample, report of unwanted childbearing by father-only was 20.0%, mother-only was 3.4%, and joint mother and father was 2.2%. Household food insecurity was higher when children were 9 months compared to 2 years. In adjusted models accounting for confounders, children born to mothers and fathers who jointly reported unwanted childbearing were at higher odds of exposure to household food insecurity at 9 months (AOR=3.31; 95% CI: 1.97,5.57) and 2 years (AOR=2.52; 95% CI: 1.12,5.68). In two-parent households, we found children raised by parents reporting unwanted childbearing were more likely to be exposed to food insecurity and potentially related stressors. Further studies that prospectively measure wantedness before the child’s birth will aid in confirming the direction of this association. PMID:25138233

Predictors of mistimed, and unwanted pregnancies among women of childbearing age in Rufiji, Kilombero, and Ulanga districts of Tanzania.

PubMed

Exavery, Amon; Kanté, Almamy Malick; Njozi, Mustafa; Tani, Kassimu; Doctor, Henry V; Hingora, Ahmed; Phillips, James F

2014-08-08

While unintended pregnancies pose a serious threat to the health and well-being of families globally, characteristics of Tanzanian women who conceive unintentionally are rarely documented. This analysis identifies factors associated with unintended pregnancies-both mistimed and unwanted-in three rural districts of Tanzania. A cross-sectional survey of 2,183 random households was conducted in three Tanzanian districts of Rufiji, Kilombero, and Ulanga in 2011 to assess women's health behavior and service utilization patterns. These households produced 3,127 women age 15+ years from which 2,199 gravid women aged 15-49 were selected for the current analysis. Unintended pregnancies were identified as either mistimed (wanted later) or unwanted (not wanted at all). Correlates of mistimed, and unwanted pregnancies were identified through Chi-squared tests to assess associations and multinomial logistic regression for multivariate analysis. Mean age of the participants was 32.1 years. While 54.1% of the participants reported that their most recent pregnancy was intended, 32.5% indicated their most recent pregnancy as mistimed and 13.4% as unwanted. Multivariate analysis revealed that young age (<20 years), and single marital status were significant predictors of both mistimed and unwanted pregnancies. Lack of inter-partner communication about family planning increased the risk of mistimed pregnancy significantly, and multi-gravidity was shown to significantly increase the risk of unwanted pregnancy. About one half of women in Rufiji, Kilombero, and Ulanga districts of Tanzania conceive unintentionally. Women, especially the most vulnerable should be empowered to avoid pregnancy at their own will and discretion.

Comparing the effects of Yasmin® and LD™ (low-dose estrogen) as contraceptive methods on menstrual cycle changes in women referred to the health care centers of Isfahan

PubMed Central

Fathizadeh, Nahid; Bafghi, Raziye Karimain; Boroumandfar, Khadijeh; Savabi, Mitra

2010-01-01

BACKGROUND: One of the biggest problem today that most developing countries are faced with is the uncontrolled population growth; a serious threat to the international community. One of the most accessible contraceptive methods is the hormonal methods in which low-dose estrogen (LD) combined pills are considered as the most common among them. The most important reason for discontinuation of the combination pills is the side effects and following the discontinuation, it can lead to unwanted pregnancy. Promotion of more new methods and providing better methods with lesser side effects can be an important step towards solving some of the problems and increasing the usage percentages of contraceptive methods. This study therefore aimed to compare the effects of Yasmin and LD on menstrual cycle changes. METHODS: In this clinical trial study, 60 women referred to the Family Planning Health Center of Isfahan in 2008 were studied that finally after the sample loss, 27 and 24 samples were placed in Yasmin and LD groups, respectively. A questionnaire was used in order to collect the data. Content validity test and re-test also were used to confirm the validity and reliability of the questionnaire. To analyze the data, SPSS software and descriptive and inferential statistical methods were used. RESULTS: The results of this study indicated that the bleeding rate in the Yasmin group within the next six month compared to taking them before was significantly lower than that in LD group (p = 0.02); but there was no significant difference in terms of menstrual bleeding duration and the two menstruation interval between the two groups (p = 0.2). There was no significant difference between the Yasmin and LD groups in terms of delay in menstruation and dysmenorrheal. Spotting rate significantly was higher in Yasmin group than that in LD group (p = 0.02). There was a significant reduction in terms of bleeding rate changes and menstrual bleeding duration in both Yasmin and LD group at the following next six months in comparison with before the consumption (p < 0.05). CONCLUSIONS: According to the results obtained, the oral combination of Yasmin pills has fewer side effects than LD pills. Therefore, it is recommended to start using Yasmin pill in the family planning units in Iran. PMID:22049290

Use Of Green Porphyrinsto Treat Neovasculature In The Eyes

DOEpatents

Levy, Julia; Miller, Joan W.; Gradoudas, Evangelos S.; Hasan, Tayyaba; Schmidt-Erfurth, Ursula

1998-08-25

Photodynamic therapy of conditions of the eye characterized by unwanted neovasculature, such as age-related macular degeneration, is effective using green porphyrins as photoactive agents, preferably as liposomal compositions.

Interaction Mechanisms of Cavitation Bubbles Induced by Spatially and Temporally Separated fs-Laser Pulses

PubMed Central

Tinne, Nadine; Kaune, Brigitte; Krüger, Alexander; Ripken, Tammo

2014-01-01

The emerging use of femtosecond lasers with high repetition rates in the MHz regime together with limited scan speed implies possible mutual optical and dynamical interaction effects of the individual cutting spots. In order to get more insight into the dynamics a time-resolved photographic analysis of the interaction of cavitation bubbles is presented. Particularly, we investigated the influence of fs-laser pulses and their resulting bubble dynamics with various spatial as well as temporal separations. Different time courses of characteristic interaction effects between the cavitation bubbles were observed depending on pulse energy and spatio-temporal pulse separation. These ranged from merely no interaction to the phenomena of strong water jet formation. Afterwards, the mechanisms are discussed regarding their impact on the medical application of effective tissue cutting lateral to the laser beam direction with best possible axial precision: the mechanical forces of photodisruption as well as the occurring water jet should have low axial extend and a preferably lateral priority. Furthermore, the overall efficiency of energy conversion into controlled mechanical impact should be maximized compared to the transmitted pulse energy and unwanted long range mechanical side effects, e.g. shock waves, axial jet components. In conclusion, these experimental results are of great importance for the prospective optimization of the ophthalmic surgical process with high-repetition rate fs-lasers. PMID:25502697

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report.

PubMed

Reiman, Amanda; Welty, Mark; Solomon, Perry

2017-01-01

Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion : Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample "strongly agreed/agreed" that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% "strongly agreed/agreed" that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence.

Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells.

PubMed

He, Xiaoli; H'ng, Shiau-Chen; Leong, David T; Hutmacher, Dietmar W; Melendez, Alirio J

2010-08-01

High renewal and maintenance of multipotency of human adult stem cells (hSCs), are a prerequisite for experimental analysis as well as for potential clinical usages. The most widely used strategy for hSC culture and proliferation is using serum. However, serum is poorly defined and has a considerable degree of inter-batch variation, which makes it difficult for large-scale mesenchymal stem cells (MSCs) expansion in homogeneous culture conditions. Moreover, it is often observed that cells grown in serum-containing media spontaneously differentiate into unknown and/or undesired phenotypes. Another way of maintaining hSC development is using cytokines and/or tissue-specific growth factors; this is a very expensive approach and can lead to early unwanted differentiation. In order to circumvent these issues, we investigated the role of sphingosine-1-phosphate (S1P), in the growth and multipotency maintenance of human bone marrow and adipose tissue-derived MSCs. We show that S1P induces growth, and in combination with reduced serum, or with the growth factors FGF and platelet-derived growth factor-AB, S1P has an enhancing effect on growth. We also show that the MSCs cultured in S1P-supplemented media are able to maintain their differentiation potential for at least as long as that for cells grown in the usual serum-containing media. This is shown by the ability of cells grown in S1P-containing media to be able to undergo osteogenic as well as adipogenic differentiation. This is of interest, since S1P is a relatively inexpensive natural product, which can be obtained in homogeneous high-purity batches: this will minimize costs and potentially reduce the unwanted side effects observed with serum. Taken together, S1P is able to induce proliferation while maintaining the multipotency of different human stem cells, suggesting a potential for S1P in developing serum-free or serum-reduced defined medium for adult stem cell cultures.

Emergency contraception amongst female college students--knowledge, attitude and practice.

PubMed

Nibabe, Wendwosen T; Mgutshini, Tennyson

2014-03-19

Unwanted teenage pregnancies have a notable detrimental impact on the learners' trajectory and have been associated with jeopardising the students' educational progress and future career prospects. These pregnancies are mostly unplanned and unintended and many are terminated, either legally or illegally. The aim of this study was to explore the contributory role played by the knowledge, attitude and practices of female college students with respect to the utilisation of emergency contraceptives. Three tertiary institutions in Dessie, Ethiopia. Quantitative self-administered questionnaires were used to collect descriptive data from 352 female college students. The study revealed that there was a high percentage (78.3%) of unwanted pregnancies amongst those engaging in sex. Significantly, nearly half (43.3%) of these unwanted pregnancies resulted in abortion. Only 10% of the students sampled admitted to ever having used emergency contraception. Even though more than half (69.9%) of the students knew about emergency contraception, only 27% of them felt confident that they understood when it was most effective. These and other observed findings confirm the need for improvement of female college students' knowledge and timely utilisation of emergency contraception.

Surgical abortion in second trimester: initial experiences in Nepal.

PubMed

Shrivastava, V; Bajracharya, L; Thapa, S

2010-01-01

In spite of legalising abortion and making safe abortion available at affordable price at accessible distance to almost everyone, unsafe abortion especially second trimester abortion is still a big health problem in Nepal. The objective of the study is to fi nd the demographic profile, reasons for seeking abortion and to see the effectiveness of Misoprostol in preparing the cervix. A prospective study was done in the two second trimester abortion trainings conducted in Maternity hospital, Kathmandu. Total 57 clients had second trimester abortion performed. Information was collected from structured questionnaire and then data was analysed. Commonest reason for seeking abortion was, multiparity (61.4%). Common reasons for second trimester abortion were, completed family size with unwanted pregnancy (61.4%), unwanted pregnancy in married (10.52%) unwanted pregnancy in unmarried (5.26%). Second trimester abortion is one of the most common procedures performed in reproductive-aged women and when performed by a skilled provider in the appropriate setting, it is one of the safest surgeries, if it is well supported by change in policy of the country and acceptability of the people.

Home and Parenting Resources Available to Siblings Depending on Their Birth Intention Status

PubMed Central

Barber, Jennifer S.; East, Patricia L.

2011-01-01

This study examines the differential availability of family and parenting resources to children depending on their birth planning status. It uses data from the National Longitudinal Survey of Youth (NLSY) that assessed family and HOME resources for 3,134 mothers and their 5,890 children, of whom 63% were reported as intended at conception, 27% as mistimed, and 10% as unwanted. Results confirm previous findings that children born as a result of unintended pregnancies (both mistimed and unwanted) have fewer total resources and fewer cognitive and emotional supports than children born as a result of intended pregnancies, net of family background controls. Fixed effects (within-mother) models show that unwanted and mistimed children had fewer parental resources than their intended siblings. Our results also indicate decreases in parental emotional resources to an older child after the birth of a mistimed younger sibling. Findings suggest that cognitive and emotional resources are differentially available to children within a family depending on their intention status, and that unintended births may lead to a decrease in parental resources for older children in the household. PMID:19489912

Adaptive top-down suppression of hippocampal activity and the purging of intrusive memories from consciousness.

PubMed

Benoit, Roland G; Hulbert, Justin C; Huddleston, Ean; Anderson, Michael C

2015-01-01

When reminded of unwanted memories, people often attempt to suppress these experiences from awareness. Prior work indicates that control processes mediated by the dorsolateral prefrontal cortex (DLPFC) modulate hippocampal activity during such retrieval suppression. It remains unknown whether this modulation plays a role in purging an intrusive memory from consciousness. Here, we combined fMRI and effective connectivity analyses with phenomenological reports to scrutinize a role for adaptive top-down suppression of hippocampal retrieval processes in terminating mnemonic awareness of intrusive memories. Participants either suppressed or recalled memories of pictures depicting faces or places. After each trial, they reported their success at regulating awareness of the memory. DLPFC activation was greatest when unwanted memories intruded into consciousness and needed to be purged, and this increased engagement predicted superior control of intrusive memories over time. However, hippocampal activity was decreased during the suppression of place memories only. Importantly, the inhibitory influence of the DLPFC on the hippocampus was linked to the ensuing reduction in intrusions of the suppressed memories. Individuals who exhibited negative top-down coupling during early suppression attempts experienced fewer involuntary memory intrusions later on. Over repeated suppressions, the DLPFC-hippocampus connectivity grew less negative with the degree that they no longer had to purge unwanted memories from awareness. These findings support a role of DLPFC in countermanding the unfolding recollection of an unwanted memory via the suppression of hippocampal processing, a mechanism that may contribute to adaptation in the aftermath of traumatic experiences.

Clinical use of an epinephrine-reduced (1/400,000) articaine solution in short-time dental routine treatments--a multicenter study.

PubMed

Daubländer, Monika; Kämmerer, Peer W; Willershausen, Brita; Leckel, Michael; Lauer, Hans-Christoph; Buff, Siegmar; Rösl, Benita

2012-08-01

The addition of epinephrine in dental local anaesthesia results in a longer and deeper anaesthesia under almost ischemic conditions. For short-time dental treatments, epinephrine-reduced anaesthetics may offer shorter and more individual anaesthesia with reduced potential side effects. The aim of this study was a clinical evaluation of anaesthetic potency and adverse effects of an epinephrine-reduced articaine formulation in dental patients undergoing short-time routine treatment. In a prospective clinical, not interventional, study between January 2008 and February 2009, 908 patients undergoing short-time dental treatment in five medical centers were anaesthetized with 4% articaine 1:400,000 epinephrine (Ubistesin, 3M/ESPE, Seefeld, Germany). Efficacy and safety in clinical use were evaluated. A follow-up after 1 day was conducted by telephone survey. A mean amount of 1.3-ml anaesthetic solution was needed to achieve a complete or sufficient anaesthesia in 97% (n = 876) of cases. A second injection had to be done in 3.7% (n = 34) before and in 11.9% (n = 108) during treatment. Here, the second injection had to be applied after a mean of 48.6 min. The mean duration of soft tissue anaesthesia after infiltration was 146.6 min, after nerve block 187.7 min. The painful treatment took a mean of 50.2 min and the total treatment time summed up to 68.8 min. In 1.7% cases (n = 15), unwanted side effects were observed. The results indicate that a lower concentration of epinephrine in combination with the 4% articaine solution leads to a high success rate of efficacy. The clinical use of a 4% articaine 1:400,000 epinephrine solution can be stated as safe and effective in short dental routine treatments. Reconsiderations concerning limitations of indication or additional contraindications are not necessary.

The medicalization of love.

PubMed

Earp, Brian D; Sandberg, Anders; Savulescu, Julian

2015-07-01

Pharmaceuticals or other emerging technologies could be used to enhance (or diminish) feelings of lust, attraction, and attachment in adult romantic partnerships. Although such interventions could conceivably be used to promote individual (and couple) well-being, their widespread development and/or adoption might lead to the 'medicalization' of human love and heartache--for some, a source of a serious concern. In this essay, we argue that the medicalization of love need not necessarily be problematic, on balance, but could plausibly be expected to have either good or bad consequences depending upon how it unfolds. By anticipating some of the specific ways in which these technologies could yield unwanted outcomes, bioethicists and others can help to direct the course of love's medicalization--should it happen to occur--more toward the 'good' side than the 'bad.'

Principles of light energy management

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

Davis, N.

1994-12-31

A review is presented on methods to minimize the effects of excess energy associated with lighting systems for plant growth. Information on lamp efficiencies and methods for separating and collecting unwanted heat is included.

Management of continuous positive airway pressure treatment compliance using telemonitoring in obstructive sleep apnoea.

PubMed

Turino, Cecilia; de Batlle, Jordi; Woehrle, Holger; Mayoral, Ana; Castro-Grattoni, Anabel Lourdes; Gómez, Sílvia; Dalmases, Mireia; Sánchez-de-la-Torre, Manuel; Barbé, Ferran

2017-02-01

Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA), but treatment compliance is often unsatisfactory. This study investigated the efficacy and cost-effectiveness of telemonitoring for improving CPAP compliance.100 newly diagnosed OSA patients requiring CPAP (apnoea-hypopnoea index >15 events·h -1 ) were randomised to standard management or a telemonitoring programme that collected daily information about compliance, air leaks and residual respiratory events, and initiated patient contact to resolve issues. Clinical/anthropometric variables, daytime sleepiness and quality of life were recorded at baseline and after 3 months. Patient satisfaction, additional visits/calls, side-effects and total costs were assessed.There were no significant differences between the standard and telemedicine groups in terms of CPAP compliance (4.9±2.2 versus 5.1±2.1 h·night -1 ), symptoms, clinical variables, quality of life and unwanted effects. Telemedicine was less expensive than standard management (EUR123.65 versus EUR170.97; p=0.022) and was cost-effective (incremental cost-effectiveness ratio EUR17 358.65 per quality-adjusted life-year gained). Overall patient satisfaction was high, but significantly more patients rated satisfaction as high/very high in the standard management versus telemedicine group (96% versus 74%; p=0.034).Telemonitoring did not improve CPAP treatment compliance and was associated with lower patient satisfaction. However, it was more cost-effective than traditional follow-up. Copyright ©ERS 2017.

Effect of anticholinergics on the overactive bladder and bowel domain of the electronic personal assessment questionnaire (ePAQ).

PubMed

Bulchandani, S; Toozs-Hobson, P; Parsons, M; McCooty, S; Perkins, K; Latthe, P

2015-04-01

Evidence suggests that OAB (overactive bladder) can occur alongside disorders of the colon, such as irritable bowel syndrome (IBS). Moreover, patients with constipation are more likely to develop OAB symptoms than those without. Anticholinergic medications (AcH) are commonly used for treating OAB, and can result in the unwanted side effects of constipation. We aimed to study the relationship of AcH, and their effects on quality of life using the electronic Personal Assessment Questionnaire (ePAQ) by assessing changes in the bowel and bladder domains, pre- and post-AcH treatment. Ninety patients completed the ePAQ pre- and post-AcH treatment from January 2011 to April 2014. Data were collected retrospectively and prospectively, and analysed using a paired t test. Effect size (ES) was calculated for OAB and bowel domains to quantify the effect on QoL. There was a significant improvement in the OAB (p = 0.0005) and bowel domains (p = 0.0005). In the bowel domains, the largest effect size was seen for IBS (0.5) followed by continence (0.4), evacuation (0.375) and a small ES was seen for constipation (0.2). There was a reduction in the "degree of bother" in OAB and bowel domains. Patients may benefit from the possible effects of AcH on their bowels, and assessment of all aspects of pelvic floor function is important before commencing AcH. This may help to counsel patients, with possibly improved compliance with therapy.

Anti-stress and neuronal cell differentiation induction effects of Rosmarinus officinalis L. essential oil.

PubMed

Villareal, Myra O; Ikeya, Ayumi; Sasaki, Kazunori; Arfa, Abdelkarim Ben; Neffati, Mohamed; Isoda, Hiroko

2017-12-22

Mood disorder accounts for 13 % of global disease burden. And while therapeutic agents are available, usually orally administered, most have unwanted side effects, and thus making the inhalation of essential oils (EOs) an attractive alternative therapy. Rosmarinus officinalis EO (ROEO), Mediterranean ROEO reported to improve cognition, mood, and memory, the effect on stress of which has not yet been determined. Here, the anti-stress effect of ROEO on stress was evaluated in vivo and in vitro. Six-week-old male ICR mice were made to inhale ROEO and subjected to tail suspension test (TST). To determine the neuronal differentiation effect of ROEO in vitro, induction of ROEO-treated PC12 cells differentiation was observed. Intracellular acetylcholine and choline, as well as the Gap43 gene expression levels were also determined. Inhalation of ROEO significantly decreased the immobility time of ICR mice and serum corticosterone level, accompanied by increased brain dopamine level. Determination of the underlying mechanism in vitro revealed a PC12 differentiation-induction effect through the modulation of intracellular acetylcholine, choline, and Gap43 gene expression levels. ROEO activates the stress response system through the NGF pathway and the hypothalamus-pituitary-adrenal axis, promoting dopamine production and secretion. The effect of ROEO may be attributed to its bioactive components, specifically to α-pinene, one of its major compounds that has anxiolytic property. The results of this study suggest that ROEO inhalation has therapeutic potential against stress-related psychiatric disorders.

Hormonal contraception and HIV acquisition risk: implications for individual users and public policies.

PubMed

Jain, Anrudh K

2012-12-01

A recent observational study among HIV-1 serodiscordant couples (uninfected women living with an infected partner) raised concerns about the safety of injectable contraceptives, especially depot medroxyprogesterone acetate (DMPA). The purpose of this paper is to assess the implications of potentially elevated risk of Human Immunodeficiency Virus (HIV) acquisition with the use of hormonal contraceptives for individual users and public policies. Two indicators expressing costs (additional unwanted births and additional maternal deaths) in terms of the same unit of benefit (per 100 HIV infections averted) are estimated by using data on competing risks of unwanted birth and HIV acquisition associated with the use of various contraceptive methods. Elevated HIV acquisition risks associated with hormonal contraception observed in the observational studies of family planning users, sex workers and HIV-1 serodiscordant couples are used. Other relevant data for Kenya, South Africa and Zimbabwe are used to illustrate the potential effect of withdrawal of DMPA at the population level. Both the risks of unwanted birth and HIV acquisition with sterilization, intrauterine devices (IUDs) and implants at the individual level are lower than those with DMPA. A shift from DMPA to an oral contraceptive (OC) or male condom by an individual could result in about 600 and a shift to no method in about 5400 additional unwanted births per 100 HIV infections averted. At the population level, the withdrawal of DMPA from Kenya, for example, could result in 7600 annual additional unwanted births and 40 annual additional maternal deaths per 100 HIV infections averted. Individual DMPA users may be advised to shift to sterilization, IUD or implant depending upon their reproductive needs and circumstances, but not to no method, OC or even condom alone. At the macro level, the decision to withdraw DMPA from family planning programs in sub-Saharan Africa is not warranted. Copyright © 2012 Elsevier Inc. All rights reserved.

Risk factors for unplanned and unwanted teenage pregnancies occurring over two years of follow-up among a cohort of young South African women

PubMed Central

Christofides, Nicola J.; Jewkes, Rachel K.; Dunkle, Kristin L.; McCarty, Frances; Shai, Nwabisa Jama; Nduna, Mzikazi; Sterk, Claire

2014-01-01

Background Although teenage pregnancies in South Africa have declined, the short and longer term health and social consequences are a potential public health concern. This longitudinal study aimed to describe the range of risk and protective factors for incident unwanted and unplanned pregnancies occurring over 2 years of follow-up among a cohort of adolescent women in the Eastern Cape, South Africa. It also investigated the relationship between gender inequality and gender-based violence and subsequent unplanned and unwanted pregnancies among the cohort. Objective Teenage girls, aged 15–18 years (n=19), who were volunteer participants in a cluster randomized controlled trial and who had data from at least one follow-up were included in this analysis. To assess risk and protective factors for incident unwanted or unplanned pregnancies, we constructed multivariate polytomous regression models adjusting for sampling clusters as latent variables. Covariates included age, having a pregnancy prior to baseline, education, time between interviews, study intervention arm, contraceptive use, experience of intimate partner violence, belief that the teenage girl and her boyfriend are mutual main partners, and socioeconomic status. Results Overall, 174 pregnancies occurred over the 2-year follow-up period. Beliefs about relationship control were not associated with unwanted and unplanned pregnancies, nor were experiences of forced first sex or coerced sex under the age of 15. Hormonal contraception was protective against unplanned pregnancies (OR 0.40; 95% CI 0.21–0.79); however, using condoms was not protective. Physical abuse (OR 1.69; 95% CI 1.05–2.72) was a risk factor for, and having a pregnancy prior to baseline was protective against an unwanted pregnancy (OR 0.25; 95% CI 0.07–0.80). Higher socioeconomic status was protective for both unplanned and unwanted pregnancies (OR 0.69; 95% CI 0.58–0.83 and OR 0.78; 95% CI 0.64–0.96). Believing that the teenage girl and her boyfriend were mutual main partners doubled the odds of reporting both an unplanned and unwanted pregnancy (OR 2.58 95% CI 1.07–6.25, and OR 2.21 95% CI 1.13–4.29). Conclusion Although some of the measures of gender inequity were not associated with unplanned and unwanted pregnancies, there is evidence of the role of both gender power and socioeconomic status. This was evident in teenage girls who experienced physical violence being more likely to have an unwanted pregnancy. Interventions to prevent teenage pregnancies need to be tailored by socioeconomic status because some teenagers may see having a pregnancy as a way to have a more secure future. Interventions that engage with relationship dynamics of teenagers are essential if unwanted and unplanned pregnancies are to be prevented. PMID:25150027

Effective Risk Management in Innovative Projects: A Case Study of the Construction of Energy-efficient, Sustainable Building of the Laboratory of Intelligent Building in Cracow

NASA Astrophysics Data System (ADS)

Krechowicz, Maria

2017-10-01

Many construction projects fail to meet deadlines or they exceed the assumed budget. This scenario is particularly common in the case of innovative projects, in which too late identification of a high risk of delays and exceeding the assumed costs makes a potentially profitable project untenable. A high risk level, far exceeding the level of risk in standard non-innovative projects, is a characteristic feature of the realization phase of innovative projects. This is associated not only with greater complexity of the design and construction phases, but also with the problems with application of new technologies and prototype solutions, lack of qualified personnel with suitable expertise in specialized areas, and with the ability to properly identify the gaps between available and required knowledge and skills. This paper discusses the process of effective risk management in innovative projects on the example of the realization phase of an innovative, energy-efficient and sustainable building of the Laboratory of Intelligent Building in Cracow - DLJM Lab, from the point of view of DORBUD S.A., its general contractor. In this paper, a new approach to risk management process for innovative construction projects is proposed. Risk management process was divided into five stages: gathering information, identification of the important unwanted events, first risk assessment, development and choice of risk reaction strategies, assessment of the residual risk after introducing risk reactions. 18 unwanted events in an innovative construction project were identified. The first risk assessment was carried out using two-parametric risk matrix, in which the probability of unwanted event occurrence and its consequences were analysed. Three levels of risks were defined: tolerable, controlled and uncontrolled. Risk reactions to each defined unwanted event were developed. The following risk reaction types were considered: risk retention, risk reduction, risk transfer and risk elimination. Three-parametric risk matrix was developed to make it possible to assess risk after implementing risk reactions. The possibility of implementing risk management was inversely proportional to the probability of unwanted event occurrence and its contribution to the project outcome. Introducing this risk management strategy allowed to significantly reduce the risk of the innovative construction project. It proved to be an effective tool to reduce risk to an acceptable level. It had a significant contribution to carrying out the project within the assumed time, budget and quality standards.

Relationship between Unwanted Pregnancy and Health-Related Quality of Life in Pregnant Women.

PubMed

Ali, Azizi

2016-06-01

To determine the relationship between unwanted pregnancy and health-related quality of life in pregnant women. Case-control study. Department of Community Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran, from October 2013 to July 2014. Of the pregnant women who presented to primary healthcare centers of Kermanshah, Iran to receive prenatal care at 6 - 10 weeks of their pregnancy, those with unwanted pregnancy were selected as cases and those with wanted pregnancy were selected as control group. The selection process was done using multi-stage stratified random sampling. Frequency matching was applied to match the two groups. Quality of life was measured by the SF-36 questionnaire and was compared by the t-test. Relationship power between pregnancy type (wanted or unwanted pregnancy) and impairment of quality of life subscales as the outcome was assessed using odds ratio (OR). Frequency distribution of matched variables was not statistically different between the two studied groups. Mean scores of mental component summary and physical component summary as well as eight subscales (physical functioning, role, bodily pain, general health, vitality, social functioning, role emotional, and mental health) were lower in the unwanted pregnancy group compared to women with wanted pregnancy (p < 0.001). The highest high impairment odds ratio was highest for the mental component summary (MCS) (OR = 9.19; 95% CI = 5.17- 16.32) and vitality subscale (OR = 5.2; 95% CI = 2.89- 9.33). Mental health of the pregnant women with unwanted pregnancy is affected more than their physical health. Mental health in women with unwanted pregnancy is 9.19 times more likely to be reduced. Among mental health subscales, vitality (energy/fatigue) showed the highest decrease.

The role of poor sleep in the relation between workplace bullying/unwanted sexual attention and long-term sickness absence.

PubMed

Nabe-Nielsen, Kirsten; Grynderup, Matias Brødsgaard; Lange, Theis; Andersen, Johan Hviid; Bonde, Jens Peter; Conway, Paul Maurice; Garde, Anne Helene; Høgh, Annie; Kaerlev, Linda; Rugulies, Reiner; Hansen, Åse Marie

2016-08-01

While exposure to bullying and unwanted sexual attention was previously found to increase the risk of sickness absence, the underlying mechanisms are largely unknown. Poor sleep can be a consequence of stressful exposures and a cause of poor health, and poor sleep is also a determinant of insufficient recovery. Therefore, the present study investigated whether poor sleep mediates and/or moderates the association between bullying and unwanted sexual attention, on the one hand, and long-term sickness absence (LTSA), on the other hand. We used questionnaire data from 7650 individuals contributing with 15,040 2-year observation periods. Workplace bullying, unwanted sexual attention, disturbed sleep, and difficulties awakening were measured at three time points, and participants were followed in registers to measure the occurrence of LTSA, defined as ≥30 consecutive days of sickness absence during the subsequent 2 years. The odds of LTSA were significantly increased by workplace bullying (OR 1.77; 95 % CI 1.50-2.12) and unwanted sexual attention (OR 1.55; 95 % CI 1.06-2.29). Together, disturbed sleep and difficulties awakening mediated 12.8 % (95 % CI 8.1-19.8) of the association between bullying and long-term sickness absence, and 8.5 % (95 % CI -0.45 to 37.1) of the association between unwanted sexual attention and long-term sickness absence in the fully adjusted model. Neither disturbed sleep nor difficulties awakening moderated these associations. As expected, bullying and unwanted sexual attention were prospectively associated with long-term sickness absence. Only a small part of this association was mediated by poor sleep.

Domestic Violence, Unwanted Pregnancy and Pregnancy Termination among Urban Women of Bangladesh

PubMed Central

2013-01-01

Objective This paper explores the relationship between domestic violence against women inflicted by husbands, unwanted pregnancy and pregnancy termination of Bangladeshi urban women. Materials and methods The study used the nationally representative 2007 Bangladesh Demographic and Health Survey (BDHS) data. The BDHS covered a representative sample of 10,996 ever married women from rural and urban areas. The BDHS used a separate module to collect information from women regarding domestic violence. The survey gathered information of domestic violence from 1,013 urban women which are the basis of the study. Simple cross tabulation, bivariate and multivariate statistical analyses were performed to analyzing data. Results Overall, the lifetime prevalence of domestic violence was 47.5%. Of the most recent pregnancies, 15.6% were unwanted and 16.0% of the women terminated pregnancy in their marital life. The multivariate binary logistic regression analyses yielded quantitatively important and reliable estimate of unwanted pregnancy and pregnancy termination. The regression analyses yielded significantly (p < 0.05) increased risk of unwanted pregnancy only for physical violence (OR = 2.35, 95% CI = 1.28-4.32) and for both physical and sexual violence (OR = 2.27, 95% CI = 1.02-5.28), and higher risk of pregnancy termination for only physical violence (OR = 1.41, 95% CI = 0.95-2.10) and for both physical and sexual violence (OR = 1.81, 95% CI = 1.07-3.04) than women who were never abused. Current age, higher parity and early marriage are also important determinants of unwanted pregnancy and pregnancy termination. Conclusion Violence against women inflicted by husbands is commonplace in Bangladesh. Any strategy to reduce the burden of unwanted pregnancy and induced abortion should include prevention of violence against women and strengthening women's sexual and reproductive health. PMID:24971097

System and Method for Suppression of Unwanted Noise in Ground Test Facilities

NASA Technical Reports Server (NTRS)

Zaman, Khairul B. M. Q. (Inventor); Clem, Michelle M. (Inventor); Fagan, Amy F. (Inventor)

2015-01-01

Systems and methods for the suppression of unwanted noise from a jet discharging into a duct are disclosed herein. The unwanted noise may be in the form of excited duct modes or howl due to super resonance. A damper member is used to reduce acoustic velocity perturbations at the velocity anti-node, associated with the half-wave resonance of the duct, weakening the resonance condition and reducing the amplitudes of the spectral peaks.

Novel ion channel targets in atrial fibrillation.

PubMed

Hancox, Jules C; James, Andrew F; Marrion, Neil V; Zhang, Henggui; Thomas, Dierk

2016-08-01

Atrial fibrillation (AF) is the most common arrhythmia in humans. It is progressive and the development of electrical and structural remodeling makes early intervention desirable. Existing antiarrhythmic pharmacological approaches are not always effective and can produce unwanted side effects. Additional atrial-selective antiarrhythmic strategies are therefore desirable. Evidence for three novel ion channel atrial-selective therapeutic targets is evaluated: atrial-selective fast sodium channel current (INa) inhibition; small conductance calcium-activated potassium (SK) channels; and two-pore (K2P) potassium channels. Data from animal models support atrial-ventricular differences in INa kinetics and also suggest atrial-ventricular differences in sodium channel β subunit expression. Further work is required to determine whether intrinsic atrial-ventricular differences in human INa exist or whether functional differences occur due to distinct atrial and ventricular action and resting potentials. SK and K2P channels (particularly K2P 3.1) offer potentially attractive atrial-selective targets. Work is needed to identify the underlying basis of SK current that contributes to (patho)physiological atrial repolarization and settings in which SK inhibition is anti- versus pro-arrhythmic. Although K2P3.1 appears to be a promising target with comparatively selective drugs for experimental use, a lack of selective pharmacology hinders evaluation of other K2P channels as potential atrial-selective targets.

The role of galectin-1 in in vitro and in vivo photodynamic therapy with a galactodendritic porphyrin.

PubMed

Pereira, Patrícia M R; Silva, Sandrina; Ramalho, José S; Gomes, Célia M; Girão, Henrique; Cavaleiro, José A S; Ribeiro, Carlos A F; Tomé, João P C; Fernandes, Rosa

2016-11-01

Conventional photodynamic agents used in clinic are porphyrin-based photosensitizers. However, they have low tumour selectivity, which may induce unwanted side-effects and damage to healthy tissues. In this study, we used a porphyrin with dendritic units of galactose (PorGal 8 ) developed by us, which can target the galactose-binding protein, galectin-1, known to be overexpressed in many tumour tissues. In vitro and in vivo studies had been conducted for the validation of PorGal 8 effectiveness. We showed a specific uptake of PorGal 8 and induction of apoptotic cell death by generating oxidative stress and alterations in the cytoskeleton of bladder cancer cells overexpressing galectin-1. We further validated the photodynamic efficiency of PorGal 8 in athymic nude mice (Balb/c nu/nu) bearing subcutaneously implanted luciferase-positive bladder cancer xenografts, overexpressing galectin-1 protein. PorGal 8 (5 μmol/kg, intraperitoneal), injected 24 h before light delivery (50.4 J/cm 2 ), inhibited tumour growth. We conclude that the use of PorGal 8 enables selective target and cytotoxicity by photodynamic therapy in cancer cells overexpressing galectin-1, preventing undesired phototoxicity in the surrounding healthy tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multiplex networks in metropolitan areas: generic features and local effects.

PubMed

Strano, Emanuele; Shai, Saray; Dobson, Simon; Barthelemy, Marc

2015-10-06

Most large cities are spanned by more than one transportation system. These different modes of transport have usually been studied separately: it is however important to understand the impact on urban systems of coupling different modes and we report in this paper an empirical analysis of the coupling between the street network and the subway for the two large metropolitan areas of London and New York. We observe a similar behaviour for network quantities related to quickest paths suggesting the existence of generic mechanisms operating beyond the local peculiarities of the specific cities studied. An analysis of the betweenness centrality distribution shows that the introduction of underground networks operate as a decentralizing force creating congestion in places located at the end of underground lines. Also, we find that increasing the speed of subways is not always beneficial and may lead to unwanted uneven spatial distributions of accessibility. In fact, for London—but not for New York—there is an optimal subway speed in terms of global congestion. These results show that it is crucial to consider the full, multimodal, multilayer network aspects of transportation systems in order to understand the behaviour of cities and to avoid possible negative side-effects of urban planning decisions. © 2015 The Author(s).

Efficient femtosecond driven SOX 17 delivery into mouse embryonic stem cells: differentiation studies

NASA Astrophysics Data System (ADS)

Thobakgale, Lebogang; Manoto, Sello Lebohang; Lemboumba, Satuurnin Ombinda; Maaza, Malik; Mthunzi-Kufa, Patience

2017-02-01

Embryonic stem cells have great promise in regenerative medicine because of their ability to self-renew and differentiate into various cell types. Delivery of therapeutic genes into cells has already been achieved using of chemical agents and viral vectors with high transfection efficiencies. However, these methods have also been documented as toxic and in the latter case they can cause latent cell infections. In this study we use femtosecond laser pulses to optically deliver genetic material in mouse embryonic stem cells. Femtosecond laser pulses in contrast to the conventional approach, minimises the risk of unwanted side effects because photons are used to create transient pores on the membrane which allow free entry of molecules with no need for delivery agents. Using an Olympus microscope, fluorescence imaging of the samples post irradiation was performed and decreased expression of stage specific embryonic antigen one (SSEA-1) consistent with on-going cellular differentiation was observed. Our results also show that femtosecond laser pulses were effective in delivering SOX 17 plasmid DNA (pSOX17) which resulted in the differentiation of mouse embryonic stem cells into endoderm cells. We thus concluded that laser transfection of stem cells for the purpose of differentiation, holds potential for applications in tissue engineering as a method of generating new cell lines.

N-Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

PubMed Central

Gottardi, Waldemar; Debabov, Dmitri

2013-01-01

Antibiotic resistance is a growing public health crisis. To address the development of bacterial resistance, the use of antibiotics has to be minimized for nonsystemic applications in humans, as well as in animals and plants. Possible substitutes with low potential for developing resistance are active chlorine compounds that have been in clinical use for over 180 years. These agents are characterized by pronounced differences in their chlorinating and/or oxidizing activity, with hypochlorous acid (HOCl) as the strongest and organic chloramines as the weakest members. Bacterial killing in clinical practice is often associated with unwanted side effects such as chlorine consumption, tissue irritation, and pain, increasing proportionally with the chlorinating/oxidizing potency. Since the chloramines are able to effectively kill pathogens (bacteria, fungi, viruses, protozoa), their application as anti-infectives is advisable, all the more so as they exhibit additional beneficial properties such as destruction of toxins, degradation of biofilms, and anticoagulative and anti-inflammatory activities. Within the ample field of chloramines, the stable N-chloro derivatives of ß-aminosulfonic acids are most therapeutically advanced. Being available as sodium salts, they distinguish themselves by good solubility and absence of smell. Important representatives are N-chlorotaurine, a natural compound occurring in the human immune system, and novel mono- and dichloro derivatives of dimethyltaurine, which feature improved stability. PMID:23295936

Multiplex networks in metropolitan areas: generic features and local effects

PubMed Central

Strano, Emanuele; Shai, Saray; Dobson, Simon; Barthelemy, Marc

2015-01-01

Most large cities are spanned by more than one transportation system. These different modes of transport have usually been studied separately: it is however important to understand the impact on urban systems of coupling different modes and we report in this paper an empirical analysis of the coupling between the street network and the subway for the two large metropolitan areas of London and New York. We observe a similar behaviour for network quantities related to quickest paths suggesting the existence of generic mechanisms operating beyond the local peculiarities of the specific cities studied. An analysis of the betweenness centrality distribution shows that the introduction of underground networks operate as a decentralizing force creating congestion in places located at the end of underground lines. Also, we find that increasing the speed of subways is not always beneficial and may lead to unwanted uneven spatial distributions of accessibility. In fact, for London—but not for New York—there is an optimal subway speed in terms of global congestion. These results show that it is crucial to consider the full, multimodal, multilayer network aspects of transportation systems in order to understand the behaviour of cities and to avoid possible negative side-effects of urban planning decisions. PMID:26400198

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

When is a medicine unwanted, how is it disposed, and how might safe disposal be promoted? Insights from the Australian population.

PubMed

Bettington, Emilie; Spinks, Jean; Kelly, Fiona; Gallardo-Godoy, Alejandra; Nghiem, Son; Wheeler, Amanda J

2017-12-19

Objective The aim of the present study was to explore disposal practices of unwanted medicines in a representative sample of Australian adults, compare this with previous household waste surveys and explore awareness of the National Return and Disposal of Unwanted Medicines (RUM) Project. Methods A 10-min online survey was developed, piloted and conducted with an existing research panel of adult individuals. Survey questions recorded demographics, the presence of unwanted medicines in the home, medicine disposal practices and concerns about unwanted medicines. Descriptive statistical analyses and rank-ordered logit regression were conducted. Results Sixty per cent of 4302 respondents reported having unwanted medicines in their household. Medicines were primarily kept just in case they were needed again and one-third of these medicines were expired. Two-thirds of respondents disposed of medicines with the household garbage and approximately one-quarter poured medicines down the drain. Only 17.6% of respondents had heard of the RUM Project, although, once informed, 91.7% stated that they would use it. Respondents ranked the risk of unintended ingestion as the most important public health message for future social marketing campaigns. Conclusions Respondents were largely unaware of the RUM Project, yet were willing to use it once informed. Limited awareness could lead to environmental or public health risks, and targeted information campaigns are needed. What is known about the topic? There is a growing international evidence base on how people dispose of unwanted medicines and the negative consequences, particularly the environmental effects of inappropriate disposal. Although insight into variation in disposal methods is increasing, knowledge of how people perceive risks and awareness of inappropriate disposal methods is more limited. What does this paper add? This study provides evidence of inappropriate medicines disposal and potential stockpiling of medicines in Australian households that could contribute to environmental and/or public health risks. It also reveals possible trends towards a higher frequency of inappropriate disposal practices in the Australian context. Insights into respondents' perceptions of associated risks and awareness of a national scheme for appropriate disposal of medicines have not previously been reported. What are the implications for practitioners? The findings of the present study provide important insights for all health professionals as stakeholders in the quality use of medicines. It is important for those health professionals who assist consumers to manage their medicines to have strategies in place that routinely identify potential stockpiling and inform consumers about appropriate methods of medicines disposal. Although the findings of this study are specific to the Australian context, they may usefully inform policy, public health campaigns and the individual practices of health professionals and other stakeholders in promoting the quality use of medicines nationally and internationally.

Eyewitness identification in simultaneous and sequential lineups: an investigation of position effects using receiver operating characteristics.

PubMed

Meisters, Julia; Diedenhofen, Birk; Musch, Jochen

2018-04-20

For decades, sequential lineups have been considered superior to simultaneous lineups in the context of eyewitness identification. However, most of the research leading to this conclusion was based on the analysis of diagnosticity ratios that do not control for the respondent's response criterion. Recent research based on the analysis of ROC curves has found either equal discriminability for sequential and simultaneous lineups, or higher discriminability for simultaneous lineups. Some evidence for potential position effects and for criterion shifts in sequential lineups has also been reported. Using ROC curve analysis, we investigated the effects of the suspect's position on discriminability and response criteria in both simultaneous and sequential lineups. We found that sequential lineups suffered from an unwanted position effect. Respondents employed a strict criterion for the earliest lineup positions, and shifted to a more liberal criterion for later positions. No position effects and no criterion shifts were observed in simultaneous lineups. This result suggests that sequential lineups are not superior to simultaneous lineups, and may give rise to unwanted position effects that have to be considered when conducting police lineups.

Predictability of the individual clinical outcome of extracorporeal shock wave therapy for cellulite

PubMed Central

Schlaudraff, Kai-Uwe; Kiessling, Maren C; Császár, Nikolaus BM; Schmitz, Christoph

2014-01-01

Background Extracorporeal shock wave therapy has been successfully introduced for the treatment of cellulite in recent years. However, it is still unknown whether the individual clinical outcome of cellulite treatment with extracorporeal shock wave therapy can be predicted by the patient’s individual cellulite grade at baseline, individual patient age, body mass index (BMI), weight, and/or height. Methods Fourteen Caucasian females with cellulite were enrolled in a prospective, single-center, randomized, open-label Phase II study. The mean (± standard error of the mean) cellulite grade at baseline was 2.5±0.09 and mean BMI was 22.8±1.17. All patients were treated with radial extracorporeal shock waves using the Swiss DolorClast® device (Electro Medical Systems, S.A., Nyon, Switzerland). Patients were treated unilaterally with 2 weekly treatments for 4 weeks on a randomly selected side (left or right), totaling eight treatments on the selected side. Treatment was performed at 3.5–4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were homogeneously distributed over the posterior thigh and buttock area (resulting in 7,500 impulses per area). Treatment success was evaluated after the last treatment and 4 weeks later by clinical examination, photographic documentation, contact thermography, and patient satisfaction questionnaires. Results The mean cellulite grade improved from 2.5±0.09 at baseline to 1.57±0.18 after the last treatment (ie, mean δ-1 was 0.93 cellulite grades) and 1.68±0.16 at follow-up (ie, mean δ-2 was 0.82 cellulite grades). Compared with baseline, no patient’s condition worsened, the treatment was well tolerated, and no unwanted side effects were observed. No statistically significant (ie, P<0.05) correlation was found between individual values for δ-1 and δ-2 and cellulite grade at baseline, BMI, weight, height, or age. Conclusion Radial shock wave therapy is a safe and effective treatment option for cellulite. The individual clinical outcome cannot be predicted by the patient’s individual cellulite grade at baseline, BMI, weight, height, or age. PMID:24920933

Predictability of the individual clinical outcome of extracorporeal shock wave therapy for cellulite.

PubMed

Schlaudraff, Kai-Uwe; Kiessling, Maren C; Császár, Nikolaus Bm; Schmitz, Christoph

2014-01-01

Extracorporeal shock wave therapy has been successfully introduced for the treatment of cellulite in recent years. However, it is still unknown whether the individual clinical outcome of cellulite treatment with extracorporeal shock wave therapy can be predicted by the patient's individual cellulite grade at baseline, individual patient age, body mass index (BMI), weight, and/or height. Fourteen Caucasian females with cellulite were enrolled in a prospective, single-center, randomized, open-label Phase II study. The mean (± standard error of the mean) cellulite grade at baseline was 2.5±0.09 and mean BMI was 22.8±1.17. All patients were treated with radial extracorporeal shock waves using the Swiss DolorClast(®) device (Electro Medical Systems, S.A., Nyon, Switzerland). Patients were treated unilaterally with 2 weekly treatments for 4 weeks on a randomly selected side (left or right), totaling eight treatments on the selected side. Treatment was performed at 3.5-4.0 bar, with 15,000 impulses per session applied at 15 Hz. Impulses were homogeneously distributed over the posterior thigh and buttock area (resulting in 7,500 impulses per area). Treatment success was evaluated after the last treatment and 4 weeks later by clinical examination, photographic documentation, contact thermography, and patient satisfaction questionnaires. The mean cellulite grade improved from 2.5±0.09 at baseline to 1.57±0.18 after the last treatment (ie, mean δ-1 was 0.93 cellulite grades) and 1.68±0.16 at follow-up (ie, mean δ-2 was 0.82 cellulite grades). Compared with baseline, no patient's condition worsened, the treatment was well tolerated, and no unwanted side effects were observed. No statistically significant (ie, P<0.05) correlation was found between individual values for δ-1 and δ-2 and cellulite grade at baseline, BMI, weight, height, or age. Radial shock wave therapy is a safe and effective treatment option for cellulite. The individual clinical outcome cannot be predicted by the patient's individual cellulite grade at baseline, BMI, weight, height, or age.

Cuttlefish Ink Melanin Encapsulated in Nanolipid Bubbles and Applied Through a Micro-Needling Procedure Easily Stains White Hair Facilitating Photoepilation.

PubMed

Trelles, Mario A; Almudever, Patricia; Alcolea, Justo M; Cortijo, Julio; Serrano, Gabriel; Expósito, Inmaculada; Royo, Josefina; Leclère, Franck Marie

2016-05-01

Photothermolysis of unwanted hair depends on the presence of melanin in the hair follicle as the chromophore, but is not effective in patients with non-pigmented, melanin-sparse hair shafts and follicles. This split-scalp, double-blind study was to monitor the efficacy of melanin bound in nanosomes to inject exogenous melanin into the hair follicles thus potentiating successful photothermolysis.
Twelve patients, phototypes II-III, with white or very fair hair, were treated with a compound containing melanin encapsulated in nanosomes (Melaser^®) together with a fluorescent marker. Two equal 6 cm² areas were marked on each side of the occiput of the subjects. The compound was applied to a randomly selected experimental side on each patient (area A), and a saline solution applied in the same manner to the contralateral control side (area B). Penetration of the melanin into the hair follicle was assessed using optical and fluorescence microscopy. Also, condition of hair structure was checked in vivo after standard laser settings used for epilation.
A slight transient erythema was observed in those areas where the compound was applied with some perifollicular edema. No such effects were noticed in those areas where saline solution was applied. No persistent complications such as scarring, hypo- or hyperpigmentation were observed in any of the experimental or control areas. Under fluorescence microscopy, the hair structures in the areas to which the compound had been applied showed a clear melanin deposit confirmed by the immunofluorescence intensity, which was highest at 2 hours after application. By optical microscopy, external melanin was deposited in hair follicles. Tests with standard settings for epilation were efficacious in damaging melanin-marked white hair.
This study strongly suggests the safety and efficacy of the application of nanosomes encapsulating melanin for the introduction of melanin into hair follicles. Changes noticed in the hair structure compromising its viability indicated potential application of this external melanin marker for white hair photoepilation.

J Drugs Dermatol. 2016;15(5):615-625.

Phenotypic Screening Approaches to Develop Aurora Kinase Inhibitors: Drug Discovery Perspectives.

PubMed

Marugán, Carlos; Torres, Raquel; Lallena, María José

2015-01-01

Targeting mitotic regulators as a strategy to fight cancer implies the development of drugs against key proteins, such as Aurora-A and -B. Current drugs, which target mitosis through a general mechanism of action (stabilization/destabilization of microtubules), have several side effects (neutropenia, alopecia, and emesis). Pharmaceutical companies aim at avoiding these unwanted effects by generating improved and selective drugs that increase the quality of life of the patients. However, the development of these drugs is an ambitious task that involves testing thousands of compounds through biochemical and cell-based assays. In addition, molecules usually target complex biological processes, involving several proteins and different molecular pathways, further emphasizing the need for high-throughput screening techniques and multiplexing technologies in order to identify drugs with the desired phenotype. We will briefly describe two multiplexing technologies [high-content imaging (HCI) and flow cytometry] and two key processes for drug discovery research (assay development and validation) following our own published industry quality standards. We will further focus on HCI as a useful tool for phenotypic screening and will provide a concrete example of HCI assay to detect Aurora-A or -B selective inhibitors discriminating the off-target effects related to the inhibition of other cell cycle or non-cell cycle key regulators. Finally, we will describe other assays that can help to characterize the in vitro pharmacology of the inhibitors.

Sexual Orientation Disparities in Mistimed and Unwanted Pregnancy Among Adult Women.

PubMed

Everett, Bethany G; McCabe, Katharine F; Hughes, Tonda L

2017-09-01

Many sexual minority women, regardless of sexual identity, engage in heterosexual behavior across the life course, which provides them opportunities to experience an unintended pregnancy. In addition, sexual minority women are more likely than others to report characteristics that may make them vulnerable to unintended pregnancy. Little research, however, has examined whether the risk of unintended pregnancy is elevated among these women. Using data from the 2006-2010 National Survey of Family Growth, logistic regression models were fitted to examine sexual orientation disparities in mistimed and unwanted pregnancies among 9,807 women aged 20-45; mixed-effects hazard models assessed disparities in the intention status of 5,238 pregnancies among these women by maternal sexual orientation. Compared with heterosexual women reporting only male partners, heterosexual women who have sex with women had higher odds of reporting a mistimed pregnancy (odds ratio, 1.4), and bisexual women had higher odds of reporting an unwanted pregnancy (1.8). When compared with pregnancies reported by heterosexual women with only male partners, those reported by heterosexual women who have sex with women were more likely to be mistimed (hazard ratio, 1.7), and those reported by bisexual and lesbian women were more likely to be unwanted (1.7-4.4). Compared with heterosexuals who have sex with men only, adult sexual minority women are at equal or greater risk of reporting an unintended pregnancy. More research addressing the reproductive health care needs of sexual minority women is needed to develop strategies to improve family planning for this population. Copyright © 2017 by the Guttmacher Institute.

Examining the geographical heterogeneity associated with risk of mistimed and unwanted pregnancy in Ghana.

PubMed

Amoako Johnson, Fiifi; Madise, Nyovani J

2009-03-01

After a decade of fertility decline, Ghana's fertility and the level of unmet need for contraception stalled in mid-transition in the late 1990s. Although the literature acknowledges this, the geographical patterns in unmet need have not been adequately documented. Spatial analysis of unmet need can reveal differences in usage and provision of contraceptive commodities, thereby pointing to geographical areas where contraceptive programmes should be strengthened. This study examines the geographical variation of the risk of mistimed and unwanted pregnancies between rural communities and also between urban communities of the three ecological zones of Ghana. The study also investigates if geographical differences in the risks of mistimed and unwanted pregnancies changed during the period when unmet need stalled at the national level. A multilevel regression model was applied to pooled data from the 1998 and 2003 Ghana Demographic and Health Surveys to examine the determinants of the risk of unintended pregnancies, while controlling for clustering of outcomes within communities. The results show that between the two surveys, there was no significant change in the levels of risk of mistimed and unwanted pregnancy. However, geographical heterogeneity in the risk of mistimed and unwanted pregnancy was observed, after controlling for relevant predictors. This showed concentration of mistimed pregnancies in some rural communities relative to others, and variation in the risk of unwanted pregnancies between urban communities. The results give a clear indication that bridging the inequality gap in contraceptive use requires programmes that are area-specific.

Can't control yourself? Monitor those bad habits.

PubMed

Quinn, Jeffrey M; Pascoe, Anthony; Wood, Wendy; Neal, David T

2010-04-01

What strategies can people use to control unwanted habits? Past work has focused on controlling other kinds of automatic impulses, especially temptations. The nature of habit cuing calls for certain self-control strategies. Because the slow-to-change memory trace of habits is not amenable to change or reinterpretation, successful habit control involves inhibiting the unwanted response when activated in memory. In support, two episode-sampling diary studies demonstrated that bad habits, unlike responses to temptations, were controlled most effectively through spontaneous use of vigilant monitoring (thinking "don't do it," watching carefully for slipups). No other strategy was useful in controlling strong habits, despite that stimulus control was effective at inhibiting responses to temptations. A subsequent experiment showed that vigilant monitoring aids habit control, not by changing the strength of the habit memory trace but by heightening inhibitory, cognitive control processes. The implications of these findings for behavior change interventions are discussed.

Perceptions of sexual coercion: learning from young people in Ibadan, Nigeria.

PubMed

Ajuwon, A J; Akin-Jimoh, I; Olley, B O; Akintola, O

2001-05-01

This study explored the problem of sexual coercion from the perspectives of 77 young people aged 14-21 in Ibadan, Nigeria, the behaviours they perceive to be sexually coercive and the contexts in which these occur through four narrative workshops. Participants were drawn from two secondary schools and 15 apprentice workshops. All four groups identified similar coercive behaviours and developed narratives of the events that typically lead up to them. Behaviours included rape, unwanted touching, incest, assault, verbal abuse, threats, unwanted kissing; forced exposure to pornographic films, use of drugs for sedation and traditional charms for seduction, and insistence on abortion if unwanted pregnancy occurs. Men were typically the perpetrators and young women the victims. Perpetrators included acquaintances, boyfriends, neighbours, parents and relatives. All the narratives revealed the inability of young people to communicate effectively with each other and resolve differences. The results suggest the need for life-skills training that facilitates communication, seeks to redress gender power imbalances, teaches alternatives to coercion as a means of resolving conflict over sexual relations and respect for sexual and reproductive rights, and provides victims with information on appropriate services, support and referral.

Emergency contraception amongst female college students – knowledge, attitude and practice

PubMed Central

Nibabe, Wendwosen T.

2014-01-01

Background Unwanted teenage pregnancies have a notable detrimental impact on the learners’ trajectory and have been associated with jeopardising the students’ educational progress and future career prospects. These pregnancies are mostly unplanned and unintended and many are terminated, either legally or illegally. Aim The aim of this study was to explore the contributory role played by the knowledge, attitude and practices of female college students with respect to the utilisation of emergency contraceptives. Setting Three tertiary institutions in Dessie, Ethiopia. Methods Quantitative self-administered questionnaires were used to collect descriptive data from 352 female college students. Results The study revealed that there was a high percentage (78.3%) of unwanted pregnancies amongst those engaging in sex. Significantly, nearly half (43.3%) of these unwanted pregnancies resulted in abortion. Only 10% of the students sampled admitted to ever having used emergency contraception. Even though more than half (69.9%) of the students knew about emergency contraception, only 27% of them felt confident that they understood when it was most effective. Conclusion These and other observed findings confirm the need for improvement of female college students’ knowledge and timely utilisation of emergency contraception. PMID:26245395

Anti-P-glycoprotein conjugated nanoparticles for targeting drug delivery in cancer treatment.

PubMed

Iangcharoen, Pantiwa; Punfa, Wanisa; Yodkeeree, Supachai; Kasinrerk, Watchara; Ampasavate, Chadarat; Anuchapreeda, Songyot; Limtrakul, Pornngarm

2011-10-01

Targeting therapeutics to specific sites can enhance the efficacy of drugs, reduce required doses as well as unwanted side effects. In this work, using the advantages of the specific affinity of an immobilized antibody to membrane P-gp in two different nanoparticle formulations were thus developed for targeted drug delivery to multi-drug resistant cervical carcinoma (KB-V1) cells. Further, this was compared to the human drug sensitive cervical carcinoma cell line (KB-3-1) cells. The two nanoparticle preparations were: NP1, anti-P-gp conjugated with poly (DL-lactic-coglycolic acid) (PLGA) nanoparticle and polyethylene glycol (PEG); NP2, anti-P-gp conjugated to a modified poloxamer on PLGA nanoparticles. The cellular uptake capacity of nanoparticles was confirmed by fluorescent microscopy. Comparing with each counterpart core particles, there was a higher fluorescence intensity of the targeted nanoparticles in KBV1 cells compared to KB-3-1 cells suggesting that the targeted nanoparticles were internalized into KB-V1 cells to a greater extent than KB-3-1 cell. The results had confirmed the specificity and the potential of the developed targeted delivery system for overcoming multi-drug resistance induced by overexpression of P-gp on the cell membrane.

Improved Plaque Assay Identifies a Novel Anti-Chlamydia Ceramide Derivative with Altered Intracellular Localization

PubMed Central

Banhart, Sebastian; Saied, Essa M.; Martini, Andrea; Koch, Sophia; Aeberhard, Lukas; Madela, Kazimierz; Arenz, Christoph

2014-01-01

Chlamydia trachomatis is a medically important human pathogen causing different diseases, including trachoma, the leading cause of preventable blindness in developing countries, and sexually transmitted infections that can lead to infertility and ectopic pregnancies. There is no vaccine against C. trachomatis at present. Broad-spectrum antibiotics are used as standard therapy to treat the infection but have unwanted side effects, such as inducing persistent or recurring infections and affecting the host microbiome, necessitating the development of novel anti-Chlamydia therapies. Here, we describe the establishment of a robust, fast, and simple plaque assay using liquid overlay medium (LOM) for the identification of anti-Chlamydia compounds. Using the LOM plaque assay, we identified nitrobenzoxadiazole (NBD)-labeled 1-O-methyl-ceramide-C16 as a compound that efficiently inhibits C. trachomatis replication without affecting the viability of the host cell. Further detailed analyses indicate that 1-O-methyl-NBD-ceramide-C16 acts outside the inclusion. Thereby, 1-O-methyl-NBD-ceramide-C16 represents a lead compound for the development of novel anti-Chlamydia drugs and furthermore constitutes an agent to illuminate sphingolipid trafficking pathways in Chlamydia infections. PMID:25001308

Computational Approaches to Drug Repurposing and Pharmacology

PubMed Central

Hodos, Rachel A; Kidd, Brian A; Khader, Shameer; Readhead, Ben P; Dudley, Joel T

2016-01-01

Data in the biological, chemical, and clinical domains are accumulating at ever-increasing rates and have the potential to accelerate and inform drug development in new ways. Challenges and opportunities now lie in developing analytic tools to transform these often complex and heterogeneous data into testable hypotheses and actionable insights. This is the aim of computational pharmacology, which uses in silico techniques to better understand and predict how drugs affect biological systems, which can in turn improve clinical use, avoid unwanted side effects, and guide selection and development of better treatments. One exciting application of computational pharmacology is drug repurposing- finding new uses for existing drugs. Already yielding many promising candidates, this strategy has the potential to improve the efficiency of the drug development process and reach patient populations with previously unmet needs such as those with rare diseases. While current techniques in computational pharmacology and drug repurposing often focus on just a single data modality such as gene expression or drug-target interactions, we rationalize that methods such as matrix factorization that can integrate data within and across diverse data types have the potential to improve predictive performance and provide a fuller picture of a drug's pharmacological action. PMID:27080087

Regulatory systems for hypoxia-inducible gene expression in ischemic heart disease gene therapy.

PubMed

Kim, Hyun Ah; Rhim, Taiyoun; Lee, Minhyung

2011-07-18

Ischemic heart diseases are caused by narrowed coronary arteries that decrease the blood supply to the myocardium. In the ischemic myocardium, hypoxia-responsive genes are up-regulated by hypoxia-inducible factor-1 (HIF-1). Gene therapy for ischemic heart diseases uses genes encoding angiogenic growth factors and anti-apoptotic proteins as therapeutic genes. These genes increase blood supply into the myocardium by angiogenesis and protect cardiomyocytes from cell death. However, non-specific expression of these genes in normal tissues may be harmful, since growth factors and anti-apoptotic proteins may induce tumor growth. Therefore, tight gene regulation is required to limit gene expression to ischemic tissues, to avoid unwanted side effects. For this purpose, various gene expression strategies have been developed for ischemic-specific gene expression. Transcriptional, post-transcriptional, and post-translational regulatory strategies have been developed and evaluated in ischemic heart disease animal models. The regulatory systems can limit therapeutic gene expression to ischemic tissues and increase the efficiency of gene therapy. In this review, recent progresses in ischemic-specific gene expression systems are presented, and their applications to ischemic heart diseases are discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Dynamic CO₂ inhalation: a novel treatment for CSR-CSA associated with CHF.

PubMed

Wan, Zhi Hui; Wen, Fang Jing; Hu, Ke

2013-05-01

Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is very common in patients with chronic congestive heart failure (CHF). A current concept of the key pathophysiological mechanism leading to CSR-CSA is a fluctuation of PaCO2 below and above the apneic threshold. A number of therapeutic approaches for CSR-CSA have been proposed-all with varying success, some of which include various modes of positive airway pressure among other strategies. However, CO2 oscillations seen in CSR-CSA have yet to be looked at as a specific therapeutic target by current treatments. Previous studies have shown that delivery of constant CO2 is efficacious in eliminating CSR-CSA by raising PaCO2, but there are serious concerns about the potential side effects, such as unwanted elevations in ventilation, work of breathing, and sympathetic nerve activity (SNA), and consequently CO2 inhalation therapy has not been recommended as a routine option for therapy. However, recent new studies into CO2 inhalation therapy have been made that may reshape its role as therapeutic. In this review, we will focus on the recent developments of administration of dynamic CO2 in the management of CSR-CSA in CHF patients.

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

NASA Astrophysics Data System (ADS)

Gitter, K.; Odenbach, S.

2011-12-01

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.

AHR Activation Is Protective against Colitis Driven by T Cells in Humanized Mice.

PubMed

Goettel, Jeremy A; Gandhi, Roopali; Kenison, Jessica E; Yeste, Ada; Murugaiyan, Gopal; Sambanthamoorthy, Sharmila; Griffith, Alexandra E; Patel, Bonny; Shouval, Dror S; Weiner, Howard L; Snapper, Scott B; Quintana, Francisco J

2016-10-25

Existing therapies for inflammatory bowel disease that are based on broad suppression of inflammation result in variable clinical benefit and unwanted side effects. A potential therapeutic approach for promoting immune tolerance is the in vivo induction of regulatory T cells (Tregs). Here we report that activation of the aryl hydrocarbon receptor using the non-toxic agonist 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) induces human Tregs in vitro that suppress effector T cells through a mechanism mediated by CD39 and Granzyme B. We then developed a humanized murine system whereby human CD4 + T cells drive colitis upon exposure to 2,4,6-trinitrobenzenesulfonic acid and assessed ITE as a potential therapeutic. ITE administration ameliorated colitis in humanized mice with increased CD39, Granzyme B, and IL10-secreting human Tregs. These results develop an experimental model to investigate human CD4 + T responses in vivo and identify the non-toxic AHR agonist ITE as a potential therapy for promoting immune tolerance in the intestine. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Novel Serial Positive Enrichment Technology Enables Clinical Multiparameter Cell Sorting

PubMed Central

Tschulik, Claudia; Piossek, Christine; Bet, Jeannette; Yamamoto, Tori N.; Schiemann, Matthias; Neuenhahn, Michael; Martin, Klaus; Schlapschy, Martin; Skerra, Arne; Schmidt, Thomas; Edinger, Matthias; Riddell, Stanley R.; Germeroth, Lothar; Busch, Dirk H.

2012-01-01

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve – especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4high/CD25high/CD45RAhigh ‘regulatory T cells’ and CD8high/CD62Lhigh/CD45RAneg ‘central memory T cells’, have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research. PMID:22545138

Cell-Based Biohybrid Drug Delivery Systems: The Best of the Synthetic and Natural Worlds.

PubMed

Banskota, Samagya; Yousefpour, Parisa; Chilkoti, Ashutosh

2017-01-01

The goal of drug delivery is to deliver therapeutics to the site of disease while reducing unwanted side effects. In recent years, a diverse variety of synthetic nano and microparticles have been developed as drug delivery systems. The success of these systems for drug delivery lies in their ability to overcome biological barriers such as the blood-brain barrier, to evade immune clearance and avoid nonspecific biodistribution. This Review provides an overview of recent advances in the design of biohybrid drug delivery systems, which combine cells with synthetic systems to overcome some of these biological hurdles. Examples include eukaryotic cells, such as stem cells, red blood cells, immune cells, platelets, and cancer cells that are used to carry drug-loaded synthetic particles. Synthetic particles can also be cloaked with naturally derived cell membranes and thereby evade immune clearance, exhibit prolonged systemic circulation, and target specific tissues by capitalizing on the interaction/homing tendency of certain cells and their membrane components to particular tissues. Different designs of cell-based biohybrid systems and their applications, as well as their promise and limitations, are discussed herein. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Albumin nanostructures as advanced drug delivery systems

PubMed Central

Karimi, Mahdi; Bahrami, Sajad; Ravari, Soodeh Baghaee; Zangabad, Parham Sahandi; Mirshekari, Hamed; Bozorgomid, Mahnaz; Shahreza, Somayeh; Sori, Masume; Hamblin, Michael R.

2016-01-01

Introduction One of the biggest impacts that the nanotechnology has made on medicine and biology, has been in the area of drug delivery systems (DDSs). Many drugs suffer from serious problems concerning insolubility, instability in biological environments, poor uptake into cells and tissues, suboptimal selectivity for targets and unwanted side effects. Nanocarriers can be designed as DDSs to overcome many of these drawbacks. One of the most versatile building blocks to prepare these nanocarriers is the ubiquitous, readily available and inexpensive protein, serum albumin. Areas covered This review covers the use of different types of albumin (human, bovine, rat, and chicken egg) to prepare nanoparticle and microparticle-based structures to bind drugs. Various methods have been used to modify the albumin structure. A range of targeting ligands can be attached to the albumin that can be recognized by specific cell receptors that are expressed on target cells or tissues. Expert opinion The particular advantages of albumin used in DDSs include ready availability, ease of chemical modification, good biocompatibility, and low immunogenicity. The regulatory approvals that have been received for several albumin-based therapeutic agents suggest that this approach will continue to be successfully explored. PMID:27216915

Recent Advances in Marine Enzymes for Biotechnological Processes.

PubMed

Lima, R N; Porto, A L M

In the last decade, new trends in the food and pharmaceutical industries have increased concern for the quality and safety of products. The use of biocatalytic processes using marine enzymes has become an important and useful natural product for biotechnological applications. Bioprocesses using biocatalysts like marine enzymes (fungi, bacteria, plants, animals, algae, etc.) offer hyperthermostability, salt tolerance, barophilicity, cold adaptability, chemoselectivity, regioselectivity, and stereoselectivity. Currently, enzymatic methods are used to produce a large variety of products that humans consume, and the specific nature of the enzymes including processing under mild pH and temperature conditions result in fewer unwanted side-effects and by-products. This offers high selectivity in industrial processes. The marine habitat has been become increasingly studied because it represents a huge source potential biocatalysts. Enzymes include oxidoreductases, hydrolases, transferases, isomerases, ligases, and lyases that can be used in food and pharmaceutical applications. Finally, recent advances in biotechnological processes using enzymes of marine organisms (bacterial, fungi, algal, and sponges) are described and also our work on marine organisms from South America, especially marine-derived fungi and bacteria involved in biotransformations and biodegradation of organic compounds. © 2016 Elsevier Inc. All rights reserved.

Electron attachment to antipyretics: Possible implications of their metabolic pathways

NASA Astrophysics Data System (ADS)

Pshenichnyuk, Stanislav A.; Modelli, Alberto

2012-06-01

The empty-level structures and formation of negative ion states via resonance attachment of low-energy (0-15 eV) electrons into vacant molecular orbitals in a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely aspirin, paracetamol, phenacetin, and ibuprofen, were investigated in vacuo by electron transmission and dissociative electron attachment (DEA) spectroscopies, with the aim to model the behavior of these antipyretic agents under reductive conditions in vivo. The experimental findings are interpreted with the support of density functional theory calculations. The negative and neutral fragments formed by DEA in the gas phase display similarities with the main metabolites of these commonly used NSAIDs generated in vivo by the action of cytochrome P450 enzymes, as well as with several known active agents. It is concluded that xenobiotic molecules which possess pronounced electron-accepting properties could in principle follow metabolic pathways which parallel the gas-phase dissociative decay channels observed in the DEA spectra at incident electron energies below 1 eV. Unwanted side effects as, e.g., hepatoxicity or carcinogenicity produced by the NSAIDs under study in human organism are discussed within the "free radical model" framework, reported earlier to describe the toxic action of the well-known model toxicant carbon tetrachloride.

Intimate partner violence and unwanted pregnancy, miscarriage, induced abortion, and stillbirth among a national sample of Bangladeshi women.

PubMed

Silverman, J G; Gupta, J; Decker, M R; Kapur, N; Raj, A

2007-10-01

To estimate (1) lifetime prevalence of physical and sexual victimisation from husbands among a national sample of Bangladeshi women, (2) associations of unwanted pregnancy and experiences of husband violence, and (3) associations of miscarriage, induced abortion, and fetal death/stillbirth and such victimisation. Cross-sectional, nationally representative study utilizing matched husband-wife data from the 2004 MEASURE Bangladesh Demographic Health Survey. Bangladesh. Married Bangladeshi women ages 13-40 years old (n = 2677). Bivariate and multivariate logistic regression analysis. Relations of intimate partner violence to unwanted pregnancy, miscarriage, induced abortion and stillbirth. Three out of four (75.6%) Bangladeshi women experienced violence from husbands. Less educated, poorer, and Muslim women were at greatest risk. Women experiencing violence from husbands were more likely to report both unwanted pregnancy (ORs(adj) 1.46-1.54) and a pregnancy loss in the form of miscarriage, induced abortion, or stillbirth (ORs(adj) 1.43-1.69). Assessed individually, miscarriage was more likely among victimised women (OR(adj) 1.81). A nonsignificant trend was detected for increased risk of induced abortion (OR(adj) 1.64); stillbirth was unrelated to violence from husbands. Intimate partner violence is extremely prevalent and relates to unwanted pregnancy and higher rates of pregnancy loss or termination, particularly miscarriages, among Bangladeshi women. Investigation of mechanisms responsible for these associations will be critical to developing interventions to improve maternal, fetal, and neonatal health. Such programmes may be vital to reducing the significant health and social costs associated with both husband violence and unwanted and adverse pregnancy outcomes.

Unwanted pregnancy and traditional self-induced abortion methods known among women aged 15 to 49.

PubMed

Sensoy, Nazli; Dogan, Nurhan; Sen, Kubra; Aslan, Halit; Tore-Baser, Ayca

2015-05-01

To determine the traditional methods known and used to terminate an unwanted pregnancy and the fertility characteristics of married women. The descriptive cross-sectional study was conducted in Turkey at Afyonkarahisar Zübeyde Hanim Child and Maternity Hospital's outpatient clinic between December 27, 2010 and January 7, 2011, and comprised married women aged 17 to 49 who presented for an examination. Questions related to socio-demographic and fertility characteristics as well as known and used traditional abortion methods were included in the questionnaire which was administered through face-to-face interviews. SPSS 18.0 was used for statistical analysis. The median age of the 600 women in the study was 29.5 (range: 17-49) years. Overall, 134 (22.3%) women had experienced an unwanted pregnancy. In 53 (39.6%) cases, the unwanted pregnancy had occurred between the ages of 30 and 39, and 116(86.6%) women had married when they were between 15 and 24 (p< 0.008) years old. Pregnancy had been concluded normally in 78(58.2%)women with an unwanted pregnancy and 34(35.8%)preferred the withdrawal method for contraception. Traditional abortion methods were known to 413(68.8%)women, but only 8(1.3%) had used any of them. The harms of using a traditional abortion method were known to 464(77.3%)women. Very few women used traditional abortion methods to terminate pregnancy. Knowing the characteristics of women and their need for family planning should be the first priority for the prevention of unwanted pregnancies.

Sexual violence and use of contraception among women with unwanted pregnancy in an Ngo Clinic, Addis Ababa.

PubMed

Dessalegn, Solomon; Kumbi, Solomon; Surur, Feruz

2008-10-01

Sexual violence is one of the most prevalent but underreported incidents. One among many consequences of sexual violence is unwanted pregnancy. To describe events related to and factors associated with sexual violence among women with unwanted pregnancy and describe knowledge and use of contraception among these women with unwanted pregnancy. This cross-sectional study was done at one NGO clinic in Addis Ababa. Data was collected from women with unwanted pregnancy seeking termination of pregnancy using a structured questionnaire in March 2003. Sociodemographic variables were analyzed with selected variables related to sexual violence, knowledge and practice of contraception among these women seeking termination of pregnancy. Of the 394 women seeking termination of pregnancy, there was unwelcome kiss in 26.9%, attempted rape in 23.9% and completed rape in 18.3%. Most, 63/72 (87.5%), of the victims of completed rape were below 25 years of age. A linear trend was observed with increasing age (P < 0.05, X2 = 24.365). Unmarried and economically dependent groups were more vulnerable to rape related pregnancy, P < 0.05. Only 18/72 (25%) reported to the police. Psychological problems were common in women with completed rape. Suicidal thoughts was reported by 8/72 (11%). Only 84/394 (21.3%) used contraceptives of which 29/84 (34.5%) used emergency contraceptives. Unwanted pregnancy as a result of rape was observed more in younger, unmarried and economically dependent women. Use of contraception including emergency contraception, reporting to legal authorities and health professionals was low.

Massage for symptom relief in patients with cancer: systematic review.

PubMed

Wilkinson, Susie; Barnes, Kelly; Storey, Lesley

2008-09-01

This paper is a report of a review to assess evidence of the effectiveness of massage for patients with cancer, in terms of reducing physical or psychological symptoms, improving quality of life, or producing unwanted side effects. Patients with cancer may use complementary therapies, including massage and aromatherapy massage. However, their use and provision by state-financed healthcare services is controversial. A systematic review was carried out, using the Cochrane principles. No meta-analysis was appropriate. An initial comprehensive search of electronic databases search was carried out in 2003 and updated in 2006. Eligible trials were randomized controlled trials, controlled before-and-after (pre-post) studies and interrupted time-series studies. Participants were adults with a diagnosis of cancer and receiving care in any healthcare setting. Interventions were limited to massage and/or aromatherapy massage carried out by a qualified therapist. Outcome measures to be included were patient-reported levels of physical and psychological indices of symptom distress and quality of life (measured using validated assessment tools). In the review, 1325 papers were considered. Ten trials met the inclusion criteria and their results suggest that massage might reduce anxiety in patients with cancer in the short term and may have a beneficial effect on physical symptoms of cancer, such as pain and nausea. However, the lack of rigorous research evidence precludes drawing definitive conclusions. Further well-designed large trials with longer follow-up periods are needed to be able to draw firm conclusions about the efficacy and effectiveness of massage for cancer patients.

Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.

PubMed

Coppen, Emma M; Roos, Raymund A C

2017-01-01

There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington's disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.

Cannabis as a Substitute for Opioid-Based Pain Medication: Patient Self-Report

PubMed Central

Reiman, Amanda; Welty, Mark; Solomon, Perry

2017-01-01

Abstract Introduction: Prescription drug overdoses are the leading cause of accidental death in the United States. Alternatives to opioids for the treatment of pain are necessary to address this issue. Cannabis can be an effective treatment for pain, greatly reduces the chance of dependence, and eliminates the risk of fatal overdose compared to opioid-based medications. Medical cannabis patients report that cannabis is just as effective, if not more, than opioid-based medications for pain. Materials and Methods: The current study examined the use of cannabis as a substitute for opioid-based pain medication by collecting survey data from 2897 medical cannabis patients. Discussion: Thirty-four percent of the sample reported using opioid-based pain medication in the past 6 months. Respondents overwhelmingly reported that cannabis provided relief on par with their other medications, but without the unwanted side effects. Ninety-seven percent of the sample “strongly agreed/agreed” that they are able to decrease the amount of opiates they consume when they also use cannabis, and 81% “strongly agreed/agreed” that taking cannabis by itself was more effective at treating their condition than taking cannabis with opioids. Results were similar for those using cannabis with nonopioid-based pain medications. Conclusion: Future research should track clinical outcomes where cannabis is offered as a viable substitute for pain treatment and examine the outcomes of using cannabis as a medication assisted treatment for opioid dependence. PMID:28861516

You have been framed! How antecedents of information need mediate the effects of risk communication messages.

PubMed

Terpstra, T; Zaalberg, R; de Boer, J; Botzen, W J W

2014-08-01

This study investigates the processes that mediate the effects of framing flood risks on people's information needs. Insight into the effects of risk frames is important for developing balanced risk communication that explains both risks and benefits of living near water. The research was inspired by the risk information seeking and processing model and related models. In a web-based survey, respondents (n = 1,457) were randomly assigned to one of three communication frames or a control frame (experimental conditions). Each frame identically explained flood risk and additionally refined the message by emphasizing climate change, the quality of flood risk management, or the amenities of living near water. We tested the extent to which risk perceptions, trust, and affective responses mediate the framing effects on information need. As expected, the frames on average resulted in higher information need than the control frame. Attempts to lower fear appeal by stressing safety or amenities instead of climate change were marginally successful, a phenomenon that is known as a "negativity bias." Framing effects were mediated by negative attributes (risk perception and negative affect) but not by positive attributes (trust and positive affect). This finding calls for theoretical refinement. Practically, communication messages will be more effective when they stimulate risk perceptions and evoke negative affect. However, arousal of fear may have unwanted side effects. For instance, fear arousal could lead to lower levels of trust in risk management among citizens. Regular monitoring of citizens' attitudes is important to prevent extreme levels of distrust or cynicism. © 2014 Society for Risk Analysis.

The Science of Prescribed Fire: to Enable a Different Kind of Control

Treesearch

Timothy E. Paysen; Marcia G. Narog; Jack D. Cohen

1998-01-01

A paradigm shift from fire suppression to fire suppression and prescription requires a shift in emphasis from simply controlling wildfire occurrence and spread to one that includes controlling characteristics of prescribed fire. Suppression focuses on preventing unwanted effects that might result from wildfire occurrence. Prescription promotes desired effects by...

Why biosecurity matters: students' knowledge of biosecurity and implications for future engagement with biosecurity initiatives

NASA Astrophysics Data System (ADS)

Ram, Rajesh; France, Bev; Birdsall, Sally

2016-01-01

Background: Research on biosecurity is important as New Zealand's agricultural export-driven economy is susceptible to biosecurity threats. Because New Zealand is reliant on the primary industries to drive its economy, bovine diseases such as foot and mouth could have a devastating effect on the economy. Purpose: Making sure that the general public are aware of the importance of maintaining biosecurity is crucial in order to protect New Zealand's economy, human health, the environment, and social and cultural values. New Zealand Year 9 students' knowledge of biosecurity was gauged as these students represented the next generation of individuals tasked to maintain biosecurity in New Zealand. Design: A qualitative approach using the interpretive mode of inquiry was used to investigate the knowledge about biosecurity with New Zealand Year 9 students. Questionnaires and interviews were the data collection tools. Sample: One hundred and seventy-one students completed a questionnaire that consisted of Likert-type questions and open-ended questions. Nine students were interviewed about their knowledge. Results: The findings showed that New Zealand Year 9 students lacked specific knowledge about unwanted plants, animals and microorganisms. These students saw illicit drug plants as unwanted plants and mainly saw possums as unwanted animals in New Zealand. Their knowledge about unwanted microorganisms in New Zealand was dominated by human-disease-causing microbes. A lack of knowledge of biosecurity issues in New Zealand was seen as the major factor in these students limited understanding of biosecurity. Conclusions: Based on these findings, it can be said that knowledge of an issue is critical in enabling individuals to develop an understanding about biosecurity. Explicit teaching of biosecurity-related curriculum topics could provide New Zealand Year 9 students with an opportunity to develop knowledge about biosecurity in New Zealand.

The clinical outcome of skeletal anchorage in interceptive treatment (in growing patients) for class III malocclusion.

PubMed

Meyns, J; Brasil, D M; Mazzi-Chaves, J F; Politis, C; Jacobs, R

2018-04-27

A systematic review of the literature was performed regarding the clinical outcome (effectiveness) of bone anchorage devices in interceptive treatment for class III malocclusion. A search of Embase, PubMed and Web of Science databases yielded 285 papers. An additional two articles were retrieved through manual searching of the reference lists. After initial abstract selection, 32 potentially eligible articles were screened in detail, resulting in a final number of eight articles included in this review. Insufficient evidence was found regarding the effects of skeletal anchorage in interceptive class III treatment to support definitive conclusions on long-term skeletal effects and stability. In the short term, it seems that bone anchors can provide more skeletal effect with less dentoalveolar compensations and less unwanted vertical changes. This does not always exclude the use of a face mask. The use of miniscrews as skeletal anchorage device does not seem to provide more skeletal effect, although it could minimize the unwanted dental effects in the upper jaw. No information regarding the need for orthognathic surgery, orthodontic treatment time or patient compliance and complications was found in the selected articles. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

40 CFR 262.214 - Laboratory management plan.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Waste Determination and Accumulation of Unwanted Material for Laboratories Owned by Eligible Academic Entities § 262.214 Laboratory management plan. An eligible academic entity must develop and retain a... a site-specific document that describes how the eligible academic entity will manage unwanted...

Home and parenting resources available to siblings depending on their birth intention status.

PubMed

Barber, Jennifer S; East, Patricia L

2009-01-01

This study examines the differential availability of family and parenting resources to children depending on their birth planning status. The National Longitudinal Survey of Youth data were analyzed, 3,134 mothers and their 5,890 children (M = 7.1 years, range = 1 month-14.8 years), of whom 63% were intended at conception, 27% were mistimed, and 10% were unwanted. Fixed-effects models show that unwanted and mistimed children had fewer resources than intended siblings. Parents' emotional resources to older children decreased after the birth of a mistimed sibling. Findings suggest that cognitive and emotional resources are differentially available to children within a family depending on intention status and that unintended births lead to decreased parental resources for older children in the household.

Predictors of mistimed, and unwanted pregnancies among women of childbearing age in Rufiji, Kilombero, and Ulanga districts of Tanzania

PubMed Central

2014-01-01

Background While unintended pregnancies pose a serious threat to the health and well-being of families globally, characteristics of Tanzanian women who conceive unintentionally are rarely documented. This analysis identifies factors associated with unintended pregnancies—both mistimed and unwanted—in three rural districts of Tanzania. Methods A cross-sectional survey of 2,183 random households was conducted in three Tanzanian districts of Rufiji, Kilombero, and Ulanga in 2011 to assess women’s health behavior and service utilization patterns. These households produced 3,127 women age 15+ years from which 2,199 gravid women aged 15–49 were selected for the current analysis. Unintended pregnancies were identified as either mistimed (wanted later) or unwanted (not wanted at all). Correlates of mistimed, and unwanted pregnancies were identified through Chi-squared tests to assess associations and multinomial logistic regression for multivariate analysis. Results Mean age of the participants was 32.1 years. While 54.1% of the participants reported that their most recent pregnancy was intended, 32.5% indicated their most recent pregnancy as mistimed and 13.4% as unwanted. Multivariate analysis revealed that young age (<20 years), and single marital status were significant predictors of both mistimed and unwanted pregnancies. Lack of inter-partner communication about family planning increased the risk of mistimed pregnancy significantly, and multi-gravidity was shown to significantly increase the risk of unwanted pregnancy. Conclusions About one half of women in Rufiji, Kilombero, and Ulanga districts of Tanzania conceive unintentionally. Women, especially the most vulnerable should be empowered to avoid pregnancy at their own will and discretion. PMID:25102924

A Risky Boundary: Unwanted Sexual Behaviour among Youth

ERIC Educational Resources Information Center

de Bruijn, Paula; Burrie, Ingrid; van Wel, Frits

2006-01-01

The aim of this research was to explore unwanted sexual behaviour amongst young people. Sexual aggression was operationalized at three levels: "verbal", "non-verbal/intimidating" and "physically violent". A total of 1,700 Dutch adolescents completed a questionnaire that included six clusters of possible determinants…

Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors.

PubMed

Botić, Tanja; Defant, Andrea; Zanini, Pietro; Žužek, Monika Cecilija; Frangež, Robert; Janussen, Dorte; Kersken, Daniel; Knez, Željko; Mancini, Ines; Sepčić, Kristina

2017-08-18

The brominated pyrroloiminoquinone alkaloids discorhabdins B, L and G and 3-dihydro-7,8- dehydrodiscorhabdin C, isolated from methanol extracts of two specimens of Latrunculia sp. sponges collected near the Antarctic Peninsula, are here demonstrated for the first time to be reversible competitive inhibitors of cholinesterases. They showed K i for electric eel acetylcholinesterase of 1.6-15.0 μM, for recombinant human acetylcholinesterase of 22.8-98.0 μM, and for horse serum butyrylcholinesterase of 5.0-76.0 μM. These values are promising when compared to the current cholinesterase inhibitors used for treatment of patients with Alzheimer's disease, to counteract the acetylcholine deficiency in the brain. Good correlation was obtained between IC 50 data and results by molecular docking calculation on the binding interactions within the acetylcholinesterase active site, which also indicated the moieties in discorhabdin structures involved. To avoid unwanted peripheral side effects that can appear in patients using some acetylcholinesterase inhibitors, electrophysiological experiments were carried out on one of the most active of these compounds, discorhabdin G, which confirmed that it had no detectable undesirable effects on neuromuscular transmission and skeletal muscle function. These findings are promising for development of cholinesterase inhibitors based on the scaffold of discorhabdins, as potential new agents for treatment of patients with Alzheimer's disease. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Highlights in Endocytosis of Nanostructured Systems.

PubMed

Voltan, Aline R; Alarcon, Kaila M; Fusco-Almeida, Ana M; Soares, Christiane P; Mendes-Giannini, Maria J S; Chorilli, Marlus

2017-01-01

The focus of this review is the cellular internalisation mechanism of nanostructured systems (NSs) and their endosomal escape for targeted drug delivery. Endocytosis is a cellular process of internalisation of different molecules and foreign microorganisms. It is currently being studied for drug delivery through nanostructured systems. The most commonly studied routes of cellular uptake are phagocytosis, macro-pinocytosis, clathrinmediated endocytosis, caveolin-mediated endocytosis, and clathrin and caveolinindependent endocytosis. The mechanism utilised by NSs for cellular entry depends on factors such as cell type and its physicochemical properties. Currently, with the development of drugs-loaded onto NSs, it has been possible to increase the therapeutic index against few diseases. The NSs can deliver the active drug at locations that conventional drugs cannot, thereby minimising unwanted side effects. On cellular entry of NSs, there is a possibility of an endosomal escape of the contents into the cytoplasm, a mechanism that can be exploited so that NSs can migrate intra-cellularly and deliver the drug to the target of interest. Designing endolysosomal escape strategy is not an easy task, but it is critical for the optimal pharmacological action on the target tissue. The cellular uptake of drugs is a very important factor in therapy. Although NSs have emerged as effective drug delivery vehicle for treatment of diseases, it is crucial to understand the mechanism of NSs endocytosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Formulation and Characterization of Aceclofenac -Aloe vera Transemulgel.

PubMed

Raju, Y Prasanna; Haritha, K; Satyanarayana, Rao P; Vandana, K R; Bindu, D Thushara; Vinesha, V; Chowdary, V Harini

2015-01-01

The present research was aimed to formulate aceclofenac transemulgel using Aloe vera as gel base. The prepared formulations were subjected to physical characterization, in-vitro and in-vivo assessment. Aceclofenac, a hydrophobic potential non steroidal anti inflammatory drug, causes ulceration upon chronic oral administration, could be formulated into transemulgel to enhance therapeutic efficacy and to lower the unwanted side effects. The transemulgel was prepared from aqueous Aloe vera gel and aceclofenac emulsion. The prepared transemulgel was evaluated for its pH, viscosity, drug content, skin irritation, in-vitro diffusion and accelerated stability studies. The prepared aceclofenac-Aloe vera tranemulgel and commercial aceclofenac gel were subjected to pharmacodynamic studies in albino rats of Wistar strain employing carrageenan induced left hind paw edema method to assess the anti-inflammatory effect. The transemulgel showed a pH of 6.78 and viscosity of 18 cps. In-vitro diffusion data revealed better permeation characteristics. Topical application of formulation found no skin irritation. Stability study has proved the integrity of the formulation. The prepared aceclofenac Aloe vera transemulgel showed better in-vitro drug release when compared with the commercial aceclofenac gel formulation. Anti-inflammatory activity in treated rats showed the significant paw volume reduction at p<0.05 compared with that of control. Thus, it is concluded that aceclofenac, a potential non steroidal anti inflammatory drug, showed high therapeutic efficiency when formulated into transemulgel using aqueous Aloe vera as gel base.

Reexamining issues of conceptualization and willing consent: the hidden role of coercion in experiences of sexual acquiescence.

PubMed

Conroy, Nicole E; Krishnakumar, Ambika; Leone, Janel M

2015-07-01

This study problematizes the literature's conceptualization of sexual compliance, predominantly defined as willing participation in, and consent to, unwanted sexual activity in the absence of immediate partner pressure. Using a feminist theoretical framework, we argue that covert forms of social coercion, including normalized expectations for heterosexual women to participate in sexual activity and maintain relationship satisfaction, ultimately pressure women into participating in unwanted sexual activity. In other words, immediate partner pressure is not necessary for a sexually coercive experience to occur. Results of the current study indicate that relationship control and media influence significantly predict sexual acquiescence, and women acquiesce to unwanted sexual activity in an effort to maintain relationships and partner satisfaction as well as to avoid negative outcomes. Women cite various forms of social coercion, such as fulfilling sexual scripts and relationship obligations, as primary reasons for participating in unwanted sexual activity without resisting their partners. © The Author(s) 2014.

The Dark Side of Forgiveness: The Tendency to Forgive Predicts Continued Psychological and Physical Aggression in Marriage

PubMed Central

McNulty, James K.

2014-01-01

Despite a burgeoning literature that documents numerous positive implications of forgiveness, scholars know very little about the potential negative implications of forgiveness. In particular, the tendency to express forgiveness may lead offenders to feel free to offend again by removing unwanted consequences for their behavior (e.g., anger, criticism, rejection, loneliness) that would otherwise discourage reoffending. Consistent with this possibility, the current longitudinal study of newlywed couples revealed a positive association between spouses’ reports of their tendencies to express forgiveness to their partners and those partners’ reports of psychological and physical aggression. Specifically, although spouses who reported being relatively more forgiving experienced psychological and physical aggression that remained stable over the first 4 years of marriage, spouses who reported being relatively less forgiving experienced declines in both forms of aggression over time. These findings join just a few others in demonstrating that forgiveness is not a panacea. PMID:21558557

Furfural production using ionic liquids: A review.

PubMed

Peleteiro, Susana; Rivas, Sandra; Alonso, José Luis; Santos, Valentín; Parajó, Juan Carlos

2016-02-01

Furfural, a platform chemical with a bright future, is commercially obtained by acidic processing of xylan-containing biomass in aqueous media. Ionic liquids (ILs) can be employed in processed for furfural manufacture as additives, as catalysts and/or as reaction media. Depending on the IL utilized, externally added catalysts (usually, Lewis acids, Brönsted acids and/or solid acid catalysts) can be necessary to achieve high reaction yields. Oppositely, acidic ionic liquids (AILs) can perform as both solvents and catalysts, enabling the direct conversion of suitable substrates (pentoses, pentosans or xylan-containing biomass) into furfural. Operating in IL-containing media, the furfural yields can be improved when the product is continuously removed along the reaction (for example, by stripping or extraction), to avoid unwanted side-reactions leading to furfural consumption. These topics are reviewed, as well as the major challenges involved in the large scale utilization of ILs for furfural production. Copyright © 2015 Elsevier Ltd. All rights reserved.

Air ionization as a control technology for off-gas emissions of volatile organic compounds.

PubMed

Kim, Ki-Hyun; Szulejko, Jan E; Kumar, Pawan; Kwon, Eilhann E; Adelodun, Adedeji A; Reddy, Police Anil Kumar

2017-06-01

High energy electron-impact ionizers have found applications mainly in industry to reduce off-gas emissions from waste gas streams at low cost and high efficiency because of their ability to oxidize many airborne organic pollutants (e.g., volatile organic compounds (VOCs)) to CO 2 and H 2 O. Applications of air ionizers in indoor air quality management are limited due to poor removal efficiency and production of noxious side products, e.g., ozone (O 3 ). In this paper, we provide a critical evaluation of the pollutant removal performance of air ionizing system through comprehensive review of the literature. In particular, we focus on removal of VOCs and odorants. We also discuss the generation of unwanted air ionization byproducts such as O 3 , NOx, and VOC oxidation intermediates that limit the use of air-ionizers in indoor air quality management. Copyright © 2017. Published by Elsevier Ltd.

Challenges in GC-MS analysis: Case studies on phenibut and ethylphenidate.

PubMed

Lee, Hui Zhi Shirley; Ong, Mei Ching; Lim, Jong Lee Wendy; Yap, Tiong Whei Angeline

2017-08-01

The challenges associated with drug analysis using GC-MS such as thermal degradation, cyclisation or unwanted side reactions causing potential erroneous identification have become evident in view of the high surge in new drugs available in the market. Two case studies illustrated how alternative methods or modifications to existing techniques can help to circumvent the limitations. In the first case study, phenibut which is a GABA analogue, cyclises to 4-phenyl-2-pyrrolidinone under thermal conditions. The identification of phenibut was achieved through derivatisation and identification of its TMS derivative. The second case study, thermal degradation was minimised on drugs of interest methylphenidate and ethylphenidate by reducing the injector port temperature to 200°C and maintaining the GC oven temperature at below 190°C in order to prevent thermal degradation of the drugs of interest. Copyright © 2017 Elsevier B.V. All rights reserved.

Adult Sexual Experiences as a Mediator Between Child Abuse and Current Secretory Immunoglobulin A Levels.

PubMed

Waldron, Jonathan C; Scarpa, Angela; Kim-Spoon, Jungmeen; Coe, Christopher L

2016-03-01

The current study investigated whether a history of child abuse is a predictor of adult immune status, with unwanted adult sexual experiences as a proximal mediator. Participants included 89 young adult women (M(age) = 19.24) who were classified as having experienced no child abuse, child physical abuse, or child sexual abuse, based upon self-reported victimization history before 14 years of age. Participants also reported on unwanted sexual experiences in young adulthood and provided four saliva samples, which were collected over two consecutive days to determine secretory immunoglobulin A (sIgA). Age and negative life events were considered as covariates. The results indicated that adult sexual victimization partially mediated the relationship between child abuse (physical and sexual) and sIgA. Specifically, child abuse experiences predicted more adult sexual victimization experiences, which in turn predicted lower sIgA levels. These findings support long-term health effects of victimization, and suggest that the influence of child abuse on sIgA may be perpetuated through adult victimization. Prevention efforts should aim to empower child maltreatment survivors with skills to prevent adult re-victimization. By thwarting future unwanted sexual experiences in adulthood, individuals will be better protected from the health impairments associated with early abuse experiences. © The Author(s) 2014.

A dual-mode disturbance-accommodating controller for the Hubble Space Telescope

NASA Astrophysics Data System (ADS)

Addington, Stewart; Johnson, C. D.

Cyclic thermal expansions and mechanical stiction effects in the Solar Arrays on the Hubble Space Telescope (HST) are triggering repeated occurrences of damped, relaxation-type flex-body vibrations of the solar arrays. Those solar array vibrations are, in turn, causing unwanted, oscillating disturbance torques on the HST main body, which cause unwanted deviations of the telescope from its specified pointing direction. In this paper we propose two strategies one can adopt in designing a telescope-pointing controller to cope with the aforementioned disturbances: (1) a `total isolation' (TI) control strategy whereby the HST controller torques are designed to adaptively counteract and cancel-out the persistent disturbing torques that are causing the unwanted telescope motions, and (2) an `array damping' (AD) control strategy whereby the HST controller torques are used to actively augment the natural dampening of the solar array vibrations and the attendant telescope motions, between triggerings of the stiction-related flex-body relaxation oscillations. Using the principles of Disturbance-Accommodating Control (DAC) Theory a dual-mode controller for a generic, planar-motion (single-axis) model of the HST is proposed. This controller incorporates both the TI and AD modes of disturbance-accommodation. Simulation studies of the closed-loop system using generic parameter values clearly indicate, qualitatively, the enhanced pointing-performance such a controller can achieve.

Simulation of a circular phased array for a portable ultrasonic polar scan

NASA Astrophysics Data System (ADS)

Daemen, Jannes; Kersemans, Mathias; Martens, Arvid; Verboven, Erik; Delrue, Steven; Van Paepegem, Wim; Degrieck, Joris; Van Den Abeele, Koen

2018-04-01

The development of new composite materials, often anisotropic in nature, requires intricate approaches to characterize these materials and to detect internal defects. The Ultrasonic Polar Scan (UPS) is able to achieve both goals. During an UPS experiment, a material spot is insonified at several angles Ψ(θ,ϕ), after which the reflected or transmitted signal is recorded. While excellent results have been obtained using an in-house developed 5-axis scanner, UPS measurements with the current set-up are too lengthy and cumbersome for in-situ industrial application. Therefore, we propose to replace the complex mechanical steering of the transducers by a hemispherical phased array consisting of small PZT elements. This allows to create a compact and portable setup without compromising the current data quality. By successively activating a specific set of elements of the array and choosing appropriate inter-element time delays, the beam can be electronically steered from any angle to a fixed position on the targeted sample. Consequently, UPS reflection measurements can be performed at this position from a wide range of angles in a timeframe of seconds. Additionally, by using apodization windows, it is possible to efficiently reduce the intensity of unwanted side lobes and to create a phase profile which closely resembles that of a bounded plane wave, leading to an easier interpretation of the recorded data. The appropriate time delays and apodization parameters can be found though a multi-objective inverse problem in which both the phase profile and the side lobe reduction are optimized. This approach enables the creation of an effective beam profile to be used during UPS experiments for the characterization and inspection of composite materials. Our simulation approach is a crucial step towards a next-generation UPS device for industrial applications and in-field measurements.

Probiotic/prebiotic correction for adverse effects of iron fortification on intestinal resistance to Salmonella infection in weaning mice.

PubMed

Lin, Feifei; Wu, Haohao; Zeng, Mingyong; Yu, Guangli; Dong, Shiyuan; Yang, Huicheng

2018-02-21

Iron fortification has been associated with a modest increase in diarrhea risk among children. Herein, we investigate the correction for this unwanted side effect with probiotic/prebiotic supplementation in weaning mice. Iron fortification with 250 ppm and 500 ppm ferrous sulfate for 30 days significantly increased the species richness of the mouse gut microbiota compared to controls. The 500 ppm-FeSO 4 diet caused a significantly decreased abundance of potentially beneficial Lactobacillus. During infection with the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), mice on the 500 ppm-FeSO 4 diet showed earlier appearance of poisoning symptoms, higher rates of weight and appetite loss, and lower survival rates, all of which were effectively reversed by supplementation with a probiotic (Lactobacillus acidophilus) or a prebiotic (inulin) for 7 days before infection. Iron fortification with 500 ppm ferrous sulfate also increased fecal shedding and spleen and liver load of viable S. Typhimurium, suggesting its promoting effect on pathogen colonization and translocation, and this negative effect was found to be well corrected by supplementation with Lactobacillus acidophilus or inulin. Light and transmission electron microscopic observation on the ileal villus structure revealed the histopathological impairment of the intestine by iron fortification with both 250 ppm and 500 ppm ferrous sulfate, and the intestinal lesions were markedly alleviated by supplementation with Lactobacillus acidophilus or inulin. These results provide experimental evidence for the increased diarrhea risk upon iron fortification with high pathogen load, and demonstrate that probiotic or prebiotic supplementation can be used to eliminate the potential harm of iron fortification on gut health.

Comparison of anesthetics in electroconvulsive therapy: an effective treatment with the use of propofol, etomidate, and thiopental.

PubMed

Zahavi, Guy Sender; Dannon, Pinhas

2014-01-01

Electroconvulsive therapy (ECT) is considered to be one of the most effective treatments in psychiatry. Currently, three medications for anesthesia are used routinely during ECT: propofol, etomidate, and thiopental. The objective of this study was to evaluate the effects of the anesthetics used in ECT on seizure threshold and duration, hemodynamics, recovery from ECT, and immediate side effects. Our study is a retrospective cohort study, in which a comparison was made between three groups of patients who underwent ECT and were anesthetized with propofol, etomidate, or thiopental. The main effect compared was treatment dose and seizure duration. All patients were chosen as responders to ECT. Data were gathered about 91 patients (39 were anesthetized with thiopental, 29 with etomidate, and 23 with propofol). Patients in the thiopental group received a lower electrical dose compared to the propofol and etomidate group (mean of 459 mC compared to 807 mC and 701 mC, respectively, P<0.001). Motor seizure duration was longer in the thiopental group compared to propofol and etomidate (mean of 40 seconds compared to 21 seconds and 23 seconds, respectively, P=0.018). Seizure duration recorded by electroencephalography was similar in the thiopental and etomidate groups and lower in the propofol group (mean of 57 seconds in both groups compared to 45 seconds, respectively, P=0.038). Patients who were anesthetized with thiopental received a lower electrical treatment dose without an unwanted decrease in seizure duration. Thiopental might be the anesthetic of choice when it is congruent with other medical considerations.

[Unwanted adolescent pregnancy and post-partum utilization of contraceptive methods].

PubMed

Núñez-Urquiza, Rosa María; Hernández-Prado, Bernardo; García-Barrios, Cecilia; González, Dolores; Walker, Dylis

2003-01-01

To describe the proportion of unwanted pregnancies among all pregnant adolescents, its association with sociodemographic characteristics, and the use of post-partum contraceptive methods. A cross-sectional study was conducted among 220 women between 13 and 19 years of age, in two semi-urban municipalities of the State of Morelos, Mexico, interviewed between 1992 and 1994. Women were interviewed at home, six to twelve weeks after their delivery date. Women were asked whether they had wanted their last pregnancy, and about knowledge and use of contraceptive methods after delivery. Adolescent pregnancies accounted for 17% of all births registered in these two municipalities. Among all adolescent mother 22.73% reported that their pregnancy had not been wanted. A positive association was found between the lack of access to health services provided by public medical insurance systems (Instituto Mexicano del Seguro Social IMSS and Instituto de Seguridad y Servicios Sociales para los Trabajadores del Estado ISSSTE) and unwanted pregnancy (adjusted OR = 3.03, 95% CI (1.31, 7.) An association was also found between living in an urban community (adjusted OR = 2.16, 95% CI (1.08, 4.33) and an unwanted pregnancy. Among all adolescent mothers, 91.3% were familiar with "the pill" as a contraceptive method; 84.72% knew about the IUD, and 63.68% knew about the condom. However, only 35% of them were actually using an effective contraceptive method six weeks after delivery. No difference in frequency of contraceptive use was found among the adolescent mothers, according to whether they wanted their last pregnancy. Only 43.39% of mothers who delivered at hospitals or health centers were using an effective contraceptive method. These findings suggest that there is a great potential for family planning programs to target adolescents, and that the use of contraceptive methods after delivery should be promoted among adolescent mothers, especially those lacking access to public medical insurance and those living in semi-urban settings. It is also recommended to conduct studies on family planning education programs that can be introduced earlier in the school system in Mexico.

Normalization of RNA-seq data using factor analysis of control genes or samples

PubMed Central

Risso, Davide; Ngai, John; Speed, Terence P.; Dudoit, Sandrine

2015-01-01

Normalization of RNA-seq data has proven essential to ensure accurate inference of expression levels. Here we show that usual normalization approaches mostly account for sequencing depth and fail to correct for library preparation and other more-complex unwanted effects. We evaluate the performance of the External RNA Control Consortium (ERCC) spike-in controls and investigate the possibility of using them directly for normalization. We show that the spike-ins are not reliable enough to be used in standard global-scaling or regression-based normalization procedures. We propose a normalization strategy, remove unwanted variation (RUV), that adjusts for nuisance technical effects by performing factor analysis on suitable sets of control genes (e.g., ERCC spike-ins) or samples (e.g., replicate libraries). Our approach leads to more-accurate estimates of expression fold-changes and tests of differential expression compared to state-of-the-art normalization methods. In particular, RUV promises to be valuable for large collaborative projects involving multiple labs, technicians, and/or platforms. PMID:25150836

Effect of the breakup context on unwanted pursuit behavior perpetration between former partners.

PubMed

De Smet, Olivia; Buysse, Ann; Brondeel, Ruben

2011-07-01

Former partners comprise the most important subgroup of stalkers. However, contextual factors related to the breakup are hardly examined to explain ex-partner pursuit. In a community sample of 194 separated persons, about one-fifth perpetrated at least one unwanted pursuit behavior in the past 2 weeks. Being female, lowly educated, and socially undesirable raised the number of perpetrated behaviors. Beyond these effects, the number of behaviors increased when the cause of the break was attributed to the ex-partner or external factors and when the ex was appraised as the breakup initiator. Breakup reasons, the ex-partner's lack in meeting family obligations and own infidelity, also related to pursuit behaviors albeit inferior to subjective attributions and appraisals of initiation. Finally, participants who felt more anxious or lonely negative showed more behaviors. The results enlighten that the breakup context gains further attention. Clinical treatment might benefit from fostering cognitive reconstructions and breakup adjustment. © 2011 American Academy of Forensic Sciences.

Elaborations on sexual assault on dates among Israeli students: risk, detrimental effect, and resilience factors.

PubMed

Shechory Bitton, Mally; Ben-David, Sarah

2014-12-01

The current study of 668 Israeli male and female students examines the prevalence of gendered risk factors for sexual assault (SA) on dates, posttraumatic stress disorder (PTSD) as a detrimental effect of SA, and self-efficacy as resiliency to refuse unwanted sex following SA. Two different sets of risk factors that increased the likelihood of SA on dates emerged from the hierarchical regression. Sexual experience, use of drugs, and private location increased the risk of being SA victims among males, whereas sexual experience, perceived provocative behavior, and alcohol use increased the risk among females. In addition, PTSD and self-efficacy to refuse unwanted sex following SA on dates were predicted by the extent of coercive sexual victimization. PTSD was also predicted by subjective perception of sexual behavior and rape myths, whereas efficacy was predicted by private location. The findings contribute to the literature by showing the contribution of various risk factors to experiencing SA, and by showing SA effect on PTSD and self-efficacy. © The Author(s) 2013.

Removal of unwanted fluid

NASA Astrophysics Data System (ADS)

Subudhi, Sudhakar; Sreenivas, K. R.; Arakeri, Jaywant H.

2013-01-01

This work is concerned with the removal of unwanted fluid through the source-sink pair. The source consists of fluid issuing out of a nozzle in the form of a jet and the sink is a pipe that is kept some distance from the source pipe. Of concern is the percentage of source fluid sucked through the sink. The experiments have been carried in a large glass water tank. The source nozzle diameter is 6 mm and the sink pipe diameter is either 10 or 20 mm. The horizontal and vertical separations and angles between these source and sink pipes are adjustable. The flow was visualized using KMnO4 dye, planer laser induced fluorescence and particle streak photographs. To obtain the effectiveness (that is percentage of source fluid entering the sink pipe), titration method is used. The velocity profiles with and without the sink were obtained using particle image velocimetry. The sink flow rate to obtain a certain effectiveness increase dramatically with lateral separation. The sink diameter and the angle between source and the sink axes don't influence effectiveness as much as the lateral separation.

All-trans retinoic acid results in irregular repair of septa and fails to inhibit proinflammatory macrophages.

PubMed

Seifart, C; Muyal, J P; Plagens, A; Yildirim, A Ö; Kohse, K; Grau, V; Sandu, S; Reinke, C; Tschernig, T; Vogelmeier, C; Fehrenbach, H

2011-08-01

All-trans retinoic acid (ATRA) is controversially discussed in emphysema therapy. We re-evaluated ATRA in the elastase model and hypothesised that beneficial effects should be reflected by increased alveolar surface area, elastin expression and downregulation of inflammatory mediators and matrix metalloproteinases (MMPs). Emphysema was induced by porcine pancreatic elastase versus saline in Sprague-Dawley rats. On days 26-37, rats received daily intraperitoneal injections with ATRA (500 μg · kg(-1) body weight) versus olive oil. Lungs were removed at day 38. Rat alveolar epithelial L2 cells were incubated with/without elastase followed by ATRA- or vehicle-treatment, respectively. ATRA only partially ameliorated structural defects. Alveolar walls exhibited irregular architecture: increased arithmetic mean thickness, reduction in surface coverage by alveolar epithelial cells type II. ATRA only partially restored reduced soluble elastin. It tended to increase the ratio of ED1(+):ED2(+) macrophages. Bronchoalveolar lavage (BAL) cells exhibited a proinflammatory state and high expression of interleukin-1β, cytokine-induced neutrophil chemoattractant-1, tumour necrosis factor-α, nuclear factor-κB, MMP-2, MMP-9, MMP-12, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in emphysema, with ATRA exerting only few effects. MMP-7 was highly induced by ATRA in healthy but not in emphysematous lungs. ATRA reduced both MMP-2 and TIMP-1 activity in BAL fluid of emphysematous lungs. ATRA-therapy may bear the risk of unwanted side-effects on alveolar septal architecture in emphysematous lungs.

Spinal anesthesia: an evergreen technique.

PubMed

Di Cianni, Simone; Rossi, Maria; Casati, Andrea; Cocco, Caterina; Fanelli, Guido

2008-04-01

Spinal anesthesia is a simple technique that provides a deep and fast surgical block through the injection of small doses of local anesthetic solution into the subarachnoid space. The purpose of this review is to provide an overview on recent developments on local anesthetic drugs, side effects, and special techniques of intrathecal anesthesia. Spinal anesthesia can be considered adequately safe, and severe complications are reasonably rare. The cardiovascular effects associated with sympathetic block are more frequent, but successfully treated with volume expansion and administration of vasoactive drugs. It is clear that the total dose of local anesthetic injected into the subarachnoid space is the most important determinant of both therapeutic and unwanted effects of spinal anesthesia. Several studies have also demonstrated the efficacy and safety of using small doses of long acting agents, such as bupivacaine or ropivacaine, to produce an adequately short spinal block in outpatients. Levopivacaine, the pure S(-)-enantiomer of racemic bupivacaine showed a lower risk of cardiovascular and central nervous system (CNS) toxicity than bupivacaine. In the last years we have assisted important changes in the health care organization, with most of the surgical procedures performed on outpatients or on elderly patients with concomitant diseases. This forced us to change the indications and clinical use of intrathecal anesthesia techniques, which have been modified according to the changing needs of surgery. The development of new drugs and special techniques for spinal anesthesia will further improve the clinical use of this old but evergreen technique.

Vasodilator Therapy: Nitrates and Nicorandil.

PubMed

Tarkin, Jason M; Kaski, Juan Carlos

2016-08-01

Nitrates have been used to treat symptoms of chronic stable angina for over 135 years. These drugs are known to activate nitric oxide (NO)-cyclic guanosine-3',-5'-monophasphate (cGMP) signaling pathways underlying vascular smooth muscle cell relaxation, albeit many questions relating to how nitrates work at the cellular level remain unanswered. Physiologically, the anti-angina effects of nitrates are mostly due to peripheral venous dilatation leading to reduction in preload and therefore left ventricular wall stress, and, to a lesser extent, epicardial coronary artery dilatation and lowering of systemic blood pressure. By counteracting ischemic mechanisms, short-acting nitrates offer rapid relief following an angina attack. Long-acting nitrates, used commonly for angina prophylaxis are recommended second-line, after beta-blockers and calcium channel antagonists. Nicorandil is a balanced vasodilator that acts as both NO donor and arterial K(+) ATP channel opener. Nicorandil might also exhibit cardioprotective properties via mitochondrial ischemic preconditioning. While nitrates and nicorandil are effective pharmacological agents for prevention of angina symptoms, when prescribing these drugs it is important to consider that unwanted and poorly tolerated hemodynamic side-effects such as headache and orthostatic hypotension can often occur owing to systemic vasodilatation. It is also necessary to ensure that a dosing regime is followed that avoids nitrate tolerance, which not only results in loss of drug efficacy, but might also cause endothelial dysfunction and increase long-term cardiovascular risk. Here we provide an update on the pharmacological management of chronic stable angina using nitrates and nicorandil.

Patients' unvoiced agendas in general practice consultations: qualitative study

PubMed Central

Barry, Christine A; Bradley, Colin P; Britten, Nicky; Stevenson, Fiona A; Barber, Nick

2000-01-01

Objective To investigate patients' agendas before consultation and to assess which aspects of agendas are voiced in the consultation and the effects of unvoiced agendas on outcomes. Design Qualitative study. Setting 20 general practices in south east England and the West Midlands. Participants 35 patients consulting 20 general practitioners in appointment and emergency surgeries. Results Patients' agendas are complex and multifarious. Only four of 35 patients voiced all their agendas in consultation. Agenda items most commonly voiced were symptoms and requests for diagnoses and prescriptions. The most common unvoiced agenda items were: worries about possible diagnosis and what the future holds; patients' ideas about what is wrong; side effects; not wanting a prescription; and information relating to social context. Agenda items that were not raised in the consultation often led to specific problem outcomes (for example, major misunderstandings), unwanted prescriptions, non-use of prescriptions, and non-adherence to treatment. In all of the 14 consultations with problem outcomes at least one of the problems was related to an unvoiced agenda item. Conclusion Patients have many needs and when these are not voiced they can not be addressed. Some of the poor outcomes in the case studies were related to unvoiced agenda items. This suggests that when patients and their needs are more fully articulated in the consultation better health care may be effected. Steps should be taken in both daily clinical practice and research to encourage the voicing of patients' agendas. PMID:10797036

Drinking Motivations and Experiences of Unwanted Sexual Advances among Undergraduate Students

ERIC Educational Resources Information Center

Novik, Melinda G.; Howard, Donna E.; Boekeloo, Bradley O.

2011-01-01

This study examined the relationship between drinking motivations and college students' experiences with unwanted sexual advances. Undergraduates, from a public university in the mid-Atlantic region, who reported recent (30 day) alcohol use (n = 289) completed an online survey midway through the spring 2007 academic semester. Experiencing an…

The Role of Learned Resourcefulness in Helping Female Undergraduates Deal with Unwanted Sexual Activity

ERIC Educational Resources Information Center

Kennett, Deborah J.; Humphreys, Terry P.; Patchell, Meghan

2009-01-01

We examined the relationship between learned resourcefulness skills and the manner in which undergraduate heterosexual women handle unwanted sexual advances/activity. Participants consisted of 150 females completing a set of questionnaires assessing general learned resourcefulness, sexual giving-in experience, sexual resourcefulness, sexual…

Primary Prevention vs. Intervention.

ERIC Educational Resources Information Center

Harris, Irving B.

This address was delivered at a conference held at the Columbia University (New York City) Graduate School of Journalism. The decision about abortion, it was stated, involves more than the particular woman who is pregnant with an unwanted fetus. Because of the impact of unwanted children on education, crime and violence, and public costs, the…

DO School-Wide Positive Behavioral Interventions and Supports, NOT Exclusionary Discipline Practices

ERIC Educational Resources Information Center

Nese, Rhonda N. T.; McIntosh, Kent

2016-01-01

All educators will inevitably face unwanted student behavior that they need to address. A ubiquitous response to unwanted behavior is exclusionary discipline practices, including time-out, office discipline referrals, and suspensions. However, extensive research has demonstrated that these practices are associated with negative outcomes, including…

Comment on "Life cycle comparison of environmental emissions from three disposal options for unused pharmaceuticals"

EPA Science Inventory

The disposal of unwanted, leftover medications is a topic of national concern. This product is a commentary on a paper in Environmental Science & Technology (doi:10.1021/es203987b) that makes an imprudent, hazardous recommendation regarding the disposal of unwanted drugs to dome...

Cognitive Defusion versus thought Distraction in the Mitigation of Learned Helplessness

ERIC Educational Resources Information Center

Hooper, Nic; McHugh, Louise

2013-01-01

Recent research suggests that attempting to avoid unwanted psychological events is maladaptive. Contrastingly, cognitive defusion, which is an acceptance-based method for managing unwanted thoughts, may provide a plausible alternative. The current study was designed to compare defusion and experiential avoidance as strategies for coping with…

Does abortion reduce the mental health risks of unwanted or unintended pregnancy? A re-appraisal of the evidence.

PubMed

Fergusson, David M; Horwood, L John; Boden, Joseph M

2013-09-01

There have been debates about the linkages between abortion and mental health. Few reviews have considered the extent to which abortion has therapeutic benefits that mitigate the mental health risks of abortion. The aim of this review was to conduct a re-appraisal of the evidence to examine the research hypothesis that abortion reduces rates of mental health problems in women having unwanted or unintended pregnancy. Analysis of recent reviews (Coleman, 2011; National Collaborating Centre for Mental Health, 2011) identified eight publications reporting 14 adjusted odds ratios (AORs) spanning five outcome domains: anxiety; depression; alcohol misuse; illicit drug use/misuse; and suicidal behaviour. For each outcome, pooled AORs were estimated using a random-effects model. There was consistent evidence to show that abortion was not associated with a reduction in rates of mental health problems (p>0.75). Abortion was associated with small to moderate increases in risks of anxiety (AOR 1.28, 95% CI 0.97-1.70; p<0.08), alcohol misuse (AOR 2.34, 95% CI 1.05-5.21; p<0.05), illicit drug use/misuse (AOR 3.91, 95% CI 1.13-13.55; p<0.05), and suicidal behaviour (AOR 1.69, 95% CI 1.12-2.54; p<0.01). There is no available evidence to suggest that abortion has therapeutic effects in reducing the mental health risks of unwanted or unintended pregnancy. There is suggestive evidence that abortion may be associated with small to moderate increases in risks of some mental health problems.

Teen Pregnancy Prevention and Feminist Values.

ERIC Educational Resources Information Center

Ortiz, Elizabeth T.

The problem of high rates of unwanted and unplanned adolescent pregnancy continues unchecked in the United States, with severe negative consequences for the young mothers, their children, and society. Prevention programs for teenage pregnancy have been less than effective. This study investigated the relationship between feminist values and…

Unwanted pregnancy and induced abortion among young women 16-22 years old in Greece: a retrospective study of the risk factors.

PubMed

Salakos, N; Koumousidis, A; Bakalianou, K; Paltoglou, G; Kalampokas, T; Iavazzo, C

2010-01-01

Unwanted pregnancies and the subsequent induced abortions are common problems of our youths in modern Greece. The aim of this study was to recognize the risk factors of the problem in an effort to find the best possible solution out of this social dead end. We interviewed 1,320 young female individuals and analyzed their answers using statistical analysis. Several useful conclusions were reached concerning the forces that are involved in unwanted pregnancy/induced abortions. We have tried to underline the strategy to combat the problem. Sexual education and the proper use of contraception remain the essential tools in this effort.

Predictors of unwanted exposure to online pornography and online sexual solicitation of youth.

PubMed

Chang, Fong-Ching; Chiu, Chiung-Hui; Miao, Nae-Fang; Chen, Ping-Hung; Lee, Ching-Mei; Chiang, Jeng-Tung

2016-06-01

This study examined factors associated with the unwanted exposure to online pornography and unwanted online sexual solicitation victimization and perpetration of youth in Taiwan. A total of 2315 students from 26 high schools were assessed in the 10th grade, with follow-up performed in the 11th grade. Self-administered questionnaires were collected. Multivariate analysis results indicated that higher levels of online game use, pornography media exposure, Internet risk behaviors, depression, and cyberbullying experiences predicted online sexual solicitation victimization, while higher levels of Internet chat room use, pornography media exposure, Internet risk behaviors, cyberbullying experiences, and offline sexual harassment predicted online sexual solicitation perpetration. © The Author(s) 2014.

Should multifetal pregnancy reduction be used for prevention of preterm deliveries in triplet or higher order multiple pregnancies?

PubMed

Papiernik, E; Grangé, G; Zeitlin, J

1998-01-01

This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.

Adolescents' Psychological Health and Experiences with Unwanted Sexual Behavior at School

ERIC Educational Resources Information Center

Timmerman, Greetje

2004-01-01

This paper examines the relationship between experiences with unwanted sexual behavior at school and adolescents' health. Adolescent boys and girls (N = 2,808) participated in a 1998/1999 survey of secondary school students in two regions of The Netherlands. The psychological issues investigated included psychosomatic problems and self-esteem. It…

The Impact of State Abortion Policies on Teen Pregnancy Rates

ERIC Educational Resources Information Center

Medoff, Marshall

2010-01-01

The availability of abortion provides insurance against unwanted pregnancies since abortion is the only birth control method which allows women to avoid an unwanted birth once they are pregnant. Restrictive state abortion policies, which increase the cost of obtaining an abortion, may increase women's incentive to alter their pregnancy avoidance…

Signal Frequency Spectra with Audacity®

ERIC Educational Resources Information Center

Gailey, Alycia

2015-01-01

The primary objective of the activity presented here is to allow students to explore the frequency components of various simple signals, with the ultimate goal of teaching them how to remove unwanted noise from a voice signal. Analysis of the frequency components of a signal allows students to design filters that remove unwanted components of a…

Exploring Patterns of Unwanted Behaviours in Adults with Prader-Willi Syndrome

ERIC Educational Resources Information Center

Pignatti, Riccardo; Mori, Ileana; Bertella, Laura; Grugni, Graziano; Giardino, Daniela; Molinari, Enrico

2013-01-01

Background: Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. Methods: The behaviour of 31 PWS adults was…

Pulse stuttering as a remedy for aliased ground backscatter

NASA Astrophysics Data System (ADS)

Bowhill, S. A.

1983-12-01

An algorithm that aides in the removal of ground scatter from low frequency Mesosphere, Stratosphere, Troposphere (MST) radar signals is examined. The unwanted ground scatter is shown as a sequence of velocity plots which are almost typical at the various altitudes. The interpulse period is changed in a cyclic way, thereby destroying the coherence of the unwanted signal. The interpulse period must be changed by an amount at least equal to the transmitted pulse width, and optimum performance is obtained when the number of different interpulse period occupies a time span greater than the coherence time of the unwanted signal. Since a 20-msec pulse width is used, it was found convenient to cycle through 50 pulses, the interpulse period changing from 2 msec to 3 msec during the 1/8-second time. This particular pattern of interpulse periods was provided by a software radar controller. With application of this algorithm, the unwanted scatter signal becomes incoherent from one pulse to the next, and therefore is perceived as noise by the coherent integrator and correlator.

Pulse stuttering as a remedy for aliased ground backscatter

NASA Technical Reports Server (NTRS)

Bowhill, S. A.

1983-01-01

An algorithm that aides in the removal of ground scatter from low frequency Mesosphere, Stratosphere, Troposphere (MST) radar signals is examined. The unwanted ground scatter is shown as a sequence of velocity plots which are almost typical at the various altitudes. The interpulse period is changed in a cyclic way, thereby destroying the coherence of the unwanted signal. The interpulse period must be changed by an amount at least equal to the transmitted pulse width, and optimum performance is obtained when the number of different interpulse period occupies a time span greater than the coherence time of the unwanted signal. Since a 20-msec pulse width is used, it was found convenient to cycle through 50 pulses, the interpulse period changing from 2 msec to 3 msec during the 1/8-second time. This particular pattern of interpulse periods was provided by a software radar controller. With application of this algorithm, the unwanted scatter signal becomes incoherent from one pulse to the next, and therefore is perceived as noise by the coherent integrator and correlator.

[Isoflavone-containing dietary supplements].

PubMed

Lehmann, Leane; Soukup, Sebastian T; Gerhäuser, Clarissa; Vollmer, Günter; Kulling, Sabine E

2017-03-01

Isoflavones (IFs) from soy and other legumes have weak estrogenic properties. Isolated IFs are available as dietary supplements and advertised to alleviate symptoms of menopause. The present chapter provides an overview of the occurrence, the chemical structure of IFs and their metabolites, the market situation and reviews the current evidence on the efficacy and safety of IF-containing dietary supplements.The biological effectiveness of IFs is attributable to the activation of the estrogen receptor (ER). Studies on the influence of IFs on endogenous estrogen levels in women show inconsistent results. So far, the European Food Safety Authority (EFSA) has rejected all submitted health claims for IFs due to insufficient scientific evidence for any of the postulated health effects. Based on the results of their recent risk assessment, the EFSA concluded that the available human studies did not support the hypothesis of adverse effects of isolated IFs on the human mammary gland, uterus or thyroid in healthy postmenopausal women. However, the assessment does not allow a general statement on the safety of IF-containing dietary supplements. Studies in animal models are often not comparable with the complex interactions in humans due to differences in the metabolism of IFs, in the developmental stage at time of consumption and in the temporarily restricted uptake of IFs during certain stages of life. So far, for none of the advertised functions is unequivocal scientific evidence available. On the basis of available data, potential unwanted side effects cannot be fully excluded. This holds particularly true for women with undiagnosed diseases, especially for those with undetected precancerous lesions in the mammary gland.

Objects of temporary contraception: an exploratory study of women's perspectives in Karachi, Pakistan

PubMed Central

Marvi, Kamyla; Howard, Natasha

2013-01-01

Objectives To explore perspectives of three modern contraceptive objects, using an emic approach, among women in a low-income community in Karachi, Pakistan. Design A qualitative interview study design was employed, using qualitative content analysis with an inductive approach and manual thematic coding. Setting Shah Faisal Colony, Karachi. Participants 20 women, potential contraceptive users of reproductive age and living within a health centre catchment, were purposively selected to provide a similar number of non-users (n=5), contraceptive injection users (n=7), pill users (n=4), and intrauterine device users (n=4). One interview was excluded because it was not recorded. No other exclusion criteria were used. Primary and secondary outcome measures The primary outcome was interpretation of potency and effects of selected family planning objects. Secondary outcome measures were knowledge of family planning and description of therapeutic approaches used and preferred. Results Awareness of family planning was high. Women described different therapeutic approaches, stating they generally preferred modern medicine for contraception as it was fastest and most powerful. They reported that fear of some contraceptive objects, particularly injections and intrauterine contraceptive devices, influenced their choices. Women explained their perceptions of how the heating effects of contraceptives could cause unwanted side effects including menstrual irregularities, weight gain and weakness, leading to disease. Conclusions Most women wanted family planning, but remained dissatisfied with the available contraceptives and their effects. While women reported that they relied on modern medicine for contraception, their descriptions of how contraceptives affected their health relied on the hot–cold explanatory idiom of traditional medicine. PMID:23906959

Sleep deprivation as an experimental model system for psychosis: Effects on smooth pursuit, prosaccades, and antisaccades.

PubMed

Meyhöfer, Inga; Kumari, Veena; Hill, Antje; Petrovsky, Nadine; Ettinger, Ulrich

2017-04-01

Current antipsychotic medications fail to satisfactorily reduce negative and cognitive symptoms and produce many unwanted side effects, necessitating the development of new compounds. Cross-species, experimental behavioural model systems can be valuable to inform the development of such drugs. The aim of the current study was to further test the hypothesis that controlled sleep deprivation is a safe and effective model system for psychosis when combined with oculomotor biomarkers of schizophrenia. Using a randomized counterbalanced within-subjects design, we investigated the effects of 1 night of total sleep deprivation in 32 healthy participants on smooth pursuit eye movements (SPEM), prosaccades (PS), antisaccades (AS), and self-ratings of psychosis-like states. Compared with a normal sleep control night, sleep deprivation was associated with reduced SPEM velocity gain, higher saccadic frequency at 0.2 Hz, elevated PS spatial error, and an increase in AS direction errors. Sleep deprivation also increased intra-individual variability of SPEM, PS, and AS measures. In addition, sleep deprivation induced psychosis-like experiences mimicking hallucinations, cognitive disorganization, and negative symptoms, which in turn had moderate associations with AS direction errors. Taken together, sleep deprivation resulted in psychosis-like impairments in SPEM and AS performance. However, diverging somewhat from the schizophrenia literature, sleep deprivation additionally disrupted PS control. Sleep deprivation thus represents a promising but possibly unspecific experimental model that may be helpful to further improve our understanding of the underlying mechanisms in the pathophysiology of psychosis and aid the development of antipsychotic and pro-cognitive drugs.

Formation and characterization of iron-binding phosphorylated human-like collagen as a potential iron supplement.

PubMed

Deng, Jianjun; Chen, Fei; Fan, Daidi; Zhu, Chenhui; Ma, Xiaoxuan; Xue, Wenjiao

2013-10-01

Iron incorporated into food can induce precipitation and unwanted interaction with other components in food. Iron-binding proteins represent a possibility to avoid these problems and other side effects, as the iron is protected. However, there are several technical problems associated with protein-iron complex formation. In this paper, the iron-binding phosphorylated human-like collagen (Fe-G6P-HLC) was prepared under physiological conditions through phosphorylated modification. One molecule of Fe-G6P-HLC possesses about 24 atoms of Fe. Spectroscopy analysis, differential scanning calorimetry (DSC) and equilibrium dialysis techniques were employed to investigate the characteristics of the Fe-G6P-HLC. The binding sites (nb) and apparent association constant (Kapp) between iron and phosphorylated HLC were measured at nb=23.7 and log Kapp=4.57, respectively. The amount of iron (Fe(2+) sulfate) binding to phosphorylated HLC was found to be a function of pH and phosphate content. In addition, the solubility and thermal stability of HLC were not significantly affected. The results should facilitate the utilization of HLC as a bioactive iron supplement in the food and medical industry and provide an important theoretical evidence for the application of HLC chelates. © 2013.

Ultrafast Excited-state Deactivation of Flavins Bound to Dodecin*

PubMed Central

Staudt, Heike; Oesterhelt, Dieter; Grininger, Martin; Wachtveitl, Josef

2012-01-01

Dodecins, a group of flavin-binding proteins with a dodecameric quaternary structure, are able to incorporate two flavins within each of their six identical binding pockets building an aromatic tetrade with two tryptophan residues. Dodecin from the archaeal Halobacterium salinarum is a riboflavin storage device. We demonstrate that unwanted side reactions induced by reactive riboflavin species and degradation of riboflavin are avoided by ultrafast depopulation of the reactive excited state of riboflavin. Intriguingly, in this process, the staggered riboflavin dimers do not interact in ground and photoexcited states. Rather, within the tetrade assembly, each riboflavin is kept under the control of the respective adjacent tryptophan, which suggests that the stacked arrangement is a matter of optimizing the flavin load. We further identify an electron transfer in combination with a proton transfer as a central element of the effective excited state depopulation mechanism. Structural and functional comparisons of the archaeal dodecin with bacterial homologs reveal diverging evolution. Bacterial dodecins bind the flavin FMN instead of riboflavin and exhibit a clearly different binding pocket design with inverse incorporations of flavin dimers. The different adoption of flavin changes photochemical properties, making bacterial dodecin a comparably less efficient quencher of flavins. This supports a functional role different for bacterial and archaeal dodecins. PMID:22451648

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

PubMed

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

Emergency contraception: knowledge, attitudes and practices among married Malay women staff at a public university in Malaysia.

PubMed

Najafi, Fatemeh; Rahman, Hejar Abdul; Hanafiah, Muhamad; Momtaz, Yadollah A; Ahmad, Zaiton

2012-11-01

There is a high rate of unintended pregnancies in Malaysia due to low contraceptive use. Only 30% of married women use modern contraceptive methods. Emergency contraception (EC) is used within a few days of unprotected sex to prevent pregnancy. The purpose of this study was to investigate the knowledge, attitudes, and practices regarding EC pill use among Malay women. A cross sectional study was conducted among married female staff using stratified random sampling from 15 faculties in the Universiti Putra Malaysia (UPM). Data about sociodemographic factors, reproductive health, knowledge, attitudes and practices regarding EC use were gathered using validated self-administered questionnaire. The response rate was 87%. Half the 294 subjects who participated had a low knowledge, 33.0% a moderate knowledge and 17.0% a good knowledge about the EC pill. Eighty-eight percent of respondents had a positive attitude and 12.0% a negative attitude toward EC. Eleven percent of respondents had previously used EC. Unplanned and unwanted pregnancies were reported by 35.0% and 14.0% of respondents, respectively. Most respondents lacked knowledge about the indications for using EC, its mechanism of action, when it can be used and its side effects. Our findings show a need to educate women about EC.

Prospects of topical protection from ultraviolet radiation exposure: a critical review on the juxtaposition of the benefits and risks involved with the use of chemoprotective agents.

PubMed

Bora, Nilutpal Sharma; Mazumder, Bhaskar; Chattopadhyay, Pronobesh

2018-05-01

Solar ultraviolet (UV) radiation exposure is known to cause inevitable damage to human skin via different mechanisms which include disruption of genetic material and generation of free radicals. In the ever emerging field of photoprotective agents, there have been constant endeavors to uphold the standards for optimum protection from solar UV-induced damages which include alarming conditions ranging from severe keratosis to malignant transformation of skin cells. Out of the various methods available for photoprotection, chemical photoprotective agents are most popular due to its ease of applicability, availability, and efficacy. However, the benevolences of chemophotoprotective agents are not excluded from the fact that all chemical agents are bound to suffer predestined consequences of toxicity and unwanted side effects. The present article focuses on the basic knowledge pertaining to achieve adequate sun protection and also on the beneficial and risk factors of using chemical agents as photoprotective formulations. The article highlights the US Food and Drug Administration (FDA) approved and unapproved UV filters; and also sheds light on the overall measures to protect an individual from UV radiation exposure, dispel misconceptions and present the newer technologies that are available in the market to accomplish ideal sun protection.

Biomedical Imaging in Implantable Drug Delivery Systems

PubMed Central

Zhou, Haoyan; Hernandez, Christopher; Goss, Monika; Gawlik, Anna; Exner, Agata A.

2015-01-01

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant-body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS. PMID:25418857

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function.

PubMed

Nam, Kihoon; Maruyama, Christina L; Wang, Ching-Shuen; Trump, Bryan G; Lei, Pedro; Andreadis, Stelios T; Baker, Olga J

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration.

Laminin-111-derived peptide conjugated fibrin hydrogel restores salivary gland function

PubMed Central

Nam, Kihoon; Maruyama, Christina L.; Wang, Ching-Shuen; Trump, Bryan G.; Lei, Pedro; Andreadis, Stelios T.

2017-01-01

Hyposalivation reduces the patient quality of life, as saliva is important for maintaining oral health. Current treatments for hyposalivation are limited to medications such as the muscarinic receptor agonists, pilocarpine and cevimeline. However, these therapies only provide temporary relief. Therefore, alternative therapies are essential to restore salivary gland function. An option is to use bioengineered scaffolds to promote functional salivary gland regeneration. Previous studies demonstrated that the laminin-111 protein is critical for intact salivary gland cell cluster formation and organization. However, laminin-111 protein as a whole is not suitable for clinical applications as some protein domains may contribute to unwanted side effects such as degradation, tumorigenesis and immune responses. Conversely, the use of synthetic laminin-111 peptides makes it possible to minimize the immune reactivity or pathogen transfer. In addition, it is relatively simple and inexpensive as compared to animal-derived proteins. Therefore, the goal of this study was to demonstrate whether a 20 day treatment with laminin-111-derived peptide conjugated fibrin hydrogel promotes tissue regeneration in submandibular glands of a wound healing mouse model. In this study, laminin-111-derived peptide conjugated fibrin hydrogel significantly accelerated formation of salivary gland tissue. The regenerated gland tissues displayed not only structural but also functional restoration. PMID:29095857

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

PubMed Central

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

In vivo marking of spontaneous or vaccine-induced fibrosarcomas in the domestic house cat, using an adenoviral vector containing a bifunctional fusion protein, GAL-TEK.

PubMed

Marini, F C; Cannon, J P; Belmont, J W; Shillitoe, E J; Lapeyre, J N

1995-09-01

We evaluated the ability of a replication-deficient, recombinant adenoviral vector to transfer the bifunctional gene GAL-TEK, which expresses a marking/therapeutic gene product, to naturally occurring cat fibrosarcomas in situ. GAL-TEK contains an in-frame fusion of the bacterial LacZ gene for histochemical marking of tumors with beta-galactosidase (beta-Gal) and the HSV tk gene for enzyme-prodrug activation of the prodrug ganciclovir (GCV) to induce selective tumor cell killing. GAL-TEK bifunctional marking and cell killing activities were tested in vitro after adenoviral vector infection of HT1080 human fibrosarcoma cells. The tk activity of GAL-TEK is shown to be almost as potent as HSV tk to catalyze conversion of GCV to GCV nucleotides and promote selective cell killing. Using 8 cats with recurring 2.5-cm2 fibrosarcomas that either arose spontaneously or were induced by vaccine, we determined experimentally the administration routes and times required for optimum GAL-TEK gene transfer by beta-Gal histological staining and reverse transcriptase polymerase chain reaction to the multiple compartments of the growing fibrosarcomas consonant with minimizing collateral infection of neighboring tissues and other unwanted side effects.

A proton therapy model using discrete difference equations with an example of treating hepatocellular carcinoma.

PubMed

Bodine, Erin N; Monia, K Lars

2017-08-01

Proton therapy is a type of radiation therapy used to treat cancer. It provides more localized particle exposure than other types of radiotherapy (e.g., x-ray and electron) thus reducing damage to tissue surrounding a tumor and reducing unwanted side effects. We have developed a novel discrete difference equation model of the spatial and temporal dynamics of cancer and healthy cells before, during, and after the application of a proton therapy treatment course. Specifically, the model simulates the growth and diffusion of the cancer and healthy cells in and surrounding a tumor over one spatial dimension (tissue depth) and the treatment of the tumor with discrete bursts of proton radiation. We demonstrate how to use data from in vitro and clinical studies to parameterize the model. Specifically, we use data from studies of Hepatocellular carcinoma, a common form of liver cancer. Using the parameterized model we compare the ability of different clinically used treatment courses to control the tumor. Our results show that treatment courses which use conformal proton therapy (targeting the tumor from multiple angles) provides better control of the tumor while using lower treatment doses than a non-conformal treatment course, and thus should be recommend for use when feasible.

Localized delivery of growth factors for periodontal tissue regeneration: role, strategies, and perspectives.

PubMed

Chen, Fa-Ming; Shelton, Richard M; Jin, Yan; Chapple, Iain L C

2009-05-01

Difficulties associated with achieving predictable periodontal regeneration, means that novel techniques need to be developed in order to regenerate the extensive soft and hard tissue destruction that results from periodontitis. Localized delivery of growth factors to the periodontium is an emerging and versatile therapeutic approach, with the potential to become a powerful tool in future regenerative periodontal therapy. Optimized delivery regimes and well-defined release kinetics appear to be logical prerequisites for safe and efficacious clinical application of growth factors and to avoid unwanted side effects and toxicity. While adequate concentrations of growth factor(s) need to be appropriately localized, delivery vehicles are also expected to possess properties such as protein protection, precision in controlled release, biocompatibility and biodegradability, self-regulated therapeutic activity, potential for multiple delivery, and good cell/tissue penetration. Here, current knowledge, recent advances, and future possibilities of growth factor delivery strategies are outlined for periodontal regeneration. First, the role of those growth factors that have been implicated in the periodontal healing/regeneration process, general requirements for their delivery, and the different material types available are described. A detailed discussion follows of current strategies for the selection of devices for localized growth factor delivery, with particular emphasis placed upon their advantages and disadvantages and future prospects for ongoing studies in reconstructing the tooth supporting apparatus.

The LAM-PCR Method to Sequence LV Integration Sites.

PubMed

Wang, Wei; Bartholomae, Cynthia C; Gabriel, Richard; Deichmann, Annette; Schmidt, Manfred

2016-01-01

Integrating viral gene transfer vectors are commonly used gene delivery tools in clinical gene therapy trials providing stable integration and continuous gene expression of the transgene in the treated host cell. However, integration of the reverse-transcribed vector DNA into the host genome is a potentially mutagenic event that may directly contribute to unwanted side effects. A comprehensive and accurate analysis of the integration site (IS) repertoire is indispensable to study clonality in transduced cells obtained from patients undergoing gene therapy and to identify potential in vivo selection of affected cell clones. To date, next-generation sequencing (NGS) of vector-genome junctions allows sophisticated studies on the integration repertoire in vitro and in vivo. We have explored the use of the Illumina MiSeq Personal Sequencer platform to sequence vector ISs amplified by non-restrictive linear amplification-mediated PCR (nrLAM-PCR) and LAM-PCR. MiSeq-based high-quality IS sequence retrieval is accomplished by the introduction of a double-barcode strategy that substantially minimizes the frequency of IS sequence collisions compared to the conventionally used single-barcode protocol. Here, we present an updated protocol of (nr)LAM-PCR for the analysis of lentiviral IS using a double-barcode system and followed by deep sequencing using the MiSeq device.

Efficient Use of Exogenous Isoprenols for Protein Isoprenylation by MDA-MB-231 Cells Is Regulated Independently of the Mevalonate Pathway*

PubMed Central

Onono, Fredrick; Subramanian, Thangaiah; Sunkara, Manjula; Subramanian, Karunai Leela; Spielmann, H. Peter; Morris, Andrew J.

2013-01-01

Mammalian cells can use exogenous isoprenols to generate isoprenoid diphosphate substrates for protein isoprenylation, but the mechanism, efficiency, and biological importance of this process are not known. We developed mass spectrometry-based methods using chemical probes and newly synthesized stable isotope-labeled tracers to quantitate incorporation of exogenously provided farnesol, geranylgeraniol, and unnatural analogs of these isoprenols containing an aniline group into isoprenoid diphosphates and protein isoprenylcysteines by cultured human cancer cell lines. We found that at exogenous isoprenol concentrations >10 μm, this process can generate as much as 50% of the cellular isoprenoid diphosphate pool used for protein isoprenylation. Mutational activation of p53 in MDA-MB-231 breast cancer cells up-regulates the mevalonate pathway to promote tumor invasiveness. p53 silencing or pharmacological inhibition of HMG-CoA reductase in these cells decreases protein isoprenylation from endogenously synthesized isoprenoids but enhances the use of exogenous isoprenols for this purpose, indicating that this latter process is regulated independently of the mevalonate pathway. Our observations suggest unique opportunities for design of cancer cell-directed therapies and may provide insights into mechanisms underlying pleiotropic therapeutic benefits and unwanted side effects of mevalonate pathway inhibition. PMID:23908355

Mixed ion/electron-conductive protective soft nanomatter-based conformal surface modification of lithium-ion battery cathode materials

NASA Astrophysics Data System (ADS)

Park, Jang-Hoon; Kim, Ju-Myung; Lee, Chang Kee; Lee, Sang-Young

2014-10-01

Understanding and control of interfacial phenomena between electrode material and liquid electrolytes are of major scientific importance for boosting development of high-performance lithium ion batteries with reliable electrochemical/safety attributes. Here, as an innovative surface engineering approach to address the interfacial issues, a new concept of mixed ion/electron-conductive soft nanomatter-based conformal surface modification of the cathode material is presented. The soft nanomatter is comprised of an electron conductive carbonaceous (C) substance embedded in an ion conductive polyimide (PI) nanothin compliant film. In addition to its structural uniqueness, the newly proposed surface modification benefits from a simple fabrication process. The PI/carbon soft nanomatter is directly synthesized on LiCoO2 surface via one-pot thermal treatment of polyamic acid (=PI precursor) and sucrose (=carbon source) mixture, where the LiCoO2 powders are chosen as a model system to explore the feasibility of this surface engineering strategy. The resulting PI/carbon coating layer facilitates electronic conduction and also suppresses unwanted side reactions arising from the cathode material-liquid electrolyte interface. These synergistic coating effects of the multifunctional PI/carbon soft nanomatter significantly improve high-voltage cell performance and also mitigate interfacial exothermic reaction between cathode material and liquid electrolyte.

Photoexpulsion of surface-grafted ruthenium complexes and subsequent release of cytotoxic cargos to cancer cells from mesoporous silica nanoparticles.

PubMed

Frasconi, Marco; Liu, Zhichang; Lei, Juying; Wu, Yilei; Strekalova, Elena; Malin, Dmitry; Ambrogio, Michael W; Chen, Xinqi; Botros, Youssry Y; Cryns, Vincent L; Sauvage, Jean-Pierre; Stoddart, J Fraser

2013-08-07

Ruthenium(II) polypyridyl complexes have emerged both as promising probes of DNA structure and as anticancer agents because of their unique photophysical and cytotoxic properties. A key consideration in the administration of those therapeutic agents is the optimization of their chemical reactivities to allow facile attack on the target sites, yet avoid unwanted side effects. Here, we present a drug delivery platform technology, obtained by grafting the surface of mesoporous silica nanoparticles (MSNPs) with ruthenium(II) dipyridophenazine (dppz) complexes. This hybrid nanomaterial displays enhanced luminescent properties relative to that of the ruthenium(II) dppz complex in a homogeneous phase. Since the coordination between the ruthenium(II) complex and a monodentate ligand linked covalently to the nanoparticles can be cleaved under irradiation with visible light, the ruthenium complex can be released from the surface of the nanoparticles by selective substitution of this ligand with a water molecule. Indeed, the modified MSNPs undergo rapid cellular uptake, and after activation with light, the release of an aqua ruthenium(II) complex is observed. We have delivered, in combination, the ruthenium(II) complex and paclitaxel, loaded in the mesoporous structure, to breast cancer cells. This hybrid material represents a promising candidate as one of the so-called theranostic agents that possess both diagnostic and therapeutic functions.

Review: Adjunctive pharmacologic approaches for benzodiazepine tapers.

PubMed

Welsh, Justine W; Tretyak, Valeria; McHugh, R Kathryn; Weiss, Roger D; Bogunovic, Olivera

2018-05-31

Many patients require discontinuation of benzodiazepines due to a reduction in drug efficacy over time, the development of a sedative use disorder, or unwanted side effects. Benzodiazepine discontinuation can pose a significant challenge for prescribing clinicians due to potential withdrawal symptoms and a recurrence of psychiatric complaints. A PubMed literature search was conducted using the medical subject heading of benzodiazepines in combination with the following key words: discontinuation, withdrawal, detoxification, cessation, dependence, addiction, substance use disorders, or long term. Twenty-one studies met the search criteria. Few medications facilitated the successful discontinuation of benzodiazepines or relief from benzodiazepine withdrawal symptoms. Studies were heterogeneous with respect to sample selection, sample size, and outcome measures. Medications targeting insomnia yielded mixed results. Similarly, studies of agents targeting anxiety symptoms demonstrated inconsistent findings in the reduction of anxiety, improvement in withdrawal symptoms, or enhancement of benzodiazepine completion rates. Anticonvulsants have supporting evidence from small case reports; carbamazepine shows some potential in assisting taper completion and reducing withdrawal severity. These conclusions should be considered in light of a number of inconsistencies across studies in the literature. The results of this review article highlight the need for additional research on optimal strategies for facilitating successful benzodiazepine tapers. Copyright © 2018 Elsevier B.V. All rights reserved.

An integrated approach to the evaluation of a metabolomic fingerprint for a phytocomplex. Focus on artichoke [Cynara cardunculus subsp. scolymus] leaf.

PubMed

Fodaroni, Giada; Burico, Michela; Gaetano, Anna; Maidecchi, Anna; Pagiotti, Rita; Mattoli, Luisa; Traldi, Pietro; Ragazzi, Eugenio

2014-04-01

The availability of reliable herbal formulations is essential in order to assure the maximal activity and to limit unwanted side-effects. The correct concentration of declared components of herbal products is a matter of health legislation and regulation, but is still a topic under debate in the field of quality control assessment. In the present work specific constituents of artichoke leaf extracts, considered as a test herbal product, were measured by standard spectrophotometric and HPLC methods (for quantitative determination of some components only), and results were correlated with the ESI-MS (showing the full metabolomic fingerprint). Phytocomplex stability over time was also investigated in batches submitted to different storage conditions. The results indicated excellent agreement between the two approaches in the measurement of total caffeoylquinic acids and chlorogenic acid contents, but the metabolomic ESI-MS method approach provides a more complete evaluation and monitoring of the composition of a herbal product, without focusing only on a single/few compound measurements. Therefore, the ESI-MS method can be proposed for the evaluation of the quality of complex matrices, such as those in a phytocomplex. Another aspect lies in the possibility to obtain a broad-spectrum stability control of herbal formulations, requiring minimal sample pre-processing procedures.

[Preclinical safety evaluation of chloral hydrate after topical application using the example of psoriatic itch].

PubMed

Wohlrab, J; Gilbrich, F; Wolff, L; Fischer, M; Philipp, S

2017-03-01

Psoriasis is known today as a T‑cell-mediated autoimmunological systemic disease. The chronic inflammatory processes involve neuroimmunological factors that are held responsible not only for various aspects of psychiatric-neurological comorbidities but also for neurosensory problems, primarily itching. Amongst other things, the significance of GABA A receptors are often discussed in this context. The topical use of chloral hydrate in semisolid preparations for antipruritic therapy goes back to Neisser and is currently experiencing a revival in individually manufactured formulations. However, it is currently unknown whether the unwanted side effects that are described for systemic use of chloral hydrate are also relevant for topical application. For lack of clinical safety data, preclinical tests for cutaneous cytotoxicity and calculations for systemic bioavailability after topical application have been performed. The present data cannot fully remove safety concerns for topical application of chloral hydrate in the formulation favoured by the NRF (Neues Rezepturformularium)-the so-called 1‑2-3-cream. A twice daily use of the 1‑2-3-cream on a maximum of 10% of the body surface can be regarded as safe. For a better assessment of harmlessness, tests for cutaneous bioavailability (concentration-time profile) on human skin and clinical studies would be necessary.

Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism

PubMed Central

Yen, Chi-Liang Eric; Nelson, David W.; Yen, Mei-I

2015-01-01

The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. PMID:25231105

Intestinal triacylglycerol synthesis in fat absorption and systemic energy metabolism.

PubMed

Yen, Chi-Liang Eric; Nelson, David W; Yen, Mei-I

2015-03-01

The intestine plays a prominent role in the biosynthesis of triacylglycerol (triglyceride; TAG). Digested dietary TAG is repackaged in the intestine to form the hydrophobic core of chylomicrons, which deliver metabolic fuels, essential fatty acids, and other lipid-soluble nutrients to the peripheral tissues. By controlling the flux of dietary fat into the circulation, intestinal TAG synthesis can greatly impact systemic metabolism. Genes encoding many of the enzymes involved in TAG synthesis have been identified. Among TAG synthesis enzymes, acyl-CoA:monoacylglycerol acyltransferase 2 and acyl-CoA:diacylglycerol acyltransferase (DGAT)1 are highly expressed in the intestine. Their physiological functions have been examined in the context of whole organisms using genetically engineered mice and, in the case of DGAT1, specific inhibitors. An emerging theme from recent findings is that limiting the rate of TAG synthesis in the intestine can modulate gut hormone secretion, lipid metabolism, and systemic energy balance. The underlying mechanisms and their implications for humans are yet to be explored. Pharmacological inhibition of TAG hydrolysis in the intestinal lumen has been employed to combat obesity and associated disorders with modest efficacy and unwanted side effects. The therapeutic potential of inhibiting specific enzymes involved in intestinal TAG synthesis warrants further investigation. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Open letter to Pope John Paul II.

PubMed

Sai, F

1991-01-01

In an Open Letter to Pope John Paul II, written on World Population Day (July 11) 1991, Dr. Fred Sai, President of International Planned Parenthood Federation (IPPF), called for a dialogue on voluntary family planning as a means of avoiding unwanted pregnancy. A half million women die each year from pregnancy-related causes--a death toll that could be dramatically reduced by universal access to low cost, effective contraception. Family planning further represents the best protection against abortion. The Catholic Church's vehement opposition to abortion and family planning methods other than periodic abstinence is in marked contrast to its support to human rights in other settings. The Church has supported struggles for economic ju stice in and among nations, sided with the poor, and advocated for transitions to democracy. At the same time, the family planning movement--which has as its overall objective the protection of the health and welfare of women, children, and families--is viewed by the Vatican as a vehicle for the enslavement rather than liberation of women. The opening of a sensitive dialogue between the Catholic Church and supporters of voluntary family planning could help couples make sound moral decisions about their families and contribute to saving the lives of millions of women, most of them poor.

Cardioselective K(ATP) channel blockers derived from a new series of m-anisamidoethylbenzenesulfonylthioureas.

PubMed

Englert, H C; Gerlach, U; Goegelein, H; Hartung, J; Heitsch, H; Mania, D; Scheidler, S

2001-03-29

Sulfonylthioureas exhibiting cardioselective blockade of ATP-sensitive potassium channels (K(ATP) channels) were discovered by stepwise structural variations of the antidiabetic sulfonylurea glibenclamide. As screening assays, reversal of rilmakalim-induced shortening of the cardiac action potential in guinea pig papillary muscles was used to probe for activity on cardiac K(ATP) channels as the target, and membrane depolarization in CHO cells stably transfected with hSUR1/hKir6.2 was used to probe for unwanted side effects on pancreatic K(ATP) channels. Changing glibenclamide's para-arrangement of substituents in the central aromatic ring to a meta-pattern associated with size reduction of the substituent at the terminal nitrogen atom of the sulfonylurea moiety was found to achieve cardioselectivity. An additional change from a sulfonylurea moiety to a sulfonylthiourea moiety along with an appropriate substituent in the ortho-position of the central aromatic system was a successful strategy to further improve potency on the cardiac K(ATP) channel. Among this series of sulfonylthioureas HMR1883, 1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methylthiourea, and its sodium salt HMR1098 were selected for development and represent a completely new therapeutic approach toward the prevention of life-threatening arrhythmias and sudden cardiac death in patients with coronary heart disease.

Library Optimization in EDXRF Spectral Deconvolution for Multi-element Analysis of Ambient Aerosols

EPA Science Inventory

In multi-element analysis of atmospheric aerosols, attempts are made to fit overlapping elemental spectral lines for many elements that may be undetectable in samples due to low concentrations. Fitting with many library reference spectra has the unwanted effect of raising the an...

Implementation of Mobile Phones in Education

ERIC Educational Resources Information Center

Gábor, Korösi; Péter, Esztelecki

2015-01-01

It is well-known that mobile phone usage during lessons is, according to social standards, unwanted not only in several countries worldwide but also in Serbia. The Ministry of Education cannot handle effectively mobile phones, tablets, and other potential alternative educational methods or supplements. Thus, the easiest solution has become…

Current Trends in Intense Pulsed Light

PubMed Central

2012-01-01

Intense pulsed light technologies have evolved significantly since their introduction to the medical community 20 years ago. Now such devices can be used safely and effectively for the cosmetic treatment of many vascular lesions, unwanted hair, and pigmented lesions. Newer technologies often give results equal to those of laser treatments. PMID:22768357

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

Kertzscher, G; Beddar, S

Purpose: To study the promising potential of inorganic scintillator detectors (ISDs) and investigate various unwanted luminescence properties which may compromise their accuracy. Methods: The ISDs were comprised of a ruby crystal coupled to a polymethyl methacrylate (PMMA) fiber-optic cable and a charged coupled device camera. A new type of ISD was manufactured and included a long-pass filter that was sandwiched between the crystal and the fiber-optic cable. The purpose of the filter was to suppress the Cerenkov and fluorescence background light induced in the PMMA (the stem signal) from striking the ruby crystal, generating unwanted ruby excitation. A variety ofmore » experiments were performed to characterize the ruby based ISDs. The relative contribution of the induced ruby signal and the stem signal were quantified while exposing the detector and a bare fiber-optic cable to a high dose rate (HDR) brachytherapy (BT) source, respectively. The unwanted ruby excitation was quantified while irradiating the fiber-optic cable with the detector volume shielded. Other experiments addressed time-dependent luminescence properties and a comparison to other commonly used organic scintillator detectors (BCF-12, BCF-60). Results: When the BT source dwelled 0.5 cm away from the fiber-optic cable, the unwanted ruby excitation amounted to >5% of the total signal if the source-distance from the scintillator was >7 cm. However, the unwanted excitation was suppressed to <1% if the ISD incorporated an optic filter. The stem signal was suppressed with a 20 nm band-pass filter and was <3% as long as the source-distance was <7 cm. The ruby based ISDs generated signal up to 20(40) times that of BCF-12(BCF-60). Conclusion: The study presents solutions to unwanted luminescence properties of ruby based ISDs for HDR BT. An optic filter should be sandwiched between the scintillator volume and the fiber-optic cable to prevent the stem signal to excite the ruby crystal.« less

Determinants of unwanted pregnancies in India using matched case-control designs

PubMed Central

2012-01-01

Background In India, while the total fertility rate has been declined from 3.39 in 1992–93 to 2.68 in 2005–06, the prevalence of unintended pregnancy is still stagnant over the same period. A review of existing literature shows that within the country, there are variations in fertility preferences between different regions. Also there is a strong argument that the availability of a health facility at the village level plays an important role in reshaping the fertility behavior of women. Keeping in mind the fact that there is no information at the village level (which is the lowest geographical boundary) in the recent round of National Family Health Survey (NFHS-3), the specific objective of this study is to examine the impact of individual and household level variables on unwanted pregnancies without controlling the village level variation. Further, once the village level variation (i.e. unobserved variation) has been controlled, it is necessary to study whether there has been any alteration in the contribution of factors from earlier results of without adjusting the village level variation. Methods This paper attempts to examine the associated factors of unwanted pregnancies, without matching the village and after matching the village, by using the matched case–control design. Nationwide data from India’s latest NFHS-3 conducted during 2005–06 was used for the present study. Frequency and pair wise matching has been applied in the present paper and conditional logistic regression analysis was used to work out the models and to find out the factors associated with unwanted pregnancies. Results A major finding of this study was that 1:3 case–control study (without matching the village) shows that women belonging to non Hindu/Muslim religion, Scheduled Tribe, women who have experienced child loss and if the previous birth interval is 24 through 36 months were significant predictors of unwanted pregnancy. However, this relationship did not hold significant after village wise matching. Other factors such as Muslim religion, women and their partners with high school education and above, women belonging to the richest wealth index and if the sex of the last child was female, emerge as significant predictors of unwanted pregnancies. Conclusions This study clearly underscores the importance of adjusting the village (PSU) level variation in explaining unwanted pregnancies. PMID:22883933

Determinants of unwanted pregnancies in India using matched case-control designs.

PubMed

Dixit, Priyanka; Ram, Faujdar; Dwivedi, Laxmi Kant

2012-08-11

In India, while the total fertility rate has been declined from 3.39 in 1992-93 to 2.68 in 2005-06, the prevalence of unintended pregnancy is still stagnant over the same period. A review of existing literature shows that within the country, there are variations in fertility preferences between different regions. Also there is a strong argument that the availability of a health facility at the village level plays an important role in reshaping the fertility behavior of women. Keeping in mind the fact that there is no information at the village level (which is the lowest geographical boundary) in the recent round of National Family Health Survey (NFHS-3), the specific objective of this study is to examine the impact of individual and household level variables on unwanted pregnancies without controlling the village level variation. Further, once the village level variation (i.e. unobserved variation) has been controlled, it is necessary to study whether there has been any alteration in the contribution of factors from earlier results of without adjusting the village level variation. This paper attempts to examine the associated factors of unwanted pregnancies, without matching the village and after matching the village, by using the matched case-control design. Nationwide data from India's latest NFHS-3 conducted during 2005-06 was used for the present study. Frequency and pair wise matching has been applied in the present paper and conditional logistic regression analysis was used to work out the models and to find out the factors associated with unwanted pregnancies. A major finding of this study was that 1:3 case-control study (without matching the village) shows that women belonging to non Hindu/Muslim religion, Scheduled Tribe, women who have experienced child loss and if the previous birth interval is 24 through 36 months were significant predictors of unwanted pregnancy. However, this relationship did not hold significant after village wise matching. Other factors such as Muslim religion, women and their partners with high school education and above, women belonging to the richest wealth index and if the sex of the last child was female, emerge as significant predictors of unwanted pregnancies. This study clearly underscores the importance of adjusting the village (PSU) level variation in explaining unwanted pregnancies.

[Historic, cultural, legal, psychosocial and educational aspects of induced abortion].

PubMed

Aguirre Zozaya, F; Iglesias, M; Reyes, R M; Iturralde, G; Martínez, M; Pineda Hernández, C

1980-08-01

The history of abortion is a very long one. Every people and nation used different and widely varied methods during the centuries to get rid of unwanted pregnancies. Unfortunately, in most instances, the great majority of these methods was equivalent to zero effectiveness, or, too often, to suicide. Legal aspects of induced abortion have changed considerably with the passing of time and according to countries; these days 36% of the world countries admit abortion on request, 24% for specific reasons only, 16% for medical reasons only, and 8% still consider it an illegal practice. In Mexico abortion is legal only when pregnancy would imply death of the mother, when it is the result of rape of minors, or when it is done on women with very serious mental pathology. Obviously abortion is not the solution to unwanted pregnancies; an improvement in the socioeconomic condition and in the quality of life of many people would be a much better, and more difficult, approach to the solution. Psychosocial factors of abortion involve concepts which are difficult to define, such as those of the wanted or of the unwanted child, and can cause problems which are very difficult to handle. Health education, and sex education in particular, should not only teach the fundamentals of reproduction, but respect and consideration for the phenomenon of procreation, and a strong sense of personal and social responsibility toward family planning.

Disclosing Unwanted Sexual Experiences: Results from a National Sample of Adolescent Women

ERIC Educational Resources Information Center

Kogan, Steven M.

2004-01-01

Objective: The aims of this study are to identify factors that influence the disclosures made by female survivors of unwanted sexual experiences (USE) in childhood and adolescence. The predictors of both the timing of disclosure (short delay, long delay, non-disclosure) and the recipient of the disclosure (disclosing ever to an adult, disclosing…

Unsafe in the Camouflage Tower: Sexual Victimization and Perceptions of Military Academy Leadership

ERIC Educational Resources Information Center

Snyder, Jamie A.; Fisher, Bonnie S.; Scherer, Heidi L.; Daigle, Leah E.

2012-01-01

Few studies have examined sexual victimization among cadets and midshipmen at the three U.S. Military Academies. Self-report data from the 2005 Service Academy Sexual Assault Survey of Cadets and Midshipmen (n = 5,220) were used to examine the extent of unwanted sexual attention, sexual harassment, unwanted sexual contact, sexual coercion, and…

Acoustics in Research Facilities--Control of Wanted and Unwanted Sound. Laboratory Design Notes.

ERIC Educational Resources Information Center

Newman, Robert B.

Common and special acoustics problems are discussed in relation to the design and construction of research facilities. Following a brief examination of design criteria for the control of wanted and unwanted sound, the technology for achieving desired results is discussed. Emphasis is given to various design procedures and materials for the control…

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2013 CFR

2013-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 27 2013-07-01 2013-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2014 CFR

2014-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 26 2014-07-01 2014-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2012 CFR

2012-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 27 2012-07-01 2012-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2010 CFR

2010-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 25 2010-07-01 2010-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

40 CFR 262.210 - Making the hazardous waste determination in the laboratory before the unwanted material is...

Code of Federal Regulations, 2011 CFR

2011-07-01

...)(3) for acute hazardous waste, or § 261.5(g)(3) for hazardous waste. (e) An unwanted material that is... 40 Protection of Environment 26 2011-07-01 2011-07-01 false Making the hazardous waste....210 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED...

Morbidity after conventional dissection of axillary lymph nodes in breast cancer patients

PubMed Central

2014-01-01

Background Conventional axillary lymph node dissection (ALND) has recently become less radical. The treatment morbidity effects of reduced ALND aggressiveness are unknown. This article investigates the prevalence of the main complications of ALND: lymphedema, range-of-motion restriction, and arm paresthesia and pain. Methods This cross-sectional study included 200 women with invasive breast cancer who underwent breast-conserving surgery (82.5%, n = 165) or mastectomy (17.5%, n = 35) with ALND from 2007 to 2011. Arm perimetry was used to assess lymphedema, defined as a difference >2 cm in the upper arm circumference between the nonsurgical and surgical arms. Range-of-motion restriction was assessed by evaluating the degree of arm abduction. Paresthesia was measured in the inner and proximal arm regions. Arm pain was assessed by directly questioning the patients and defined as either present or absent. Results The average (±SD) time between ALND and morbidity evaluation was 35 ± 18 months (range, 7-60 months). The average dissected lymph node number per patient was 14 ± 4 (range, 6-30 lymph nodes). Only 3.5% (n = 7) of the patients presented with lymphedema. Single-incision approaches to breast tumor and ALND (P = 0.04) and the presence of a postoperative seroma (P = 0.02) were associated with lymphedema in univariate analysis. Paresthesia was the most frequent side effect observed (53% of patients, n = 106). This complication was associated with increased age (P < 0.0001) and a larger dissected lymph node number (P = 0.01) in univariate and multivariate analysis. Additionally, 24% (n = 48) of patients had noticeable limited arm abduction. Among the patients, 27.5% (n = 55) experienced sporadic arm pain corresponding to the surgically treated armpit. In multivariate analysis, the pain risk was 1.9-fold higher in patients who underwent ALND corresponding to their dominant arm (95% CI, 1.0-3.7, P = 0.04). Conclusion Conventional ALND in breast cancer patients can result in unwanted complications. However, the current lymphedema prevalence is lower than that of the other analyzed side effects. PMID:24670000

Counseling in the clinical setting to prevent unintended pregnancy: an evidence-based research agenda.

PubMed

Moos, Merry K; Bartholomew, Neva E; Lohr, Kathleen N

2003-02-01

Unintended pregnancies account for about half of all pregnancies in the United States and, in 1995, numbered nearly 3 million pregnancies. They pose appreciable medical, emotional, social and financial costs on women, their families and society. The US is not attaining national goals to decrease unintended pregnancies, and little is known about effective means for reducing unintended pregnancy rates in adults or adolescents.To examine the evidence about the effectiveness, benefits and harms of counseling in a clinical setting to prevent unintended pregnancy in adults and adolescents and to use the evidence to propose a research agenda.We identified English-language articles from comprehensive searches of the MEDLINE, CINAHL, PsychLit and other databases from 1985 through May 2000; the main clinical search terms included pregnancy (mistimed, unintended, unplanned, unwanted), family planning, contraceptive behavior, counseling, sex counseling, and knowledge, attitudes and behavior. We also used published systematic reviews, hand searching of relevant articles, the second Guide to Clinical Preventive Services and extensive peer review to identify important articles not otherwise found and to assure completeness. Of 673 abstracts examined, we retained 354 for full article review; of these, we used 74 for the systematic evidence review and abstracted data from 13 articles for evidence tables. Four studies addressed the effectiveness of counseling in a clinical setting in changing knowledge, skills and attitudes about contraception and pregnancy; all had poor internal validity and generalizability and collectively did not provide definitive guidance about effective counseling strategies. Nine studies (three in teenage populations) addressed the relationship of knowledge on contraceptive use and adherence. Knowledge of correct contraceptive methods may be positively associated with appropriate use, but reservations about the method itself, partner support of the method, and women's beliefs about their own fertility are important determinants of method adherence that may attenuate the knowledge effect. Many factors influence contraceptive use and adherence; among them are age, marital status, ambivalence about becoming pregnant, attitudes of partner, side effects, satisfaction with provider and costs; however, the impact of such factors may not be consistent across populations defined by cultural, age or other factors. The studies themselves differed materially in outcome variables, populations and methodologies and did not yield a body of work that can reliably identify specific influences on contraceptive use and adherence. No literature reports on harms of counseling or on the costs or cost-effectiveness of different approaches to counseling about unintended conceptions in the primary care setting. Virtually no experimental or observational literature reliably answers questions about the effectiveness of counseling in the clinical setting to reduce rates of unintended (unwanted, mistimed) pregnancies in this country. Existing studies suffer from appreciable threats to internal validity and loss to follow-up and are extremely heterogeneous in terms of populations studied and outcomes measured. The quality of the existing research does not provide strong guidance for recommendations about clinical practice but does suggest directions for future investigations. Numerous issues warrant rigorous investigation.

Performance analysis of microcomputer based differential protection of UHV lines under selective phase switching

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

Bhatti, A.A.

1990-04-01

This paper examines the effects of primary and secondary fault quantities as well s of mutual couplings of neighboring circuits on the sensitivity of operation and threshold settings of a microcomputer based differential protection of UHV lines under selective phase switching. Microcomputer based selective phase switching allows the disconnection of minimum number of phases involved in a fault and requires the autoreclosing of these phases immediately after the extinction of secondary arc. During a primary fault a heavy current contribution to the healthy phases tends to cause an unwanted tripping. Faulty phases physically disconnected constitute an isolated fault which beingmore » coupled to the system affects the current and voltage levels of the healthy phases still retained in the system and may cause an unwanted tripping. The microcomputer based differential protection, appears to have poor performance when applied to uncompensated lines employing selective pole switching.« less

Optimisation of a low cost SLM for diffraction efficiency and ghost order suppression

NASA Astrophysics Data System (ADS)

Bowman, R.; D'Ambrosio, V.; Rubino, E.; Jedrkiewicz, O.; di Trapani, P.; Padgett, M. J.

2011-11-01

Spatial Light Modulators (SLMs) are a powerful tool in many optics laboratories, but due to the technology required for their fabrication, they are usually very expensive. Recently some inexpensive devices have been produced, however their phase shift range is less than 2π, leading to a loss of diffraction efficiency for the SLM. We show how to improve the first order diffraction efficiency of such an SLM by adjusting the blazing function, and obtain a 1.5 times increase in first order diffracted power. Even a perfect SLM with 2π phase throw can produce undesired effects in some situations; for example in holographic optical tweezers it is common to find unwanted "ghost spots" near to the array of first-order spots. Modulating the amplitude, by spatially modulating the blazing function, allows us to suppress the ghost spots. This increases the contrast between desired and unwanted spots by more than an order of magnitude.

Men's knowledge of and attitude with respect to family planning in a suburban Nigerian community.

PubMed

Odu, O O; Ijadunola, K T; Komolafe, J O; Adebimpe, W T

2006-01-01

Men's Knowledge of and attitudes to family planning (FP) in suburban and rural Nigeria is still poor despite a global move to increase the involvement of men in reproductive health matters. A cross-sectional survey was conducted to determine men's knowledge of and attitude to family planning at Ganmo, a sub-urban community on the outskirts of Ilorin, Nigeria. The study employed an interviewer administered semi-structured questionnaire to elicit information from 360 men in the households. Only males above the age of 15 years resident in the community were selected for interview A proportionate sampling procedure was employed in selecting the required numberof men from each of the 32 compounds that make up the community. Nearly all men (96.5%) were aware of family planning and a majority of them were aware of some common methods of family planning e.g. Oral Contraceptive Pills (OCPs) (72.5%), Injectables (69.2%), Condoms (86.6%) and Traditional methods (70.6%). Knowledge of other alternative female methods was low e.g. Norplant (17.5%), IUCD (26.3%), Diaphragm (39.8%), Vaginal cream (30.2%), Vaginal tablet (37.8%) and Vaginal sponge (16.8%), and Tubal Ligation (51.3%). Knowledge of male controlled FP methods like Withdrawal (49.6%), Rhythm or periodic abstinence (54.6%) and Vasectomy (28.6%) was also poor. The Respondents had low knowledge of common side effects of FP methods e.g. nausea (9.8%), vomiting (13.1%), abnormal menstruation (34.4%), pain (23.2%) and unwanted weight gain (17.0%); some 25.3%% of respondents had no knowledge of any side effects. The attitude of respondents to family planning was also relatively poor as only a moderate proportion of men supported the FP concept (52.7%) and the Nigerian Population Policy (54.8%) of "four children to a woman". Some 54.8% of respondents were in support of men discussing about FP with their spouses. The major reasons for non-approval of FP by men were the fear of side-effects (70.4%) and perception of FP as being against religion (52.1%). The predictors of poor FP attitude were not having formal education, practice of polygyny and to a lesser extent being a Muslim. The study concluded that, men at Ganmo have limited knowledge of, and poor attitude to FP An intensive drive at a community based adult reproductive health education was advocated among other recommendations.

Resurgence of instrumental behavior after an abstinence contingency

PubMed Central

Bouton, Mark E.; Schepers, Scott T.

2014-01-01

In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of “contingency management” treatments, in which unwanted behavior (e.g., substance abuse) is reduced by reinforcing alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. Two experiments with rats therefore examined the effects of adding a negative “abstinence” contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. Experiment 2 found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute. Results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the “context” of infrequent reinforcement—a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment. PMID:24366673

Resurgence of instrumental behavior after an abstinence contingency.

PubMed

Bouton, Mark E; Schepers, Scott T

2014-06-01

In resurgence, an extinguished instrumental behavior (R1) recovers when a behavior that has replaced it (R2) is also extinguished. The phenomenon may be relevant to understanding relapse that can occur after the termination of "contingency management" treatments, in which an unwanted behavior (e.g., substance abuse) is reduced by reinforcing an alternative behavior. When reinforcement is discontinued, the unwanted behavior might resurge. However, unlike most resurgence experiments, contingency management treatments also introduce a negative contingency, in which reinforcers are not delivered unless the client has abstained from the unwanted behavior. In two experiments with rats, we therefore examined the effects of adding a negative "abstinence" contingency to the resurgence design. During response elimination, R2 was not reinforced unless R1 had not been emitted for a minimum period of time (45, 90, or 135 s). In both experiments, adding such a contingency to simple R1 extinction reduced, but did not eliminate, resurgence. In Experiment 2, we found the same effect in a yoked group that could earn reinforcers for R2 at the same points in time as the negative-contingency group, but without the requirement to abstain from R1. Thus, the negative contingency per se did not contribute to the reduction in resurgence. These results suggest that the contingency reduced resurgence by making reinforcers more difficult to earn and more widely spaced in time. This could have allowed the animal to learn that R1 was extinguished in the "context" of infrequent reinforcement-a context more like that of resurgence testing. The results are thus consistent with a contextual (renewal) account of resurgence. The method might provide a better model of relapse after termination of a contingency management treatment.

EFFECT OF ALTERNATING WETTING AND DRYING IRRIGATION METHODS ON PHOTOSYNTHESIS AND TEMPERATURE OF RICE AND WEED PLANTS.

USDA-ARS?s Scientific Manuscript database

Reduced input systems such as alternating wetting and drying (AWD) and furrow irrigation can potentially reduce water costs and limit the release of greenhouse gases in rice production, but also can introduce unwanted crop stresses that compromise crop yield and quality, as well as introducing compl...

Forestry Herbicides

Treesearch

Jerry L. Michael; William L. Boyer

1983-01-01

If you own or manage pine timberlands in the South, you know only too well that unwanted vegetation can be stubborn when you arc trying to reforest, convert a stand, or improve pine growth by reducing competition. Are you aware. however, that many forestry herbicides are proving effective in eliminating this undesirable vegetation, both before and after pine...

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,…

Avoiding unwanted vicinity effects with attract-and-kill tactics for harlequin bug, Murgantia histrionica (Hahn)

USDA-ARS?s Scientific Manuscript database

In the development of an attract-and-kill approach for the management of harlequin bug (HB), Murgantia histrionica (Hahn), we evaluated attraction and retention of HB by pheromone-baited traps in the field. In release-recapture and on-farm experiments, traps combining collard plants with commercial ...

Tree-breeding technique: some effects of continuous bagging

Treesearch

Jonathan W. Wright

1951-01-01

In tree-breeding operations, it is standard practice to protect the tree flowers with vegetable parchment or sausage-casing bags during the pollination period so no unwanted pollen can get to them. Since the bags often damage the tree, they are usually removed as soon as the pollination period ends - within 2 or 3 weeks.

Effect of synthetic auxin herbicides on seed development and viability in genetically-engineered glyphosate-resistant alfalfa

USDA-ARS?s Scientific Manuscript database

Feral populations of cultivated crops have the potential to function as bridges and reservoirs that contribute to the unwanted movement of novel genetically engineered (GE) traits. Recognizing that feral alfalfa has the potential to lower genetic purity in alfalfa seed production fields when it is g...

Effect of ammate on unwanted growth in oak--yellow-poplar stands in New Jersey

Treesearch

S. Little; H. A. Somes

1954-01-01

Stands of mixed oaks and yellow-poplar form the most valuable forest crop on many sites in central and northern New Jersey and in the Delaware Valley of southern New Jersey. However, these stands often contain shrubs and low-value hardwood trees that prevent satisfactory restocking of cutover areas.

A technique for thermal desorption analyses suitable for thermally-labile, volatile compounds

USDA-ARS?s Scientific Manuscript database

Our group has for some time studied below ground plant produced volatile signals affecting nematode and insect behavior. The research requires repeated sampling of intact plant/soil systems in the lab as well as the field with the help of probes to minimize unwanted effects on the systems we are stu...

How to acquire new biological activities in old compounds by computer prediction

NASA Astrophysics Data System (ADS)

Poroikov, V. V.; Filimonov, D. A.

2002-11-01

Due to the directed way of testing chemical compounds' in drug research and development many projects fail because serious adverse effects and toxicity are discovered too late, and many existing prospective activities remain unstudied. Evaluation of the general biological potential of molecules is possible using a computer program PASS that predicts more than 780 pharmacological effects, mechanisms of action, mutagenicity, carcinogenicity, etc. on the basis of structural formulae of compounds, with average accuracy ˜85%. PASS applications to both databases of available samples included hundreds of thousands compounds, and small collections of compounds synthesized by separate medicinal chemists are described. It is shown that 880 compounds from Prestwick chemical library represent a very diverse pharmacological space. New activities can be found in existing compounds by prediction. Therefore, on this basis, the selection of compounds with required and without unwanted properties is possible. Even when PASS cannot predict very new activities, it may recognize some unwanted actions at the early stage of R&D, providing the medicinal chemist with the means to increase the efficiency of projects.

The effects of suppressing intrusive thoughts on dream content, dream distress and psychological parameters.

PubMed

Kröner-Borowik, Tana; Gosch, Stefanie; Hansen, Kathrin; Borowik, Benjamin; Schredl, Michael; Steil, Regina

2013-10-01

Suppressing unwanted thoughts can lead to an increased occurrence of the suppressed thought in dreams. This is explainable by the ironic control theory, which theorizes why the suppression of thoughts might make them more persistent. The present study examined the influence of thought suppression on dream rebound, dream distress, general psychiatric symptomatology, depression, sleep quality and perceived stress. Thirty healthy participants (good sleepers) were investigated over a period of 1 week. Half were instructed to suppress an unwanted thought 5 min prior to sleep, whereas the other half were allowed to think of anything at all. Dream content was assessed through a dream diary. Independent raters assessed whether or not the dreams were related to the suppressed target thought. The results demonstrated increased target-related dreams and a tendency to have more distressing dreams in the suppression condition. Moreover, the data imply that thought suppression may lead to significantly increased general psychiatric symptomatology. No significant effects were found for the other secondary outcomes. © 2013 European Sleep Research Society.

Prevalence and Determinants of Unintended Pregnancy Among Women in South-Western Nigeria.

PubMed

Lamina, M A

2015-09-01

To study the prevalence of unwanted pregnancy in urban and rural settlements in Southwestern Nigeria. A prospective cross-sectional study of women within reproductive age. Community-based study of unwanted pregnancy was conducted in 2012. They were women of reproductive age who had experienced unintended and/or unwanted pregnancies and they were randomly selected from rural and urban areas of Ogun state in Nigeria. A semi-structured questionnaire was used for data collection. The prevalence of unintended/unwanted pregnancy, associated factors including the views, perception and attitudes of community members in both urban and rural settlements and the pattern of help-seeking behavior on the problem. The age range of respondents was 15-48 years (mean age 31.2± 6.7 years). One thousand, two hundred and twenty-one (51.6%) of the respondents were married. The percentage of illiterate respondents was 3.5% in urban area and 4.1% in rural area. There was a statistically significant association between level of education and use of a method to avoid or delay pregnancy (p < 0.001). The prevalence of unintended pregnancy was 35.9% while that of induced abortion was 33.5%. Quality of service was the most important factor in the choice of a place for pregnancy termination in urban and rural areas. Economic reasons were often cited as reasons women make use of abortion services. Unwanted pregnancy constitutes a problem, even at the community level. The high contraceptive awareness should be translated to an increased use so as to bridge the large gap of unmet need.

Trends in youth internet victimization: findings from three youth internet safety surveys 2000-2010.

PubMed

Jones, Lisa M; Mitchell, Kimberly J; Finkelhor, David

2012-02-01

The purpose of this research was to explore the trends in youth reports of unwanted online sexual solicitation, harassment, and exposure to pornography over time. The study was based on three separate cross-sectional national telephone surveys of approximately 1,500 youth Internet users, aged 10 through 17 years. Data were collected in 2000, 2005, and 2010. Nine percent of youth reported an unwanted sexual solicitation in 2010. This continued the decline in unwanted sexual solicitations that occurred between 2000 (19%) and 2005 (13%), resulting in a total 50% decrease between 2000 and 2010. Twenty-three percent of youth reported an unwanted exposure to pornography, a decline from 34% in 2005, following an increase between 2000 and 2005 (25% to 34%). However, marking the only trend to show an increase over the past 5 years, 11% of youth reported an online harassment experience, which was an increase from 9% in 2005, and 6% in 2000. Some differences in these trends were noted for subgroups of youth across age, gender, and race. The trends in unwanted experiences online over the past decade identified by three Youth Internet Safety Surveys may contradict impressions that the general population, professionals, and the media have about what is happening. Trends provide evidence for some optimism that protective adaptations to the online environment have been successful; however, online harassment appears to be increasing for youth, particularly girls, and may require additional mobilization. Copyright © 2012 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

PubMed

Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

2018-03-01

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Anti-proliferative and anti-angiogenic effects of CB2R agonist (JWH-133) in non-small lung cancer cells (A549) and human umbilical vein endothelial cells: an in vitro investigation.

PubMed

Vidinský, B; Gál, P; Pilátová, M; Vidová, Z; Solár, P; Varinská, L; Ivanová, L; Mojžíš, J

2012-01-01

Non-small cell lung cancer has one of the highest mortality rates among cancer-suffering patients. It is well known that the unwanted psychotropic effects of cannabinoids (CBs) are mediated via the CB(1) receptor (R), and selective targeting of the CB(2)R would thus avoid side effects in cancer treatment. Therefore, the aim of our study was to evaluate the effect of selective CB(2)R agonist, JWH-133, on A549 cells (non-small lung cancer) and human umbilical vein endothelial cells (HUVECs). Cytotoxicity assay and DNA fragmentation assay were employed to evaluate the influence of JWH-133 (3-(1,1-dimethylbutyl)- 1-deoxy-Δ8-tetrahydrocannabinol) on investigated cancer cells. In addition, migration assay and gelatinase zymography were performed in HUVECs to asses JWH-133 anti-angiogenic activity. Our study showed that JWH-133 exerted cytotoxic effect only at the highest concentration used (10(-4) mol/l), while inhibition of colony formation was also detected at the non-toxic concentrations (10(-5)-10(-8) mol/l). JWH-133 was also found to be able to induce weak DNA fragmentation in A549 cells. Furthermore, JWH-133 at non-toxic concentrations inhibited some steps in the process of angiogenesis. It significantly inhibited endothelial cell migration after 17 h of incubation at concentrations of 10(-4)-10(-6) mol/l. In addition, JWH-133 inhibited MMP-2 secretion as assessed by gelatinase zymography. The present study demonstrates the in vitro anti-proliferative and anti-angiogenic potential of CB(2)R agonist, JWH-133, in nonsmall lung cancer cells and HUVECs. Our results generate a rationale for further in vivo efficacy studies with this compound in preclinical cancer models.

Does It Matter What You Call It? The Relationship Between Labeling Unwanted Sexual Experiences and Distress

ERIC Educational Resources Information Center

Harned, Melanie S.

2004-01-01

Using cross-sectional data from 2 samples of women attending a university (N = 1,395), the author examined the relationship among women's labeling of their unwanted sexual experiences (USEs) with dating partners and a variety of psychological and school-related outcomes. Three competing path analysis models were tested to determine whether the…

Lithium purification technique

DOEpatents

Keough, Robert F.; Meadows, George E.

1985-01-01

A method for purifying liquid lithium to remove unwanted quantities of nitrogen or aluminum. The method involves precipitation of aluminum nitride by adding a reagent to the liquid lithium. The reagent will be either nitrogen or aluminum in a quantity adequate to react with the unwanted quantity of the impurity to form insoluble aluminum nitride. The aluminum nitride can be mechanically separated from the molten liquid lithium.

Lithium purification technique

DOEpatents

Keough, R.F.; Meadows, G.E.

1984-01-10

A method for purifying liquid lithium to remove unwanted quantities of nitrogen or aluminum. The method involves precipitation of aluminum nitride by adding a reagent to the liquid lithium. The reagent will be either nitrogen or aluminum in a quantity adequate to react with the unwanted quantity of the impurity to form insoluble aluminum nitride. The aluminum nitride can be mechanically separated from the molten liquid lithium.

From Latin Americans to Latinos: Latin American Immigration in US: The Unwanted Children

ERIC Educational Resources Information Center

Moraña, Ana

2007-01-01

It is my understanding that Latin American immigrants in the United States, during the contested process of becoming Latinos (US citizens or the offspring of Latin Americans born in US) are for the most part socially portrayed as unwanted, messy children who need to be educated before they can become American citizens. Whether they can be called…

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2011 CFR

2011-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2012 CFR

2012-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

40 CFR 262.206 - Labeling and management standards for containers of unwanted material in the laboratory.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chemical reaction, (B) Whether the unwanted material has been used or is unused, (C) A description of the... the air, adverse chemical reactions, and dangerous situations that may result in harm to human health... contents of the container include, but are not limited to: (A) The name of the chemical(s), (B) The type or...

The Prevalence of Childhood Sexual Abuse and Adolescent Unwanted Sexual Contact among Boys and Girls Living in Victoria, Australia

ERIC Educational Resources Information Center

Moore, Elya E.; Romaniuk, Helena; Olsson, Craig A.; Jayasinghe, Yasmin; Carlin, John B.; Patton, George C.

2010-01-01

Objectives: Childhood sexual abuse (CSA) is associated with both short- and long-term adverse mental and physical health consequences, yet there remains considerable controversy about the prevalence of CSA in the general population. There is also little prospective data on unwanted sexual contact (USC) collected during adolescence. Methods: Data…

"The Red Zone": Temporal Risk for Unwanted Sex among College Students

ERIC Educational Resources Information Center

Flack, William F., Jr.; Caron, Marcia L.; Leinen, Sarah J.; Breitenbach, Katherine G.; Barber, Ann M.; Brown, Elaine N.; Gilbert, Caitlin T.; Harchak, Taylor F.; Hendricks, Melissa M.; Rector, Catherine E.; Schatten, Heather T.; Stein, Heather C.

2008-01-01

The "red zone" usually refers to the first few weeks of the first semester at college, when female students are believed to be at greatest risk for experiencing unwanted sex. We tested this notion using data from a survey study of 207 first-and second-year students (121 women, 84 men) at a small, liberal arts university. Results demonstrated only…

Bioengineered baculoviruses as new class of therapeutics using micro and nanotechnologies: principles, prospects and challenges.

PubMed

Paul, Arghya; Hasan, Anwarul; Rodes, Laetitia; Sangaralingam, Mugundhine; Prakash, Satya

2014-05-01

Designing a safe and efficient gene delivery system is required for success of gene therapy trials. Although a wide variety of viral, non-viral and polymeric nanoparticle based careers have been widely studied, the current gene delivery vehicles are limited by their suboptimal, non-specific therapeutic efficacy and acute immunological reactions, leading to unwanted side effects. Recently, there has been a growing interest in insect-cell-originated baculoviruses as gene delivery vehicles for diverse biomedical applications. Specifically, the emergence of diverse types of surface functionalized and bioengineered baculoviruses is posed to edge over currently available gene delivery vehicles. This is primarily because baculoviruses are comparatively non-pathogenic and non-toxic as they cannot replicate in mammalian cells and do not invoke any cytopathic effect. Moreover, emerging advanced studies in this direction have demonstrated that hybridizing the baculovirus surface with different kinds of bioactive therapeutic molecules, cell-specific targeting moieties, protective polymeric grafts and nanomaterials can significantly improve the preclinical efficacy of baculoviruses. This review presents a comprehensive overview of the recent advancements in the field of bioengineering and biotherapeutics to engineer baculovirus hybrids for tailored gene therapy, and articulates in detail the potential and challenges of these strategies for clinical realization. In addition, the article illustrates the rapid evolvement of microfluidic devices as a high throughput platform for optimizing baculovirus production and treatment conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

The combination of huperzine A and imidazenil is an effective strategy to prevent diisopropyl fluorophosphate toxicity in mice.

PubMed

Pibiri, Fabio; Kozikowski, Alan P; Pinna, Graziano; Auta, James; Kadriu, Bashkim; Costa, Erminio; Guidotti, Alessandro

2008-09-16

Diisopropyl fluorophosphate (DFP) causes neurotoxicity related to an irreversible inhibition of acetylcholinesterase (AChE). Management of this intoxication includes: (i) pretreatment with reversible blockers of AChE, (ii) blockade of muscarinic receptors with atropine, and (iii) facilitation of GABA(A) receptor signal transduction by benzodiazepines. The major disadvantage associated with this treatment combination is that it must to be repeated frequently and, in some cases, protractedly. Also, the use of diazepam (DZP) and congeners includes unwanted side effects, including sedation, amnesia, cardiorespiratory depression, and anticonvulsive tolerance. To avoid these treatment complications but safely protect against DFP-induced seizures and other CNS toxicity, we adopted the strategy of administering mice with (i) small doses of huperzine A (HUP), a reversible and long-lasting (half-life approximately 5 h) inhibitor of AChE, and (ii) imidazenil (IMI), a potent positive allosteric modulator of GABA action selective for alpha(5)-containing GABA(A) receptors. Coadministration of HUP (50 microg/kg s.c., 15 min before DFP) with IMI (2 mg/kg s.c., 30 min before DFP) prevents DFP-induced convulsions and the associated neuronal damage and mortality, allowing complete recovery within 18-24 h. In HUP-pretreated mice, the ED(50) of IMI to block DFP-induced mortality is approximately 10 times lower than that of DZP and is devoid of sedation. Our data show that a combination of HUP with IMI is a prophylactic, potent, and safe therapeutic strategy to overcome DFP toxicity.

The combination of huperzine A and imidazenil is an effective strategy to prevent diisopropyl fluorophosphate toxicity in mice

PubMed Central

Pibiri, Fabio; Kozikowski, Alan P.; Pinna, Graziano; Auta, James; Kadriu, Bashkim; Costa, Erminio; Guidotti, Alessandro

2008-01-01

Diisopropyl fluorophosphate (DFP) causes neurotoxicity related to an irreversible inhibition of acetylcholinesterase (AChE). Management of this intoxication includes: (i) pretreatment with reversible blockers of AChE, (ii) blockade of muscarinic receptors with atropine, and (iii) facilitation of GABAA receptor signal transduction by benzodiazepines. The major disadvantage associated with this treatment combination is that it must to be repeated frequently and, in some cases, protractedly. Also, the use of diazepam (DZP) and congeners includes unwanted side effects, including sedation, amnesia, cardiorespiratory depression, and anticonvulsive tolerance. To avoid these treatment complications but safely protect against DFP-induced seizures and other CNS toxicity, we adopted the strategy of administering mice with (i) small doses of huperzine A (HUP), a reversible and long-lasting (half-life ≈5 h) inhibitor of AChE, and (ii) imidazenil (IMI), a potent positive allosteric modulator of GABA action selective for α5-containing GABAA receptors. Coadministration of HUP (50 μg/kg s.c., 15 min before DFP) with IMI (2 mg/kg s.c., 30 min before DFP) prevents DFP-induced convulsions and the associated neuronal damage and mortality, allowing complete recovery within 18–24 h. In HUP-pretreated mice, the ED50 of IMI to block DFP-induced mortality is ≈10 times lower than that of DZP and is devoid of sedation. Our data show that a combination of HUP with IMI is a prophylactic, potent, and safe therapeutic strategy to overcome DFP toxicity. PMID:18784370

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients.

PubMed

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-07-19

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Prediction of anaerobic power values from an abbreviated WAnT protocol.

PubMed

Stickley, Christopher D; Hetzler, Ronald K; Kimura, Iris F

2008-05-01

The traditional 30-second Wingate anaerobic test (WAnT) is a widely used anaerobic power assessment protocol. An abbreviated protocol has been shown to decrease the mild to severe physical discomfort often associated with the WAnT. Therefore, the purpose of this study was to determine whether a 20-second WAnT protocol could be used to accurately predict power values of a standard 30-second WAnT. In 96 college females, anaerobic power variables were assessed using a standard 30-second WAnT protocol. Maximum power values as well as instantaneous power at 10, 15, and 20 seconds were recorded. Based on these results, stepwise regression analysis was performed to determine the accuracy with which mean power, minimum power, 30-second power, and percentage of fatigue for a standard 30-second WAnT could be predicted from values obtained during the first 20 seconds of testing. Mean power values showed the highest level of predictability (R2 = 0.99) from the 20-second values. Minimum power, 30-second power, and percentage of fatigue also showed high levels of predictability (R2 = 0.91, 0.84, and 0.84, respectively) using only values obtained during the first 20 seconds of the protocol. An abbreviated (20-second) WAnT protocol appears to effectively predict results of a standard 30-second WAnT in college-age females, allowing for comparison of data to published norms. A shortened test may allow for a decrease in unwanted side effects associated with the traditional WAnT protocol.

Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment

PubMed Central

Stip, E; Lungu, O V; Anselmo, K; Letourneau, G; Mendrek, A; Stip, B; Lipp, O; Lalonde, P; Bentaleb, L A

2012-01-01

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation. PMID:22714121

Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases.

PubMed

Henkes, Leonhard M; Haus, Patricia; Jäger, Felix; Ludwig, Joachim; Meyer-Almes, Franz-Josef

2012-01-15

Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class II, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. Copyright © 2011 Elsevier Ltd. All rights reserved.

Convection shapes the trade-off between antibiotic efficacy and the selection for resistance in spatial gradients

NASA Astrophysics Data System (ADS)

Gralka, Matti; Fusco, Diana; Martis, Stephen; Hallatschek, Oskar

2017-08-01

Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance. Importantly, our model takes into account the influence of convection, resulting for instance from blood flow. Using stochastic simulations, we study the fates of individual resistance mutations and quantify the trade-off between the killing of wild-type cells and the rise of resistance mutations: shallow gradients and convection into the antibiotic region promote wild-type death, at the cost of increasing the establishment probability of resistance mutations. We can explain these observed trends by modeling the adaptation process as a branching random walk. Our analysis reveals that the trade-off between death and adaptation depends on the relative length scales of the spatial drug gradient and random dispersal, and the strength of convection. Our results show that convection can have a momentous effect on the rate of establishment of new mutations, and may heavily impact the efficiency of antibiotic treatment.

Gene delivery for periodontal tissue engineering: current knowledge - future possibilities.

PubMed

Chen, Fa-Ming; Ma, Zhi-Wei; Wang, Qin-Tao; Wu, Zhi-Fen

2009-08-01

The cellular and molecular events of periodontal healing are coordinated and regulated by an elaborate system of signaling molecules, pointing to a primary strategy for functional periodontal compartment regeneration to replicate components of the natural cellular microenvironment by providing an artificial extracellular matrix (ECM) and by delivering growth factors. However, even with optimal carriers, the localized delivery of growth factors often requires a large amount of protein to stimulate significant effects in vivo, which increases the risk and unwanted side effects. A simple and relatively new approach to bypassing this dilemma involves converting cells into protein producing factories. This is done by a so-called gene delivery method, where therapeutic agents to be delivered are DNA plasmids that include the gene encoding desired growth factors instead of recombinant proteins. As localized depots of genes, novel gene delivery systems have the potential to release their cargo in a sustained and controlled manner and finally provide time- and space- dependent levels of encoded proteins during all stages of tissue regrowth, offering great versatility in their application and prompting new tissue engineering strategy in periodontal regenerative medicine. However, gene therapy in Periodontology is clearly in its infancy. Significant efforts still need to be made in developing safe and effective delivery platforms and clarifying how gene delivery, in combination with tissue engineering, may mimic the critical aspects of natural biological processes occurring in periodontal development and repair. The aim of this review is to trace an outline of the state-of-the-art in the application of gene delivery and tissue engineering strategies for periodontal healing and regeneration.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

PubMed

Facchini, Gustavo; Eberlin, Samara; Clerici, Stefano Piatto; Alves Pinheiro, Ana Lucia Tabarini; Costa, Adilson

2017-12-01

Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients. © 2017 Wiley Periodicals, Inc.

Enhanced endocannabinoid tone as a potential target of pharmacotherapy.

PubMed

Toczek, Marek; Malinowska, Barbara

2018-07-01

The endocannabinoid system is up-regulated in numerous pathophysiological states such as inflammatory, neurodegenerative, gastrointestinal, metabolic and cardiovascular diseases, pain, and cancer. It has been suggested that this phenomenon primarily serves an autoprotective role in inhibiting disease progression and/or diminishing signs and symptoms. Accordingly, enhancement of endogenous endocannabinoid tone by inhibition of endocannabinoid degradation represents a promising therapeutic approach for the treatment of many diseases. Importantly, this allows for the avoidance of unwanted psychotropic side effects that accompany exogenously administered cannabinoids. The effects of endocannabinoid metabolic pathway modulation are complex, as endocannabinoids can exert their actions directly or via numerous metabolites. The two main strategies for blocking endocannabinoid degradation are inhibition of endocannabinoid-degrading enzymes and inhibition of endocannabinoid cellular uptake. To date, the most investigated compounds are inhibitors of fatty acid amide hydrolase (FAAH), an enzyme that degrades the endocannabinoid anandamide. However, application of FAAH inhibitors (and consequently other endocannabinoid degradation inhibitors) in medicine became questionable due to a lack of therapeutic efficacy in clinical trials and serious adverse effects evoked by one specific compound. In this paper, we discuss multiple pathways of endocannabinoid metabolism, changes in endocannabinoid levels across numerous human diseases and corresponding experimental models, pharmacological strategies for enhancing endocannabinoid tone and potential therapeutic applications including multi-target drugs with additional targets outside of the endocannabinoid system (cyclooxygenase-2, cholinesterase, TRPV1, and PGF 2α -EA receptors), and currently used medicines or medicinal herbs that additionally enhance endocannabinoid levels. Ultimately, further clinical and preclinical studies are warranted to develop medicines for enhancing endocannabinoid tone. Copyright © 2018 Elsevier Inc. All rights reserved.

The Red Flour Beetle Tribolium castaneum as a Model to Monitor Food Safety and Functionality.

PubMed

Grünwald, Stefanie; Adam, Iris V; Gurmai, Ana-Maria; Bauer, Ludmila; Boll, Michael; Wenzel, Uwe

2013-01-01

: Food quality is a fundamental issue all over the world. There are two major requirements to provide the highest quality of food: having the lowest reachable concentrations of health-threatening ingredients or contaminants and having the optimal concentrations of health-improving functional ingredients. Often, the boundaries of both requirements are blurred, as might be best exemplified by nutraceuticals (enriched food products invented to prevent or even treat diseases), for which undesirable side effects have been reported sometimes. Accordingly, there is an increasing need for reliable methods to screen for health effects of wanted or unwanted ingredients in a complex food matrix before more complex model organisms or human probands become involved. In this chapter, we present the red flour beetle Tribolium castaneum as a model organism to screen for effects of complex foods on healthspan or lifespan by assessing the survival of the beetles under heat stress at 42 °C after feeding different diets. There is a higher genetic homology between T. castaneum and humans when compared to other invertebrate models, such as Drosophila melanogaster or Caenorhabditis elegans. Therefore, the red flour beetle appears as an interesting model to study interactions between genes and food ingredients, with relevance for stress resistance and lifespan. In that context, we provide data showing reduced lifespans of the beetles when the food-relevant contaminant benz(a)pyrene is added to the flour they were fed on, whereas a lifespan extension was observed in beetles fed on flour enriched with an extract of red wine.

Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus.

PubMed

Hamady, Zaed Z R; Scott, Nigel; Farrar, Mark D; Lodge, J Peter A; Holland, Keith T; Whitehead, Terence; Carding, Simon R

2010-04-01

Human growth factors are potential therapeutic agents for various inflammatory disorders affecting the gastrointestinal tract. However, they are unstable when administered orally and systemic administration requires high doses increasing the risk of unwanted side effects. Live microorganism-based delivery systems can overcome these problems although they suffer from the inability to control heterologous protein production and there are concerns regarding biosafety and environmental contamination. To overcome these limitations we have developed a new live bacteria drug-delivery system using the human commensal gut bacterium Bacteroides ovatus engineered to secrete human growth factors in response to dietary xylan. The anaerobic nature of B ovatus provides an inherent biosafety feature. B ovatus strains expressing human keratinocyte growth factor-2, which plays a central role in intestinal epithelial homeostasis and repair (BO-KGF), were generated by homologous recombination and evaluated using the dextran sodium sulfate (DSS)-induced model of intestinal epithelial injury and colitis. In response to xylan BO-KGF produced biologically active KGF both in vitro and in vivo. In DSS treated mice administration of xylan and BO-KGF had a significant therapeutic effect in reducing weight loss, improving stool consistency, reducing rectal bleeding, accelerating healing of damaged epithelium, reducing inflammation and neutrophil infiltration, reducing expression of pro-inflammatory cytokines, and accelerating production of goblet cells. BO-KGF and xylan treatment also had a marked prophylactic effect limiting the development of inflammation and disruption of the epithelial barrier. This novel, diet-regulated, live bacterial drug delivery system may be applicable to treating various bowel disorders.

Pharmacological Activity and Clinical Use of PDRN

PubMed Central

Squadrito, Francesco; Bitto, Alessandra; Irrera, Natasha; Pizzino, Gabriele; Pallio, Giovanni; Minutoli, Letteria; Altavilla, Domenica

2017-01-01

PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects. PMID:28491036

Diagnosing and treating depression in epilepsy.

PubMed

Elger, Christian E; Johnston, Samantha A; Hoppe, Christian

2017-01-01

At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Evaluation of the effect of formic acid and sodium formate on hair reduction in rat

PubMed Central

Banihashemi, Mahnaz; Rad, Abolfazl Khajavi; Yazdi, Seyed Abbas Tabatabaee; Rakhshande, Hasan; Ghoyonlo, Vahid Mashayekhi; Zabihi, Zahra; Yousefzadeh, Hadis

2011-01-01

Hirsutism is a common problem in dermatology that imposes high socioeconomical costs on medical care. Consequently, researchers are actively searching for cheaper and safer methods for therapeutic treatment. The objective of the present study is to evaluate formic oil, enriched from formic acid, for the removal of unwanted hair. In this study, 32 female rats (150–200 g) were randomly divided into four groups and maintained with normal water and food availability. A patch of skin was shaved on each rat for application of test solutions. The control group was treated with local once-daily applications of normal saline. The formic acid, acetic acid, and sodium formate groups were treated with once-daily applications of formic acid (pH 5.5), acetic acid (pH 5.5), or sodium formate, respectively. After 2 weeks, horizontally cut sample biopsies were removed, and the numbers of hair follicles were counted under high field microscopy by a specialist blinded to the treatments. Kolmogorov–Smirnov test results indicated a nonparametric distribution for the rat groups. ANOVA analysis indicated no statistically significant differences between groups (P < 0.05). There weren’t any side effects or evidence for toxicity during the study period. However, hair follicle counts showed a descending order of control, acetic acid, formic acid, and sodium formate. Although the sodium formate group had the lowest hair follicle numbers, the difference was not statistically significant (P > 0.05). Formic acid was not effective in reducing hair follicle numbers in rats. PMID:21760741

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic.

PubMed

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R Craig

2015-10-07

Exposure to antibiotics induces the expression of mutagenic bacterial stress-response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress-response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. © 2015 The Authors.

The SOS response increases bacterial fitness, but not evolvability, under a sublethal dose of antibiotic

PubMed Central

Torres-Barceló, Clara; Kojadinovic, Mila; Moxon, Richard; MacLean, R. Craig

2015-01-01

Exposure to antibiotics induces the expression of mutagenic bacterial stress–response pathways, but the evolutionary benefits of these responses remain unclear. One possibility is that stress–response pathways provide a short-term advantage by protecting bacteria against the toxic effects of antibiotics. Second, it is possible that stress-induced mutagenesis provides a long-term advantage by accelerating the evolution of resistance. Here, we directly measure the contribution of the Pseudomonas aeruginosa SOS pathway to bacterial fitness and evolvability in the presence of sublethal doses of ciprofloxacin. Using short-term competition experiments, we demonstrate that the SOS pathway increases competitive fitness in the presence of ciprofloxacin. Continued exposure to ciprofloxacin results in the rapid evolution of increased fitness and antibiotic resistance, but we find no evidence that SOS-induced mutagenesis accelerates the rate of adaptation to ciprofloxacin during a 200 generation selection experiment. Intriguingly, we find that the expression of the SOS pathway decreases during adaptation to ciprofloxacin, and this helps to explain why this pathway does not increase long-term evolvability. Furthermore, we argue that the SOS pathway fails to accelerate adaptation to ciprofloxacin because the modest increase in the mutation rate associated with SOS mutagenesis is offset by a decrease in the effective strength of selection for increased resistance at a population level. Our findings suggest that the primary evolutionary benefit of the SOS response is to increase bacterial competitive ability, and that stress-induced mutagenesis is an unwanted side effect, and not a selected attribute, of this pathway. PMID:26446807

Legal Briefing: Unwanted Cesareans and Obstetric Violence.

PubMed

Pope, Thaddeus Mason

2017-01-01

A capacitated pregnant woman has a nearly unqualified right to refuse a cesarean section. Her right to say "no" takes precedence over clinicians' preferences and even over clinicians' concerns about fetal health. Leading medical societies, human rights organizations, and appellate courts have all endorsed this principle. Nevertheless, clinicians continue to limit reproductive liberty by forcing and coercing women to have unwanted cesareans. This "Legal Briefing" reviews recent court cases involving this type of obstetric violence. I have organized these court cases into the following six categories: 1. Epidemic of Unwanted Cesareans 2. Court-Ordered Cesareans 3. Physician-Coerced Cesareans 4. Physician-Ordered Cesareans 5. Cesareans for Incapacitated Patients 6. Cesareans for Patients in a Vegetative State or Who Are Brain Dead. Copyright 2017 The Journal of Clinical Ethics. All rights reserved.